Science of Synthesis

Wicha, J., Science of Synthesis, (2009) 48, 97.

General Introduction

Reduction of carbonyl compounds to the respective alkanes is one of the classic transformations of organic synthesis, with numerous historical connotations and broad application in current laboratory practice.[‌1‌–‌5‌] Reduction can be carried out in a direct manner when neither derivatives are prepared nor manageable intermediates, such as alcohols, are isolated, or through appropriate derivatives (‌Scheme 1‌). Reduction with zinc or amalgamated zinc and hydrochloric acid (the Clemmensen reduction) is the most frequently used method of direct deoxygenation of carbonyl compounds. Several other methods for direct deoxygenation of aldehydes, ketones, and (in some cases) carboxylic acids and esters, are available. Deoxygenation of aldehydes and ketones through their respective hydrazones (the Wolff–Kishner reduction) has a broad application in organic synthesis (‌Scheme 2‌). The most often used variation (the Huang-Minlon modification) involves formation of the hydrazone from the carbonyl compound and 85% hydrazine hydrate in a high-boiling alcoholic solvent, such as ethylene glycol, and then potassium hydroxide induced thermal fragmentation of the hydrazone. Various modifications of the Wolff–Kishner reduction, differing in the derivatization step or the hydrazone fragmentation step, are available. However, in all procedures strongly alkaline conditions are applied. Reduction of complex aldehydes and ketones is conveniently performed via their tosylhydrazones (‌Scheme 3‌); these derivatives are reduced with mixed metal hydrides or boranes under relatively mild conditions. Sodium cyanoborohydride in the presence of a protic acid, or catecholborane, appear to be the preferred reagents. Transformation of aldehydes or ketones into dithioacetals followed by reduction provides a mild and general method for deoxygenation (‌Scheme 4‌). Thioacetals can be formed by an acid-catalyzed reaction of the carbonyl compound with thiols, usually ethane-1,2-dithiol or propane-1,2-dithiol. The reduction step is carried out using Raney nickel or more specific reagents, such as tributyltin hydride in the presence of radical initiators. In other cases, deoxygenation is achieved by transforming the ketone into the respective enol trifluoromethanesulfonate, followed by catalytic hydrogenation.

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References

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• 8.Meeeee-Meee, (8888) M 8e, 888.
• 8.Meeeee-Meee, (8888) M 8e, 88.