Bis(amino)cyclopropenylidene (BAC) Catalyzed Aza-Benzoin Reaction

Abstract

A bis(amino)cyclopropenylidene (BAC) catalyzed aza-benzoin reaction between aldehydes and phosphinoyl imines has been developed. The reaction is general with a wide range of aromatic aldehydes and aromatic imines. The reaction displays excellent chemoselectivity favoring aza-benzoin products over homobenzoin products.

An Overview on the N-Heterocyclic Carbene-Catalyzed Aza-Benzoin Condensation Reaction

“…After fruitless attempts with Boc and tosyl imines, P,P-diphenyl N-[(aryl)(tosyl)methyl] phosphinic amides, the more practical surrogates of the corresponding protected imines, gave productive results in the reaction with aromatic aldehydes in the presence of bis(diethylamino)cyclopropenium salt VI (Scheme 13) [18]. Non-enolizable N-protected aryl trifluoromethyl ketimines have been used as acceptor partners in coupling with a series of highly-reactive furan-2-carbaldehydes to produce the corresponding α-amino-α-trifluoromethyl ketones, bearing a valuable quaternary stereocenter, in moderate to good yields (32-87%) in the presence of triazolium salt I-3 (Scheme 12) [32].…”

“…After fruitless attempts with Boc and tosyl imines, P,P-diphenyl N-[(aryl)(tosyl)methyl] phosphinic amides, the more practical surrogates of the corresponding protected imines, gave productive results in the reaction with aromatic aldehydes in the presence of bis(diethylamino)cyclopropenium salt VI (Scheme 13) [18]. 9 …”

“…The wide choice of chiral azolium salts reported in the literature allows access to the asymmetric version of the reaction, affording enantio-enriched α-amino ketones [17]. In addition to NHCs, bis(amino)-cyclopropenylidenes (BACs) have also been successfully applied as umpolung-promoting species [18]. The nucleophilic attack of a Breslow Intermediate on the electrophilic imine, a second proton transfer step and subsequent elimination furnish the condensation product, at the same time regenerating the catalyst.…”

“…The wide choice of chiral azolium salts reported in the literature allows access to the asymmetric version of the reaction, affording enantio-enriched α-amino ketones [17]. In addition to NHCs, bis(amino)-cyclopropenylidenes (BACs) have also been successfully applied as umpolung-promoting species [18].…”

Promotion of Organic Reactions by Non‐Benzenoid Carbocyclic Aromatic Ions

“…[68] After using BAC 233 for the umpolung activation of aromatic aldehydes,s ubsequent coupling with aromatic phosphinoylimines produced the corresponding aza-benzoin adducts in good to excellent yields with moderate catalyst loadings (Scheme 33). [68] After using BAC 233 for the umpolung activation of aromatic aldehydes,s ubsequent coupling with aromatic phosphinoylimines produced the corresponding aza-benzoin adducts in good to excellent yields with moderate catalyst loadings (Scheme 33).…”