One-pot in situ formation and reaction of trimethyl(trichloromethyl)silane: application to the synthesis of 2,2,2-trichloromethylcarbinols

2,2,2-Trichloromethylcarbinols are 1 are valuable synthetic intermediates with a multitude of uses. A scalable procedure for the synthesis of TMS-protected-2,2,2-trichloromethylcarbinols and 2,2,2-trichloromethylcarbinols 1 was developed that employs the in situ generation and reaction of trimethyl(trichloromethyl)silane (CCl(3)-TMS). The procedure avoids the exposure of the carbonyl compounds to the strongly basic conditions typically used for this transformation and also avoids isolation of the difficult-to-handle CCl(3)-TMS. This procedure was applied to diastereoselective trichloromethyl additions to 2-substituted 4-piperidinones and to reactions with a variety of structurally diverse aldehydes and ketones.