Tetramethyldisiloxane: A Practical Organosilane Reducing Agent

Abstract

The chemistry of tetramethyldisiloxane (TMDS) is largely composed of the reduction of functional groups with increasing applications for carboncarbon bond formation. This reagent can be a safe alternative to H 2 , LiAlH 4 , and other reactive reagents. Notable are the amide conversion to amines and aldehydes, nitro group reductions, nitrile reductions, hydrogenolysis of arylchlorine bonds, reductive formation of sulfides, reductive etherification, reductive opening of ketals, reductive demethoxylation, and formation of nitriles with homologation. Selectivity can be carried out by the choice of catalysts. This review of recent chemistry will focus on synthetically applied reactions of the recent past. Displayed reactions are chosen to be representative of the referenced work, but are also chosen to illustrate a new viewpoint. Finally, where applicable, the results of competing hydrosilanes are presented to compare to the results obtained with TMDS.

Reduction of cysteine‐S‐protecting groups by triisopropylsilane

“…This fact has largely been misunderstood in the peptide chemistry literature. Silicon is metallic in nature and has low electronegativity relative to hydrogen resulting in polarization of the Si―H bond . This polarization causes hydrogen to be hydridic and results in a milder reducing agent than the usual aluminum‐based, boron‐based, and other metal‐based hydrides .…”

A Manganese N‐Heterocyclic Carbene Catalyst for Reduction of Sulfoxides with Silanes

“…The choice of the reaction solvent (THF, toluene or acetonitrile) was done depending on the solubility of the substrates. This work represents the first application of TMDS as a reducing agent in Mn‐mediated reactions . Noteworthy, PMHS and TMDS have been successfully applied in reduction reactions with several Earth abundant metals such as Fe, Ni, Co, and Zn …”

“…Thus, replacement of phenylsilane by cheaper and safer silanes is highly desirable. Among commercially available silanes, diphenylsilane (Ph 2 SiH 2 ) and triethylsilane (Et 3 SiH) represent a good choice for a small and medium scale processes, while tetramethyldisiloxane (TMDS) and polymethylhydrosiloxane (PMHS) are the best options for large scale synthesis . Other cheap silanes, such as triethoxysilane present safety problems since can disproportionate partially to SiH 4 , which is a pyrophoric and explosive gas .…”

“…In the case of TMDS, toluene was added to increase the solubility of the substrate. A further advantage of the use of TMDS is the benign silicon‐based by‐products that are formed (mainly octamethylcyclotetrasiloxane), which are essentially non‐toxic and can be readily removed under reduced pressure or chromatographically …”

Controlled Reduction of Carboxamides to Alcohols or Amines by Zinc Hydrides

“…[1] Among them, reduction of carboxamides, commonly mediated by metal hydrides,i so ne of the most frequently used processes that potentially delivers three possible products:a ldehydes,a lcohols,a nd amines (Scheme 1A). In contrast, alcohols or amines could be formed when I fragments through either CÀNo rC ÀOb ond scission, respectively,a nd the resulting aldehydes or imine/iminium intermediates are reduced by the second hydride.Atpresent, the state-of-the-art approaches for reduction of amides to alcohols are catalytic hydrogenation by well-defined pincer complexes,b ased on Ru, Fe,a nd Mn, under ah ighly pressurized H 2 atmosphere, [4] whereas those for the production of amines are facilitated by either hydrosilylation [5] with various metals [6] or organoboranes [7] as catalysts or electrophilic activation of amides with triflic anhydride. In contrast, alcohols or amines could be formed when I fragments through either CÀNo rC ÀOb ond scission, respectively,a nd the resulting aldehydes or imine/iminium intermediates are reduced by the second hydride.Atpresent, the state-of-the-art approaches for reduction of amides to alcohols are catalytic hydrogenation by well-defined pincer complexes,b ased on Ru, Fe,a nd Mn, under ah ighly pressurized H 2 atmosphere, [4] whereas those for the production of amines are facilitated by either hydrosilylation [5] with various metals [6] or organoboranes [7] as catalysts or electrophilic activation of amides with triflic anhydride.…”