Synthesis of Tertiary β-Hydroxy Amides via Acylsilanes

Significance

The article introduces an elegant synthetic route towards tertiary β-hydroxy amides which are difficult to access via the classical aldol addition with ketones as substrates. In this approach the lithium enolates of acetamides are used to perform a nucleophilic attack on acylsilanes. A subsequent Brook rearrangement, which transfers the silyl group from the carbon to the neighboring oxygen, effects an intrinsic Umpolung leading to β-silyloxy homoenolates which are trapped with various electrophiles yielding the respective β-hydroxy amides. By using an enantiomerically pure acetamide as chiral auxiliary β-hydroxy amides can be obtained with diastereomeric ratios of 10:1. Surprisingly, better diastereoselectivities are obtained under thermodynamic conditions.