Hendrickson Reagent (Triphenylphosphonium Anhydride Trifluoromethane Sulfonate)

Introduction

The Hendrickson reagent (triphenylphosphonium anhydride trifluoromethane sulfonate) was first reported in 1975.[ ¹ ] It is readily prepared at 0 °C in dichloromethane from triphenylphosphine oxide and trifluromethanesulfonic anhydride in a 2:1 ratio and used directly as prepared in dichloromethane without the need for isolation.[1] [2] The Hendrickson reagent is a highly effective and versatile dehydrating reagent due to the strong electron-withdrawing capabilities of the triflyl group and special affinity for oxygen based on the very strong P–O bond.[ ³ ] It is selective for attack on oxygen without any intrinsic nucleophiles, avoiding formation of unwanted by-products. It has successfully been employed in ester, ether and amide formation as well as in the rapid conversion of aldoximes into nitriles, to yield a variety of alkyl and aryl aldoximes.[ ^2–4 ] These reactions occur in a manner that is analogous to the Mitsunobu reaction, involving an intermediate alkoxyphosphonium salt.[5] [6] The advantages of the Hendrickson reagent over the Mitsunobu reagent are that the recovered triphenylphosphine oxide may be recycled by treatment with trifluromethanesulfonic anhydride, the use of explosive azodicarboxylates is not required and competing side reactions are avoided.[ ⁷ ] Furthermore, a number of methods have recently been reported that can easily overcome, or avoid, the formation and removal of the double-stoichiometric amount of triphenylphosphine oxide, a common problem of phosphine-based dehydrating agents. These methods employ novel derivatives of the Hendrickson reagent such as a copolymer-supported triphenylphosphine ditriflate, an insoluble support allowing for the easy removal of triphenylphosphine[ ⁸ ] or cyclic analogues that can eliminate the step of oxidizing the phosphine into the corresponding oxide prior to trifluoromethylsulfonation.[9] [10]

Scheme 1 Preparation of the Hendrickson reagent

• References

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