Organocatalyzed Asymmetric 1,6-Conjugate Addition of para-Quinone Methides with Dicyanoolefins

Abstract

A chiral thiourea catalyzed asymmetric 1,6-conjugate addition of para-quinone methides with dicyanoolefins has been developed. The reaction provided an efficient approach to the synthesis of chiral diarylmethine skeletons in good yields (up to 99% yield) with high diastereo- and enantioselectivity (>20:1 dr and up to 99.5:0.5 er), also on a gram scale. The preliminary mechanistic study showed that the remote stereocontrol was achieved through intermolecular hydrogen-bond interaction between the chiral thiourea catalyst and the para-quinone methides directly for the first time.

Enantioselective Rauhut–Currier‐Type 1,6‐Conjugate Addition of Methyl Vinyl Ketone to para‐Quinone Methides

“…The enantioselective 1,6‐conjugate reactions of p ‐QMs have been developed for the construction of chiral C−C, C−B, and C−S bonds. The C‐nucleophiles in these asymmetric additions involve malonates,, aldehydes, pyrroles, glycine derivatives,, oxindoles,– dicyanoolefins, naphthols, and cyclopropanes . Methodologies involving p ‐QMs have become a prevailing approach towards the formation of optically active diarylmethine compounds.…”

Overview on the Recent Strategies for the Enantioselective Synthesis of 1, 1‐Diarylalkanes, Triarylmethanes and Related Molecules Containing the Diarylmethine Stereocenter

“…In 2016, Li et al developed ac hiral thiourea organocatalyzed asymmetric1 ,6-conjugate addition of para-quinone methides with dicyanoolefins for the enantioselective synthesis of molecules containing unsymmetrical 1, 1-diaryl motif (Scheme60). [92] Using the chiral thiourea organocatalyst (40 f)h igh yields (up to 99 %y ield) and stereoselectivity (> 20:1 d.r.a nd up to 99.5:0.5 er) was observed.…”

Recent Advances in the Catalytic Enantioselective Reactions of para‐Quinone Methides

“…The first example of a chiral‐thiourea‐catalyzed enantioselective 1,6‐conjugate addition of dicyanoolefins to p ‐QMs was established by Lin, Yao, and co‐workers to access chiral diarylmethine skeletons . In the presence of thiourea C14 and trimethylamine, 2,6‐di‐ tert‐butyl ‐4‐arylidenecyclohexa‐2,5‐dienones 52 reacted smoothly with dicyanoolefins 53 to afford a range of chiral diarylmethine derivatives 54 in 47–99 % yield with 12–99 % ee and >20:1 d.r.…”