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Tetrahedron Letters.

Vol. 33. No. 39. Pp. 5689-5692,1992

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SUPPRESS)ON OF RACEMQAllWl DUWNG THE

DlASlEREOSELECllVE C-3 FUNCTK)NAlJZAllON OF

5-HYDROXYYETHYL-2-PHENYL~~2~~~-~RANONES

Julie A. Wurster, Lawrence J. Wilson, Gregory T. Morin and Dennis Liotta*

Department of Chemistry, Emory University, Atlanta, Georgia 30322

Summary: The methodotogy described herein examines the enantio- and stereoselective C-3 functionatiition of 5-

hydroxymethyl-2-(5H)-furanones via 1, eolgenocuprete addftii as weft as the invotvernsnt of temperature and TMSCI in

the selectivity. The results impfy that reactions carried out at -78°C and those carried out at 0°C to R.T. in the presence of

TMSCI exhibit both hi

diastereosetection and enantioaektii.

Chiral butyrofadones have shown con&Amble potential as synthetic intennediies in asymmetric synthesis. For

example, Hanessian and co-workers have used chfral butymlactones and butenofides in the stereoco ntrofled synthesis of

acyclic molecules bearing muttiie stereocenters.1-4 In this methodology, the crucial ste reosekhie

functionatkation of

the C-3 position in the butenofii

systems was effected by the 1.baddffion of a nudecphite.

In conjunction with several ongoing projects, we sought to develop methodology for the C-3 functionaliiation of 1

via 1,4-addition of an organocuprate reagent (Scftama 1). Our initiil questions centered on the stereoselective

scheme 1:

introduction of the nucleophile at C-3 and slrppression of racemization atthe actdii C-4 proton. The starting butenolide

(l) was synthesized from protected hydroxymethyl butymtactone P

(available

from L-gbtamic acid5) by sutfenytatii and

subsequent elimination (Schama 2). The unexpected degree of racemizatiin at C-4 which was observed during the

synthesis of 1(82.48%

enantiomedc excess (e#,

could be cimunwented via crystakation of 1 to enantiomedcally pure

form (100% ee) from a chloroform/ petroteum ether mixture. The determination of the enantiomerfc purity6 of the starting

material and that of subsequent reaction products, necessttated the use of racemic material as a standard comparison.

The racemate of a (prepared via methods described by Hanessian)7 was converted to racemic 1 using the same

synthetic manipulations depicted in Scheme 2.

With butenolide (l) in hand, we turned to the main focus of our study, which was the 1 ,r(-organocuprate additions

to 1. Organocuprate additions can be problematic in cases in which the Gilman reagents decompose at approximately the

same temperature at which they react. *vg Reported sotutions to this pmbbm include the use of CUB&~&

to form the

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