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Since its introduction by Ellman in 1997 as a chiral ammonia equivalent,1 enantiopure 2-methyl-2-propanesulfinamide (tert-butanesulfinamide) has been demonstrated to be a versatile chiral auxiliary and has found extensive use both in academics and industry. Condensation of tert-butanesulfinamide with aldehydes and ketones proceeds under mild conditions and provides tert-butanesulfinyl imines in high yields. 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.
These tert-butanesulfinyl imines have been used as intermediates in the asymmetric synthesis of many versatile building blocks2 including syn- and anti- 1,2- or 1,3-amino alcohols,3,4 α-branched and α,α-dibranched amines,5 and α- or β-amino acids and esters6,7 (Scheme 1). Several researchers have taken advantage of the robust chemistry of tert-butanesulfinyl imines in the synthesis of antibiotics, biologically active compounds and other complex natural products.8 Furthermore, tert-butanesulfinyl imines have been used in the synthesis of asymmetric ligands,9 and in a few cases, appears as the chirality-bearing component.10
Scheme 1
Recently, tert-butanesulfinyl imines have been employed in the synthesis of chiral heterocycles. A few groups have synthesized chiral aziridines through a common tert-butanesulfinyl imine intermediate (Scheme 2). Morton and co-workers synthesized chiral aziridines using trimethylsulfonium iodide with good yields and diastereoselectivities.11a Chemla and Ferreira reacted a racemic allenylzinc substrate with various tert-butanesulfinyl imines to achieve trans-ethynylaziridines as diastereomerically and enantiomerically pure compounds in good yields.11b
Scheme 2
Additionally, Dondas and De Kimpe devised an efficient route to pyrrolidines and piperidines using a common racemic tert-butanesulfinyl amine (Scheme 3), which is easily achieved from the sulfinyl imine by reduction with NaBH4.12 Their synthesis highlights a one-pot cascade cyclization and fragmentation, which allows for very high yields and purity of the cyclized product.
Scheme 3
Ellman’s research group has also reported the synthesis of chiral heterocycles. In an extension of their work on synthesis of 1,3-amino-alcohols,4a Ellman carried out the asymmetric syntheses of (-)-halosaline and (-)-8-epihalosaline (Scheme 4).
Scheme 4
Another recent report describes the intermolecular self-condensation of chiral tert-butanesulfinyl imines in a synthesis for the pyrrolizidine alkaloid SC-53116 (Scheme 5).13 In a later report, Ellman demonstrated the facile synthesis of chiral 2-substituted pyrrolidines (Scheme 6) that proceeds with high yields and diastereoselectivities.14
Scheme 5
Scheme 6
Sigma-Aldrich is pleased to be able to offer this versatile and useful auxiliary in both enantiomeric and racemic forms for your research.
| Product Name |
Product # |
| (R)-(+)-2-Methyl-2-propanesulfinamide |
497401 |
| (S)-(-)-2-Methyl-2-propanesulfinamide |
513210 |
| 2-Methyl-2-propanesulfinamide |
560871 |
References:
(1) Liu, G. et al. J. Am. Soc. Chem. 1997, 119, 9913.
(2) For a recent review, see: Ellman, J. A.; Owens, T. D.; Tang, T. P. Acc. Chem. Res. 2002, 35, 984.
(3) 1,2-amino alcohols: (a) Zhong, Y.-W. et al. J. Am. Soc. Chem. 2005, 127, 11956. (b) Evans, J. W.; Ellman, J. A. J. Org. Chem. 2003, 68, 9948. (c) Tang, T. P. et al. J. Org. Chem. 2001, 66, 3707. (d) Barrow, J. C. et al. Tetrahedron Lett. 2001, 42, 2051.
(4) 1,3-amino alcohols: (a) Kochi, T. et al. J. Am. Soc. Chem. 2003, 125, 11276. (b) Kochi, T. et al. J. Am. Soc. Chem. 2002, 124, 6518.
(5) (a) Cogan, D. A. et al. Tetrahedron 1999, 55, 8883. (b) Cogan, D. A.; Ellman, J. A. J. Am. Soc. Chem. 1999, 121, 268. (c) see ref 1.
(6) a-amino acids: (a) Avenoza, A. et al. Synthesis 2005, 575. (b) Naskar, D. et al. Tetrahedron Lett. 2003, 44, 8865.
(7) b-amino acids and esters: (a) Jacobsen, M. F.; Skrydstrup, T. J. Org. Chem. 2003, 68, 7122. (b) Tang, T. P.; Ellman, J. A. J. Org. Chem. 2002, 67, 7819. (c) Tang, T. P.; Ellman, J. A. J. Org. Chem. 1999, 64, 12.
(8) Some recent examples: (a) Lu, B. Z. et al. Org. Lett. 2005, 7, 2599. (b) Kochi, T.; Ellman, J. A. J. Am. Soc. Chem. 2004, 126, 15652. (c) Higashibayashi, S. et al. Tetrahedron Lett. 2004, 45, 3707.
(9) Kato, T. et al. Tetrahedron: Asymmetry 2004, 15, 3693.
(10) (a) Schenkel L. B.; Ellman, J. A. J. Org. Chem. 2004, 69, 1800. (b) Schenkel, L. B.; Ellman, J. A. Org. Lett.
2003, 5, 545. (c) Owens, T. D. et al. J. Org. Chem. 2003, 68, 3.
(11) (a) Morton, D. et al. Synlett 2003, 1985. (b) Chemla, F.; Ferreira, F. J. Org. Chem. 2004, 69, 8244.
(12) Dondas, H. A.; De Kimpe, N. Tetrahedron Lett. 2005, 46, 4179.
(13) Schenkel, L. B.; Ellman, J. A. Org. Lett. 2004, 6, 3621.
(14) Brinner, K. M.; Ellman, J. A. Org. Biomol. Chem. 2005, 3, 2109.
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