Organic Chemistry Portal
Organic Chemistry Highlights

Tuesday, November 5, 2004
Chryssostomos Chatgilialoglu,
Consiglio Nazionale delle Ricerche, Bologna

(TMS)3SiH in organic synthesis: Part 2

There are many examples in the literature where (TMS)3SiH and Bu3SnH behave similarly as reducing agents in radical chain reactions. However, there is an increasing number of cases where the two reagents behave differently. Herein, I will give two recent examples of the use of (TMS)3SiH in organic synthesis that confirm this diversity.

The first example deals with Barton reductive radical decarboxylation that consists of the reaction of easily prepared N-hydroxypyridine-2-thione ester with Bu3SnH. The efficiency of this radical chain reaction with (TMS)3SiH replacing Bu3SnH was unknown until recently. Satoshi Shuto and coworkers used the Barton reductive decarboxylation as the key step to construct the chiral cis-cyclopropane structure in compounds designed as antidopaminergic agents (J. Org. Chem. 2003, 68, 9255. DOI: 10.1021/jo0302206) . Indeed, the decarboxylation of ester 1 proceeded smoothly at rt with both (TMS)3SiH and Bu3SnH, but the reaction with silane gave a higher cis selectivity. The propagation steps consist of the addition of silyl or stannyl radical to the thiocarbonyl moiety followed by a decarboxylation to generate radical 2. DFT calculations suggested a π-type structure for radical 2. The hydrogen abstraction from the sterically demanding (TMS)3SiH could occur from the less-hindered side of radical 2 affording the observed cis selectivity.

N-Alkoxylamines are a class of initiators in 'living' radical polymerization. A new methodology for their synthesis mediated by (TMS)3SiH has been developed by Rebecca Braslau and coworkers (Org. Lett. 2004, 6, 2233. DOI: 10.1021/ol049271v) . The method consists of the trapping of alkyl radicals generated in situ by stable nitroxide radicals. To accomplish this simple reaction sequence, an alkyl bromide or iodide was treated with (TMS)3SiH in the presence of thermally generated t-BuO. radicals. The reaction is not a radical chain process and stoichiometric quantities of the radical initiator are required. This method allows the generation of a variety of carbon-centered radicals such as primary, secondary, tertiary, benzylic, allylic, and α-carbonyl, which can be trapped with various nitroxides.

C. Chatgilialoglu, Org. Chem. Highlights 2004, November 5.