Lei Zhang

Multicomponent multicatalyst reactions (MC)2R: one-pot synthesis of 3,4-dihydroquinolinones.

A Rh/Pd/Cu catalyst system led to an efficient synthesis of dihydroquinolinones in one-pot, two operations. The reaction features the first triple metal-catalyzed transformations in one reaction vessel, without any intermediate workup. The conjugate-addition/amidation/amidation reaction sequence is highly modular, divergent, and practical.

A New Multicomponent Multicatalyst Reaction (MC)2R: Chemoselective Cycloaddition and Latent Catalyst Activation for the Synthesis of Fully Substituted 1,2,3-Triazoles

A multicomponent multicatalyst reaction (MC)(2)R for constructing fully substituted 1,2,3-triazoles is reported. An application of chemoselectivity and latent catalysis in a sequence of multicatalytic reactions confers control over a number of undesired processes, where all of the reagents coexist in the same reaction vessel. The sequence of a chemoselective copper-catalyzed azide alkyne cycloaddition followed by a palladium/copper-catalyzed Sonogashira cross-coupling afforded 1,2,3-triazoles regioselectively with good to high yields and a broad scope.

The Use of Silyl Ketene Acetals and Enol Ethers in the Catalytic Enantioselective Alkylative Ring Opening of Oxa/Aza Bicyclic Alkenes

Silyl ketene acetals and enol ethers are employed as reactive and functional group tolerant nucleophiles in the enantioselective rhodium-catalyzed alkylative ring opening of a diverse class of oxa/azabicyclic alkenes. This method provides access to enantioenriched dihydronaphthalene and cyclohexene scaffolds, which have the potential to be derivatized toward core motifs of naphthoquinone and sesquiterpene natural products.

Metal-ligand binding interactions in rhodium/palladium-catalyzed synthesis of dihydroquinolines.

A domino Rh- and Pd-catalyzed synthesis of dihydroquinolines is disclosed. Two metals and two ligands are placed in one reaction vessel along with the two reactive reagents to afford selective sequential coupling despite the potential for side reactions. In this report, we describe mechanistic investigations attempting to discern the catalyst-ligand interactions occurring in this domino reaction. Through these studies, the reactivity and relative catalyst ligand loadings were successfully tuned to efficiently access the heterocyclic products.

Chiral Cp Ligands in Rhodium-Catalyzed Asymmetric C–H Functionalization

Significance: The asymmetric Baeyer–Villiger oxidation of prochiral and racemic cyclic ketones effectively synthesized optically active εand γlactones. The desymmetrization of racemic cyclohexanones interestingly showed a reversal of migratory aptitude with high levels of enantioselectivity. Comment: The authors continued their use of chiral N,N′-dioxide-metal catalysts for the Baeyer– Villiger oxidation reaction. During the desymmetrization of meso-cyclohexanones and meso-cyclobutanones, the electronic and steric nature of the substituents appeared to have no effect on enantioselectivity; the opposite was true for the kinetic resolution of racemic cyclohexanones. O R + MCPBA ∗

Artificial Rh(III)–Metalloenzyme-Catalyzed Asymmetric C–H Activation

Significance: A highly active, artificial rhodium(III) metalloenzyme that catalyzes an asymmetric synthesis of dihydroisoquinolones through C–H activation is reported. A biotinylated rhodium(III) complex is successfully incorporated into streptavidin. With active-site mutagenesis, the engineered enzyme displayed up to 100-fold reaction rate increase compared to the activity of the unbound rhodium complex. Comment: As Cp is the only permanently bound ligand on rhodium in the catalytic cycle, it has been difficult to render this reaction enantioselective until recently. This report provides an alternative solution for this problem. Based on the concerted metalation–deprotonation mechanism, the authors used docking modeling and introduced a basic carboxylate moiety in the active site. With kinetic isotope effect experiments, the importance of this mutation in accelerating the catalysis is demonstrated. [RhCp*Cl2]2 (2 mol%) S112Y-K121E Sav Mutant (0.66 mol%)

Palladium-Catalyzed Asymmetric Allyl–Allyl Cross-Coupling

Significance: The asymmetric allyl–allyl crosscoupling gives rise to products of the Cope rearrangement, for which no precedents of the catalytic enantioselective variant existed. Practical features are the facile formation of allyl chlorides from the corresponding alcohol without purification, and that the alkene geometry of the crotyl boronate does not need to be defined to afford the same stereochemical outcome. It is noteworthy that excellent catalyst control is required to favor the desired [3,3′]-reductive elimination pathway versus the alternative [1,1′] pathway. High enantioselectivity and diastereoselectivity are additional features. Comment: While L1 can provide excellent reactivity with cinnamyl chlorides (R1 = Ar), L2 is found to be more suitable for non-aromatic allyl chlorides (R1 = Alk). Secondary allyl chlorides are also competent in the reaction, though they generally give lower yields. The highly versatile reactivity with regards to crotyl boronate alkene geometry and secondary versus primary allyl chlorides is rationalized in the proposed mechanism. A series of isomerizations occur for the allyl fragments on the palladium complex to minimize steric effects prior to the enantio-discriminating [3,3′]-reductive elimination step. R2 B(pin)