2-Methyl-2-propanesulfinamide (Ellman’s Sulfinamide): A Versatile Chiral Reagent

Introduction

Enantiopure 2-methyl-2-propanesulfinamide (tert-butane­sulfinamide) was introduced by Ellman in 1997. [¹] As a chiral ammonia equivalent, it can easily condense with aldehydes and ketones to afford tert-butanesulfinyl imines in high yields (Scheme 1). [²] The tert-butanesulfinyl group activates these imines for the addition of many different classes of nucleophiles and serves as a powerful chiral ­directing group to provide products with generally high diastereoselectivity. Subsequent removal of the tert-butanesulfinyl group under mild conditions cleanly provides the amine products. Many versatile building blocks [³] including syn- and anti-1,2- or 1,3-amino alcohols, [4] [5] α-branched and α,α-dibranched amines, [6] α- or β-amino acids and esters [7] [8] can be efficiently synthesized by using this methodology. In addition, this methodology can also be used in the synthesis of antibiotics, biologically active compounds, and other complex natural products. [9] Furthermore, tert-butanesulfinamide has been used in the synthesis of asymmetric ligands [¹0] or catalysts [¹¹] , and in a few cases, appears as the chirality-bearing component. [¹²]

Scheme 1 Synthesis of sulfinyl aldimines or ketimines

Each configuration of 2-methyl-2-propanesulfinamid is readily available in a two-step process of catalytic asymmetric oxidation of tert-butyl disulfide, followed by the reaction of the tert-butanethiosulfinate product 4 with an amide anion (Scheme 2). [¹³]

Scheme 2 Preparation of (R)-tert-butanesulfinamide

References

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• 1,2-amino alcohols:
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• 6c   , 
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• Some recent examples:
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