The Role of Acyloxyphosphonium Ions and the Stereochemical Influence of Base in the Phosphorane‐Mediated Esterification of Alcohols

Abstract

The Mitsunobu reaction [1][2][3][4] is widely employed in both condensation and displacement reactions of alcohols with various nucleophiles and normally proceeds with inversion of stereochemistry when chiral secondary alcohols are used. The mechanism of the reaction continues to receive attention and the present view is summarized in Scheme 1. Although the [*] Dr.

DualPhos: a versatile, chemoselective reagent for two-carbon aldehyde to latent ( E )-alkenal homologation and application in the total synthesis of phomolide G

“…Treatment of acid 34 with DDQ in CH 2 Cl 2 allowed selective deprotection of the methoxybenzyl ether to give seco acid 35 . This compound was subjected to a standard Mitsunobu reaction [53–56] employing DIAD to yield the macrolactone 36 . Stepwise removal of the protecting groups was achieved by removal of the TBS group using TBAF to give 37 , followed by acidic hydrolysis using TFA in wet-acetonitrile to afford phomolide G 38 identical in all respects to that of the natural [43] corrected [30] structure.…”

Mechanism of the Mitsunobu Reaction: An Ongoing Mystery

“…The report by Ahn and co-workers 10 was followed, in 2003, by a report by McNulty and co-workers, who also looked at the role of the acyloxyphosphonium intermediate A2 . 21 Using a benzoyl peroxide and a trialkylphosphine, which are prone to form acyloxyphosphonium A2 intermediates, they found that the presence of a basic species in the reaction mixture had a significant effect on the stereochemical outcome of the resulting esterification. In the absence of a base, an intermediate like A2 led directly to product formation with retention of stereochemistry relative to the starting material.…”