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DOI: 10.1055/s-0029-1219339
2-Methyl-2-propanesulfinamide (Ellman’s Sulfinamide): A Versatile Chiral Reagent
Publication History
Publication Date:
25 January 2010 (online)
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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
- 1
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