One-Pot in Situ Formation and Reaction of Trimethyl(trichloromethyl)silane: Application to the Synthesis of 2,2,2-Trichloromethylcarbinols

• Published in: Journal of organic chemistry 2012-03, Vol.77 (6), p.2999-3004
• Main Authors: Henegar, Kevin E, Lira, Ricardo
• Format: Article
• Language: English
• Subjects: Aldehydes - chemical synthesis; Aldehydes - chemistry; Aliphatic compounds; Chemistry; Exact sciences and technology; Heterocyclic compounds; Heterocyclic compounds with only one n hetero atom and condensed derivatives; Ketones - chemical synthesis; Ketones - chemistry; Methanol - analogs & derivatives; Methanol - chemical synthesis; Methanol - chemistry; Molecular Structure; Organic chemistry; Piperidones - chemical synthesis; Piperidones - chemistry; Preparations and properties; Trimethylsilyl Compounds - chemistry
• ISSN: 0022-3263; 1520-6904
• DOI: 10.1021/jo3001063

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 (CCl3-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 CCl3-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.