Preparation of Enantiopure Substituted Piperidines Containing 2-Alkene or 2-Alkyne Chains: Application to Total Syntheses of Natural Quinolizidine-Alkaloids

Abstract

S3 Experimental Section General Experimental Methods: IR spectra were recorded as KBr pellets. The 1 H NMR (300 MHz) and 13 C NMR (75 MHz) spectra were recorded in D 2 O or CDCl 3. The J values are given in Hz. MS (EI) spectra were obtained at 70 eV. PE is petroleum ether (60-90 o). N O 8a A Typical Procedure for Preparation of (7aS,11S,13R)-11-Isopropenyl-13phenyl-7a,8,10,11-tetrahydro-9H,13H-naphtho[1,2-e]pyrido[2,1-b][1,3]oxazine (8a): To a cold solution (ice-water bath) of 6 (4.32 g, 10 mmol) in dry THF (70 mL) was added isopropenylmagnesium bromide (0.5 M in THF, 6 mL, 30 mmol) dropwise under nitrogen. After the reaction was stirred at 0 °C for 1.0 h (monitored by TLC), a saturated aqueous solution of NH 4 Cl (30 mL) was added to quench the reaction. Then the resultant mixture was extracted with CH 2 Cl 2 (3 x 30 mL). The combined organic layers were washed with H 2 O and brine and dried over anhydrous Na 2 SO 4. After removal of the solvent, the residue was purified by chromatography (silica gel, EtOAc:PE ＝ 1:15) to give the desired product 8a (3.26 g, 92%) as a colorless crystal, mp 130-131 o C, [α] D

Synthesis and Structural Elucidation of 1,2‐Disubstituted 3‐Fluoropiperidines

“…As shown in Scheme , separated samples of cis ‐ and trans ‐ 5d were each converted into Ts‐protected 3‐fluoro‐substituted forms of the 2‐substituted piperidine natural products pelletierine and coniine by a Wacker oxidation and hydrogenation respectively. In each instance, no incompatibility with the fluoro‐group was detected and both cis ‐ and trans ‐diastereomers of 10 and 11 were isolated and characterized.…”

Catalytic Dynamic Resolution Applied to the Synthesis of 2,6-Disubstituted Piperidines: Preparation of (+)-Lupetidine and (–)-Epidihydropinidine

“…Starting from ( R )- N -Boc-2-piperidine ethanol, Passarella et al synthesized (2 R ,6 S )- 19 in five steps and used it to prepare both enantiomers of epidihydropinine. 20 Highly regioselective Wacker oxidation 21 of trans - 19 afforded the pelletierine derivative 20 in 92% yield.…”

Synthesis of quinolizidine-containing lycopodium alkaloids and related natural products

“…40 diastereomeric mixture at C 9 . The mixtures were deprotonated followed by treatment with methyliodide to produce the α-amino nitrile 21.5.…”