Asymmetric reactions merging organocatalysis and metal catalysis significantly broaden the scope of organic synthesis.N evertheless,t he accomplishment of stereoselective annulations combining two types of dipole species,i ndependently generated from the activations of organocatalysts and metal complexes,s till remains as ac hallenging task. Now, Morita-Baylis-Hillman carbonates from isatins and carbamate-functionalized allyl carbonates could be chemoselectively activated by achiral Lewis basic tertiary amines and chiral iridium complexes.T he zwitterionic allylic ylides and 1,4-pallyliridium dipoles formed in situ are assembled in ah ighly stereoselective [4+ +3] annulation pattern. Similar cooperative catalytic strategy could be applied for the reactions of Morita-Baylis-Hillman carbonates and vinyl aziridines,furnishing an asymmetric [3+ +3] annulation reaction also with excellent stereocontrol. Scheme 1. Lewis base and transition-metal activations trategies for MBH derivatives and cooperative catalysis.

Here we report that the chemoselective activation of Tsujis 2-(cyanomethyl)allyl carbonates to generate the palladium-trimethylenemethane 1,3-dipoles via a deprotonation strategy can be realized in the presence of Morita-Baylis-Hillman carbonates from substantial activated ketones. The following S N 2'-addition enables the formation of new 1,3dipole species having an activated alkene moiety through a second deprotonation process, which then undergo cascade [1+2]/[3+2] annulations to furnish complex bicyclic [3.1.0]hexane frameworks having three contiguous quaternary stereogenic centers with good to excellent enantioselectivity. Moreover, by using benzoyl aldehyde-derived substrates, a [1+4]/[3+2] annulation sequence is similarly developed to produce fused cyclopenta[b]furan architectures.

Here we report that a palladium(0) complex can mediate the unprecedented intermolecular coupling reaction of 1,3-enynes and N-sulfonylimines regio- and stereoselectively, and the resultant palladium­(II) species undergo a cascade Suzuki reaction with organoboronic reagents. The substrate scope is substantial for the asymmetric three-component process, and the enantioenriched all-carbon tetra-substituted alkene derivatives are efficiently constructed in a modular and cis-difunctionalized manner. Control experiments and density functional theory (DFT) calculations support the idea that the palladium(0) acts as a π-Lewis base catalyst by chemoselectively forming η2-complexes with the alkene moiety of 1,3-enynes, thus increasing the nucleophilicity of the alkyne group based on the principle of vinylogy, to attack imines enantioselectively. The preferable formation of aza-palladacyclopentene intermediates, via a 90° single bond rotation from the resultant π-allyl complex, guarantees the formal cis-carbopalladation of alkyne group. In addition, a palladium(0)-catalyzed enantioselective reductive coupling of 1,3-enyne and imine is realized by using formic acid as hydrogen transfer reagent.

Asymmetric reactions merging organocatalysis and metal catalysis significantly broaden the scope of organic synthesis.N evertheless,t he accomplishment of stereoselective annulations combining two types of dipole species,i ndependently generated from the activations of organocatalysts and metal complexes,s till remains as ac hallenging task. Now, Morita-Baylis-Hillman carbonates from isatins and carbamate-functionalized allyl carbonates could be chemoselectively activated by achiral Lewis basic tertiary amines and chiral iridium complexes.T he zwitterionic allylic ylides and 1,4-pallyliridium dipoles formed in situ are assembled in ah ighly stereoselective [4+ +3] annulation pattern. Similar cooperative catalytic strategy could be applied for the reactions of Morita-Baylis-Hillman carbonates and vinyl aziridines,furnishing an asymmetric [3+ +3] annulation reaction also with excellent stereocontrol. Scheme 1. Lewis base and transition-metal activations trategies for MBH derivatives and cooperative catalysis.

An asymmetric intermolecular Rauhut-Currier reaction of α'-alkylidene 2-cyclohexenones and (7-aza)isatinylidene malononitriles is realized under the double activation catalysis of natural quinine and 2-mercaptobenzoic acid, finally affording formal 3-arylated spiro (7-aza)oxindole derivatives in fair to excellent enantioselectivity after a tandem cyclization/aromatization process (up to 96% ee).