Staudinger-aza-Wittig reaction

An elegant synthesis of the spiroaminal containing domain of azaspiracids 201 makes use of a Staudinger-aza-Wittig reaction in a cascade sequence to generate the spiroaminal 202 <06T5338 06JA15114>. 

Bravo et al. treated (Ss)-(+)-p-toluenesulfinamide (63), prepared by hydrolysis of 44,23 with triphenylphosphine in the presence of DEAD to give the N-sulfinyl iminophosphorane 64 in 92% yield.45 The Staudinger, aza-Wittig reaction of 64 with methyl or ethyl trifluoropyruvate afforded the unstable sulfinimine 65. Attempts to purify the imino sulfinimines by flash chromatography resulted in hydrolysis. 

Hartung, R., Paquette, L. Recent synthetic appiications of the tandem Staudinger/Aza-Wittig reaction. Chemtracts 2004,17, 72-82. 

S.4.4 One-pot tandem Staudinger/aza-Wittig reactions with carbonyls... 

An example of the use of the tandem Staudinger/aza-Wittig reaction to form a seven-membered ring comes from the total synthesis of the alkaloid (-)-stemospironine (76).34 In this example, azidoaldehyde 74 was treated with triphenylphosphine to form a seven-membered cyclic imine which was then followed by an in situ sodium borohydride reduction to afford 75. Treatment of the resulting amine with iodine initiated the formation of the pyrrolidino butyrolactone system of the final target. 

The intramolecular version of the tandem Staudinger/aza-Wittig reaction is often referred to as Eguchi aza-Wittig protocol (cf. references 14f, 60, 119-120, etc.)... 

Scheme 7.11 Staudinger-aza-Wittig reaction in a catch and release reactor and its application to multistep flow synthesis.

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