Highly Stereoselective Addition of Organometallic Reagents to N-tert-Butanesulfinyl Imines Derived from 3- and 4-Substituted Cyclohexanones

Abstract

Addition of alkyl or aryl Grignard reagents to N-sulfinyl imines derived from 3- and 4-substituted cyclohexanones proceeds with good yields and with excellent diasteroselectivity. The selectivity of the reaction is controlled by the ring substituent rather than the sulfinyl group stereochemistry, and therefore racemic tert-butanesulfinamide can be employed.

1,2-Additions on Chiral N-Sulfinylketimines: An Easy Access to Chiral α-Tertiary Amines

“…Finally, in 2018 Reddy and co-workers developed the addition of diarylmethyllithiums to a variety of aldimines and gave three examples of the addition of diphenylmethyl- Ar 2 -Li Scheme 10 Addition of lithium acetylides to N-sulfinylketimines Also in 2004, the Ellman group investigated the additions of Grignard reagents to cyclohexyl-derived N-sulfinylketimines (Scheme 16). 27 The N-sulfinylketimines were obtained as a 1:1 ratio of E/Z isomers; the diastereoselectivity is governed by the equatorial attack of the ketimine and is independent of the chirality of the sulfoxide.…”

“…Scheme 15 Synthesis of ethyl -ethynyl-3,3,3-trifluoroalaninate Also in 2004, the Ellman group investigated the additions of Grignard reagents to cyclohexyl-derived N-sulfinylketimines (Scheme 16). 27 The N-sulfinylketimines were obtained as a 1:1 ratio of E/Z isomers; the diastereoselectivity is governed by the equatorial attack of the ketimine and is independent of the chirality of the sulfoxide.…”

tert-Butanesulfinimines: structure, synthesis and synthetic applications

“…Indeed, by contrast to all other reactions presented above, the sense of the stereoinduction of the addition of Grignard reagents to 24 has been proved to be controlled by the ring substituents rather than by the sulfinyl group, giving adducts 25 with good yields (455%) and excellent diastereoselectivities (493 : 7 dr) (Scheme 13). 43 The selectivity of these reactions is determined by equatorial attack on the lowest energy chair conformation and is independent of the stereochemistry of the sulfinyl group. Therefore, with these substrates, less expensive racemic tert-butanesulfinyl auxiliary can be used in practice.…”

Palladium(II)-Catalyzed C(sp2)–H Carbonylation of Sterically Hindered Amines with Carbon Monoxide

“…As shown in Scheme , pregnane-3,20-dione, cyclic 20-(1,2-ethanediyl acetal) 4 was synthesized from the commercially available pregnenolone via a known approach . The carbonyl group was transformed to imine via condensation of methylamine, followed by attack of phenyllithium to afford steroid-derived benzylamine 1v . With our newly developed palladium-catalyzed C–H carbonylation reaction as the key step, the precursor 1v was transferred to lactam 2v in 23% yield.…”