Synthesis of Ketones with Alkyl Phosphonates and Nitriles as Acyl Cation Equivalent: Application of Dephosphonylation Reaction of β-Functionalized Phosphonate with Hydride

Abstract

The preparation of several α-substituted ketones is performed in a one-pot procedure with alkyl phosphonates and aromatic nitriles by subsequent treatment of LiAlH₄. A new method for nitriles used as an acyl cation equivalent is described.

Notes

To tell between “dephosphorylation” and “dephosphonylation”, we use the term “dephosphonylation” as a limited meaning of P-C bond cleavage in compound including phosphonate group.

In general, the addition of organolithium compounds to aliphatic nitriles are subjected to various side reactions, notably α-deprotonation (ref. 1(d)). We investigated the result on that, and described that in previous report (ref. 4(b)).

In earlier report (ref 3), several experiments with β-keto phosphonate were carried out to investigate the detailed mechanism. When reduction of β-keto phosphonate 5 with LiAlD₄ was followed by quenching with dilute H₂SO₄, the reaction afforded the ketone 6 containing no deuterium. In case of using LiAlH₄ and deuterized acid, the reaction gave the ketone 7 involving two deuteriums. Because ketones do not exchange its α-proton rapidly, this two result can be the evidence that hydride attacked the phosphorus atom directly. However in the case of enamine, proton exchange is occured rapidly in hydrolysis step, so above experiment cannot be adapted in this paper. But mechanisms of these two reactions are presumed to be identical.