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Synthesis 2011(12): 1946-1953  
DOI: 10.1055/s-0030-1260032
PAPER
© Georg Thieme Verlag Stuttgart ˙ New York

Lithium Aldol Reactions of α-Chloroaldehydes Provide Versatile Building Blocks for Natural Product Synthesis

Shira D. Halperin, Baldip Kang, Robert Britton*
Department of Chemistry, Simon Fraser University, Burnaby, BC, V5A 1S6, Canada
Fax: +1(778)7824889; e-Mail: rbritton@sfu.ca;
Further Information

Publication History

Received 14 March 2011
Publication Date:
06 May 2011 (online)

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Abstract

The lithium aldol reaction of α-chloroaldehydes provides 1,2-anti-configured β-ketochlorohydrins. The scope of this reaction is demonstrated as well as its application to the synthesis of the C4-C15 segment of haterumalide NA.

Key words

α-chloroaldehydes - aldol reaction - stereoselective synthesis - heterocycles - natural products

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15

The stereochemical assignment of all new β-ketochloro-hydrins was confirmed by conversion into known compounds, or the corresponding epoxy alcohols (1. catecholborane, THF, -10 ˚C; 2. KOH, EtOH, 0 ˚C to r.t.) and subsequent analysis of coupling constants and NOE data.

18

The β-ketochlorohydrins 13, 18, 20, and 22 derived from
α-chlorohydrocinnamaldehyde decomposed to varying degrees when purified by silica gel flash chromatography.

25

For the preparation of α-chloroaldehydes used in this work, see references 5, 6, 7, and 14.