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A One‐Pot Asymmetric Sequential Amination‐Alkylation of Aldehydes: Expedient Synthesis of Aliphatic Chiral Amines
Author(s) -
Wakchaure Vijay N.,
Mohanty Rashmi R.,
Shaikh Ahson J.,
Nugent Thomas C.
Publication year - 2007
Publication title -
european journal of organic chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.825
H-Index - 155
eISSN - 1099-0690
pISSN - 1434-193X
DOI - 10.1002/ejoc.200600781
Subject(s) - chemistry , alkylation , alkyl , amination , organic chemistry , aldimine , reagent , yield (engineering) , diastereomer , amine gas treating , reductive amination , boron trifluoride , medicinal chemistry , primary (astronomy) , catalysis , physics , astronomy , metallurgy , materials science
A one‐pot asymmetric sequential amination‐alkylation method has been developed for the synthesis of alkyl‐alkyl′ α‐chiral primary amines (aliphatic primary amines with a chiral center adjacent to the nitrogen atom) from aldehydes. In situ aldimine formation from non‐branched, α‐branched, and β‐branched aliphatic aldehydes with ( R )‐ or ( S )‐α‐(methylbenzyl)amine [catalyzed by 5 mol‐% Ti(O i Pr) 4 ] followed by reaction with a methyl, ethyl, or n ‐butyl cuprate complex in the presence of boron trifluoride or an allyl Grignard reagent provides good yield (77–88 %) and diastereomeric excess (77–92 %) for amines 2 or 5 . To further demonstrate the usefulness of this method, several of the secondary amine products ( 2d , 2e , and 5 ) were hydrogenolyzed, providing the corresponding enantioenriched alkyl‐alkyl′ α‐chiral primary amines 3d , 3e , and 6 (86–96 % yield).(© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2007)