Efficient Synthesis of Cyclopropanecarboxylic Acid Esters Starting from the Conjugate Addition of Lithium Ester Enolates to 1-Chlorovinyl p-Tolyl ­Sulfoxides

Abstract

An efficient synthesis of tert-butyl cyclopropanecarboxylates was achieved in three steps using 1-chlorovinyl p-tolyl sulfoxides as key materials. The conjugate addition of lithium ester enolates to the sulfoxides gave tert-butyl 4-chloro-4-(p-tolylsulfinyl)butanoates in high yield. The p-tolylsulfinyl group in the resultant adducts was then removed by the sulfoxide–magnesium exchange reaction with i-PrMgCl at –60 °C. Cyclization of the desulfinylated products, tert-butyl 4-chlorobutanoates, took place in the presence of NaHMDS in a THF–DMPU mixture to afford tert-butyl cyclopropanecarboxylates in good yield. The asymmetric synthesis of both enantiomers of tert-butyl cyclopropanecarboxylate was successfully achieved using optically active (E)- and (Z)-sulfoxides with high enantiomeric excesses.

Key words

conjugate addition - cyclization - chiral auxiliaries - 1-chlorovinyl p-tolyl sulfoxides - cyclopropanecarboxylates

• References and Notes

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