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Categories: C-C Bond Formation > Heteroatom-containing Molecules > (Poly)Chlorinated Alkanes, Trihalomethyl Carbinols

Synthesis of trichloromethyl carbinols

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Trichlorocarbinols are useful intermediates. They are usually prepared by base-promoted addition of chloroform to carbonyl compounds in the presence of strong bases, which requires low temperatures to minimize the extent of the Cannizzaro reaction. DBU promotes this addition in the absence of solvent at room temperature. Washing with water removes the amidine and gives product in high yields.
V. K. Aggarwal, A. Mereu, J. Org. Chem., 2000, 65, 7211-7212.

Trihaloacetic acids can been converted to trichloromethyl and tribromomethyl ketones in good yield by a catalyzed reaction with aldehydes followed by oxidation. A coupling of organozinc intermediates with trichloroacetyl chloride gives trichloromethyl ketones.
E. J. Corey, J. O. Link, Y. Shao, Tetrahedron Lett., 1992, 33, 3435-3438.

In a synthesis of 2,2,2-trichloromethylcarbinols, a combination of sodium trichloroacetate in the presence of malonic acid enables an efficient transformation of electron deficient aldehydes in DMSO, whereas electron-rich aldehydes did not require the addition of malonic acid. By performing this decarboxylative reaction in continuous flow, scale-up of the reaction could be achieved with a simple and safe setup.
A. B. Jensen, A. T. Lindhardt, J. Org. Chem., 2014, 79, 1174-1183.

Versatile trichloromethyl carbinols can be prepared in one pot from primary alcohols by treatment with Dess-Martin periodinane in CHCl3 followed by 1,5,7-triazabicyclo[4.4.0]dec-5-ene (TBD).
M. K. Gupta, Z. Li, T. S. Snowden, J. Org. Chem., 2012, 77, 4854-4860.

A scalable procedure for the synthesis of TMS-protected-2,2,2-trichloromethylcarbinols and 2,2,2-trichloromethylcarbinols employs an 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.
K. E. Henegar, R. Lira, J. Org. Chem., 2012, 77, 2999-3004.