CCDC 237474 available at http://www.ccdc.cam.ac.uk.
Variation of the thiocarbonyl moiety (thiocarbonyl-imidazole, or CSOPh) gave 1,2-dihydropyridine 12 (R =
4-MeOC6H4) in 43% and 59% yields, respectively.
12a
Typical Procedure for the Preparation of a 1,2-Dihydropyridine:
A solution of 7-azanortricyclanol 9 (R = 4-MeOC6H4) (350 mg, 0.74 mmol) in THF (4 mL) was added dropwise to a slurry of KH (30% dispersion in mineral oil; 148 mg, 1.11 mmol) in THF (4 mL) at 0 °C. After 20 min, CS2 (55 mL, 0.91 mmol) was added and the mixture stirred for a further 15 min before addition of MeI (55 mL, 0.88 mmol). The solution was then warmed to r.t. over 20 min, after which time H2O (20 mL) was added dropwise. The aqueous layer was extracted with Et2O (3 × 20 mL) and the combined organic layers were dried (MgSO4) and evaporated under reduced pressure. Purification of the residue by column chromatography (40% Et2O in petrol ether) gave a white solid foam, xanthate (350 mg, 84%); R
f
= 0.5 (50% Et2O in petrol ether). Selected diagnostic data: 1H NMR (400 MHz, CDCl3, rotamers observed): d = 5.51 (0.4 H, t, J = 1.3 Hz, CHO), 5.50 (0.6 H, t, J = 1.3 Hz, CHO), 2.53 (1.8 H, s, SMe) and 2.52 (1.2 H, s, SMe). A solution of Bu3SnH (211 mL, 0.78 mmol, 1.1 equiv) and AIBN (23 mg, 0.14 mmol, 0.2 equiv) in toluene (5 mL) was added via syringe pump over 2.25 h to a solution of the above xanthate (400 mg, 0.71 mmol) in toluene (25 mL) at reflux. The mixture was then stirred for an additional 45 min before being cooled and worked-up according to the method of Curran and Chang.
[12b]
Purification of the residue by column chromatography
(30-50% Et2O in petrol ether) gave a colourless oil, 1,2-dihydropyridine 12 (R = 4-MeOC6H4) (202 mg, 62%);
R
f
= 0.5 (60% Et2O in petrol ether). IR (film): 2979 (m), 2933 (m), 1723 (s), 1633 (m), 1596 (m), 1513 (s), 1393 (m), 1370 (m), 1288 (s), 1250 (s), 1176 (m), 1144 (s), 1088 (s), 814 (m), 732 (m), 715 (m), 662 (s), 579 (s) cm-1. 1H NMR (500 MHz, CDCl3): d = 8.01-7.75 (1 H, m, =CHN), 7.70 (2 H, d, J = 8.0 Hz, 2 × CH of Ts), 7.30 (2 H, d, J = 8.0 Hz, 2 × CH of Ts), 6.97 (2 H, d, J = 8.2 Hz, 2 × CH of MeOAr), 6.76 (2 H, d, J = 8.2 Hz, 2 × CH of MeOAr), 6.10-5.90 (1 H, m, CCH=), 5.41 (1 H, dd, J = 9.8, 5.5 Hz, CHCH=), 5.01-4.89 (1 H, m, CHN), 3.77 (3 H, s, OMe), 2.69 (1 H, dd, J = 13.1, 8.2 Hz, H of CH2), 2.59 (1 H, dd, J = 13.1, 5.2 Hz, H of CH2), 2.43 (3 H, s, Me of Ts), 1.48 (9 H, s, t-Bu). 13C NMR (100 MHz, DMSO, 373K): d = 159.3 (Cquat of MeOAr), 152.0 (C=O), 144.5 (Cquat of Ts), 139.4 (Cquat of Ts), 134.1 (=CHN), 131.3 (2 × CH of Ts), 130.7 (2 × CH of MeOAr), 128.7 (Cquat of MeOAr), 127.6 (2 × CH of Ts), 124.3 (CHCH=), 119.9 (TsCquat), 118.0 (CCH=, br), 114.9 (2 × CH of MeOAr), 84.3 (CMe3), 56.1 (OMe), 54.9 (CHN, br), 40.2 (ArCH2), 28.4 (3 × Me of Boc) and 21.7 (Me of Ts). MS (CI, NH3): m/z (%) = 473 (100) [M + NH4
+] and 354 (30). C25H33O5N2S requires [M]: 473.2110; found [M + NH4]: 473.2098.
