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Synthesis 2007(7): 1082-1090  
DOI: 10.1055/s-2007-965956
PAPER
© Georg Thieme Verlag Stuttgart · New York

An Efficient Asymmetric Route to Tertiary Carbinols: Synthesis of (R)-Mevalonolactone

S. Roy, A. Sharma, B. Dhotare, P. Vichare, A. Chattopadhyay, S. Chattopadhyay*
Bio-Organic Division, Bhabha Atomic Research Centre, Mumbai 400 085, India
Fax: +91(22)5505151; e-Mail: schatt@barc.gov.in;
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Publication History

Received 5 December 2006
Publication Date:
12 March 2007 (online)

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Abstract

An efficient strategy for the asymmetric construction of tertiary carbinols has been devised using cyclohexylideneglyceraldehyde as a chiral template. This involves (a) addition of a Grignard reagent (R1MgX) to cyclohexylideneglyceraldehyde, followed by oxidation with pyridinium chlorochromate to give the alkylated ketone, and (b) addition of a second Grignard reagent (R2MgX) to the previously formed ketone. For alkyl chain lengths up to that of n-decane, in the second Grignard reagent (R2MgX) or the ketone formed in the first reaction, the reaction proceeded with complete diastereoselectivity; with longer chains, the selectivity dropped. The presence of a C=C bond in the second Grignard reagent (R2MgX) or the ketone also reduced the diastereoselectivity of the reaction. When, with regard to chain lengths of the alkyl groups in the Grignard reactions, R2 > R1, the reaction proceeded with syn selectivity, and vice versa. In general, the C-3 epimers of the target tertiary carbinols could be prepared easily by altering the sequence of the addition of the Grignard reagents (R1MgX and R2MgX) to cyclo­hexylideneglyceraldehyde. This strategy, using inexpensive chemicals, was applied in the simple enantiomeric synthesis of (R)-mevalonolactone.

Key words

asymmetric synthesis - chiral pool - Grignard reaction - tertiary alcohols