The
convenient and scalable preparative approach for the two-step
α-methylation of ketones is described. The optimized protocols
for regioselective preparation of enaminones with further diastereoselective
and functional groups tolerant hydrogenation to α-methylketones
are developed. The scope and limitations of the proposed methodology
are discussed. The advantages compared to known procedures are demonstrated.
The unexpected role of acetone in the hydrogenation is suggested.
The evaluation of the method for both early building block synthesis
and late-stage CH-functionalization is shown. The elaborate procedures’ preparability and scalability are
demonstrated by the synthesis of several α-methyl ketones up
to 100 g amount.
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