Organophosphorus Catalysis to Bypass Phosphine Oxide Waste

Abstract

The conversion of oxygen-containing compounds is often achieved by the use of phosphorus reagents. The newly formed phosphine oxide bond delivers the enthalpic gain that drives reactions, such as the Wittig, Mitsunobu, and Appel reaction, to completion. However, phosphine oxides are recognized as undesirable waste products and in the past decade several methods have emerged that address this issue by in situ regeneration of the phosphorus reagent. This Minireview outlines the two distinct strategies and underpinning research that led to these advances. The potential of the emerging field of phosphorus catalysis in chemistry is shown and new developments that may stimulate further research are described.

A General One‐Pot Synthesis of 2H‐Indazoles Using an Organophosphorus–Silane System

“…Balancing the required reactivity versus the desired reaction selectivity of the intermediate was considered crucial to avoid undesired side reactions, that is, nonproductive reduction of the nitro group, the aldehyde, or imine functionality. Surprisingly, phenylsilane, which is a well‐established reagent for the reduction of tertiary phosphine oxides, was less efficient (55 % yield; Table , entry 8), whereas triphenylsilane and methyldiethoxysilane led to the desired product in only a trace amount or a very low yield (Table , entries 9 and 10). To our surprise, easily separable and inexpensive 2,4,6,8‐tetramethylcyclotetrasiloxane (TMCTS) was comparably effective to diphenylsilane and afforded 3 in 73 % yield (Table , entry 11).…”

Novel Base‐Free Catalytic Wittig Reaction for the Synthesis of Highly Functionalized Alkenes

“…One option to overcome this intrinsic inefficiency is the development of catalytic Wittig reactions that exploit a redox‐based strategy. The key step in this reaction is the in situ reduction of the formed phosphine oxide by a suitable silane reducing agent enabling the employment of catalytic amounts of phosphine . This strategy has also been applied to the Appel, aza‐Wittig, and Staudinger reaction .…”

Chemoselective Reduction of Phosphine Oxides by 1,3‐Diphenyl‐Disiloxane

“…MeOTf) to furnish phosphines from their corresponding oxides. [5] Such conditions are marred by indiscriminate functional group reduction and necessitate special precautions for handling on a large scale. Silanes are thus preferred due to their improved chemoselectivity, [6] yet remain incompatible with many functional groups as they require elevated temperatures and additives such as Ti(O i Pr) 4 [7] (Scheme 1).…”