Chiral cobalt(ii) complex-promoted asymmetric para-Claisen rearrangement of allyl α-naphthol ethers.

Due to experiencing a challenging dearomatization process, the aromatic sigmatropic rearrangement of allyl naphthyl ethers is a difficult yet efficient method to build useful naphthalenone skeletons. Here, we report a para-Claisen rearrangement-based asymmetric dearomatization of allyl α-naphthol ethers enabled by a N,N'-dioxide/CoII complex. A variety of naphthalenones were obtained in moderate to good yields with good to excellent ee values. Interestingly, by exchanging the allyl group on the ether and that at the para-position of the benzene ring, enantiodivergent synthesis can be achieved. Experimental studies and DFT calculations revealed that aryl allyl ethers tend to transform via a stepwise allyl π-complex migration pathway, while, alkyl allyl ethers transformed through a concerted ortho-Claisen rearrangement/Cope rearrangement sequence.

Asymmetric Formal Coupling of ß-Ketoesters with Quinones Promoted by a Chiral Bifunctional N-Heterocyclic Olefin.

A highly enantioselective formal coupling of ß-ketoesters with quinones was accomplished by a chiral bifunctional N-heterocyclic olefin organocatalyst. With as low as 1 mol % catalyst loading, a number of enantioenriched quinone derivatives were afforded in good yields with high enantioselectivities and regioselectivities (up to 96% yield, 98% ee, and 19:1 rr). Gram-scale synthesis and the high inhibitory effect of several products on the viability of cancer cells demonstrate the potential utility of the current method.

Water enables diastereodivergency in bispidine-based chiral amine-catalyzed asymmetric Mannich reaction of cyclic N-sulfonyl ketimines with ketones.

Tuning diastereoselectivity is a great challenge in asymmetric catalysis for the inherent stereochemical bias of the substrates. Here, we report a diastereodivergent asymmetric Mannich reaction of cyclic N-sulfonyl ketimines with ketones catalyzed by a bispidine-based chiral amine catalyst, in which additional water switches the diastereoselectivity efficiently. Both chiral anti- and syn-benzosultams with potential anti-HIV-1 activity are obtained in excellent yields and good to excellent ee values. Control experiments and density functional theory (DFT) calculations were applied to study the diastereodivergent mechanism, which reveal that the diastereodivergent catalysis should be state-determined, and the water reverses the energies of states to realize the diastereodivergency. The findings are quite new and might inspire more diastereodivergent asymmetric synthesis.

Catalytic Asymmetric Hydroacyloxylation/Ring-Opening Reaction of Ynamides, Acids, and Aziridines.

A highly enantioselective three-component reaction of ynamides with carboxylic acids and 2,2'-diester aziridines has been realized by using a chiral N,N'-dioxide/Ho(OTf)3 complex as a Lewis acid catalyst. The process includes the formation of an α-acyloxyenamide intermediate through the addition of carboxylic acids to ynamides and the following enantioselective nucleophilic addition to in-situ-generated azomethine ylides induced by the chiral catalyst. A range of amino acyloxyenamides are delivered in moderate to good yields with good ee values. In addition, a possible catalytic cycle with a transition model is proposed to elucidate the reaction mechanism.