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Highly Efficient and Practical Pyrrolidine–Camphor‐Derived Organocatalysts for the Direct α‐Amination of Aldehydes
Author(s) -
Liu PangMin,
Magar Dhananjay R.,
Chen Kwunmin
Publication year - 2010
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.201000695
Subject(s) - chemistry , pyrrolidine , amination , enantioselective synthesis , organocatalysis , stereoselectivity , catalysis , camphor , aldol reaction , organic chemistry , reductive amination , nucleophile , enamine , combinatorial chemistry
A series of pyrrolidine–camphor‐derived organocatalysts ( 1 – 4 ) were designed and synthesised. These organocatalysts were used for direct α‐amination of aldehydes with dialkyl azodicarboxylates to give the desired α‐aminated products in high chemical yields (up to 92 %) and with high to excellent levels of stereoselectivity (up to >99 % ee ). The reactions proceeded rapidly (within 5 min) with low catalyst loading (5 mol‐%) at ambient temperature. Enantioselective aminations of asymmetric α,α‐disubstituted aldehydes in the catalytic system were studied, with reasonable to high stereoselectivities (up to 75 % ee ) being obtained. The utility of this methodology was demonstrated with the synthesis of derivatives of β‐amino‐γ‐butyrolactone and a tetrasubstitutedcyclohexane‐derived amino alcohol with high stereoselectivities. Transition models were proposed for the asymmetric α‐amination reactions; they involve hydrogen‐bond interactions between the nucleophilic enamine formed in situ and the nitrogen source.