Asymmetric synthesis of chiral N-sulfinyl 3-alkyl- and 3-arylpiperidines by α-alkylation of N-sulfinyl imidates with 1-chloro-3-iodopropane.
α-Alkylation of N-sulfinyl imidates with 1-chloro-3-iodopropane successfully led to 2-substituted N-tert-butanesulfinyl-5-chloropentanimidates in acceptable diastereomeric ratios (dr 67/33 to 72/28) and good yields (74-86%). Subsequent reduction with NaBH(4) led to the corresponding 2-substituted N-tert-butanesulfinyl-5-chloropentylamines, which could be cyclized to a range of new chiral 3-substituted N-tert-butanesulfinylpiperidines using NaH in DMSO. Finally, the N-tert-butanesulfinylpiperidines could be efficiently deprotected to enantiomerically pure 3-alkyl- and 3-arylpiperidine hydrochlorides.
Department of Sustainable Organic Chemistry and Technology, Faculty of Bioscience Engineering, Ghent University, Coupure Links 653, B-9000 Ghent, Belgium.
Filip
F
Colpaert
Sven
S
Mangelinckx
Norbert
N
De Kimpe
D000478:Alkylation; D003500:Cyclization; D006847:Hydrocarbons, Iodinated / Q000737:chemistry*; D007096:Imidoesters / Q000737:chemistry*; D015394:Molecular Structure; D010880:Piperidines / Q000138:chemical synthesis* / Q000737:chemistry*; D013237:Stereoisomerism; D013452:Sulfonium Compounds / Q000138:chemical synthesis* / Q000737:chemistry*
C557182:3-iodopropane; D006847:Hydrocarbons, Iodinated; D007096:Imidoesters; D010880:Piperidines; D013452:Sulfonium Compounds