Inherently chiral phosphonatocavitands as artificial chemo ...before use. Resolution of enantiomers was performed using a Lachrom Elite HPLC using commercial semi-preparative chiral

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Supporting Information

Inherently chiral phosphonatocavitands as artificial chemo and enantioselective receptors of natural ammoniums

Jérôme Vachon,[a] Steven Harthong,[a] Erwann Jeanneau,[b] Christophe Aronica,[a], Nicolas

Vanthuyne,[c] Christian Roussel[c] and Jean-Pierre Dutasta[a]*

[a] Laboratoire de Chimie, CNRS, École Normale Supérieure de Lyon, 46 allée d’Italie, F-69364 Lyon (France) [email protected]

[b] Centre de Diffractométrie Henri Longchambon, Université Claude Bernard – Lyon 1, 43 boulevad du 11 Novembre 1918, F-69622 Villeurbanne (France)

[c] Chirosciences, Université Paul Cézanne, Case A62, avenue Escadrille Normandie Niemen F-13397 Marseille (France)

CONTENT OF THE SUPPORTING INFORMATION : General Remarks……………. …………………...………………………………………….. 4 Synthesis of cavitands (±)-3 “ABii(PS,PN,C11)” and 4 “ABii(PS,bisPN,C11)”………………..5 Synthesis of cavitand (±)-5 “ABii(PO,PN,C11)”…………….…………….………………… 6 Synthesis of cavitands (±)-6 “ABii(PS,CH2,C11)” and 7 “ABii(PS,bisCH2,C11)”…………….. 7 Synthesis of cavitand (±)-8 “ABii(PO,CH2,C11)”…………………………….……………… 8 Synthesis of cavitands (±)-11 “ABii(PO)Ci(PS)”, (±)-12 “ABii(PO)CDio(PS)” and 13 “ABii(PO)CDii(PS)”………………………………………………………………………….. 9 Synthesis of cavitand (±)-15 (C11H23) and (Ra)-15 (C11H23)……………..…….…………… 12 Synthesis of cavitand (±)-16 (C11H23) and (Ra)-16 (C11H23)………………….…………….. 13 Figure S1 : 1H NMR (CDCl3, 500MHz, 293K) of (±)-1 ..…..………………….…………… 15 Figure S2 : 1H NMR (CDCl3, 500MHz, 293K) of (±)-1 (expansion)…..………………...…. 16 Figure S3 : 1H NMR (CDCl3, 500MHz, 293K) of (±)-1 (expansion)…..……………...……. 17 Figure S4 : 13C NMR (CDCl3, 125.75 MHz, 293K) of (±)-1……..………………….……… 18 Figure S5 : 13C NMR (CDCl3, 125.75 MHz, 293K) of (±)-1 (expansion)……..…….……… 19 Figure S6 : 13C NMR (CDCl3, 125.75 MHz, 293K) of (±)-1 (expansion)…………………... 20 Figure S7 : jmod (CDCl3, 125.75 MHz, 293K) of (±)-1…………………………………..… 21 Figure S8 : jmod (CDCl3, 125.75 MHz, 293K) of (±)-1 (expansion)……………………….. 22 Figure S9 : jmod (CDCl3, 125.75 MHz, 293K) of (±)-1 (expansion)………..……………… 23 Figure S10 : 31P (CDCl3, 202.45 MHz, 293K) of (±)-1 …………………………………...... 24 Figure S11 : Semi-Preparative HPLC Optical Resolution of (±)-1 ........................................ 25 Figure S12 : 1H NMR (CDCl3, 500MHz, 293K) of (±)-3 ………………………………..…. 26 Figure S13 : 13C NMR (CDCl3, 50.32 MHz, 293K) of (±)-3 ……………………………..… 27 Figure S14 : 31P (CDCl3, 81.01 MHz, 293K) of (±)-3 ………………..…………………….. 28 Figure S15 : 1H NMR (CDCl3, 200MHz, 293K) of (±)-4 …………………………………... 29 Figure S16 : 13C NMR (CDCl3, 50.32 MHz, 293K) of (±)-4 ……………………………..… 30 Figure S17 : 31P (CDCl3, 81.01 MHz, 293K) of (±)-4………………...…………………..… 31 Figure S18 : 1H NMR (CDCl3, 200MHz, 293K) of (±)-5 ………………………………...… 32 Figure S19 : 13C NMR (CDCl3, 50.32 MHz, 293K) of (±)-5……………............................... 33 Figure S20 : 31P (CDCl3, 81.01 MHz, 293K) of (±)-5 …..………………………...……...… 34 Figure S21 : 1H NMR (CDCl3, 200MHz, 293K) of (±)-6 …………………........................... 35 Figure S22 : 13C NMR (CDCl3, 125.75 MHz, 293K) of (±)-6…………………………….… 36 Figure S23 : 31P (CDCl3, 81.01 MHz, 293K) of (±)-6 ………………….…….…………….. 37 Figure S24 : 1H NMR (CDCl3, 200MHz, 293K) of 7………………..…….……..…………. 38

Supplementary Material (ESI) for Organic & Biomolecular ChemistryThis journal is © The Royal Society of Chemistry 2011

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Figure S25 : 13C NMR (CDCl3, 125.75 MHz, 293K) of 7 .…………………………………. 39 Figure S26 : 31P (CDCl3, 81.01 MHz, 293K) of 7..…………………………………………. 40 Figure S27 : 1H NMR (CDCl3, 500MHz, 293K) of (±)-8………………………………….... 41 Figure S28 : 1H NMR (CDCl3, 500MHz, 293K) of (±)-8 (expansion) .…………………..… 42 Figure S29 : 13C NMR (CDCl3, 50.32 MHz, 293K) of (±)-8 ……..………………………… 43 Figure S30 : 13C NMR (CDCl3, 50.32 MHz, 293K) of (±)-8 (expansion)…………………... 44 Figure S31 : 13C NMR (CDCl3, 125.75 MHz, 293K) of (±)-8 (expansion)…………………. 45 Figure S32 : 31P (CDCl3, 202.45 MHz, 293K) of (±)-8 ……………..…………………….... 45 Figure S33 : jmod (CDCl3, 125.75 MHz, 293K) of (±)-8………………...…………………. 46 Figure S34 : Semi-Preparative HPLC Optical Resolution of (±)-8 ………………...………. 47 Figure S35 : 1H NMR (CDCl3, 500MHz, 293K) of (±)-11 ………………............................. 48 Figure S36 : HSQC (CDCl3, F1 :125.75 MHz, F2 : 500 Mhz, 293K) of (±)-11.………….... 49 Figure S37 : HMBC (CDCl3, F1 :125.75 MHz, F2 : 500 Mhz, 293K) of (±)-11………….....50 Figure S38 : 31P (CDCl3, 81.01 MHz, 293K) of (±)-11 .…………………............................. 51 Figure S39 : 1H NMR (CDCl3, 500MHz, 293K) of (±)-12 …………………………………. 52 Figure S40 : 1H NMR (CDCl3, 500MHz, 293K) of (±)-12 (expansion) ………………...….. 53 Figure S41 : jmod (CDCl3, 125.75 MHz, 293K) of (±)-12 ………………...…………..…… 54 Figure S42 : 31P (CDCl3, 202.45 MHz, 293K) of (±)-12 ........................................................ 55 Figure S43 : 1H NMR (CDCl3, 500MHz, 293K) of 13 ………………...…………………… 56 Figure S44 : 13C NMR (CDCl3, 125.75 MHz, 293K) of 13 ………………………………… 57 Figure S45 : jmod (CDCl3, 125.75 MHz, 293K) of 13 …..…………………………………. 58 Figure S46 : 31P (CDCl3, 81.01 MHz, 293K) of 13 …….……..……...…………………….. 59 Figure S47 : 1H NMR (CDCl3, 500MHz, 293K) of (±)-15 …………………………………. 60 Figure S48 : 13C (CDCl3, 125.75 MHz, 293K) of (±)-15…...……….………………………. 61 Figure S49 : 31P (CDCl3, 202.45 MHz, 293K) of (±)-15 ………………………………….... 62 Figure S50 : 1H NMR (CDCl3, 500MHz, 293K) of (±)-16 .…………………..…………….. 63 Figure S51 : 1H NMR (CDCl3, 500MHz, 293K) of (±)-16 (expansion)..…………………… 64 Figure S52 : 13C (CDCl3, 125.75 MHz, 293K) of (±)-16………………………………..…... 65 Figure S53 : 31P (CDCl3, 202.45 MHz, 293K) of (±)-16 ………………...…………………. 66 Figure S54 : ECD spectra of compounds 1, 8 and 16………………...……………………... 67 Figure S55 : Complexation experiment : Nicotine@(±)-1 ………...………………………... 68 Figure S56 : Complexation experiment : Adrenaline@(±)-1 ……………............................. 69 Figure S57 : Complexation experiment : Ephedrine@(±)-1 ………………………………....70 Figure S58 : Complexation experiment : Pseudoephedrine@(±)-1…………………............. 71 Figure S59 : Complexation experiment : Norephedrine@(±)-1…………………...………... 72 Figure S60 : Complexation experiment : Adrenaline@(±)-5 ……………………………….. 73 Figure S61 : Complexation experiment : Nicotine@(±)-8 ....…………………...……..…… 74 Figure S62 : Complexation experiment : Adrenaline@(±)-8.................................................. 75 Figure S63 : Complexation experiment : Ephedrine@(±)-8 ………………………………... 76 Figure S64 : Complexation experiment : Pseudoephedrine@(±)-8………………………… .77 Figure S65 : Complexation experiment : Ephedrine@(±)-11……..……………………....... 78 Figure S66 : Complexation experiment : Adrenaline@(±)-16 .…….……..…………...…… 79 Figure S67 : Complexation experiment : Pseudoephedrine@(±)-16 ……………………….. 80 Figure S68 : Complexation experiment : Ephedrine/Pseudoephedrine/Norephedrine@(-)-1 81 Figure S69 : Complexation experiment : Ephedrine/Pseudoephedrine/Norephedrine@(+)-1 82 Figure S70 : Complexation experiment : Ephedrine/Pseudoephedrine/Norephedrine@(-)-8 83 Figure S71 : Complexation experiment : Ephedrine/Pseudoephedrine/Norephedrine@(+)-8 84 X-ray crystallography Data collection ……...……………...…….……..…………...……… 85


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Figure S72 : Thermal ellipsoid plot of the crystallographic structure of [8•CHCl3•CH3OH] (probability level 50%)………………………………………………………………....…… 86 Figure S73 : Thermal ellipsoid plot of the crystallographic structure of 12 (probability level 50%)…………………………………………………………………………………………..86 Table S1. Crystal Data and Structure Refinement for [8•CHCl3•CH3OH] and 12.….……… 87


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GENERAL REMARKS

Reactions were carried out using commercial available reagents in oven-dried apparatus.

Toluene, Et2O and THF were dried and distilled from sodium benzophenone under nitrogen

just before use. CH2Cl2 was dried over powdered CaH2 and distilled under nitrogen just

before use. Resolution of enantiomers was performed using a Lachrom Elite HPLC using

commercial semi-preparative chiral column Chiralpak IC (250 x 10 mm, 5 µm) or Chiralpak

IA (250 x 10 mm, 5 µm) thermostated at 30 °C with UV detector at 254 nm and CD detector

at 277 nm. Enantiomeric excesses (ee) were determined by HPLC using commercial

analytical chiral column Chiralpak IC (250 x4.6 mm, 5 µm) or Chiralpak IA (250 x 4,6 mm, 5

µm) using same conditions. Optical rotations were measured on a Perkin-Elmer 241 MC

polarimeter, equipped with a sodium lamp (589 nm), a mercury lamp (578, 546, 436 and 365

nm), a 10 cm double envelop cell thermostated at 25°C and were reported as follows: [α]25D

(c g/100 mL, in solvent). NMR experiments were recorded on 200 MHz (4.7 T) or 500 MHz

(11.7 T) NMR spectrometers. J Coupling constants are in Hz; chemical shifts are in δ values

relative to Me4Si (1H and 13C) or H3PO4 85% (31P). 13C and 31P NMR spectra are proton

decoupled. Spectra are reported as follows: chemical shift (δ ppm), multiplicity (s = singlet, d

= doublet, t = triplet, q = quartet, m = multiplet), coupling constants (Hz), integration and

assignment. HRMS was recorded on a commercial apparatus (ESI Source, TOF). Mass

spectra were acquired on an ion trap instrument, detecting positive (+) ions in the ESI mode.

Electronic Circular Dichroism (ECD) spectra were recorded on a JASCO J-815 CD

spectrometer in a 1.0 cm quartz cell; λ are given in nm and molar circular dichroic

absorptions Δε in cm2.mmol−1.


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Synthesis of cavitands (±)-3 “ABii(PS,PN,C11)” and 4 “ABii(PS,bisPN,C11)”

Triethylamine (120 µL, 0,87 mmol) was added to a solution of compound 2 (300 mg, 0.22

mmol) in toluene (30 mL). Hexamethylphosphorous triamide (40 µL, 0,22 mmol) was added

at 75°C. The resultant mixture was stirred at 75°C for 90 min, sulfur (30 mg, 0.93 mmol) was

then added and the solution was stirred at 75°C for one more hour. After evaporation of the

solvent, the crude compound was purified by silica gel column chromatography (eluent

CH2Cl2/pentane: from 1:1 to 3:1 then CH2Cl2/ethyl acetate: from 1:0 to 7:3) to give the di-

bridged compound 4 (47 mg, 13%), the mono-bridged compound 3 (140 mg, 43%) and the

starting compound 2 (60 mg, 20%).

(±)-3 “ABii(PS,PN,C11)”

LSIMS m/z 1486.7618 [M + H]+ (calc. 1486.7545)

31P NMR (CDCl3, 300 K, 81.01 MHz): δ 66.67 (1P, SPN), 77.88

(1P, SPPh), 78.70 (1P, SPPh)

1H NMR (CDCl3, 300 K, 200.13 MHz): δ 0.87 (m, 12H, CH3),

1.26 (m, 72H, -CH2-(CH2)9-CH3), 2.27 (m, 8H, -CH2- (CH2)9-

CH3), 2.98 (d, 6H, PN-CH3, 3JP-H = 12.3 Hz), 4.35 (t, 1 H, CHc, 3J

= 7.4 Hz), 4.56 (t, 1 H, CHd, 3J = 7.4 Hz), 4.68 (m, 2 H, CHa + CHb), 6.50 (m, 2H, H1b + H1c),

6.63 (m, 2H, H1a + H1d), 7.11 (m, 2H, H2b + H2c), 6.63 (m, 2H, H2a + H2d), 7.53 (m, 4H, H4 +

H5), 8.14 (m, 4H, H3)

13C NMR (CDCl3, 300 K, 125.75 MHz): δ 14.14 (-CH2-(CH2)9-CH3), 22.72 (-CH2-(CH2)7-

CH2-CH3), 28.02 (-CH2-(CH2)9-CH3), 29.43 (-CH2-(CH2)9-CH3), 29.75 (-CH2-(CH2)9-CH3),

30.58 (-CH2-CH2-(CH2)8-CH3), 30.94 (-CH2-CH2-(CH2)8-CH3), 31.69 (-CH2-CH2-(CH2)8-

CH3), 31.96 (-CH2-CH2-(CH2)8-CH3), 33.66 (-CH2-CH2-(CH2)8-CH3), 33.84 (CHc), 35.46

(CHa/b/d), 35.76 (CHa/b/d) 35.98 (CHa/b/d), 37.55 (CH3-N-P), 111.47 (CH1b/c), 111.98 (CH1b/c),

119.16 (CH1a/d), 119.41 (CH1a/d), 121.30 (CH2), 121.73 (CH2), 122.60 (CH2), 122.92 (CH2),

128.31 (d, C4a/b, 3J = 15.5 Hz), 128.35 (d, C4a/b, 3J = 15.5 Hz), 129.37 (CAr), 129.83 (CAr),

130.42 (CAr), 131.10 (d, C3, 2J = 11.5 Hz), 132.67 (C5), 133.63 (CAr), 134.70 (CAr), 135.14

(CAr), 135.79 (CAr), 136.03 (CAr), 146.38 (m, CAr-OP), 151.51 (CAr-OH), 151.76 (CAr-OH)


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4 “ABii(PS,bisPN,C11)”

LSIMS m/z 1613.7224 [M + Na]+ (calc. 1613.7240)

31P NMR (CDCl3, 300 K, 81.01 MHz): δ 68.64 (2P, SPN), 79.31

(2P, SPPh)


1.27 (m, 72H, -CH2-(CH2)9-CH3), 2.27 (m, 8H, -CH2- (CH2)9-

CH3), 2.94 (d, 12H, PN-CH3, 3JP-H = 11.9 Hz), 4.56 (t, 2 H, CHb, 3J = 7.1 Hz), 4.69 (t, 2 H, CHa, 3J = 7.1 Hz), 6.61 (m, 4H, H1), 7.14 (s, 1H, H2a/c), 7.17 (s, 2H,

H2b), 7.21 (s, 1H, H2a/c), 7.52 (m, 4H, H4 + H5), 8.14 (dd, 4H, 3JH-H = 7.2 Hz, 3JP-H = 14.6 Hz,

H3)


CH2-CH3), 27.97 (-CH2-(CH2)9-CH3), 29.42 (-CH2-(CH2)9-CH3), 29.74 (-CH2-(CH2)9-CH3),

30.92 (-CH2-CH2-(CH2)8-CH3), 31.22 (-CH2-CH2-(CH2)8-CH3), 31.96 (-CH2-CH2-(CH2)8-

CH3), 35.74 (CHa/b), 36.02 (CHa/b), 37.53 (d, CH3-N-P, 2J = 3.8 Hz), 119.87 (m, CH1), 121.39

(CH2a/c), 121.80 (CH2b), 122.16 (CH2a/c), 128.23 (d, C4, 3J = 15.8 Hz), 131.13 (d, C3, 2J = 12.0

Hz), 132.05 (d, CP, 1J = 162.3 Hz) 132.05 (C5), 134.39 (CAr), 134.60 (CAr), 134.82 (CAr),

135.07 (CAr), 146.32 (CAr-OP), 146.54 (CAr-OP), 146.88 (CAr-OP), 147.06 (CAr-OP).

Synthesis of cavitand (±)-5 “ABii(PO,PN,C11)”

m-Chloroperoxybenzoic acid (66.5 mg, 0,38 mmol) was added to

a solution of cavitand (±)-3 (100 mg, 0.07 mmol) in CHCl3 (10

mL). The mixture was stirred at room temperature for 1 h. After

evaporation of the solvent, the crude compound was purified by

silica gel column chromatography (eluent CH2Cl2/THF from 9:1

to 1:1) to give (±)-5 as a white solid (35 mg, 35%).

LSIMS m/z 1438.8303 [M + H]+ (calc. 1438.8231)

31P NMR (CDCl3, 300 K, 81.01 MHz): δ -1.67 (1P, SPN), 8.13 (1P, SPPh), 8.73 (1P, SPPh)

1H NMR (CDCl3, 300 K, 500.10 MHz): δ 0.86 (m, 12H, CH3), 1.24 (m, 72H, -CH2-(CH2)9-

CH3), 2.10 (m, 2H, (-CH2- (CH2)9-CH3)c), 2.26 (m, 6H, -CH2- (CH2)9-CH3), 2.85 (d, 6H, PN-

CH3, 3JP-H = 10.7 Hz), 4.31 (t, 1 H, CHc, 3J = 7.7 Hz), 4.53 (t, 1 H, CHd, 3J = 7.5 Hz), 4.69 (m,


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2 H, CHb+ CHa), 6.62 (s, 1H, H1b), 6.65 (s, 1H, H1c), 6.89 (s, 1H, H1d), 6.94 (s, 1H, H1a), 7.05

(s, 1H, H2c), 7.07 (s, 1H, H2b), 7.19 (s, 1H, H2d), 7.23 (s, 1H, H2a), 7.50 (m, 4H, H4), 7.59 (m,

2H, H5), 8.02 (m, 4H, H3)

13C NMR (CDCl3, 300 K, 50.32 MHz): δ 14.13 (-CH2-(CH2)9-CH3), 22.71 (-CH2-

(CH2)9-CH3), 27.93 (m, -CH2-(CH2)9-CH3), 29.42 (m, -CH2-(CH2)9-CH3), 29.74 (m, -CH2-

(CH2)9-CH3), 30.38 ((-CH2-(CH2)9-CH3)b/a/d), 30.76 ((-CH2-(CH2)9-CH3)a/b/d), 30.99 ((-CH2-

(CH2)9-CH3)a/b/d), 31.96 (m, -CH2-(CH2)9-CH3), 33.61 ((-CH2-(CH2)9-CH3)c), 33.80 (CHc),

35.43 (CHd), 35.86 (CHb), 36.96 (CHa), 36.91 (CH3-N-P), 110.67 (CH1c), 111.54 (CH1b),

116.86 (CH1d), 117.21 (CH1a), 121.30 (CH2d), 121.82 (CH2a), 122.53 (CH2c), 122.82 (CH2b),

126.51 (d, CP, 1J = 202.0 Hz), 126.75 (d, CP, 1J = 202.0 Hz), 128.32 (CAr entre Hb et H2b),

128.39 (CAr entre Hd et H2c), 128.43 (d, C4, 3J = 15.9 Hz), 128.59 (d, C4, 3J = 15.9 Hz), 129.26

(CAr between Hc et H2c), 129.96 (CAr between Hc et H2b), 131.70 (m, C3), 131.44, 133.10 (m,

C5), 134.08 (CAr entre Ha et H2d), 134.59 (CAr entre Ha et H2a), 135.76 (CAr entre Hd et H2d),

135.86 (CAr entre Ha et H2b), 145.40 (CAr-OP near H1b), 145.63 (CAr-OPN near H1c), 146.04

(CAr-OP near H1a + CAr-OP near H1d), 146.43 (CAr-OP near H1a), 146.89 (CAr-OPN near H1d),

152.37 (CAr-OHc), 152.99 (CAr-OHb)

Synthesis of cavitands (±)-6 “ABii(PS,CH2,C11)” and 7 “ABii(PS,bisCH2,C11)”

To a solution of compound 2 (160 mg, 0,116 mmol) in dry DMF (15 mL) was added, under

N2 atmosphere, potassium carbonate (40 mg, 0,289 mmol) and iodochloromethane (20,5 mg,

0,116 mmol) in DMF (5 mL). The mixture was stirred at 90 °C for 15 h and then poured into

water (100mL). The solution was extracted with ethyl acetate (4 x 50 mL), and the combined

organic phases were washed with brine, dried over Na2SO4 and evaporated to dryness under

vacuum to give a brown residue. The crude compound was purified by silica gel column

chromatography (eluent CH2Cl2/EtOAc from 99:1 to 95:5) to give compound 7 as a white

solid (40 mg, 21%). Further elution with CH2Cl2/EtOAc from 95:5 to 9:1 gave compound (±)-

6 as a white solid (85 mg, 53%).

(±)-6 “ABiiPSCH2C11”

LSIMS m/z 1393.7827 [M + H]+ (calc. 1393.7743) 31P NMR (CDCl3, 300 K, 81.01 MHz) : δ 77.69 (1P), 77.67 (1P).


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1H NMR (CDCl3, 300 K, 500.10 MHz) δ 0.87 (m, 12H, CH3), 1.25-1.44 (m, 72H, -CH2-

(CH2)9-CH3), 2.27 (m, 8H, (-CH2- (CH2)9-CH3)), 4.33 (t, J = 7.5 Hz, 1 H), 4.60-4.73 (m, 3 H),

4.78 (d, J = 7.2 Hz, 1 H), 5.66 (d, J = 7.2 Hz, 1 H), 6.42 (s, 1H), 6.43 (s, 1H), 6.56 (s, 1H),

6.68 (s, 1H), 7.10 (s, 1H), 7.11 (s, 1H), 7.24 (m, 4H), 7.25 (s, 1H), 7.52 (b, 4H), 7.59 (m, 2H),

8.15 (m, 4H). 13C NMR (CDCl3, 300 K , 125.75 MHz) δ 15.54, 24.11, 29.40 (d), 30.83 (b), 31.18 (b), 31.32,

31.69, 32.33, 32.54, 33.36 (b), 34.62, 34.62, 35.30, 37.15, 37.32, 37.48, 100.74, 112.22,

113.25, 119.30, 120.70, 122.16, 123.27, 123.34, 124.36, 129.75 (d, 3J = 15.7 Hz), 129.85 (d, 3J = 15.2 Hz), 131.15, 131.41, 132.23, 132.40 (d, 2J = 11.1 Hz), 133.54, 133.74, 133.32 (d, 2J

= 10.3 Hz), 134.64, 135.62, 137.09, 137.42, 140.79, 147.20, 147.28, 147.36, 152.71, 152.97,

156.42, 156.81.

7 “ABiiPSbisCH2C11”

LSIMS m/z 1427.7619 [M + Na]+ (calc. 1427.7636) 31P NMR (CDCl3, 300 K, 81.01 MHz) : δ 78.29 (2P). 1H NMR (CDCl3, 300 K, 500.10 MHz) δ 0.86 (m, 12H, CH3), 1.24-

1.43 (m, 72H, -CH2-(CH2)9-CH3), 2.22-2.28 (m, 8H, (-CH2- (CH2)9-

CH3)), 4.64 (d, J = 7.3 Hz, 2H), 4.69 (t, J = 8.1 Hz, 2H), 4.74 (t, J =

8.1 Hz, 2H), 5.70 (d, J = 7.2 Hz, 2 H), 6.55 (s, 1H), 6.56 (s, 1H), 6.57

(s, 1H), 6.66 (s, 1H), 7.17 (s, 1H), 7.18 (s, 1H), 7.19 (s, 2H), 7.52 (m, 4H), 7.61 (t, J = 7.1 Hz,

2H), 8.11 (d, J = 7.3 Hz, 2H), 8.14 (d, J = 7.2 Hz, 2H). 13C NMR (CDCl3, 300 K , 125.75 MHz) δ 14.14, 22.71, 27.94, 28.00, 29.38, 29.42, 29.80,

29.89, 30.23, 30.88, 31.96, 36.02, 36.34, 99.76, 117.09, 118.11, 119.84, 120.34, 121.25,

122.25, 128.44 (d, 3J = 15.8 Hz), 128.37, 128.50, 131.04 (d, 2J = 11.8 Hz), 132.16, 132.98,

134.30, 135.67, 137.75, 138.99, 145.95 (d, 2J = 11.8 Hz), 145.97, 155.06, 155.16.

Synthesis of cavitand (±)-8 “ABii(PO,CH2,C11)”

m-Chloroperoxybenzoic acid (32.9 mg, 0,133 mmol) was added to a

solution of cavitand (±)-6 (62 mg, 0,044 mmol) in CHCl3 (5 mL). The

mixture was stirred at room temperature for 2 h. After evaporation of

the solvent, the crude compound was purified by silica gel column

chromatography (eluent CH2Cl2 to CH2Cl2/THF 9:1 to

CH2Cl2/THF/Acetone 7:1:2) to give compound (±)-8 as a white solid


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(57 mg, 95%).

LSIMS m/z 1361.8268 [M + H]+ (calc. 1361.8200) 31P NMR (CDCl3, 300 K, 202.45 MHz) : δ 10.57 (1P), 9.63 (1P). 1H NMR (CDCl3, 300 K, 500.10 MHz) δ 0.86 (m, 12H, CH3), 1.25 (m, 72H, -CH2-(CH2)9-

CH3), 2.20 (m, 8H, (-CH2- (CH2)9-CH3)), 4.31 (t, J = 7.4 Hz, 1 H), 4.60 (m, 2 H), 4.69 (m, 2

H), 5.61 (d, J = 6.9 Hz, 1 H), 6.34 (s, 1H), 6.53 (s, 1H), 7.04 (s, 1H), 7.09 (s, 1H), 7.19 (s,

1H), 7.23 (s, 1H), 7.48 (m, 4H), 7.54 (q, J = 7.0 Hz, 1H), 7.58 (q, J = 7.2 Hz, 1H), 8.00 (m,

4H). 13C NMR (CDCl3, 300 K , 125.75 MHz) δ 14.13 (d), 22.71 (d), 28.00 (m), 29.43 (m), 29.75

(m), 29.87, 29.92, 30.33, 30.36, 30.73, 30.90, 31.96 (m), 33.15, 33.85, 35.95, 36.07, 99.48,

110.65, 110.99, 116.98, 117.14, 120.88, 122.15, 123.36, 124.85, 125.54, 125.66 (d, CP, 1J =

204.3 Hz), 126.21 (d, CP, 1J = 203.9 Hz), 128.19, 128.26, 128.49, 128.54, 128.55 (d, 3J = 16.4

Hz), 128.76 (d, 3J = 16.3 Hz), 129.67, 130.13, 130.39, 131.55 (d, 2J = 10.2 Hz), 131.67 (d, 2J

= 10.2 Hz), 132.35, 133.18, 133.31, 133.43, 134.47, 135.34, 139.78, 145.00, 145.08, 145.39,

145.48, 145.90, 145.99, 146.08, 152.08, 152.13, 155.46.

9 “ABiiPOBisCH2C11”

Already described in: M. Suman, M. Freddi, C. Massera, F. Ugozzoli,

and E. Dalcanale, J. Am. Chem. Soc., 2003, 125, 12068.

Synthesis of cavitands (±)-11 “ABii(PO)Ci(PS)”, (±)-12 “ABii(PO)CDio(PS)” and 13

“ABii(PO)CDii(PS)”.

a) The azeotropic distillation, by means of a Dean and Stark apparatus, of a

suspension of compound 10 (135 mg, 0,1 mmol) in toluene (12 mL) was performed overnight

under dry argon to remove traces of water from the starting material. Afterwards, pyridine

(0,5 mL, 6,2 mmol), and dichlorophenylphosphine (30 µL, 0,22 mmol) were added dropwise

at 0°C. The resultant mixture was stirred at 0°C for 45 min and then allowed to reach room

temperature. Sulfur (10 mg, 0,31 mmol) was then added and the solution was heated at reflux

temperature for 6 h. The resulting mixture was concentrated under vacuum to give a beige


S10

residue (250 mg). Silica gel column chromatography (eluent CH2Cl2/THF: from 1:0 to 9:1) of

the residue afforded compounds (±)-12 (40 mg, 25%) and 13 (40 mg, 25%).

b) The azeotropic distillation, by means of a Dean and Stark apparatus, of a

suspension of compound 10 (135 mg, 0,1 mmol) in toluene (12 mL) was performed overnight

under dry argon to remove traces of water from the starting material. Afterwards, pyridine

(0,5 mL, 6,2 mmol), and dichlorophenylphosphine (15 µL, 0,11 mmol) were added dropwise

at 0°C. The resultant mixture was stirred at 0°C for 45 min and then allowed to reach room

temperature. Sulfur (10 mg, 0,31 mmol) was then added and the solution was heated at reflux

temperature for 6 h. The resulting mixture was concentrated under vacuum to give a beige

residue (250 mg). Silica gel column chromatography (eluent: CH2Cl2/THF: from 1:0 to 2:1

and next CH2Cl2/CH3OH 9:1) of the residue afforded the 11 compound (43 mg, 29%).

(±)-11 “ABii(PO)Ci(PS)”

LSIMS m/z 1509.7786 [M + Na]+ (calc. 1509.7791)

31P NMR (CDCl3, 300 K, 202.45 MHz): 8.56 (1P), 9.42 (1P),

76.89 (1P)

1H NMR (CDCl3, 300 K, 200.13 MHz): 0.85 (m, 12H, CH3), 1.26

(m, 72H, -CH2-(CH2)9-CH3), 2.12 (m, 4H, -CH2- (CH2)9-CH3),

2.26 (m, 4H, -CH2- (CH2)9-CH3), 4.33 (m, 1H, CHc), 4.33 (m, 3H, CHa,b,d), 6.48 (s, 1H, H1),

6.63 (s, 1H, H1), 6.81 (s, 1H, H1), 6.96 (s, 1H, H1), 7.01 (s, 1H, H2), 7.14 (s, 1H, H2), 4.24 (s,

1H, H2), 7.27 (s, 1H, H2), 7.49 (m, 7H, H4a,b,d + H5d), 7.57 (m, 2H, H5a,b), 8.00 (m, 4H, H3a,b),

8.15 (m, 2H, H3d)


CH2-CH3), 28.02 (-CH2-(CH2)7-CH2-CH2-CH3), 29.63 (-CH2-(CH2)9-CH3), 30.15 (-CH2-

(CH2)9-CH3), 30.73 (-CH2-CH2-(CH2)8-CH3), 31.44 (-CH2-CH2-(CH2)8-CH3), 31.89 (-CH2-

CH2-(CH2)8-CH3), 33.50 (-CH2-CH2-(CH2)8-CH3), 33.75 (CHc), 35.82 (CHa,b,d), 110.13

(CH1), 112.69 (CH1), 117.13 (CH1), 118.15 (CH1), 121.65 (CH2), 121.93 (CH2), 122.62

(CH2), 123.16 (CH2), 128.30 (C4), 131.07 (C3-PS), 131.57 (C3-PO), 132.61 (C5-PO), 133.23 (C5-

PS), 134.39 (CAr), 136.60 (CAr), 146.28 (d, CAr-OP), 152.47 (CAr-OH)

(±)-12 “ABii(PO)CDio(PS)”


S11

LSIMS m/z 1625.7659 [M + H]+ (calc. 1625.7620)

31P NMR (CDCl3, 298 K, 202.45 MHz): δ 8.96 (1P, PO), 10.51

(1P, PO), 77.70 (1P, PS), 79.25 (1P, PS)


1.30 (m, 72H, -CH2-(CH2)9-CH3), 2.31 (m, 4H, -CH2- (CH2)9-

CH3), 2.37 (m, 4H, -CH2- (CH2)9-CH3), 4.73 (t, 1 H, 3J = 7.55,

CHb), 4.77 (m, 2 H, CHa + CHc), 4.86 (t, 1 H, 3J = 7.58, CHd), 6.27 (s, 1H, H1d), 6.31 (s, 1H,

H1c), 6.37 (dd, 2H, 3JH-H = 7.8 Hz, 3JP-H = 14.1 Hz, H3d), 6.64 (m, 2H, H4d), 6.74 (s, 1H, H1b),

7.01 (s, 1H, H2a), 7.33 (m, 3H, H2a + H2b), 7.35 (s, 1H, H2d + H5d), 7.37 (s, 1H, H2c), 7.46 (m,

4H, H4a + H4c), 7.56 (m, 4H, H4b + H5a+ H5c), 7.63 (t, 1 H, 3J = 7.1, H5b), 7.90 (dd, 2H, 3JH-H =

7.3 Hz, 3JP-H = 14.2 Hz, H3a), 7.99 (dd, 2H, 3JH-H = 7.4 Hz, 3JP-H = 14.8 Hz, H3c), 8.06 (dd, 2H, 3JH-H = 7.3 Hz, 3JP-H = 14.1 Hz, H3b)


CH3), 28.01 (m, -CH2-(CH2)9-CH3), 29.42 (m, -CH2-(CH2)9-CH3), 29.73 (m, -CH2-(CH2)9-

CH3), 30.49 (-CH2-(CH2)9-CH3), 31.58 (-CH2-(CH2)9-CH3), 31.95 (m, -CH2-(CH2)9-CH3),

36.07 (CHd), 36.23 (CHa + CHb + CHc), 118.10 (CH1), 118.97 (CH1), 121.85 (CH2b + CH2b),

121.00 (CH2d), 122.22 (CH2c) 123.90 (d, CPSd, 1J = 126.3 Hz), 125.68 (d, CPOa, 1J = 202.7

Hz), 126.06 (d, CPOb, 1J = 206.0 Hz), 128.50 (C4a + C4b + C4c), 128.83 (d, C4d, 3J = 14.2 Hz),

128.56 (d, C4, 3J = 16.1 Hz), 129.27 (C7/8), 130.84 (d, CPSd, 1J = 155.9 Hz), 130.94 (d, C3c, 2J

= 11.49 Hz), 131.63 (C3a + C3b), 132.35 (d, C3d, 2J = 10.81 Hz), 133.00 (C5c), 133.39 (C5a +

C5b), 133.39 (CAr entre Hd et H2d), 133.91 (CAr entre Hd et H2c), 134.35 (C5d), 134.70 (CAr

entre Hb et H2b), 134.00 (CAr entre Hb et H2a), 135.24 (CAr entre Ha et H2a), 135.58 (CAr entre

Hc et H2c), 135.73 (CAr entre Hc et H2b), 136.00 (CAr entre Ha et H2b), 145.94 (CAr-OPSc near

H2c + CAr-OPSc near H2b + CAr-OPOb near H2b + CAr-OPOb near H2a + CAr-OPOa near H2a),

146.40 (d, CAr-OPOa near H1d, 2J = 9.9 Hz), 148.70 (CAr-OPSd near H2d), 149.16 (CAr-OPSd

near H2c)

13 “ABii(PO)CDii(PS)”.

LSIMS m/z 1647.7445 [M + Na]+ (calc. 1647.7479)

31P NMR (CDCl3, 300 K, 82.01 MHz): δ 8.46 (2P, PO), 79.42

(2P, PS)


S12

1H NMR (CDCl3, 298 K, 500.10 MHz): δ 0.86 (m, 12H, CH3), 1.29 (m, 72H, -CH2-(CH2)9-

CH3), 2.32 (m, 8H, -CH2-(CH2)9-CH3), 4.73 (t, 2 H, CHb, 3J = 7.35 Hz), 4.77 (t, 2 H, CHa, 3J =

7.25 Hz), 6.63 (s, 1H, H1c), 6.77 (s, 2H, H1b), 6.93 (s, 1H, H1a), 7.26 (s, 1H, H2a/c), 7.28 (s, 2H,

H2b), 7.30 (s, 1H, H2a/c), 7.49 (m, 8H, H4), 7.57 (m, 4H, H5), 8.03 (dd, 4H, 3JH-H = 7.48 Hz, 3JP-

H = 14.03 Hz, H3-PO), 8.13 (dd, 4H, 3JH-H = 7.48 Hz, 3JP-H = 14.73 Hz, H3-PS)


CH2-CH3), 28.02 (-CH2-(CH2)7-CH2-CH2-CH3), 29.42 (-CH2-(CH2)9-CH3), 29.75 (-CH2-

(CH2)9-CH3), 30.95 (-CH2-CH2-(CH2)8-CH3), 31.30 (-CH2-CH2-(CH2)8-CH3), 31.96 (-CH2-

CH2-(CH2)8-CH3), 36.04 (CHb/a), 36.15 (CHa/b), 117.77 (CH1a), 119.06 (CH1b), 120.26 (CH1c),

122.05 (m, CH2), 126.42 (d, CPO, 1J = 202.8 Hz), 128.28 (d, C4-PS, 3J = 15.6 Hz), 128.46 (d,

C4-P0, 3J = 16.1 Hz), 131.11 (d, C3-PS, 2J = 11.6 Hz), 131.73 (d, C3-PO, 2J = 9.9 Hz), 131.86 (d,

CPS, 1J = 162.3 Hz), 132.70 (C5-PS), 133.19 (C5-PO), 134.51 (CAr entre Ha et H2b), 134.83 (CAr

between Hb et H2c), 135.05 (CAr entre Ha et H2a), 135.37 (CAr between Hb et H2b), 145.79 (d,

CAr-OPO near H1b, 2J = 9.5), 146.27 (d, CAr-OPO near H1a, 2J = 10.8), 146.54 (d, CAr-OPS

near H1c, 2J = 10.2), 146.80 (d, CAr-OPS near H1b, 2J = 10.0)

Synthesis of cavitand (±)-15 (C11H23) and (Ra)-15 (C11H23)

In a dry Schlenk containing compounds 14 (0.083 mmol, 1 eq.), 2,2’-bis(bromomethyl)-1,1’-

binaphthyl (44 mg, 0.1000 mmol) and cesium carbonate (81 mg, 0.2487 mmol), was added

dry acetonitrile (5 mL). The mixture was heated at 80 °C for 150 min. The solvent was

concentred, the residue dissolved in CH2Cl2 (20 mL), washed with water (20 mL) and brine

(20 mL). The organic phase was dried over Na2SO4 and the solvent removed in vacuo. Silica

gel column chromatography (eluent: CH2Cl2/cyclohexane: 1:1 (100 mL) then CH2Cl2 (100

mL) then CH2Cl2/EtOAc: 1:1 (100 mL)) of the residue afforded compound 15 (97% yield) as

a white solid.

Compound 15

LSIMS m/z 1819.8398 [M + Na]+ (calc. 1819.8424)

31P NMR (CDCl3, 300 K, 202.45 MHz): 79.26, 78.45, 77.71.

1H NMR (CDCl3, 300 K, 200.13 MHz): 0.87 (m, 12H), 1.06-

1.63 (m, 72H), 1.87 (m, 1H), 1.96 (m, 1H), 2.25-2.33 (m, 6H),

4.29 (d, 1H, J = 9.3 Hz), 4.49 (d, 1H, J = 12.6 Hz), 4.61 (d, 2H,


S13

J = 9.3 Hz), 4.68 (t, 1H, J = 7.5 Hz), 4.75 (t, 1H, J = 7.5 Hz), 4.88 (t, 1H, J = 8.3 Hz), 5.11 (d,

1H, J = 12.4 Hz), 6.10 (s, 1H), 6.60 (s, 1H), 6.71 (s, 1H), 6.94 (s, 1H), 6.98 (d, 1H, J = 8.5

Hz), 7.12 (m, 3H), 7.25 (m, 1H), 7.34 (d, 2H, J = 5.6 Hz), 7.37 (d, 1H, J = 7.6 Hz), 7.45-7.63

(m, 11H), 7.70 (d, 1H, J = 8.5 Hz), 7.76 (s, 2H), 7.84 (d, 1H, J = 8.2 Hz), 7.94 (d, 1H, J = 8.2

Hz), 8.00 (d, 1H, J = 8.5 Hz), 8.06 (d, 1H, J = 8.5 Hz), 8.08 (d, 1H, J = 7.4 Hz), 8.15 (d, 1H, J

= 7.4 Hz) 8.18 (d, 1H, J = 7.4 Hz), 8.24 (d, 1H, J = 7.3 Hz), 8.27 (d, 1H, J = 7.3 Hz).

13C NMR (CDCl3, 298 K, 125.75 MHz): δ 14.13, 22.71, 23.31, 25.23, 27.90, 27.97, 28.07,

28.11, 29.43, 29.71, 29.75, 29.79, 29.82, 30.84, 31.31, 31.62, 31.71, 31.96, 32.00, 25.56,

35.72, 35.84, 35.92, 66.62, 68.81, 107.21, 107.90, 119.03, 119.37, 121.54, 121.69, 123.52,

123.75, 125.70, 125.79, 126.24, 126.41, 126.59, 128.00, 128.17, 128.19, 128.23, 128.29,

128.35, 128.42, 128.46, 128.91, 130.96, 131.03, 131.05, 131.10, 131.12, 131.19, 131.51,

131.70, 131.74, 131.89, 132.52, 132.64, 132.72, 132.81, 133.00, 133.04, 133.13, 133.26,

133.37, 133.62, 133.86, 134.42, 134.86, 134.98, 135.37, 135.84, 135.94, 136.80, 145.86,

145.94, 146.00, 146.06, 146.22, 146.31, 154.27, 154.95.

Synthesis of cavitand (±)-16 (C11H23) and (Ra)-16 (C11H23)

m-Chloroperoxybenzoic acid (33 mg, 0,1335 mmol) was added to a solution of cavitand 15

(0.0334 mmol) in CHCl3 (5 mL). The mixture was stirred at room temperature for 2 h. After

evaporation of the solvent, the crude compound was purified by silica gel column

chromatography (eluent CH2Cl2 to CH2Cl2/THF 95:5 to CH2Cl2/THF/Acetone 9:1) to give

compound 16 as a white solid (91%).

Compound 16

LSIMS m/z 1749.9256 [M + H]+ (calc. 1749.9217)

31P NMR (CDCl3, 300 K, 202.45 MHz): 7.93, 8.08, 8.67

1H NMR (CDCl3, 300 K, 200.13 MHz): 0.87 (m, 12H), 1.15-

1.44 (m, 72H), 1.90 (m, 1H), 2.10 (m, 1H), 2.19-2.34 (m, 6H),

4.19 (d, 1H, J = 9.0 Hz), 4.60 (d, 1H, J = 12.3 Hz), 4.67 (t, 1H, J

= 7.5 Hz), 4.75 (t, 2H, J = 7.4 Hz), 4.88 (d, 1H, J = 9.1 Hz),

4.95 (t, 1H, J = 8.4 Hz), 5.01 (d, 1H, J = 12.1 Hz), 6.52 (s, 1H), 6.92 (d, 1H, J = 5.0 Hz), 6.94

(d, 1H, J = 5.0 Hz), 7.00 (s, 1H), 7.08 (s, 1H), 7.12-7.22 (m, 4H), 7.29-7.35 (m, 2H), 7.37 (t,

1H, J = 7.5 Hz), 7.43-7.52 (m, 5H), 7.57-7.62 (m, 4H), 7.67 (t, 1H, J = 7.2 Hz), 7.74 (d, 1H, J

= 8.6 Hz), 7.79 (d, 1H, J = 8.3 Hz), 7.82 (d, 1H, J = 8.6 Hz), 7.93 (q, 2H, J = 8.6 Hz), 7.98 (d,


S14

2H, J = 7.4 Hz), 8.01 (b, 3H), 8.05 (d, 1H, J = 8.3 Hz) 8.17 (d, 1H, J = 8.3 Hz), 8.20 (d, 1H, J

= 8.3 Hz).

13C NMR (CDCl3, 298 K, 125.76 MHz): δ 174.23, 155.74, 146.62, 146.53, 146.10, 146.02,

145.80, 145.72, 145.66, 145.58, 136.37, 135.67, 135.45, 134.94, 134.47, 133.41, 133.24,

133.22, 133.15, 133.04, 132.40, 131.91, 131.80, 131.75, 131.73, 131.69, 131.61, 129.50,

128.96, 128.66, 128.53, 128.43, 128.31, 128.16, 127.95, 127.59, 127.24, 126.52, 126.48,

126.45, 126.31, 126.15, 126.07, 123.85, 123.79, 121.65, 117.44, 117.00, 106.51, 106.31,

70.10, 68.22, 68.15, 65.29, 63.24, 35.92, 35.84, 34.82, 34.16, 32.00, 31.96, 31.94, 31.88,

31.43, 30.98, 30.91, 30.76, 29.84, 29.75, 29.73, 29.71, 29.66, 29.57, 29.47, 29.43, 29.42,

29.40, 29.37, 29.27, 29.15, 28.02, 27.99, 27.90, 27.77, 24.91, 22.73, 22.70, 22.69, 14.14,

14.12, 14.11.

[α]D20 = 112 ° (c ~ 0.1 in acetone)


[ppm]8 6 4 2

8.08

63

8.07

12

8.05

85

8.04

34

7.96

63

7.88

17

7.86

98

7.85

42

7.65

57

7.61

69

7.59

06

7.58

30

7.57

42

7.55

88

7.54

88

7.44

89

7.43

95

7.32

39

7.23

86

7.08

25

7.03

65

6.92

41

6.45

98

5.70

98

4.71

33

2.29

55

2.25

52

2.09

19

2.07

83

1.44

14

1.42

95

1.25

42

0.88

13

1.13

48

1.98

912.

0005

1.95

901.

0569

1.05

131.

0932

4.02

932.

4207

1.02

940.

9562

2.00

580.

9655

1.00

00

1.04

30

1.09

051.

0416

1.02

58

5.91

461.

9740

8.02

9963

.351

1

11.9

266

[ppm]8 6 4 2

1.98

912.

0005

1.95

901.

0569

1.05

131.

0932

4.02

932.

4207

1.02

940.

9562

2.00

580.

9655

1.00

00

1.04

30

1.09

051.

0416

1.02

58

5.91

461.

9740

8.02

9963

.351

1

11.9

266

R

R

R

RO

OP

O

O

O

PO

O

OHO

HO

N

N

(±)-1

Figure S1: 1H NMR (CDCl3, 500MHz, 293K) of (±)-1

S15


R

R

R

RO

OP

O

O

O

PO

O

OHO

HO

N

N

(±)-1

[ppm]9.0 8.5 8.0 7.5 7.0 6.5

8.08

63

8.07

12

8.05

85

8.04

34

7.96

63

7.89

71

7.88

17

7.86

98

7.85

42

7.71

76

7.65

57

7.64

11

7.61

69

7.59

06

7.58

30

7.57

42

7.55

88

7.54

88

7.44

89

7.43

95

7.32

39

7.23

86

7.08

25

7.03

65

6.92

41

6.45

98

1.13

48

1.98

91

2.00

05

1.95

90

1.05

691.

0513

1.09

324.

0293

1.02

94

0.95

62

2.00

58

0.96

55

1.00

00

[ppm]9.0 8.5 8.0 7.5 7.0 6.5

2.42

07


S16



R

R

R

RO

OP

O

O

O

PO

O

OHO

HO

N

N

(±)-1

[ppm]5 4 3 2

5.70

98

5.69

40

4.71

33

4.56

92

4.17

49

2.29

55

2.25

52

2.09

19

2.07

83

1.44

14

1.42

95

1.25

42

0.88

13

0.86

77

1.04

30

1.09

05

1.04

16

1.02

58

5.91

46

1.97

40

8.02

99

63.3

511

11.9

266

[ppm]5 4 3 2

S17


[ppm]150 100 50

152.

6137

152.

4373

152.

2861

139.

9273

139.

9064

131.

4857

131.

4061

131.

2007

131.

1209

129.

4460

128.

6275

128.

5903

128.

5006

128.

4621

32.1

238

32.0

417

32.0

130

29.9

411

29.9

148

29.8

629

29.8

381

29.8

257

29.7

946

29.5

281

29.5

152

29.4

844

28.1

973

28.1

184

28.0

671

28.0

397

22.7

894

22.7

702

14.2

168

[ppm]150 100 50

R

R

R

RO

OP

O

O

O

PO

O

OHO

HO

N

N

(±)-1

Figure S4: 13C NMR (CDCl3, 125.75 MHz, 293K) of (±)-1

S18


[ppm]150 140 130 120 110

153.

0907

152.

8479

152.

6137

152.

4373

152.

2861

146.

0221

145.

9378

139.

9273

139.

9064

137.

5210

135.

9404

134.

8549

134.

3053

133.

3270

133.

2351

131.

4857

131.

4061

131.

2007

131.

1209

129.

6200

129.

5333

129.

4460

129.

2682

128.

6275

128.

5903

128.

5006

128.

4621

128.

3712

128.

2004

128.

0749

122.

4363

122.

3482

117.

3529

[ppm]150 140 130 120 110

R

R

R

RO

OP

O

O

O

PO

O

OHO

HO

N

N

(±)-1


S19


[ppm]35 30 25 20 15

32.1

238

32.0

417

32.0

130

31.2

868

30.8

428

29.9

411

29.9

148

29.8

629

29.8

381

29.8

257

29.7

946

29.5

281

29.5

152

29.4

844

28.1

973

28.1

184

28.0

671

28.0

397

22.7

894

22.7

702

14.2

168

14.2

072

[ppm]35 30 25 20 15

R

R

R

RO

OP

O

O

O

PO

O

OHO

HO

N

N

(±)-1


S20


[ppm]140 120 100 80 60 40 20

53.9

243

51.4

245

44.6

663

36.5

628

33.6

442

32.1

254

32.0

417

32.0

136

31.6

442

31.2

842

31.0

044

30.8

436

30.0

974

29.9

413

29.9

161

29.8

631

29.8

383

29.8

257

29.7

953

29.5

306

29.5

157

29.4

856

28.9

606

28.1

980

28.1

181

28.0

661

28.0

387

22.9

268

22.7

907

22.7

714

22.0

538

14.3

532

10.9

109

[ppm]140 120 100 80 60 40 20

R

R

R

RO

OP

O

O

O

PO

O

OHO

HO

N

N

(±)-1

Figure S7: jmod (CDCl3, 125.75 MHz, 293K) of (±)-1

S21


[ppm]130 120 110

133.

3332

131.

4862

131.

4063

131.

1988

131.

1229

129.

4175

129.

2670

128.

5904

128.

4618

128.

3723

128.

2036

123.

5822

122.

4399

122.

3476

121.

9850

117.

3596

117.

2346

111.

3528

110.

3009

[ppm]130 120 110

133.

3332

131.

4862

131.

4063

131.

1988

131.

1229

129.

4175

129.

2670

128.

5904

128.

4618

128.

3723

128.

2036

123.

5822

122.

4399

122.

3476

121.

9850

117.

3596

117.

2346

111.

3528

110.

3009

R

R

R

RO

OP

O

O

O

PO

O

OHO

HO

N

N

(±)-1

Figure S8: jmod (CDCl3, 125.75 MHz, 293K) of (±)-1 (expansion)

S22


[ppm]35 30 25 20 15

36.5

628

36.2

487

35.9

218

34.0

443

33.9

244

33.6

442

32.1

254

32.0

417

32.0

136

31.6

442

31.2

842

31.0

044

30.8

436

30.0

974

29.9

413

29.9

161

29.8

631

29.8

383

29.8

257

29.7

953

29.5

306

29.5

157

29.4

856

28.9

606

28.1

980

28.1

181

28.0

661

28.0

387

22.9

268

22.7

907

22.7

714

22.0

538

14.3

532

[ppm]35 30 25 20 15

R

R

R

RO

OP

O

O

O

PO

O

OHO

HO

N

N

(±)-1


S23


1.00

000.

9872

R

R

R

RO

OP

O

O

O

PO

O

OHO

HO

N

N

(±)-1

Figure S10: 31P (CDCl3, 202.45 MHz, 293K) of (±)-1

[ppm]15 10 5

9.55

539.

3843

[ppm]15 10 5

S24


R

R

R

RO

OP

O

O

O

PO

O

OHO

HO

N

N

Figure S11: Optical Resolution of (±)-1

■ Semi-préparative HPLC

(±)-1

S25



[ppm]8 6 4 2

8.15

65

8.14

10

8.12

63

7.57

01

7.50

49

7.49

63

7.48

98

7.48

12

7.26

58

7.23

07

7.12

77

7.10

24

6.64

12

6.61

77

6.48

10

2.97

83

2.95

36

2.28

82

2.27

25

2.25

78

2.24

58

2.23

24

1.44

57

1.43

17

1.41

67

1.40

40

1.39

22

1.37

79

1.25

12

1.24

11

0.87

37

0.86

36

0.86

03

3.82

24

1.92

543.

9023

0.85

771.

0683

1.90

13

1.83

171.

7808

1.00

000.

9243

0.93

970.

9043

5.66

75

5.94

772.

1698

73.0

331

11.6

824

8 6 4 2

8.15

65

8.14

10

8.12

63

7.57

01

7.50

49

7.49

63

7.48

98

7.48

12

7.26

58

7.23

07

7.12

77

7.10

24

6.64

12

6.61

77

6.48

10

2.97

83

2.95

36

2.28

82

2.27

25

2.25

78

2.24

58

2.23

24

1.44

57

1.43

17

1.41

67

1.40

40

1.39

22

1.37

79

1.25

12

1.24

11

0.87

37

0.86

36

0.86

03

3.82

24

1.92

543.

9023

0.85

771.

0683

1.90

13

1.83

171.

7808

1.00

000.

9243

0.93

970.

9043

5.66

75

5.94

772.

1698

73.0

331

11.6

824

R R

R R

OH

OH

O

OP

N

S

O

O

PS

O

OP

S

S26



R R

R R

OH

OH

O

OP

N

S

O

O

PS

O

OP

S

[ppm]150 100 50

146.

1551

146.

0712

132.

7443

132.

6365

131.

0968

131.

0052

129.

8293

128.

4340

128.

3293

128.

3114

128.

2068

122.

9341

122.

5730

121.

7338

37.5

325

37.5

068

35.9

638

35.7

399

35.4

549

33.8

281

33.6

314

31.9

572

31.6

131

30.9

521

30.5

890

29.7

807

29.7

352

29.6

631

29.4

223

28.0

645

28.0

471

27.9

737

22.7

085

150 100 50

146.

1551

146.

0712

132.

7443

132.

6365

131.

0968

131.

0052

129.

8293

128.

4340

128.

3293

128.

3114

128.

2068

122.

9341

122.

5730

121.

7338

37.5

325

37.5

068

35.9

638

35.7

399

35.4

549

33.8

281

33.6

314

31.9

572

31.6

131

30.9

521

30.5

890

29.7

807

29.7

352

29.6

631

29.4

223

28.0

645

28.0

471

27.9

737

22.7

085

S27



R R

R R

OH

OH

O

OP

N

S

O

O

PS

O

OP

S

[ppm]78 76 74 72 70 68 66

78.7

985

77.9

378

66.6

809

[ppm]78 76 74 72 70 68 66

78.7

985

77.9

378

66.6

809

S28


[ppm]8 6 4 2

8.12

09

8.08

467.

5337

7.50

60

7.47

717.

2436

7.21

06

7.17

477.

1411

6.60

91

4.68

90

4.55

79

2.97

202.

9107

2.26

77

1.39

37

1.26

09

0.87

19

3.94

58

6.21

26

5.13

40

4.20

49

4.01

91

13.0

748

8.67

80

82.4

892

14.4

128

1.64

04

[ppm]8 6 4 2

8.12

09

8.08

467.

5337

7.50

60

7.47

717.

2436

7.21

06

7.17

477.

1411

6.60

91

4.68

90

4.55

79

2.97

202.

9107

2.26

77

1.39

37

1.26

09

0.87

19

3.94

58

6.21

26

5.13

40

4.20

49

4.01

91

13.0

748

8.67

80

82.4

892

14.4

128

1.64

04


R

R

R

RO

OP

N

S

O

O

PS

O

OP

S

O

O

PS

N

S29


[ppm]160 140 120 100 80 60 40 20

147.

0614

146.

8821

146.

5393

146.

3289

135.

0684

134.

8254

134.

5995

134.

3947

133.

6656

132.

5821

131.

2475

131.

0097

130.

4407

128.

3915

128.

0765

122.

1592

121.

7961

121.

3950

119.

8755

77.6

700

77.0

357

76.4

009

37.5

670

37.4

918

36.0

242

35.7

425

31.9

624

31.2

255

30.9

210

29.7

417

29.4

233

27.9

728

22.7

134

[ppm]160 140 120 100 80 60 40 20

147.

0614

146.

8821

146.

5393

146.

3289

135.

0684

134.

8254

134.

5995

134.

3947

133.

6656

132.

5821

131.

2475

131.

0097

130.

4407

128.

3915

128.

0765

122.

1592

121.

7961

121.

3950

119.

8755

77.6

700

77.0

357

76.4

009

37.5

670

37.4

918

36.0

242

35.7

425

31.9

624

31.2

255

30.9

210

29.7

417

29.4

233

27.9

728

22.7

134


R

R

R

RO

OP

N

S

O

O

PS

O

OP

S

O

O

PS

N

S30


[ppm]80 78 76 74 72 70 68

79.3

029

68.6

357

1.00

00

1.04

59

[ppm]80 78 76 74 72 70 68

79.3

029

68.6

357

1.00

00

1.04

59


R

R

R

RO

OP

N

S

O

O

PS

O

OP

S

O

O

PS

N

S31



[ppm]8 6 4 2

8.06

75

8.03

50

7.61

74

7.59

42

7.56

30

7.30

28

7.11

48

7.00

81

6.95

67

6.70

99

6.68

72

4.74

80

4.59

81

4.37

57

2.94

44

2.89

06

2.33

08

2.16

16

1.30

86

0.92

32

3.75

84

6.05

84

2.55

143.

2800

2.61

91

1.82

191.

2200

1.00

00

6.46

29

11.1

320

83.9

810

16.6

122

[ppm]8 6 4 2

8.06

75

8.03

50

7.61

74

7.59

42

7.56

30

7.30

28

7.11

48

7.00

81

6.95

67

6.70

99

6.68

72

4.74

80

4.59

81

4.37

57

2.94

44

2.89

06

2.33

08

2.16

16

1.30

86

0.92

32

3.75

84

6.05

84

2.55

143.

2800

2.61

91

1.82

191.

2200

1.00

00

6.46

29

11.1

320

83.9

810

16.6

122

R R

R R

OH

OH

O

OP

N

O

O

O

PO

O

OP

O

S32



R R

R R

OH

OH

O

OP

N

O

O

O

PO

O

OP

O

S33[ppm]200 150 100 50

152.

9855

152.

3595

145.

5400

135.

7927

134.

5699

134.

0673

133.

1192

131.

7762

131.

5959

129.

9795

129.

2583

128.

7637

128.

4253

122.

5691

116.

8214

111.

5194

110.

7330

36.9

308

35.9

714

35.4

667

33.6

299

31.9

646

29.7

481

29.4

319

27.9

651

22.7

147

14.1

319

[ppm]200 150 100 50

152.

9855

152.

3595

145.

5400

135.

7927

134.

5699

134.

0673

133.

1192

131.

7762

131.

5959

129.

9795

129.

2583

128.

7637

128.

4253

122.

5691

116.

8214

111.

5194

110.

7330

36.9

308

35.9

714

35.4

667

33.6

299

31.9

646

29.7

481

29.4

319

27.9

651

22.7

147

14.1

319


[ppm]15 10 5 0

8.76

898.

1335

-1.6

942

[ppm]15 10 5 0

8.76

898.

1335

-1.6

942


R R

R R

OH

OH

O

OP

N

O

O

O

PO

O

OP

O

S34



[ppm]8 6 4 2

8.15

99

8.14

55

8.13

09

7.59

85

7.58

61

7.51

61

7.24

51

7.23

87

7.21

96

7.11

18

7.09

79

6.68

51

6.56

15

6.43

31

6.42

40

5.66

89

5.65

45

4.78

51

4.77

06

4.72

75

4.71

15

4.69

57

4.68

57

4.67

04

4.65

69

4.32

52

4.31

02

2.28

51

2.27

06

2.25

73

1.43

36

1.37

84

1.25

42

4.39

56

2.26

504.

3003

2.76

492.

2324

1.03

491.

0562

2.30

47

0.90

48

0.93

083.

4743

1.00

00

7.92

98

98.2

450

20.2

632

8 6 4 2

8.15

99

8.14

55

8.13

09

7.59

85

7.58

61

7.51

61

7.24

51

7.23

87

7.21

96

7.11

18

7.09

79

6.68

51

6.56

15

6.43

31

6.42

40

5.66

89

5.65

45

4.78

51

4.77

06

4.72

75

4.71

15

4.69

57

4.68

57

4.67

04

4.65

69

4.32

52

4.31

02

2.28

51

2.27

06

2.25

73

1.43

36

1.37

84

1.25

42

4.39

56

2.26

504.

3003

2.76

492.

2324

1.03

491.

0562

2.30

47

0.90

48

0.93

083.

0743

1.00

00

7.92

98

78.2

450

13.2

632

R R

R R

OH

OH

O

OO

OP

S

O

OP

S

S35


[ppm]160 140 120 100 80 60 40

156.

8075

152.

7141

147.

2770

147.

2035

134.

6353

134.

3610

134.

2804

132.

4585

132.

3700

131.

4139

129.

9260

129.

8491

129.

8054

129.

7242

123.

3432

123.

2678

122.

1551

112.

2180

37.4

784

37.3

176

37.1

518

35.3

030

34.6

192

33.3

606

32.5

376

32.3

265

31.6

940

31.3

192

31.1

784

30.8

287

29.4

455

29.3

855

24.1

135

[ppm]160 140 120 100 80 60 40

156.

8075

152.

7141

147.

2770

147.

2035

134.

6353

134.

3610

134.

2804

132.

4585

132.

3700

131.

4139

129.

9260

129.

8491

129.

8054

129.

7242

123.

3432

123.

2678

122.

1551

112.

2180

37.4

784

37.3

176

37.1

518

35.3

030

34.6

192

33.3

606

32.5

376

32.3

265

31.6

940

31.3

192

31.1

784

30.8

287

29.4

455

29.3

855

24.1

135

R R

R R

OH

OH

O

OO

OP

S

O

OP

S


S36


[ppm]82 80 78 76 74 77

.691

177

.668

4[ppm]82 80 78 76 74

77.6

911

77.6

684


R R

R R

OH

OH

O

OO

OP

S

O

OP

S

S37


Figure S24: 1H NMR (CDCl3, 200MHz, 293K) of 7

R

R

R

RO

OO

O

PS

O

OP

S

O

O

[ppm]8 6 4 2

8.15

46

8.14

02

8.12

49

8.11

03

7.60

52

7.53

03

7.52

38

7.51

50

7.18

53

7.17

77

7.16

81

6.65

65

6.57

25

6.55

99

6.55

69

5.71

22

5.69

79

4.73

99

4.65

32

4.63

86

2.28

43

2.27

22

2.23

32

1.42

90

1.38

36

1.36

04

1.25

10

1.23

59

0.87

98

0.87

35

0.86

63

0.85

99

0.85

22

4.00

00

2.09

453.

9340

3.41

34

0.85

040.

9161

1.66

73

1.84

20

1.83

862.

0398

1.67

08

8.01

85

74.0

033

25.8

936

8 6 4 2

8.15

46

8.14

02

8.12

49

8.11

03

7.60

52

7.53

03

7.52

38

7.51

50

7.18

53

7.17

77

7.16

81

6.65

65

6.57

25

6.55

99

6.55

69

5.71

22

5.69

79

4.73

99

4.65

32

4.63

86

2.28

43

2.27

22

2.23

32

1.42

90

1.38

36

1.36

04

1.25

10

1.23

59

0.87

98

0.87

35

0.86

63

0.85

99

0.85

22

4.00

00

2.09

453.

9340

3.41

34

0.85

040.

9161

1.66

73

1.84

20

1.83

862.

0398

1.67

08

8.01

85

12.8

936

S38


[ppm]150 100 50

155.

1581

155.

0570

145.

9686

145.

8825

138.

9905

137.

7508

135.

6723

134.

3000

132.

9766

132.

1626

131.

0800

130.

9866

130.

8559

128.

5001

128.

3744

122.

2548

121.

2471

120.

3429

118.

1127

117.

0950

99.7

636

36.3

443

36.0

211

31.9

606

30.8

816

30.2

336

29.8

878

29.7

959

29.4

238

29.3

828

28.0

002

27.9

414

22.7

120

150 100 50

155.

1581

155.

0570

145.

9686

145.

8825

138.

9905

137.

7508

135.

6723

134.

3000

132.

9766

132.

1626

131.

0800

130.

9866

130.

8559

128.

5001

128.

3744

122.

2548

121.

2471

120.

3429

118.

1127

117.

0950

99.7

636

36.3

443

36.0

211

31.9

606

30.8

816

30.2

336

29.8

878

29.7

959

29.4

238

29.3

828

28.0

002

27.9

414

22.7

120

Figure S25: 13C NMR (CDCl3, 125.75 MHz, 293K) of 7

R

R

R

RO

OO

O

PS

O

OP

S

O

O

S39


R

R

R

RO

OO

O

PS

O

OP

S

O

O

[ppm]82 80 78 76

78.2

938

[ppm]82 80 78 76

Figure S26: 31P (CDCl3, 81.01 MHz, 293K) of 7

S40


[ppm]8 6 4 2

7.53

12

7.48

49

7.23

40

7.18

65

7.09

09

7.04

02

6.95

70

6.70

16

6.53

44

6.34

01

5.61

67

5.60

28

4.71

11

4.69

10

4.67

31

4.65

71

4.61

16

4.59

77

4.31

06

2.25

10

2.15

31

1.41

00

1.24

04

0.85

65

4.20

06

0.95

371.

0232

4.65

18

1.21

610.

9948

1.03

351.

3767

1.05

651.

0937

1.03

23

1.00

00

1.95

052.

5200

1.26

83

9.04

85

83.9

527

13.8

947

[ppm]8 6 4 2

7.53

12

7.48

49

7.23

40

7.18

65

7.09

09

7.04

02

6.95

70

6.70

16

6.53

44

6.34

01

5.61

67

5.60

28

4.71

11

4.69

10

4.67

31

4.65

71

4.61

16

4.59

77

4.31

06

2.25

10

2.15

31

1.41

00

1.24

04

0.85

65

4.20

06

0.95

371.

0232

4.65

18

1.21

610.

9948

1.03

351.

3767

1.05

651.

0937

1.03

23

1.00

00

1.95

052.

5200

1.26

83

9.04

85

83.9

527

13.8

947

R R

R R

OH

OH

O

OO

O

PO

O

OP

O


S41


[ppm]8.0 7.5 7.0 6.5 6.0

8.04

308.

0153

7.99

997.

9715

7.59

287.

5784

7.54

527.

5312

7.48

49

7.23

407.

1865

7.09

097.

0402

6.95

70

6.70

16

6.53

44

6.34

01

5.61

675.

6028

4.20

06

0.95

371.

0232

4.65

18

1.21

610.

9948

1.03

351.

3767

1.05

65

1.09

37

1.03

23

1.00

00

[ppm]8.0 7.5 7.0 6.5 6.0

8.04

308.

0153

7.99

997.

9715

7.59

28

7.48

49

7.23

407.

1865

7.09

097.

0402

6.95

70

6.70

16

6.53

44

5.61

675.

6028

4.20

06

0.95

371.

0232

4.65

18

1.21

610.

9948

1.03

351.

3767

1.05

65

1.09

37

1.03

23

1.00

00

R R

R R

OH

OH

O

OO

O

PO

O

OP

O

Figure S28: 1H NMR (CDCl3, 500MHz, 293K) of (±)-8 (expansion)

S42


[ppm]150 100 50

155.

4556

152.

1328

152.

0801

133.

4388

132.

3463

131.

7147

131.

6340

131.

5886

131.

5076

128.

8189

128.

6897

128.

6210

128.

5427

128.

4927

128.

2625

36.0

691

35.9

529

33.8

526

33.1

500

31.9

714

31.9

575

30.9

040

30.7

341

30.3

628

30.3

316

29.7

457

29.4

377

29.4

186

28.0

204

27.9

500

22.7

232

22.7

100

14.1

434

[ppm]150 100 50

155.

4556

152.

1328

152.

0801

133.

4388

132.

3463

131.

7147

131.

6340

131.

5886

131.

5076

128.

8189

128.

6897

128.

6210

128.

5427

128.

4927

128.

2625

36.0

691

35.9

529

33.8

526

33.1

500

31.9

714

31.9

575

30.9

040

30.7

341

30.3

628

30.3

316

29.7

457

29.4

377

29.4

186

28.0

204

27.9

500

22.7

232

22.7

100

14.1

434

R R

R R

OH

OH

O

OO

O

PO

O

OP

O


S43


155.

4556

152.

1328

152.

0801

145.

9870

145.

4784

145.

0854

139.

7769

135.

5295

135.

3408

133.

4388

133.

3149

133.

1806

132.

3463

131.

7147

131.

6340

131.

5886

131.

5076

130.

3909

130.

1283

129.

6712

128.

8189

128.

6897

128.

6210

128.

5427

128.

4927

128.

2625

128.

1855

123.

3601

122.

1526

121.

6122

120.

8828

117.

1431

110.

9868

155.

4556

152.

1328

152.

0801

145.

9870

145.

4784

145.

0854

139.

7769

135.

5295

135.

3408

133.

4388

133.

3149

133.

1806

132.

3463

131.

7147

131.

6340

131.

5886

131.

5076

130.

3909

130.

1283

129.

6712

128.

8189

128.

6897

128.

6210

128.

5427

128.

4927

128.

2625

128.

1855

123.

3601

122.

1526

121.

6122

120.

8828

117.

1431

110.

9868

R R

R R

OH

OH

O

OO

O

PO

O

OP

O

99.4

833

[ppm]160 140 120 [ppm]160 140 120

Figure S30: 13C NMR (CDCl3, 50.32 MHz, 293K) of (±)-8 (expansion)

S44


[ppm]40 30 20 10

36.0

691

35.9

529

33.8

526

33.1

500

31.9

714

31.9

575

30.9

040

30.7

341

30.3

628

30.3

316

29.7

457

29.4

377

29.4

186

28.0

204

27.9

500

22.7

232

22.7

100

14.1

434

14.1

337

[ppm]40 30 20 10

36.0

691

35.9

529

33.8

526

33.1

500

31.9

714

31.9

575

30.9

040

30.7

341

30.3

628

30.3

316

29.7

457

29.4

377

29.4

186

28.0

204

27.9

500

22.7

232

22.7

100

14.1

434

14.1

337

R R

R R

OH

OH

O

OO

O

PO

O

OP

O

[ppm]20 15 10 5

10.5

666

9.63

04

[ppm]20 15 10 5

10.5

666

9.63

04

Figure S31: 13C NMR (CDCl3, 125.75 MHz, 293K)of (±)-8 (expansion)


S45


[ppm]140 120 100 80 60 40

155.

4589

152.

1276

146.

0781

145.

9879

145.

4756

145.

3918

145.

0836

145.

0063

139.

7768

135.

5322

135.

3437

134.

4726

133.

4088

132.

3472

130.

3933

128.

2633

127.

0261

126.

4800

125.

4036

124.

8561

123.

4175

116.

8848

111.

0566

99.4

001

33.1

455

32.0

061

30.9

444

30.7

373

29.7

533

29.4

425

28.0

442

22.7

357

[ppm]140 120 100 80 60 40

155.

4589

152.

1276

146.

0781

145.

9879

145.

4756

145.

3918

145.

0836

145.

0063

139.

7768

135.

5322

135.

3437

134.

4726

133.

4088

132.

3472

130.

3933

128.

2633

127.

0261

126.

4800

125.

4036

124.

8561

123.

4175

116.

8848

111.

0566

99.4

001

33.1

455

32.0

061

30.9

444

30.7

373

29.7

533

29.4

425

28.0

442

22.7

357

R R

R R

OH

OH

O

OO

O

PO

O

OP

O


S46


Figure S34: Semi-Preparative HPLC Optical Resolution of (±)-8

R R

R R

OH

OH

O

OO

O

PO

O

OP

O

1st elutedenantiomer

Racemic

CD (295 nm)

CD (295 nm)

2nd elutedenantiomer

CD (295 nm)

S47


[ppm]8 6 4 2

8.14

72

8.00

48

7.56

84

7.49

14

7.27

42

7.13

86

7.08

20

6.95

96

6.81

40

6.63

53

6.48

41

4.69

93

4.33

02

2.26

49

2.12

75

1.39

93

1.23

32

0.85

75

0.85

14

1.99

614.

3535

2.57

708.

2905

1.38

921.

5112

1.27

611.

0728

0.99

541.

0433

0.80

80

3.00

00

0.70

56

7.87

93

112.

9075

18.3

072

[ppm]8 6 4 2

8.14

72

8.00

48

7.56

84

7.49

14

7.27

42

7.13

86

7.08

20

6.95

96

6.81

40

6.63

53

6.48

41

4.69

93

4.33

02

2.26

49

2.12

75

1.39

93

1.23

32

0.85

75

0.85

14

1.99

614.

3535

2.57

708.

2905

1.38

921.

5112

1.27

611.

0728

0.99

541.

0433

0.80

80

3.00

00

0.70

56

7.87

93

112.

9075

18.3

072


R R

R R

OH

OH

O

OP

S

O

O

PO

O

OP

O

S48


Figure S36: HSQC (CDCl3, F1: 125.75 MHz, F2 500 MHz, 293K) of (±)-11

S49F2 [ppm]8 6 4 2

F1

[pp

m]

160

140

120

100

80

60

40

F2 [ppm]8 6 4 2

F1

[pp

m]

160

140

120

100

80

60

40

R R

R R

OH

OH

O

OP

S

O

O

PO

O

OP

O


F2 [ppm]8 6 4 2

F1

[pp

m]

160

140

120

100

80

60

40

F2 [ppm]8 6 4 2

F1

[pp

m]

160

140

120

100

80

60

40

Figure S37: HMBC (CDCl3, F1: 125.75 MHz, F2 500 MHz, 293K) of (±)-11

R R

R R

OH

OH

O

OP

S

O

O

PO

O

OP

O

S50


[ppm]80 60 40 20

76.4

230

8.95

387.

9843

[ppm]80 60 40 20

76.4

230

8.95

387.

9843

R R

R R

OH

OH

O

OP

S

O

O

PO

O

OP

O


S51


[ppm]8 6 4 2

7.57

97

7.56

39

7.54

39

7.53

75

7.52

79

7.47

36

7.46

62

7.46

05

7.45

16

7.36

94

7.35

53

7.32

79

7.23

75

7.01

74

6.74

75

6.64

74

6.63

77

6.31

31

6.27

87

2.38

85

2.37

42

2.36

01

2.31

82

2.30

41

1.89

88

1.43

52

1.35

04

1.33

58

1.25

90

0.87

47

0.86

77

0.86

15

0.85

65

1.95

592.

0303

1.93

85

1.01

514.

1926

4.19

421.

2142

1.44

872.

1789

0.83

25

0.86

361.

8480

1.94

160.

8504

0.90

23

1.00

003.

0605

8.32

60

4.51

64

78.1

515

13.3

241

[ppm]8 6 4 2

7.57

97

7.56

39

7.54

39

7.53

75

7.52

79

7.47

36

7.46

62

7.46

05

7.45

16

7.36

94

7.35

53

7.32

79

7.23

75

7.01

74

6.74

75

6.64

74

6.63

77

6.31

31

6.27

87

2.38

85

2.37

42

2.36

01

2.31

82

2.30

41

1.89

88

1.43

52

1.35

04

1.33

58

1.25

90

0.87

47

0.86

77

0.86

15

0.85

65

1.95

592.

0303

1.93

85

1.01

514.

1926

4.19

421.

2142

1.44

872.

1789

0.83

25

0.86

361.

8480

1.94

160.

8504

0.90

23

1.00

003.

0605

8.32

60

4.51

64

78.1

515

13.3

241


R

R

R

RO

OP

S

O

O

PO

O

OP

O

O

O

PS

S52


[ppm]8.0 7.5 7.0 6.5

8.08

238.

0677

8.05

408.

0394

8.01

758.

0026

7.98

787.

9729

7.92

617.

9114

7.89

777.

8831

7.63

777.

5797

7.56

397.

5439

7.53

75

7.52

797.

4736

7.46

627.

4605

7.45

16

7.36

94

7.35

537.

3279

7.23

757.

0174

6.74

756.

6474

6.63

776.

3783

6.36

57

6.31

31

1.95

59

2.03

03

1.93

85

1.01

51

4.19

26

4.19

42

1.21

421.

4487

2.17

89

0.83

25

0.86

36

1.84

80

1.94

16

0.85

040.

9023

[ppm]8.0 7.5 7.0 6.5

8.08

238.

0677

8.05

408.

0394

8.01

758.

0026

7.98

787.

9729

7.92

617.

9114

7.89

777.

8831

7.63

777.

5797

7.56

397.

5439

7.53

75

7.52

797.

4736

7.46

627.

4605

7.45

16

7.36

94

7.35

537.

3279

7.23

757.

0174

6.74

756.

6474

6.63

776.

3783

6.36

57

6.31

31

1.95

59

2.03

03

1.93

85

1.01

51

4.19

26

4.19

42

1.21

421.

4487

2.17

89

0.83

25

0.86

36

1.84

80

1.94

16

0.85

040.

9023


R

R

R

RO

OP

S

O

O

PO

O

OP

O

O

O

PS

S53


[ppm]150 100 50

146.

4161

145.

9407

135.

9962

135.

7167

135.

0269

134.

7062

134.

3849

133.

9103

133.

6325

133.

4492

133.

0533

132.

8734

132.

4415

131.

6857

131.

0379

130.

8580

128.

9505

128.

7706

122.

2565

122.

0405

121.

8246

119.

1614

119.

0174

118.

0457

35.9

917

31.9

577

31.5

850

30.4

933

29.7

369

29.4

207

28.0

158

27.8

456

22.7

105

[ppm]150 100 50

146.

4161

145.

9407

135.

9962

135.

7167

135.

0269

134.

7062

134.

3849

133.

9103

133.

6325

133.

4492

133.

0533

132.

8734

132.

4415

131.

6857

131.

0379

130.

8580

128.

9505

128.

7706

122.

2565

122.

0405

121.

8246

119.

1614

119.

0174

118.

0457

35.9

917

31.9

577

31.5

850

30.4

933

29.7

369

29.4

207

28.0

158

27.8

456

22.7

105


R

R

R

RO

OP

S

O

O

PO

O

OP

O

O

O

PS

S54


[ppm]80 60 40 20

79.1

830

77.6

245

10.6

737

9.52

30

[ppm]80 60 40 20

79.1

830

77.6

245

10.6

737

9.52

30


R

R

R

RO

OP

S

O

O

PO

O

OP

O

O

O

PS

S55


[ppm]8 6 4 2

8.15

41

8.13

92

8.12

47

8.10

97

8.06

04

8.04

54

8.03

23

8.01

74

7.59

407.

5804

7.56

83

7.55

36

7.50

61

7.49

11

7.48

26

7.46

77

7.29

92

7.28

19

7.26

227.

2372

6.93

72

6.77

21

6.63

70

4.77

40

4.75

84

4.73

16

2.32

23

1.45

62

1.40

09

1.38

88

1.25

53

0.87

75

0.86

41

3.53

444.

3140

4.13

628.

3575

3.46

32

0.84

382.

1867

0.92

98

4.00

00

8.71

46

17.1

528

71.8

794

18.0

821

[ppm]8 6 4 2

8.15

41

8.13

92

8.12

47

8.10

97

8.06

04

8.04

54

8.03

23

8.01

74

7.59

407.

5804

7.56

83

7.55

36

7.50

61

7.49

11

7.48

26

7.46

77

7.29

92

7.28

19

7.26

22

7.23

72

6.93

72

6.77

21

6.63

70

4.77

40

4.75

84

4.73

16

2.32

23

1.45

62

1.40

09

1.38

88

1.25

53

0.87

75

0.86

41

3.53

444.

3140

4.13

628.

3575

3.46

32

0.84

382.

1867

0.92

98

4.00

00

8.71

46

17.1

528

71.8

794

18.0

821

Figure S43: 1H NMR (CDCl3, 500MHz, 293K) of 13

R

R

R

RO

OP

S

O

O

PO

O

OP

O

O

O

PS

S56


[ppm]150 100 50

146.

8418

146.

7635

146.

5893

146.

3187

135.

3603

135.

0536

134.

8300

134.

5169

133.

1959

132.

7044

132.

5075

131.

7796

131.

7006

131.

1616

131.

0691

128.

5291

128.

4003

128.

3493

128.

2250

122.

1162

122.

0154

119.

0634

117.

7720

36.1

475

36.0

443

31.9

609

31.6

012

31.3

035

30.9

536

29.7

446

28.0

237

22.7

097

22.6

687

[ppm]150 100 50

146.

8418

146.

7635

146.

5893

146.

3187

135.

3603

135.

0536

134.

8300

134.

5169

133.

1959

132.

7044

132.

5075

131.

7796

131.

7006

131.

1616

131.

0691

128.

5291

128.

4003

128.

3493

128.

2250

122.

1162

122.

0154

119.

0634

117.

7720

36.1

475

36.0

443

31.9

609

31.6

012

31.3

035

30.9

536

29.7

446

28.0

237

22.7

097

22.6

687

Figure S44: 13C NMR (CDCl3, 125.75 MHz, 293K) of 13

R

R

R

RO

OP

S

O

O

PO

O

OP

O

O

O

PS

S57


[ppm]150 100 50

146.

8404

146.

5132

146.

3240

146.

2426

145.

7275

135.

3647

135.

0582

134.

8335

134.

5165

133.

2249

132.

7625

132.

5130

131.

8686

130.

9130

128.

2621

127.

2375

125.

6242

122.

1279

120.

2784

119.

0763

117.

8433

77.2

930

77.0

389

76.7

852

36.2

195

36.0

378

31.9

672

31.3

132

30.9

583

29.7

509

29.4

292

28.0

313

22.7

159

[ppm]150 100 50

146.

8404

146.

5132

146.

3240

146.

2426

145.

7275

135.

3647

135.

0582

134.

8335

134.

5165

133.

2249

132.

7625

132.

5130

131.

8686

130.

9130

128.

2621

127.

2375

125.

6242

122.

1279

120.

2784

119.

0763

117.

8433

77.2

930

77.0

389

76.7

852

36.2

195

36.0

378

31.9

672

31.3

132

30.9

583

29.7

509

29.4

292

28.0

313

22.7

159

Figure S45: jmod (CDCl3, 125.75 MHz, 293K) of 13

R

R

R

RO

OP

S

O

O

PO

O

OP

O

O

O

PS

S58


[ppm]100 80 60 40 20

79.4

249

8.46

74

[ppm]100 80 60 40 20

79.4

249

8.46

74

Figure S46: 31P (CDCl3, 81.01 MHz, 293K) of 13

R

R

R

RO

OP

S

O

O

PO

O

OP

O

O

O

PS

S59


[ppm]8 6 4 2

8.00

71

7.99

01

7.75

92

7.71

02

7.69

33

7.58

48

7.56

94

7.56

07

7.55

38

7.51

49

7.50

67

7.49

13

7.47

57

7.46

72

7.46

10

7.34

40

7.33

28

7.19

02

7.12

92

7.11

18

6.99

36

6.94

53

6.71

24

6.60

35

6.09

89

4.62

43

4.60

57

1.44

82

1.24

84

1.00

98

0.88

77

0.87

42

0.86

09

2.05

222.

4614

2.19

891.

0468

1.18

601.

1102

2.02

721.

0854

11.9

657

0.85

612.

4635

0.43

751.

0594

0.99

922.

4230

1.09

481.

2320

1.10

661.

1193

0.96

79

1.00

001.

1513

1.18

451.

5141

2.07

081.

0138

1.00

56

7.24

001.

3126

1.22

22

72.5

178

26.5

590

8 6 4 2

8.00

71

7.99

01

7.75

92

7.71

02

7.69

33

7.58

48

7.56

94

7.56

07

7.55

38

7.51

49

7.50

67

7.49

13

7.47

57

7.46

72

7.46

10

7.34

40

7.33

28

7.19

02

7.12

92

7.11

18

6.99

36

6.94

53

6.71

24

6.60

35

6.09

89

4.62

43

4.60

57

1.44

82

1.24

84

1.00

98

0.88

77

0.87

42

0.86

09

2.05

222.

4614

2.19

891.

0468

1.18

601.

1102

2.02

721.

0854

11.9

657

0.85

612.

4635

0.43

751.

0594

0.99

922.

4230

1.09

481.

2320

1.10

661.

1193

1.00

001.

1513

1.18

451.

5141

2.07

081.

0138

1.00

56

6.24

001.

3126

1.22

22

12.5

590


R R

R R

O

O

O

OP

S

O

O

PS

O

OP

S

S60


Figure S48: 13C (CDCl3, 125.75 MHz, 293K) of (±)-15

[ppm]150 100 50

134.

4235

132.

6391

131.

1883

131.

1218

131.

0999

131.

0474

131.

0316

130.

9584

129.

2352

128.

9081

128.

4627

128.

4227

128.

3509

128.

2886

128.

2316

128.

1921

128.

1656

127.

9951

126.

2361

125.

6980

31.9

978

31.9

618

31.7

068

29.8

195

29.7

884

29.7

510

29.7

070

29.4

315

28.1

063

28.0

680

27.9

724

27.8

993

22.7

101

[ppm]150 100 50

134.

4235

132.

6391

131.

1883

131.

1218

131.

0999

131.

0474

131.

0316

130.

9584

129.

2352

128.

9081

128.

4627

128.

4227

128.

3509

128.

2886

128.

2316

128.

1921

128.

1656

127.

9951

126.

2361

125.

6980

31.9

978

31.9

618

31.7

068

29.8

195

29.7

884

29.7

510

29.7

070

29.4

315

28.1

063

28.0

680

27.9

724

27.8

993

22.7

101

R R

R R

O

O

O

OP

S

O

O

PS

O

OP

S

S61


[ppm]85 80 75

79.2

577

78.4

482

77.7

131

[ppm]85 80 75

79.2

577

78.4

482

77.7

131

R R

R R

O

O

O

OP

S

O

O

PS

O

OP

S


S62



R R

R R

O

O

O

OP

O

O

O

PO

O

OP

O

[ppm]10 8 6 4 2

8.02

57

7.99

60

7.96

90

7.94

26

7.92

64

7.91

02

7.81

15

7.79

39

7.73

13

7.71

42

7.57

89

7.56

76

7.50

94

7.47

65

7.46

30

7.45

05

7.43

59

7.35

59

7.28

65

7.26

28

7.19

20

7.14

61

7.08

83

7.05

37

6.92

49

6.90

21

4.73

35

2.27

33

1.41

13

1.24

68

1.23

30

0.85

85

0.84

66

2.02

409.

1102

2.36

941.

3860

1.24

004.

0719

6.71

852.

1297

2.37

211.

2878

1.95

940.

9790

1.82

872.

8003

1.01

41

0.89

400.

8818

0.93

612.

0392

1.19

591.

0908

1.00

00

5.98

581.

2167

1.17

65

82.3

098

13.5

812

10 8 6 4 2

8.02

57

7.99

60

7.96

90

7.94

26

7.92

64

7.91

02

7.81

15

7.79

39

7.73

13

7.71

42

7.57

89

7.56

76

7.50

94

7.47

65

7.46

30

7.45

05

7.43

59

7.35

59

7.28

65

7.26

28

7.19

20

7.14

61

7.08

83

7.05

37

6.92

49

6.90

21

4.73

35

2.27

33

1.41

13

1.24

68

1.23

30

0.85

85

0.84

66

2.02

409.

1102

2.36

941.

3860

1.24

004.

0719

6.71

852.

1297

2.37

211.

2878

1.95

940.

9790

1.82

872.

8003

1.01

41

0.89

400.

8818

0.93

612.

0392

1.19

591.

0908

1.00

00

5.98

581.

2167

1.17

65

73.3

098

13.5

812

S63


[ppm]8.0 7.5 7.0

8.05

998.

0453

8.00

877.

9921

7.97

737.

9625

7.94

477.

9274

7.83

027.

8130

7.80

597.

7893

7.75

047.

7332

7.58

257.

4907

7.48

087.

4761

7.46

607.

4502

7.37

587.

3197

7.29

427.

2049

7.17

967.

1565

7.14

027.

1222

7.07

836.

9981

6.94

376.

9338

6.92

70

2.08

95

10.2

730

2.54

93

1.41

241.

2709

4.79

63

7.60

97

1.43

42

3.13

89

5.73

90

1.49

81

1.15

58

2.22

22

1.00

00

[ppm]8.0 7.5 7.0

8.05

998.

0453

8.00

877.

9921

7.97

737.

9625

7.94

477.

9274

7.83

027.

8130

7.80

597.

7893

7.75

047.

7332

7.58

257.

4907

7.48

087.

4761

7.46

607.

4502

7.37

587.

3197

7.29

427.

2049

7.17

967.

1565

7.14

027.

1222

7.07

836.

9981

6.94

376.

9338

6.92

70

2.08

95

10.2

730

2.54

93

1.41

241.

2709

4.79

63

7.60

97

1.43

42

3.13

89

5.73

90

1.49

81

1.15

58

2.22

22

1.00

00


R R

R R

O

O

O

OP

O

O

O

PO

O

OP

O

S64


[ppm]200 150 100 50

133.

0400

131.

8087

131.

7507

131.

7301

131.

6907

131.

6130

128.

6611

128.

5377

128.

4388

128.

3118

32.0

013

31.9

636

31.9

447

29.8

450

29.7

539

29.7

345

29.7

139

29.6

614

29.5

736

29.4

738

29.4

357

29.4

213

29.4

036

29.3

726

29.2

765

28.0

241

27.9

997

27.9

073

22.7

301

22.7

066

22.6

948

14.1

451

14.1

246

200 150 100 50

133.

0400

131.

8087

131.

7507

131.

7301

131.

6907

131.

6130

128.

6611

128.

5377

128.

4388

128.

3118

32.0

013

31.9

636

31.9

447

29.8

450

29.7

539

29.7

345

29.7

139

29.6

614

29.5

736

29.4

738

29.4

357

29.4

213

29.4

036

29.3

726

29.2

765

28.0

241

27.9

997

27.9

073

22.7

301

22.7

066

22.6

948

14.1

451

14.1

246

Figure S52: 13C (CDCl3, 125.75 MHz, 293K) of (±)-16

R R

R R

O

O

O

OP

O

O

OP

O

O

OP

O

S65


[ppm]14 12 10 8 6 4 2

8.67

278.

0801

7.92

75

[ppm]14 12 10 8 6 4 2

8.67

278.

0801

7.92

75


R R

R R

O

O

O

OP

O

O

O

PO

O

OP

O

S66


Figure S54: Electronic Circular Dichroism (ECD)

C ~ 4.10-5 M (CH2Cl2)

R

R

R

RO

OP

O

O

O

PO

O

OHO

HO

N

N

R R

R R

OH

OH

O

OO

O

PO

O

OP

O

-60

-40

-20

0

20

40

60

255 275 295 315 335 355 375 395

(−)-8(+)-8(+)-1(−)-1

∆ε∆ε ∆ε∆ε[cm2.mmol-1]

1 8

R R

R R

O

O

O

OP

O

O

O

PO

O

OP

O

-80

130

0

100

225 400250 300 350

CD[mdeg]

Wavelength [nm] αd20 = 112°(c ~ 0,1 acetone)

(Ra)-16

C ~ 1.10-5 M (CH2Cl2)

* As compound 8 display no optical rotation at all the wavelenghts tested, signs of (+) and (-)-8 refers to the CD sign at 295 nm measured by the CD detector directly on the HPLC.

*

S67


Figure S55:Complex (S)-Nicotine@(±)-1

■31P NMR (CDCl3, 500MHz, 293K)

(±)-1

(±)-1 /[(S)-Nico][pic]1 : 0.25

(±)-1 /[(S)- Nico][pic]1 : 0.5

(±)-1 /[(S)- Nico][pic]1 : 1

(S)- Nico][pic]

(a)

(b)

(c)

(d)

(g)

[ppm]12 11 10 11 10

(+)-1 /[(S)- Nico][pic]1 : 1

(−)-1 /[(S)- Nico][pic]1 : 1

(e)

(f)

[ppm]4.5

Ha Hb Hc

[ppm]4.5

Ha Hb Hc

7.0 6.5 6.0 5.5

H1b HdH1a

H2cH2b

7.0 6.5 6.0 5.5

H1b HdH1a

H2cH2b

■1H NMR (CDCl3, 500MHz, 293K)

NMeH

N

O2N

NO2

NO2

O

[(S)−Nicotine][pic]

S68

2c

1c

d

1d2d

a

1a

2a

2b1b

c

RR

RR

HOc

HOb

O

OP

3b

4b5b

O b

O

O

P 3a

4a

5a

O

O

ON

N

98

7

6

R = C11H23

12b


Figure S56: Complex Adrenaline@(±)-1

1

ABiiPO(Quinox)

R

R

R

RO

OP

O

O

O

PO

O

OHO

HO

N

N

[ppm]14 12 10 8 14 12 10 8

293K, (±)-1

293K, (±)-1 /[L-Adr][pic]1 : 1

253K, (±)-1 /[L-Adr][pic]1 : 1

253K, (±)-1 /[L-Adr][pic]1 : 0.4

253K, (±)-1

[ppm]- 1.2 - 1.4 - 1.6 [ppm]- 1.2 - 1.4 - 1.6

■1H NMR (CDCl3) ■

31P NMR (CDCl3)

(a)

(b)

(c)

(d)

(g)

253K, (+)-1 /[L-Adr][pic]1 : 1

253K (−)-1 /[L-Adr][pic]1 : 1

(e)

(f)

OH H2NHO

HO

Me

S69


[ppm]- 0.6 - 0.8 - 1.0 - 1.2 - 1.4 - 1.6 [ppm]- 0.6 - 0.8 - 1.0 - 1.2 - 1.4 - 1.6

293K, (±)-1 / [(−)-Eph][pic]1 : 1

293K, (±)-1 / [(−)-Eph][pic]1 : 0.4

233K, (±)-1 / [(−)-Eph][pic]1 : 1

233K, (+)-1 / [(−)-Eph][pic]1 : 0.4

233K, (+)-1 / [(−)-Eph][pic]1 : 1

233K, (−)-1 / [(−)-Eph][pic]1 : 1

[ppm]15 14 13 12 11 10 [ppm]15 14 13 12 11 10

CH3 CH3NHCH3 NHCH3 d.r ~ 1 : 1

1

ABiiPO(Quinox)

R

R

R

RO

OP

O

O

O

PO

O

OHO

HO

N

N

■1H NMR (CDCl3) ■

31P NMR (CDCl3)

OHMe

NH2Me(−)-(1R,2S)

Figure S57: Complex Ephedrine@(±)-1

S70


[ppm]- 1.0 - 1.5 - 2.0 [ppm]- 1.0 - 1.5 - 2.0 [ppm]13 12 11 [ppm]13 12 11

CH3

CH3NHCH3

NHCH3

d.r ~ 2.2 : 1

293K, (±)-1 / [(+)-PE][pic]1 : 1

293K, (±)-1 / [(+)-PE][pic]1 : 0.4

233K, (±)-1 / [(+)-PE][pic]1 : 1

233K, (±)-1 / [(+)-PE][pic]1 : 0.4

233K, (+)-1 / [(−)-PE][pic]1 : 1

233K, (−)-1 / [(−)-PE][pic]1 : 1

1

ABiiPO(Quinox)

R

R

R

RO

OP

O

O

O

PO

O

OHO

HO

N

N

OHMe

NH2Me(+)-(1S,2S)

Figure S58: Complex Pseudoephedrine@(±)-1

S71


1

ABiiPO(Quinox)

R

R

R

RO

OP

O

O

O

PO

O

OHO

HO

N

N

293K, (±)-1

293K, (±)-1 /[(−)-NorE][pic]1 : 0.4

233K, (±)-1 /[(−)-NorE][pic]1 : 0.4

233K, (±)-1

[ppm]14 12 10 8 14 12 10 8

■31P NMR (CD2Cl2, 500MHz)■

1H NMR (CD2Cl2, 500MHz)

(a)

(b)

(c)

[ppm]- 1.4 - 1.8 - 2.2 - 2.6 - 1.4 - 1.8 - 2.2 - 2.6

233K, (+)-1 /[(−)-NorE][pic]1 : 1

233K, (−)-1 /[(−)-NorE][pic]1 : 1

(d)

(e)

(f)

OHMe

NH3

(−)-(1R,2S)

CH3

CH3

d.r ~ 2.5 : 1

Figure S59: Complex Norephedrine@(±)-1

S72



[ppm]- 0.4 - 0.6 - 0.8 - 1.0 - 1.2 [ppm]- 0.4 - 0.6 - 0.8 - 1.0 - 1.2 [ppm]20 15 10 5 0 - 5 [ppm]20 15 10 5 0 - 5

298K, (±)-5

298K, (±)-5 /[L-Adr][pic]1 : 0.4

3

1 11

d.r ~1 : 1CH3

OH H2NHO

HO

Me

R R

R R

OH

OH

O

OP

N

O

O

O

PO

O

OP

O

5

■31P NMR (CDCl3, 500MHz)■

1H NMR (CDCl3, 500MHz)

No split

S73


[ppm]6.5 6.0 5.5 5.0 [ppm]6.5 6.0 5.5 5.0

R R

R R

OH

OH

O

OO

O

PO

O

OP

O

NMeHN

O2N

NO2

NO2

O

Figure S61: Complex Nicotine@(±)-8

[ppm]14 12 10 8 6 [ppm]14 12 10 8 6

[(+)-8]298K

[Nico]@[(±)-8]0.4:1298K

d.r: 1:1

■31P NMR (CD2Cl2, 500MHz)

■1H NMR (CD2Cl2, 500MHz)

8

S74


[ppm]- 0.6 - 0.8 - 1.0 - 1.2 - 1.4 [ppm]- 0.6 - 0.8 - 1.0 - 1.2 - 1.4

R R

R R

OH

OH

O

OO

O

PO

O

OP

O


OH H2NHO

HO

Me

[(+)-8]298K

[Adr]@[(±)-8]0.4:1298K

■31P NMR (CD2Cl2, 500MHz)■

1H NMR (CD2Cl2, 500MHz)

[Adr]@[(±)-8]0.4:1233K

[ppm]14 12 10 8 [ppm]14 12 10 8

d.r: ~ 1:1

8

S75



[ppm]0.5 0.0 - 0.5 - 1.0 [ppm]0.5 0.0 - 0.5 - 1.0

[Eph]@[(±)-8]0.4:1298K

d.r: 1.3:1 (−−−−)/(+)

[ppm]14 13 12 11 10 [ppm]14 13 12 11 10

[Eph]@[(±)-8]0.4:1233K

[Eph]@[(+)-8]1:1

233K

[Eph]@[(−)-8]1:1

233K

R R

R R

OH

OH

O

OO

O

PO

O

OP

O OHMe

NH2Me(−)-(1R,2S)

[(±)-8]233K8

S76


[ppm]0.5 0.0 - 0.5 - 1.0 [ppm]0.5 0.0 - 0.5 - 1.0

d.r: 2.5:1 (++++)/(−−−−)

[ppm]13.0 12.5 12.0 11.5 11.0 10.5 [ppm]13.0 12.5 12.0 11.5 11.0 10.5

R R

R R

OH

OH

O

OO

O

PO

O

OP

O


OHMe

NH2Me(+)-(1S,2S)

[PE]@[(±)-8]0.4:1298K

[PE]@[(±)-8]0.4:1233K

[PE]@[(+)-8]1:1

233K

[PE]@[(−)-8]1:1

233K

8

S77


[ppm]0.6 0.4 0.2 0.0 - 0.2 - 0.4

NCH3 CH3


298K, (±)-11

298K, (±)-11 /[Eph][pic]1 : 0.4



R R

R R

OH

OH

O

OP

S

O

O

PO

O

OP

O

OHMe

NH2Me(−)-(1R,2S)

[ppm]80 60 40 20 [ppm]80 60 40 20

1

d.r ~1 : 1No split

1 11 11

S78


[ppm]- 0.4 - 0.6 - 0.8 - 1.0 - 0.4 - 0.6 - 0.8 - 1.0 [ppm]11 10 9 8 7 [ppm]11 10 9 8 7

1 : 1

[Ra]@[L] [Sa]@[L]




253K, (±)-16

253K, (±)-16/[L-Adr][Pic]1:0.4

R R

R R

O

O

O

OP

O

O

O

PO

O

OP

O

O2N NO2

NO2

OOH H2NHO

HO

Me

16

S79


[ppm]16 14 12 10 8 6 4 [ppm]16 14 12 10 8 6 4

R R

R R

O

O

O

OP

O

O

O

PO

O

OP

O O2N NO2

NO2

OOHMe

NH2Me

(+)-(1S,2S)-10

(+)-PE@(±)-161:0.4293K

■31P NMR (CDCl3, 500MHz)

■1H NMR (CDCl3, 500MHz)

[ppm]- 0.2 - 0.4 - 0.6 - 0.8 - 1.0 [ppm]- 0.2 - 0.4 - 0.6 - 0.8 - 1.0

1 11.5 1.5

(±)-16293K


(+)-PE@(±)-161:0.4253K

(+)-PE@(Ra)-161:0.4253K

(±)-16253K

16

S80


■ 31P NMR (CD2Cl2, 500MHz)■ 1H NMR (CD2Cl2, 500MHz)

(a) [(−)-1]@[Ephedrine] 1:1, (b) [(−)- 1]@[Pseudoephedrine] 1:1, (c) [(−)-1]@[Norephedrine] 1:1, (d) [(−)-1]@[Ephedrine] [Pseudo-ephedrine][Ephedrine] 3:1:1:1 and (e) [(−)-1]@[Ephedrine][Pseudo-ephedrine][Ephedrine] 1:1:1:1

Figure S68: Chemioselective Experiment: Ephedrine/Pseudoephedrine/Norephedrine@(−)-1

[ppm]- 0.5 - 1.0 - 1.5 [ppm]- 0.5 - 1.0 - 1.5 [ppm]13.0 12.5 12.0 11.5 11.0 [ppm]13.0 12.5 12.0 11.5 11.0

(a)

(b)

(c)

(d)

(e)

11.8

11.8

S81


[ppm]- 1.0 - 1.5 - 2.0 - 2.5 [ppm]- 1.0 - 1.5 - 2.0 - 2.5 [ppm]16 14 12 10 [ppm]16 14 12 10


(a) [(+)-1]@[Ephedrine] 1:1, (b) [(+)- 1]@[Pseudoephedrine] 1:1, (c) [(+)-1]@[Norephedrine] 1:1, (d) [(+)-1]@[Ephedrine] [Pseudo-ephedrine][Ephedrine] 3:1:1:1 and (e) [(+)-1]@[Ephedrine][Pseudo-ephedrine][Ephedrine] 1:1:1:1

Figure S69: Chemioselective Experiment: Ephedrine/Pseudoephedrine/Norephedrine@(+)-1

(a)

(b)

(c)

(d)

(e)

11.7

11.7

S82


[ppm]0.5 0.0 - 0.5 - 1.0 - 1.5 - 2.0 [ppm]0.5 0.0 - 0.5 - 1.0 - 1.5 - 2.0

(a)

(b)

(c)

(d)

(e)

[ppm]16 14 12 10 [ppm]16 14 12 10

Norephedrine

Ephedrine

Pseudoephedrine


(a) [(−)-8]@[Ephedrine] 1:1, (b) [(−)- 8]@[Pseudoephedrine] 1:1, (c) [(−)-8]@[Norephedrine] 1:1, (d) [(−)-8]@[Ephedrine] [Pseudo-ephedrine][Ephedrine] 3:1:1:1 and (e) [(−)-8]@[Ephedrine][Pseudo-ephedrine][Ephedrine] 1:1:1:1

Figure S70: Chemioselective Experiment: Ephedrine/Pseudoephedrine/Norephedrine@(−)-8

S83


[ppm]0.0 - 0.5 - 1.0 - 1.5 - 2.0 [ppm]0.0 - 0.5 - 1.0 - 1.5 - 2.0 [ppm]14 13 12 11 10 [ppm]14 13 12 11 10

(a)

(b)

(c)

(d)

(e)


(a) [(+)-8]@[Ephedrine] 1:1, (b) [(+)- 8]@[Pseudoephedrine] 1:1, (c) [(+)-8]@[Norephedrine] 1:1, (d) [(+)-8]@[Ephedrine] [Pseudo-ephedrine][Ephedrine] 3:1:1:1 and (e) [(+)-8]@[Ephedrine][Pseudo-ephedrine][Ephedrine] 1:1:1:1

Figure S71: Chemioselective Experiment: Ephedrine/Pseudoephedrine/Norephedrine@(+)-8

11.6

S84


S 85

X-ray crystallography Data collection: Processing of the data was performed by the

KappaCCD analysis softwares.2 The lattice constants were refined by least-square refinement.

No absorption correction was applied to the data sets.

Structure solution and refinement: Each system was attributed according to the observed

systematic extinctions and the structures have been solved in the appropriate space group. The

structure was solved by direct methods using the SIR97 program,3 combined to Fourier

difference syntheses and refined against F using reflections with [I/σ(I) > 2] with the

CRYSTALS program for all compounds.4 All atomic displacements parameters for non-

hydrogen atoms have been refined with anisotropic terms. After anisotropic refinement, all

the hydrogen atoms are found with a Fourier Difference. The crystallographic data and

refinement details are in Table S1 ([8•CHCl3•CH3OH] CCDC reference number: 783437; 12

reference number: 783436).

1 Nonius, Kappa CCD Program Package: COLLECT, DENZO, SCALEPACK, SORTAV, Nonius B. V., Delft, Netherlands, 1997‐2001. 2 Cascarano, G.; Altomare, A.; Giacovazzo, C.; Guagliardi, A.; Moliterni, A. G. G.; Siliqi, D.; Burla, M. C.; Polidori, G.; Camalli, M. Acta Cryst. 1996, A52, C79. 3 Watkin, D. J.; Prout, C. K.; Carruthers, J. R.; Betteridge, P. W. Cristal Issue 11, Chemical Crystallography Laboratory, Oxford, UK, 1999.


S 86

Figure S1. Thermal ellipsoid plot of the crystallographic structure of [8•CHCl3•CH3OH] (probability

level 50%).

Figure S2. Thermal ellipsoid plot of the crystallographic structure of 12 (probability level 50%).


S 87

Table S1. Crystal Data and Structure Refinement for [8•CHCl3•CH3OH] and 12.

8•CHCl3•CH3OH 12

molecular formula C87H123Cl3O11P2 C96H124O10P4S2

formula weight 1513.23 1626.06

crystal system Triclinic Monoclinic

space group P-1 (No. 2) P21/c (No. 14)

Z 2 4

a (Å) 11.9557 (4) 14.338 (1)

b (Å) 15.3805(4) 34.567 (3)

c (Å) 22.8398(6) 18.529 (2)

α (°) 95.810(2) 90.0

β (°) 95.876 (2) 106.02 (1)

γ (°) 90.902(2) 90.0

V (Å3) 4155.9 (2) 8827 (1)

Τ (Κ) 100 100

λ (Kα) 1.5418 1.5418

Dc (g cm–3) 1.209 1.224

µ (mm–1) 1.816 1.686

h - 13 - 13 -17 - 16

K - 17 - 17 0 40

l 0 - 26 0 22

parameters 928 1009

absorption correction analytical analytical

reflections collected/unique 60303/13020 64964/15413

unique reflections I > 2σ(I) 13020 15406

θmax (°) 62.17 67.35

Rint 0.050 0.063

Goodness-of-fit 1.042 1.07

R1 (I > 2σ(I)) a 0.092 0.130

wR2 (I > 2σ(I)) b 0.200 0.295

Δρmin / Δρmax (e Å–1) –1.67 / 2.55 –1.37 /1.21

a R1 = Σ||Fo|–|Fc||/Σ|Fo|; b wR2 = Σ[w((Fo2–Fc

2)2/ΣwFo4]1/2


Documents

Inherently chiral phosphonatocavitands as artificial chemo ...before use. Resolution of enantiomers was performed using a Lachrom Elite HPLC using commercial semi-preparative chiral