Effective asymmetric vinylogous Mannich reaction of isatin imines with α,α-dicyanoolefins in the presence of a simple chiral amide phosphonium bifunctional phase transfer catalyst

Abstract

A Mannich reaction between N-Boc isatin imine and α,α-dicyanoolefin as well as subsequent oxidative cleavage of the malonic nitrile moiety were described.

Bifunctional Ion Pair Catalysts from Chiral α‐Amino Acids

“…Furthermore, asymmetric vinylogous Mannich reactions utilizing α,α‐dicyanoolefins 33 were subsequently investigated by amide‐phosphonium salts M for preparing chiral 3,3‐disubstituted oxindoles, and many substituted dicyanoolefins were well tolerated in this catalytic system with high yield and stereoselectivities achieved (Scheme ) . Similar strategy was also illustrated in the reaction between 3,5‐disubstituted‐4‐nitroisoxazoles 36 and isatin‐derived imines 35 , which could be applied to the formal synthesis of (+)‐AG‐041R (Scheme ) …”

Chiral Phase-Transfer Catalysts with Hydrogen Bond: A Powerful Tool in the Asymmetric Synthesis

“…Lu and co-workers also reported asymmetric alkylation of glycine imine reactions that were promoted by this class of bifunctional phase-transfer catalysts, affording the substituted glycine imines with high yields and ees (Scheme 31) [52]. Subsequently, Wu and co-workers, using their developed phosphonium salts, reported an asymmetric vinylogous Mannich-type reaction between the ketimines that were derived from isatins and α,α-dicyanoolefins (Scheme 30) [51]. A variety of substituents with electron-withdrawing groups and electro-donating groups on the phenyl ring of the substrates were well tolerated in high yields and ee values.…”

“…Various substituents on the phenyl ring of the para-quinone methides were well tolerated in providing the corresponding diarylmethines with high yields and ee values, which can be transformed into (R)-methyl 3-(4-hydroxyphenyl)-3-phenylpropanoate for the preparation of GPR40 agonists. Subsequently, Wu and co-workers, using their developed phosphonium salts, reported an asymmetric vinylogous Mannich-type reaction between the ketimines that were derived from isatins and α,α-dicyanoolefins (Scheme 30) [51]. A variety of substituents with electron-withdrawing groups and electro-donating groups on the phenyl ring of the substrates were well tolerated in high yields and ee values.…”

Asymmetric Allylic Alkylation with Deconjugated Carbonyl Compounds: Direct Vinylogous Umpolung Strategy

“…[7] Encouraged by these results, we explored the potential asymmetric version by the cooperative catalysis of Pd(OAc) 2 and chiral PTC. [8] While poor yield and enantioselectivity were obtained with ammonium salt C1 (Table 1, entry 4), it was found that better reaction could be attained by employing the l-amino-acid-derived phosphonium salts C2-C4 (entries 5-7), [9] and agood ee value was gained with C4 at À10 8 8C(entry 8). We further modified the phosphonium moiety of C4-based PTCs (entries 9-11), and excellent yield and enantioselectivity were achieved with C7,b earing a3 , 5-dimethylphenyl group (entry 11).…”

“…Fort he reactions with 2a,u niformly high to excellent enantioselectivities were obtained by introducing diverse substituents into the oxindole core of the nucleophiles 1 (entries 2-6), whereas slightly lower yields were observed for those with electron-withdrawing groups (entries 4-6). Outstanding enantiocontrol was attained for other 3-aryl-substituted oxindoles (entries [7][8][9]. Notably,a n oxindole bearing a1 -pyrrolyl group could be successfully applied (entry 10), and outstanding ee values were generally afforded by introducing various benzyl (entries [11][12][13] or [b] ee [%] [c] 1 [d] -K OAc Toluene 8--2 [d] TBAB KOAc Toluene 87 9-3 [d,e] TBAB KOAc Toluene 81 [b] ee [%] [c] 1H [e] The absolutec onfiguration of chiral 3n was determined by X-ray analysis of its derivative 12' ' (see the SupportingInformation).…”