Ortho-Phosphinoarenesulfonamide-Mediated Staudinger Reduction of Aryl and Alkyl Azides

Abstract

Conventional Staudinger reductions of organic azides are sluggish with aryl or bulky aliphatic azides. In addition, Staudinger reduction usually requires a large excess of water to promote the decomposition of the aza-ylide intermediate into phosphine oxide and amine products. To overcome the challenges above, we designed a novel triaryl phosphine reagent 2c with an ortho-SO2NH2 substituent. Herein, we report that such phosphine reagents are able to mediate the Staudinger reduction of both aryl and alkyl azides in either anhydrous or wet solvents. Good to excellent yields were obtained in all cases (even at a diluted concentration of 0.01 M). The formation of B-TAP, a cyclic aza-ylide, instead of phosphine oxide, eliminates the requirement of water in the Staudinger reduction. In addition, computational studies disclose that the intramolecular protonation of the aza-ylide by the ortho-SO2NH2 group is kinetically favorable and responsible for the acceleration of Staudinger reduction of the aryl azides.

Synthesis of Bench‐stable Polycyclic Organophosphorus Heterocycles via Staudinger‐type Annulations of ortho‐Azidophenols

“…Our studies were initially inspired by pioneering works [7] on the stabilization of penta‐coordinated P(V) species and the annulation strategy [8] we recently developed. We have demonstrated that B‐TAP heterocycles have increased stability over uncyclized P(V) aza‐ylides [8] and thereby can serve as a driving force for Staudinger reduction [9] . We speculated that such a framework might enhance the stability of penta‐coordinated P(V) compounds as well.…”

“…We have demonstrated that B-TAP heterocycles have increased stability over uncyclized P(V) aza-ylides [8] and thereby can serve as a driving force for Staudinger reduction. [9] We speculated that such a framework might enhance the stability of penta-coordinated P(V) compounds as well. Specifically, we proposed that the annulation of orthophosphinoarenesulfonyl fluoride with ortho-azidophenols would construct an unprecedented [5,5,0]-bicyclic P(V) scaffold with the aid of a silicon additive (Scheme 1, d).…”

Chemodivergent Staudinger Reactions of Secondary Phosphine Oxides and Application to the Total Synthesis of LL–D05139β Potassium Salt

“…From the view of the functionalization of the organic azide, [16] all three nitrogen atoms in trimethylsilyl azide were excluded during the annulation, and trimethylsilyl fluoride was formed. This result was intriguing to us since the conventional Staudinger reaction predominately followed the pathway where two nitrogen atoms were excluded from the azide [14a,15b] . We proposed that multiple nitrogen atom exclusion modes could be reached by a single organophosphorus reagent if its reactivity could be tuned by additional reagents or catalysts.…”