Preparation and novel applications of trihalomethyl carbinols

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Date
2015
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University of Alabama Libraries
Abstract

Trihalomethyl carbinols have been widely used in organic chemistry and pharmaceutical chemistry as useful intermediates in the preparation of a wide variety of functional groups. Since the discovery of the Jocic reaction in 1897, significant effort has been put into the research of the reaction mechanism as well as the application of trichloromethyl carbinols. Upon deprotonation, the resultant gem-dichloroepoxide serves as a key intermediate to furnish a wide variety of organic molecules. These possible products include: carboxylic acids, amides, esters, heterocycles, etc. Herein, we report a convenient one-pot method to convert primary alcohols to their corresponding trichloromethyl carbinols using Dess-Martin periodinane in chloroform followed by the addition of a commercially available guanidine base 1,5,7-triazabicyclo [4.4.0]dec-5-ene (TBD). A variation of this one-pot method was also developed when basic conditions are not suitable. This method exhibit great functional group tolerance, as well as absolute stereochemical fidelity. By bypassing the formation and the isolation of the intermediate aldehyde, this operationally simple method also reduces preparation time and limits waste associated with workup and purification. In addition, a one-pot method to furnish primary, secondary and tertiary amides from their corresponding trichloromethyl carbinols was developed. Notably, when used in conjunction with our one-pot trichloromethyl carbinol conversion procedure, this represents the first method to access one-carbon homologated amides from any primary alcohols or aldehydes in two steps. This method boasts excellent compatibility with a wide range of function groups including aryl, alkyl, alkenyl, chiral substituents, and unprotected amino acids. Thirdly, we report a method to generate primary alcohols from the corresponding trichloromethyl carbinols. Similar to the amide homologation procedure, this showcases a two-step method to convert primary alcohols and aldehydes to their corresponding one-carbon homologated alcohols. The excellent substrate scope and ease of operation make this method an attractive and versatile approach to one-carbon homologation. Finally, we report some preliminary results on the enantioselective trihalomethylation of aldehydes. A series of chiral catalysts and Lewis acids were screened. Some catalyst systems showed excellent potential, matching the current best published results in asymmetric trifluoromethylations of aldehydes.

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Electronic Thesis or Dissertation
Keywords
Chemistry, Organic chemistry
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