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Metal‐Dependent Reaction Tuning with Cyclopentylmetal Reagents: Application to the Asymmetric Synthesis of (+)‐α‐Conhydrine and ( S )‐2‐Cyclopentyl‐2‐phenylglycolic Acid
Author(s) -
Roy Siddharth,
Sharma Anubha,
Mula Soumyaditya,
Chattopadhyay Subrata
Publication year - 2009
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.200801603
Subject(s) - chemistry , reagent , halide , bromide , metal , organic chemistry , medicinal chemistry , grignard reaction , enantioselective synthesis , tertiary alcohols , combinatorial chemistry , catalysis
Tuning in : The reaction of halocyclopentane organometallic reagents can be tuned by the choice of metal (see scheme). Cyclopentylmagnesium bromide reduces aldehydes and ketones to the corresponding alcohols. However, in the presence of ZnCl 2 , normal Grignard addition to the ketones gives tertiary alcohols with complete diastereoselectivity. These protocols were used in the asymmetric synthesis of two medicinally important compounds.The reaction profile of the cyclopentyl organometallic reagents with the aliphatic ketones can be tuned to reduction or addition by changing the metal atom. Cyclopentylmagnesium bromide (CPMB) reduces aromatic and aliphatic aldehydes and ketones to the corresponding alcohols without any CC bond formation and shows good diastereoselectivity in the reduction of the substituted cyclic and polycyclic ketones as well as chiral α‐oxygenated aliphatic ketones. However, in the presence of 10 mol % of ZnCl 2 , the cyclopentylmagnesium halides follow a normal Grignard addition to the ketones to give tertiary alcohols with complete diastereoselectivity. The reductive as well as the addition protocols were used for the asymmetric synthesis of two medicinally important compounds, (+)‐α‐conhydrine and ( S )‐2‐cyclopentyl‐2‐phenylglycolic acid.