Perfluoroarene Interaction-Controlled Chiral Phosphoric Acid-Catalyzed Enantioselective Michael Addition of Difluoroenoxysilanes to Azadienes: a Combination of Experimental and Theoretical Studies

Abstract

A catalytic and highly enantioselective Mukaiyama–Michael addition of difluoroenoxysilanes to azadienes has been developed using perfluorinated aryl-incorporating chiral monophosphoric acid (PF-CPA) as an effective, multipoint-controlled chiral catalyst. The inherent perfluoroaryl substituent is finely beneficial not only for achieving high catalytic activity but also for creating a compact and confined chiral environment for highly enantioselective transformations. Theoretical studies showed that the π–π interaction and hydrogen bond between PF-CPA and substrates play a crucial role in determining the stereochemical outcomes in comparison with those of phenyl, binaphthyl, and partially fluorinated aryls.

An update on chiral phosphoric acid organocatalyzed stereoselective reactions

“…The increased Brønsted acidity of chiral phosphoric acids containing perfluoroarenes was utilized by Lan, Wang, and their colleagues in the enantioselective Michael addition of less reactive nucleophiles, difluoroenoxysilanes to azadienes (Scheme 10). 60 Asymmetric 1,4-difluoroalkylation was enabled by the presence of perfluoroaryl-incorporated ent-CPA18. Under optimal reaction conditions, a series of aurone-derived azadienes were reacted with different difluoroenoxysilanes, leading to the desired products in moderate to excellent yields with excellent enantiocontrol (yields of 61-98% and 91->99% ee).…”

“…The increased Brønsted acidity of chiral phosphoric acids containing perfluoroarenes was utilized by Lan, Wang, and their colleagues in the enantioselective Michael addition of less reactive nucleophiles, difluoroenoxysilanes to azadienes (Scheme 10). 60…”

Copper‐Catalyzed 1,4‐Addition of a Silicon Nucleophile to Azadienes

“…In 2016, Zhao's group pioneered the development of catalytic Michael addition of azadienes and its cascade reactions to afford either diastereomeric series of benzofuran‐fused lactams and tetrahydropyridines [3b] . Subsequently, phosphites, [4a] tritylthiol, [4b] rhodanines, [4c] β,γ‐unsaturated γ‐lactones, [4d] 5H‐thiazol‐4‐ones, [4e] indoles, [4f–g] 2‐naphthols, [4h] 3‐homoacyl coumarin, [4i] α‐thiocyanoindanones, [4j] and difluoroenoxysilanes [4k] were employed as nucleophiles to react with azadienes by other groups. Despite the many efficient approaches to 1,4‐addition of azadienes, only a few conjugate addition reactions of heteroatomic nucleophiles have been reported and almost all of the reported nucleophiles are typical nucleophiles, such as carbanions, aromatic rings, phosphites and tritylthiol.…”

Copper-Catalyzed Enantioselective 1,2-Allylation of Azadienes with Allylboronates

“…Subsequently, they presented some sophisticated examples of the Pd-catalyzed cycloadditions between azadienes and vinylethylene carbonates or vinyl oxetanes to access chiral nine- and ten-membered benzofuran-fused heterocycles . These azadienes can also serve as two-atom synthons to undergo [2 + 3] or [2 + 1] cycloaddition reactions. , Furthermore, such species can act as suitable Michael acceptors in conjugate addition reactions. − In 2018, Zhou’s group disclosed an organocatalytic asymmetric 1,4-conjugate addition of phosphites to azadienes . Later on, the enantioselective Michael additions of azadienes with tritylthiol, rhodanines, β,γ-unsaturated γ-lactones, 5 H -thiazol-4-ones, indoles, 2-naphthols, 3-homoacyl coumarin, α-thiocyanoindanones, difluoroenoxysilanes and PhMe 2 SiBpin were established by other groups to provide the 1,4-adducts in high yields with good to high stereoselectivities.…”