An asymmetric vinylogous Mannich reaction between α,α-dicyanoolefins and N-Boc isatin imines has been developed by employing 1 mol% bifunctional amide phosphonium salt as a phase transfer catalyst and K2CO3 as a base. When α,α-dicyanoolefins derived from aryl methyl ketones were used as substrates, the normal Mannich adducts of 3,3-disubstituted aminooxindoles were obtained in good to excellent yields with high ee values, while α,α-dicyanoolefins derived from tetralone, propiophenone and methyl tert-butyl ketone led to cyclized products through a cascade sequence of Mannich reaction and intramolecular cyclization. The α,α-dicyanoolefin moiety in the Mannich adduct may be used as an aryl methyl ketone surrogate and the corresponding 3,3-disubstituted aminooxindole ketones may be effectively obtained after removal of the malonic nitrile by KMnO4 oxidation on a gram scale.

This paper describes a simple and practical protocol for the direct synthesis of monosulfonylated hydroquinones through a transition-metal-free cross-coupling between quinones and sulfonyl hydrazides in water. The procedure tolerates a variety of quinones and widely available sulfonyl hydrazides.Download high-res image (111KB)Download full-size image

Asymmetric 1,6-addition of malonates to para-quinone methides has been developed by using amide-phosphonium salts derived from easily available chiral α-amino acids as bifunctional phase transfer catalysts. Stabilized para-quinone methides with various substituents on the phenyl ring were reacted with diphenyl malonates to give functionalized diaryl methines in excellent yields and high to excellent ee’s. Furthermore, to show the utility of this methodology, a gram scale synthesis of an 1,6-addition adduct and its further elaboration into the key intermediate for synthesis of GPR40 agonists were also described.

A highly efficient cascade sequence for syntheses of 2,3-disubstituted imidazo[1,2-a]pyridines with exclusive regioselectivity in moderate to excellent yields has been developed. This cascade was initiated through propargylation of 2-aminopyridines at pyridine-nitrogen with propargyl alcohol derivatives using Cu(II)-Pybox as catalyst and followed by an intramolecular cyclization and isomerization. Besides 2-aminopyridine, less reactive 2-aminopyrimidine, 2-aminopyrazine and 3-aminopyridazine were also suitable in this cascade.

The first copper-catalyzed enantioselective propargylation of trialkyl methantricarboxylate with propargylic alcohol derivatives was developed. The tricarboxylate unit in the obtained adducts could be easily transformed into a malonate moiety by treating with in situ generated NaOEt in excellent yield without racemization.

An enantioselective Michael addition has been developed to give 3-substituted indolinoazepines by using indoloazepines as nucleophiles and propargyl aldehyde as electrophile under the promotion of a combination of a chiral secondary amine and trichloro acetic acid. By following the optimized protocol, a library of chiral indolinoazepines with a different substitution pattern was obtained in good to excellent yields and excellent enantioselectivities.Keywords: conjugate addition; indolinoazepine; indoloazepine; organocatalysis; propargyl aldehyde

Diastereo- and enantioselective preparation of 2,2-disubstituted benzofuran-3(2H)-one has been realized by a pybox-copper catalyzed reaction between 2-substituted benzofuran-3(2H)-one and propargyl acetate. The utility of this method was demonstrated by further transformation of the terminal alkyne into a methyl ketone without loss of enantiomeric purity.

An expedient enantioselective synthesis of highly substituted hydrocarbazoles has been realized by an organocatalyzed formal [3 + 3] cycloaddition between acrolein and 2,3-disubstituted indoles. Tricyclic hydrocarbazoles were obtained from a broad range of 2,3-disubstituted indoles and acrolein in good to excellent yields and excellent enantioselectivites.

We have developed a highly efficient cascade sequence for asymmetric synthesis of indoloquinolizidines with absolute control of cis-H2/H12b relative geometry in good to excellent yields and excellent enantioselectivities. This cascade was triggered by the Ru(II)–TsDPEN-catalyzed asymmetric transfer hydrogenation of imino diesters, with subsequent spontaneous lactamization with discrimination between the two diastereotopic 2-alkoxy-2-oxoethyl groups. The synthetic utility of this strategy was demonstrated by the asymmetric preparation of dihydrocorynantheol, geissoschizol, and isogeissoschizol.

cis-2,3-Dihydro-4-perfluoroalkyl-1H-1,5-benzodiazepines were stereoselectively synthesized using a one-pot, catalyst-free, three-component reaction. This novel, efficient and convenient approach was used to synthesize 22 related products in moderate to excellent yields, demonstrating the scope and potential economic impact of the reaction.

An expedient diastereoselective synthesis of highly functionalized indolo[2,3-α]quinolizidines adopting a cis H2/H12b geometry has been realized by a Pictet−Spengler/lactamization cascade sequence. The absolute stereochemistry at C2, C3, and C12b was governed by the originally created chirality of the Michael adduct through organocatalyzed conjugate addition of dialkyl malonates to α,β-unsaturated aldehydes.

An asymmetric vinylogous Mannich reaction between α,α-dicyanoolefins and N-Boc isatin imines has been developed by employing 1 mol% bifunctional amide phosphonium salt as a phase transfer catalyst and K2CO3 as a base. When α,α-dicyanoolefins derived from aryl methyl ketones were used as substrates, the normal Mannich adducts of 3,3-disubstituted aminooxindoles were obtained in good to excellent yields with high ee values, while α,α-dicyanoolefins derived from tetralone, propiophenone and methyl tert-butyl ketone led to cyclized products through a cascade sequence of Mannich reaction and intramolecular cyclization. The α,α-dicyanoolefin moiety in the Mannich adduct may be used as an aryl methyl ketone surrogate and the corresponding 3,3-disubstituted aminooxindole ketones may be effectively obtained after removal of the malonic nitrile by KMnO4 oxidation on a gram scale.

cis-2,3-Dihydro-4-perfluoroalkyl-1H-1,5-benzodiazepines were stereoselectively synthesized using a one-pot, catalyst-free, three-component reaction. This novel, efficient and convenient approach was used to synthesize 22 related products in moderate to excellent yields, demonstrating the scope and potential economic impact of the reaction.