Leading Questions How do you deoxygenate alcohols, ethers, and other sp₃ CO functional groups using silane reducing agents and Lewis acids?

saraheidi There are a variety of silane reducing agents and Lewis acids that you can use under mild conditions to achieve reductive deoxygenation of alcohols or ethers. The general mechanism of such a reaction begins with the "activation" of the CO group by a Lewis acid, as sp³ CO groups are generally not good leaving groups. After the alcohol or ether is transformed into an eligible leaving group, it will vacate the molecule and leave behind a carbocation. The hydride source, in this case a hydrosilane, will then donate a proton to the carbocation in an S_N1 reaction. The figure below demonstrates this.

jessead Because a carbocation is formed in this mechanism, generally only sp³ CO groups that generate stable carbocations (i.e tertiary or resonance stablized) can be effectively reduced using Lewis acids; additionally, several equivalents of the Lewis acid are needed to aid the reduction. This is observed with the use of Lewis acids like AlCl₃ or BF₃ with a hydrosilane. However, one novel combination of a Lewis acid and hydrosilane has been found to effectively reduce primary and secondary alcohols/ethers in catalytic amounts.

saraheidi The use of B(C₆F₅)₃ as a Lewis acid and triethylsilane (Et₃SiH) as a hydride source reverses the selectivity for sp₃ CO groups from tertiary > secondary >> primary to primary > secondary >> tertiary, as seen in the figure below. This has been determined to be a result of the reaction proceeding via an S_N2 pathway rather than the traditional S_N1 pathway.

jessead Other combinations of Lewis acids and hydrosilanes used for reductive deoxygenation are InCl₃ with Ph₂SiClH and TiCl₄ with Et₃SiH. The indium catalyst is useful in the mild deoxygenation of secondary, tertiary, and benzylic alcohols, while the ability of the titanium in TiCl₄ to activate CO bonds makes the catalyst convenient for deoxygenating allylic alcohols and allyl ethers.