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Synlett 2003(8): 1221-1222
DOI: 10.1055/s-2003-39913
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© Georg Thieme Verlag Stuttgart ˙ New York

Mitsunobu Reagent [Triphenyl-phosphine (TPP) and Diethyl Azodi-carboxylate (DEAD)/Diisopropyl azodicarboxylate (DIAD)]

Satish Kumar Nune*
C/O Prof. K. C. Kumara Swamy, , School of Chemistry, University of Hyderabad, Hyderabad - 500 046, Andhra Pradesh, India.
e-Mail: nunesatish@yahoo.com;
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Publication History

Publication Date:
11 June 2003 (online)

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Introduction

The Mitsunobu reaction is perhaps the most favored method for the inversion of chiral secondary alcohols. [1] It involves the reaction of an acid component (RCO2H) with a mixture of triphenylphosphine (TPP), diethyl azodicarboxylate (DEAD)/diisopropyl azodicarboxylate (DIAD), and an alcohol (Scheme [1] ). [1] It is supposed that the initial nucleophilic addition of TPP to DEAD/DIAD affords the betaine I; [2] [3] attack of an acid followed by an alcohol on I leads to the formation of a highly reactive alkoxyphosphonium intermediate II which undergoes nucleophilic displacement with virtually complete inversion of configuration at the electrophilic center under mild and nearly neutral conditions. The traditionally used acidic component can be replaced by metal halides (LiBr), [4a] silanols, [4b] amides/ imides, [4c] nitronates, [4d] fluorinated alcohols [4e] and compounds possessing an active methylene group,4f thus rendering the reaction widely applicable in organic synthesis.

Scheme 1