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Mechanistic Insight into Stereoselective Carbolithiation
Author(s) -
Gessner Viktoria H.,
Koller Stephan G.,
Strohmann Carsten,
Hogan AnneMarie,
O'Shea Donal F.
Publication year - 2011
Publication title -
chemistry – a european journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.687
H-Index - 242
eISSN - 1521-3765
pISSN - 0947-6539
DOI - 10.1002/chem.201000814
Subject(s) - lithium amide , sparteine , chemistry , lithium (medication) , adduct , moiety , diastereomer , alkyl , amide , stereoselectivity , amine gas treating , stereochemistry , organic chemistry , catalysis , enantioselective synthesis , medicine , endocrinology
This article addresses the mechanistic features of asymmetric carbolithiation of β‐methylstyrenes. While often the presence of functional groups is required to obtain high enantioselectivities in carbolithiation reactions, simple β‐methylstyrene also gives high selectivities in (−)‐sparteine‐mediated addition of alkyl lithium compounds. Computational studies on the carbolithiation of β‐methylstyrene with (−)‐sparteine show that the observed selectivities are the result of repulsion effects in the diastereomeric transition states between the (−)‐sparteine ⋅ alkyl lithium adduct and the β‐methylstyrene, upon approximation of the two reactants. In contrast, for the ortho ‐amino β‐methylstyrene ( E )‐benzyl(2‐propenylphenyl)amine ( 4 ) X‐ray structure analyses of intermediate lithium amides indicate a carbolithiation mechanism in which one side of the double bond is shielded by the amide moiety, leaving only one side free for approach of the chiral alkyl lithium adduct.