IPNBSH

A Reagent for the Simple Reduction of Alcohols

Introduction

Developed by the Movassaghi group at MIT, N-isopropylidene-N’-2-nitrobenzenesulfonyl hydrazine (IPNBSH, 687855) is a useful reagent for the mild deoxygenation of allylic, propargylic, and aliphatic alcohols to the corresponding alkenes, allenes, and alkanes.



The reaction conditions are straightforward and general. Treatment of the alcohol with IPNBSH under Mitsunobu conditions generates an intermediate hydrazone adduct. In situ hydrolysis of this species furnishes a hydrazine which fragments under the reaction conditions, liberating 2-nitrobenzenesulfinic acid, nitrogen gas, and the reduced product (rearranged as a result of a sigmatropic extrusion of dinitrogen from the diazene intermediate). The reaction proceeds in common solvents such as THF and toluene.



The use of IPNBSH has several advantages over NBSH (2-nitrobenzenesulfonyl hydrazide). While somewhat more sensitive toward sterically hindered substrates, IPNBSH is dramatically more stable than NBSH, which decomposes rapidly in solution and is not amenable to storage for long periods even in the solid state. In some cases, the more thermally stable IPNBSH has exhibited enhanced reactivity over NBSH in difficult reductive fragmentations, as demonstrated in Movassaghi’s total syntheses of
(–)-acylfulvene and (–)-irofulven.

References: (1) Movassaghi, M.; Ahmad, O. K. J. Org. Chem. 2007, 72, 1838. (2) Movassaghi, M. et al. Angew. Chem., Int. Ed. 2006, 45, 5859. (2) Myers, A. G. et al. J. Org. Chem. 1997, 62, 7507.

Advantages

• Straight-forward, one-pot, deoxygenation of alcohols
• Uniform set of reaction conditions applicable to various alcohol types (primary, allylic, propargylic)
• Easy access to allenes
• Shelf-stable reagent

Representative Applications

Reduction of Allylic Alcohols (with Allylic Transposition)

IPNBSH is an excellent reagent for the one-pot deoxygenation of allylic alcohols to yield mono- or disubstituted olefins. The reagent is tolerant of advanced, functionalized intermediates, and yields of the allyically transposed olefins are generally high.

References: (1) Movassaghi, M.; Ahmad, O. K. J. Org. Chem. 2007, 72, 1838. (2) Movassaghi, M. et al. Angew. Chem., Int. Ed. 2006, 45, 5859.

Reduction of Propargylic Alcohols (Preparation of Allenes)

Treatment of propargylic alcohols with IPNBSH serves as a simple method for the preparation of mono- and 1,3-disubstituted allenes via reduction/allyic transposition.

Reference: Movassaghi, M.; Ahmad, O. K. J. Org. Chem. 2007, 72, 1838.

Other Reduction Reactions

IPNBSH has also been demonstrated to be effective in the reduction of aliphatic alcohols, as well as in the reduction of allylic halides (with allylic transposition). The former process is best effected by using phenylhydrazine in place of TFE–H₂O. Reduction of allylic halides is achieved by N-alkylation of the anion derived from IPNBSH, followed by in situ hydrolysis.

Reference: Movassaghi, M.; Ahmad, O. K. J. Org. Chem. 2007, 72, 1838.

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