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Highly Regio‐ and Enantioselective γ‐Alkylation of Linear α,β‐Unsaturated Aldehydes
Author(s) -
Kutwal Mahesh S.,
Appayee Chandrakumar
Publication year - 2017
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.201700645
Subject(s) - alkylation , chemistry , regioselectivity , electrophile , enantioselective synthesis , kinetic resolution , selectivity , structural isomer , catalysis , organocatalysis , amine gas treating , organic chemistry , combinatorial chemistry
Asymmetric alkylation is one of the most useful carbon–carbon bond‐forming reactions in synthetic organic chemistry. Chiral‐amine‐catalyzed alkylation reactions often lack regioselectivity owing to multiple reactive centers. In particular, the alkylation of linear 2‐enals through dienamine catalysis produces a mixture of regioisomers owing to reactive α‐ and γ‐positions. A few attempts have been made to mask the α‐reactive center to achieve γ‐selectivity. Controlling the enantioselectivity at the remote γ‐position has also been found to be quite challenging. Herein, we achieved the highly regioselective γ‐alkylation of linear α,β‐unsaturated aldehydes by using trifluoroethanol (TFE) as a cosolvent. Further, we demonstrated in situ kinetic resolution for enantioenrichment of the γ‐alkylated products. This method brings together the activation of an electrophile facilitated by TFE and in situ kinetic resolution to achieve excellent selectivity in dienamine catalysis.