Mechanism
Weinreb and Nahm originally proposed the following reaction mechanism to explain the selectivity shown in reactions of the Weinreb-Nahm amide. Their suggestion was that the tetrahedral intermediate (A below) formed as a result of nucleophilic acyl substitution by the organometallic reagent is stabilized by chelation from the methoxy group as shown. This intermediate is stable only at low temperatures, requiring a low-temperature quench.
This chelation is in contrast to the mechanism for formation of the over-addition product wherein collapse of the tetrahedral intermediate allows a second addition. The mechanistic conjecture on the part of Weinreb was immediately accepted by the academic community, but it was not until 2006 that it was confirmed by spectroscopic and kinetic analyses.
Read more about this topic: Weinreb Ketone Synthesis
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