Enantioselective Copper‐Catalyzed Conjugate Addition to Trisubstituted Cyclohexenones: Construction of Stereogenic Quaternary Centers

Abstract

Trimethyl‐ and triethylaluminum undergo enantioselective conjugate addition to 3‐ and 2‐substituted cyclohexenones in the presence of catalytic amounts of a Cu salt and a phosphoramidite ligand L* (see scheme). Thus, chiral quaternary centers can be built with up to 96.6 % ee. Functionalized enones lead to bicyclic structures by a subsequent aldol reaction.

Formation of Quaternary Stereogenic Centers by NHC–Cu‐Catalyzed Asymmetric Conjugate Addition Reactions with Grignard Reagents on Polyconjugated Cyclic Enones

“…These were successfully realized by the addition of diorganozinc reagents to very activated substrates, such as Meldrum acid derivatives,4–6 nitroolefins7 and doubly activated cyclic enones 8. An improvement was achieved by the introduction of trialkylaluminum reagents to nonactivated trisubstituted cyclic enones 9–12…”

Catalytic Enantioselective Alkylations of Tetrasubstituted Olefins. Synthesis of All-Carbon Quaternary Stereogenic Centers through Cu-Catalyzed Asymmetric Conjugate Additions of Alkylzinc Reagents to Enones

“…Study of the full scope of this method and development of catalytic asymmetric additions to -substituted enones 7 and the related acyclic substrates will be disclosed in due course. (7) The protocol described herein is ineffective with the less activated but also less sterically hindered -substituted cyclic enones (see ref 3). affords (R)-9 in 57% ee (versus 90% ee with undistilled toluene).…”

1,3‐bis[N‐sulfonyl‐(1R,2S)‐1,3‐diphenyl‐2‐aminopropanol]benzene: An excellent ligand for titanium‐catalyzed asymmetric AlPh3(THF) additions to aldehydes

“…32 Organoaluminum compounds are more reactive than organozinc or organoboron reagents and have been applied to diversified organic syntheses [33][34][35][36][37][38][39][40][41] and to asymmetric catalytic reactions. [42][43][44][45][46] To continue our effort to develop amino alcohol ligands [47][48][49][50] for asymmetric catalytic reactions and also to demonstrate the application of AlAr 3 (THF) compounds, we herein report asymmetric AlPh 3 (THF) additions to a variety of aldehydes catalyzed by an in situ formed titanium(IV) catalyst of 1,3-bis[N-sulfonyl-(1R,2S)-1,3-diphenyl-2-aminopropanol]benzene (1). Compound 1 has been reported to be an excellent ligand in titanium-catalyzed ZnEt 2 additions to aldehydes.…”