Multifunctional catalysis: stereoselective construction of α-methylidene-γ-lactams via an amidation/Rauhut-Currier sequence.

Mixing of acryloylchloride, dienone 2, N,N-diisopropylethylamine with chiral organocatalyst 5a, which could simultaneously act as Brønsted and Lewis base catalysts, led to a one-pot amidation/Rauhut-Currier sequence, affording α-methylidene-γ-lactams 4. Catalyst 5a could be recovered and reused by acid/base extraction without any loss of catalytic activity in the stepwise protocol.

Direct Catalytic Asymmetric Aldol Reaction of α-Alkylamides.

A catalytic asymmetric aldol reaction directly employing amides as latent enolates has remained elusive because of the resistance of amides to enolization. A direct aldol reaction of α-alkylamides without any electron-withdrawing group harnessed by specific activation of 7-azaindoline amides under soft Lewis acid/Brønsted base cooperative catalysis is reported. Diastereo- and enantioselective coupling with ynals and aromatic aldehydes as well as divergent functional group interconversion of the amide provided expeditious access to a variety of aliphatic and aromatic chiral building blocks.

Direct Catalytic Asymmetric Mannich-Type Reaction of Alkylamides.

Direct enolate formation coupled with subsequent enantioselective C-C bond formation remains a topic of intense interest in asymmetric catalysis. This methodology is achieved even with low acidic amides without an electron-withdrawing group at the α-position in the context of a Mannich-type reaction. Acetate-, propionate-, and butyrate-type 7-azaindoline amides served as enolate precursors to afford the desired Mannich adducts with high stereoselectivity, and ligand-enabled diastereo-divergency provided access to both anti/syn diastereomers.

Direct Catalytic Asymmetric Mannich-Type Reaction of α- and β-Fluorinated Amides.

The last two decades have witnessed the emergence of direct enolization protocols providing atom-economical and operationally simple methods to use enolates for stereoselective C-C bond-forming reactions, eliminating the inherent drawback of the preformation of enolates using stoichiometric amounts of reagents. In its infancy, direct enolization relied heavily on the intrinsic acidity of the latent enolates, and the reaction scope was limited to readily enolizable ketones and aldehydes. Recent advances in this field enabled the exploitation of carboxylic acid derivatives for direct enolization, offering expeditious access to synthetically versatile chiral building blocks.

Phosphine-Catalyzed β,γ-Umpolung Domino Reaction of Allenic Esters: Facile Synthesis of Tetrahydrobenzofuranones Bearing a Chiral Tetrasubstituted Stereogenic Carbon Center.

An enantio-, diastereo-, regio-, and chemoselective phosphine-catalyzed β,γ-umpolung domino reaction of allenic esters with dienones has been developed for the first time. The designed sequence, involving oxy-Michael and Rauhut-Currier reactions, produced highly functionalized tetrahydrobenzofuranones, bearing a chiral tetrasubstituted stereogenic center, in up to 96 % ee.

Facile regio- and stereoselective metal-free synthesis of all-carbon tetrasubstituted alkenes bearing a C(sp3)-F unit via dehydroxyfluorination of Morita-Baylis-Hillman (MBH) adducts.

Highly E-selective all-carbon tetrasubstituted alkenes with a C(sp(3))-F unit have been synthesized through a dehydroxyfluorination of Morita-Baylis-Hillman (MBH) adducts which can be readily prepared from α,β-unsaturated carbonyl compounds and α-keto esters. A variety of subsequent transformations afforded monofluoromethyl substituted heterocycles in high yields.

P-chirogenic organocatalysts: application to the aza-Morita-Baylis-Hillman (aza-MBH) reaction of ketimines.

The P-chirogenic organocatalysts were found to promote the enantioselective aza-Morita-Baylis-Hillman reaction of ketimines derived from acyclic α-keto esters. In the P-chirogenic organocatalyzed aza-MBH reactions, α,α-disubstituted α-amino acid derivatives were obtained in high yields with high enantioselectivities (up to 97% ee).

Organocatalyzed formal [2 + 2] cycloaddition of ketimines with allenoates: facile access to azetidines with a chiral tetrasubstituted carbon stereogenic center.

An enantioselective organocatalyzed aza-MBH-type reaction of ketimines and allenoates has been developed. The present formal [2 + 2] cycloaddition produces highly functionalized azetidines with a chiral tetrasubstituted carbon stereogenic center in good to excellent yields and high enantioselectivities.

Vanadium-catalyzed enantioselective Friedel-Crafts-type reactions.

Vanadium-mediated enantioselective Friedel-Crafts (FC)-type reactions were established using the dinuclear vanadium complex (R(a),S,S)-1a. The vanadium complex promoted the FC-type reaction of imines with 2-naphthols or indoles to give corresponding adducts with high enantioselectivities.