Formula (CH3)3CS(O)NH2 Pubchem 3382465 | Molar mass 121.2 g/mol | |
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Appearance white to off-white crystalline solid | ||
tert-Butanesulfinamide is an organosulfur compound and a member of the class of sulfinamides. Both enantiomeric forms are commercially available and are relevant to the asymmetric synthesis of amines as a chiral ammonia equivalent. This methodology was introduced in 1997 by Jonathan A. Ellman.
Contents
Synthesis
Chiral tert-butanesulfinamide can be prepared by enantioselective oxidation of inexpensive di-tert-butyl disulfide to the thiosulfinate followed by disulfide bond cleavage by lithium amide. In the original scope the chiral ligand used together with vanadyl acetylacetonate was prepared by condensing a chiral aminoindanol with 3,5-di-tert-butyl salicylaldehyde.
Amine synthesis
Condensation with ketones and aldehydes yield the corresponding N-tert-butanesulfinyl aldimines and ketimines. These intermediates are more resistant to hydrolysis than other imines but more reactive towards nucleophiles. A nucleophile adds diastereoselectively over the imine group in an electrophilic addition with the tert-butanesulfinyl group acting as a chiral auxiliary. This tert-butanesulfinyl group is also a protecting group. On addition of hydrochloric acid the tert-butanesulfinyl group is removed forming the chiral primary ammonium salt or amine (from aldehyde precursor) or the chiral secondary amine (ketone precursor).
Typical nucleophiles are Grignard reagents, organozinc compounds, organolithium compounds, and enolates.
Chiral sulfinimines as intermediates for the asymmetric synthesis of amines have also been developed by Franklin A. Davis.
Applications
tert-Butanesulfinamide has been used as an auxiliary in an asymmetric synthesis of cetirizine (more potent than the racemic mixture of the drug) starting from p-chlorobenzaldehyde and phenylmagnesium bromide: