Organic & Biomolecular Chemistry
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major isomer, CDCl3) δ: 138.3, 138.25, 138.20 (3 × quat. (m, 1H, H-4), 3.76 (m, 1H, H-3), 3.48 (m, 1H, H-6a), 3.16 (∼d,
benzyl), 135.2 (C-8), 128.3–127.5 (arom.), 117.1 (C-9), 81.3 1H, J = 10.8 Hz, H-5), 2.83 (dd, 1H, J = 13.4, 7.8 Hz, H-6a′), 2.46
(C-3), 78.2 (C-4), 73.2, 71.8, 71.6 (3 × OC̲H2Ph), 71.1 (C-6), 61.6 (m, 3H, H-2, H-5′, H-6b), 2.31 ppm (∼td, 1H, J = 14.5, 7.1 Hz,
(C-5), 60.6 (C-2), 38.4 ppm (C-7). 1H NMR (600 MHz, minor H-6b′). 13C NMR (CDCl3) δ: 138.2, 138.1 (2 × quat. benzyl),
isomer, selected signals, CDCl3) δ: 3.89 (m, 2H, H-3, H-4), 135.3 (C-7a), 135.2 (C-7b), 128.3–127.6 (arom.), 117.3 (C-8a),
3.18 ppm (ddd, 1H, J = 7.2, 7.1, 3.8 Hz). 13C NMR (150 MHz, 116.7 (C-8b), 87.7 (C-3), 81.0 (C-4), 71.6, 71.1 (2 × C
minor isomer, selected signals, CDCl3) δ: 82.0 (C-3), 78.6 (C-4), 68.0 (C-2), 57.0 (C-5), 56.8 (C-6a), 35.7 ppm (C-6b).
̲H2OPh),
60.1 (C-5), 59.5 (C-2), 34.6 ppm (C-7).
(2R,3R,4R)-1,2-Diallyl-3,4-dibenzyloxypyrrolidine (24). HRMS:
(3R,4R)-2,2-Diallyl-3,4-dibenzyloxypyrrolidine (14). Bromo- found: m/z = 364.2270; calc. for C24H30NO2 (M + H+): 364.2277;
nitrile 5 was subjected to general procedure C. Diallyl deriva- elem. anal.: found: C – 79.12, H – 8.10, N – 3.78%; calcd
tive 14 was obtained as orange oil (68%). Elem. anal.: found: C – 79.30, H – 8.04, N – 3.85%; [α]2D3 = 38.5; Rf = 0.5 (hexanes :
C – 79.12, H – 8.04, N – 3.92%; calcd C – 79.30, H – 8.04, AcOEt 3 : 1). 1H NMR (CDCl3) δ: 7.28 (m, arom.), 7.31 (m.
N – 3.85%; [α]2D3 = −20.6; Rf = 0.4 (DCM : MeOH 20 : 1). 1H NMR arom.), 5.92 (m, 1H, H-7a), 5.78 (m, 1H, H-7b), 5.05 (m, 4H,
(500 MHz, CDCl3) δ: 7.31 (m, arom.), 5.86 (m, 2H, H-7a, H-7b), H-8a, H-8a′, H-8b, H-8b′), 4.60 (d, 1H, J = 11.9 Hz, 1 ×
5.08 (m, 4H, H-8a, H-8a′, H-8b, H-8b′), 4.61 (d, 1H, J = 11.7 Hz, OCH2
̲ Ph), 4.46 (m, 3H, 3 × OCH2̲ Ph), 3.98 (m, 1H, H-4), 3.84
1 × OCH2Ph), 4.50 (m, 3H, 3 × OCH2Ph), 4.05 (m, 1H, H-4), (dd, 1H, J = 5.2, 1.4 Hz, H-3), 3.50 (m, 2H, H-6a, H-5), 2.85 (dd,
̲
̲
3.76 (d, 1H, J = 3.1 Hz, H-3), 3.27 (dd, 1H, J = 12.2, 6.7 Hz, 1H, J = 13.3, 7.9 Hz, H-6a′), 2.65 (∼dt, 1H, J = 9.4, 4.7 Hz, H-2),
H-5), 2.89 (dd, 1H, J = 12.2, 4.4 Hz, H-5′), 2.29 ppm (m, 4H, 2.46 (m, 1H, H-6b), 2.32 ppm (m, 2H, H-5′, H-6b′). 13C NMR
H-6a, H-6a′, H-6b, H-6b′). 13C NMR (125 MHz, CDCl3) δ: 138.4, (CDCl3) δ: 138.2, 138.0 (2 × quat. benzyl), 136.1 (C-7b), 135.2
138.1 (2 × quat. benzyl), 134.9, 133.9 (C-7a, C-7b), 128.4–127.5 (C-7a), 128.4–127.6 (arom.), 117.3 (C-8a), 116.3 (C-8b), 83.4
(arom.), 118.2, 117.9 (C-8a, C-8b), 88.5 (C-3), 85.2 (C-4), 71.9, (C-3), 81.1 (C-4), 71.7, 71.3 (2 × C
71.7 (2 × OCH2Ph), 65.3 (C-2), 49.1 (C-5), 42.9, 38.6 ppm (C-6a, 57.0 (C-6a), 31.8 ppm (C-6b).
C-6b).
H2OPh), 66.0 (C-2), 58.0 (C-5),
̲
(3S,4R)-2,2-Diallyl-3,4-dibenzyloxypyrrolidine (19). Bromo- (25). To a solution of 23 (65 mg, 0.18 mmol) in dry toluene
nitrile 6 was subjected to general procedure C. Diallyl derivative (1 mL), under an argon atmosphere and at room temperature,
19 was obtained as orange oil (64%). HRMS: found: m/z = CF3CO2H (30 μL) was added. Then, the Grubbs–Hoveyda II
364.2274; calc. for C24H30NO2 (M + H+): 364.2277; [α]2D3
=
(6 mg, 10 mol%) catalyst was added and the mixture was
−49.9; Rf = 0.4 (DCM : MeOH 20 : 1). 1H NMR (600 MHz, heated to 60 °C. After 12 h of stirring at this temperature, the
CDCl3) δ: 7.31 (m, arom.), 5.95 (m, 1H, H-7a), 5.75 (m, 1H, reaction was cooled to room temperature and Amberjet 4400
H-7b), 5.03 (m, 4H, H-8a, H-8a′, H-8b, H-8b′), 4.70 (d, 1H, J = OH (250 mg) was added. After 30 min, the ion-exchange resin
11.8 Hz, 1 × OCH2
4.53 (d, 1H, J = 12.1 Hz, 1 × OCH2
1 × OCH2
̲
Ph), 4.60 (d, 1H, J = 12.1 Hz, 1 × OCH2
̲ Ph), was filtered off and the filtrate was concentrated. Preparative
̲
Ph), 4.46 (d, 1H, J = 11.8 Hz, TLC (1 mm, hexanes : AcOEt 1 : 1) yielded the product 25 as
̲
Ph), 3.98 (∼td, 1H, J = 5.1, 3.3 Hz, H-4), 3.64 (d, 1H, yellow oil (56 mg, 94%). HRMS: found: m/z = 336.1964; calc.
J = 5.3 Hz, H-3), 3.04 (dd, 1H, J = 12.4, 3.2 Hz, H-5), 2.94 (dd, for C22H26NO2 (M + H+): 336.1964; elem. anal.: found: C –
1H, J = 12.4, 4.9 Hz, H-5′), 2.59 (dd, 1H, J = 14.3, 7.6 Hz, H-6a), 78.56, H – 7.38, N – 4.40%; calcd C – 78.77, H – 7.51, N –
2.39 (dd, 1H, J = 14.3, 7.3 Hz, H-6a′), 2.19 ppm (m, 2H, H-6b, 4.18%; [α]2D3 = 54.5; Rf = 0.4 (hexanes : AcOEt 2 : 1). 1H NMR
H-6b′). 13C NMR (150 MHz, CDCl3) δ: 138.48, 138.45 (2 × quat. (600 MHz, CDCl3) δ: 7.30 (m, arom.), 5.73 (ddd, 1H, J = 9.4,
benzyl), 134.9 (C-7a), 134.3 (C-7b), 128.3–127.5 (arom.), 118.1, 5.1, 2.1 Hz, H-7), 5.66 (ddd, 1H, J = 10.0, 2.7, 1.6 Hz, H-6), 4.56
117.8 (C-8a, C-8b), 84.0 (C-3), 77.7 (C-4), 72.6, 71.7 (2 × (m, 3H, 3 × OCH2
̲ Ph), 4.46 (d, 1H, J = 12.0 Hz, 1 × OCH̲2Ph),
OCH2Ph), 63.7 (C-2), 48.7 (C-5), 42.9 (C-6b), 38.6 ppm (C-6a). 3.96 (m, 1H, H-2), 3.77 (dd, 1H, J = 7.0, 2.2 Hz, H-1), 3.41 (m,
̲
Allylation of 15. To a stirred solution of 15 (421 mg, 1H, H-5), 3.27 (∼d, 1H, J = 10.5 Hz, H-3), 2.76 (m, H-5′), 2.47
1.3 mmol) in MeCN (13 mL), at room temperature, pulverized (dd, 1H, J = 10.6, 6.3 Hz, H-3′), 2.39 (m, 1H, H-8), 2.27 (m, 1H,
K2CO3 (1.5 g) was added in one portion. Then, allyl bromide H-8a), 2.19 ppm (m, 1H, H-8′). 13C NMR (150 MHz, CDCl3) δ:
(0.12 mL, 1.4 mmol, 1.1 equiv.) was added and the resulting 138.15, 138.13 (2 × quat. benzyl), 128.3–127.6 (arom.), 124.9
mixture was vigorously stirred for 24 h. Subsequently, the (C-6), 124.6 (C-7), 90.7 (C-1), 81.9 (C-2), 72.0, 71.2 (2 ×
solids were filtered off using Celite and the filtrate was concen-
trated. Flash chromatography (100% hexanes to 100% ethyl
C̲
acetate) gave 23 (260 mg, 55%) and 24 (61 mg, 13%), both as 26). To a stirred solution of 25 (71 mg, 0.21 mmol) in MeOH,
yellow oils. under an argon atmosphere and at room temperature,
(2S,3R,4R)-1,2-Diallyl-3,4-dibenzyloxypyrrolidine (23). HRMS: Pd(OH)2/C (250 mg) was added. The argon was replaced with
found: m/z = 364.2277; calc. for C24H30NO2 (M + H+): 364.2277; hydrogen (from a balloon) and the reaction was carried out
elem. anal.: found: C – 79.40, H – 8.05, N – 3.98%; calcd under a hydrogen atmosphere for 12 h. After this time, the
C – 79.30, H – 8.04, N – 3.85%; [α]2D3 = −32.1; Rf = 0.7 (hexanes : mixture was filtered through Celite and the filtrate was concen-
1
AcOEt 3 : 1). H NMR (CDCl3) δ: 7.31 (m, arom.), 5.89 (m, 2H, trated to give 26 as a yellow solid (30 mg, 91%). The NMR
H-7a, H-7b), 5.09 (m, 4H, H-8a, H-8a′, H-8b, H-8b′), 4.58 (d, spectra and [α] were in accordance with the literature.38
1H, J = 12.3 Hz, 1 × OCH2
̲
Ph), 4.45 (m, 3H, 3 × OCH2
̲
Ph), 3.87 HRMS: found: m/z = 158.1183; calc. for C8H16NO2 (M + H+):
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