Bicarbonate-binding catalysis for the enantioselective desymmetrization of keto sulfonium salts.

Herein, an enantioselective desymmetrization of cyclic keto sulfonium salts through enantioselective deprotonation/ring opening process by anion-binding catalysis is presented. We report a squaramide/HCO3- complex as catalytic active species which is able to stereo-differentiate two enantiomeric protons, triggering the ring opening event taking advantage of the great tendency of sulfonium salts to act as leaving groups. Thus, this desymmetrization methodology give rise to ß-methylsulfenylated sulfa-Michael addition type products with excellent yields and very good enantioselectivities. The bifunctional organocatalyst has been demonstrated to be capable of activating simultaneously the base and the keto sulfonium salt by DFT calculations and experimental proofs.

Enantioselective Inverse-Electron Demand Aza-Diels-Alder Reaction: ipso,α-Selectivity of Silyl Dienol Ethers.

A highly efficient enantioselective inverse-electron-demand aza-Diels-Alder reaction between aza-sulfonyl-1-aza-1,3-butadienes and silyl (di)enol ethers has been developed. The presented methodology allows the synthesis of benzofuran-fused 2-piperidinol derivatives with three contiguous stereocenters in a highly selective manner, as even the hemiaminal center is completely stereocontrolled. Density functional theory (DFT) calculations support that the hydrogen-bond donor-based bifunctional organocatalyst selectively triggers the reaction through the ipso,α-position of the dienophile, in contrast to the reactivity observed for dienolates in situ generated from ß,γ-unsaturated derivatives. Moreover, the calculations have clarified the mechanism of the reaction and the ability of the hydrogen-bond donor core to hydrolyze selectively the E isomer of the dienol ether. Furthermore, to demonstrate the applicability of silyl enol ethers as nucleophiles in the asymmetric synthesis of interesting benzofuran-fused derivatives, the catalytic system has also been implemented for the highly efficient installation of an aromatic ring in the piperidine adducts.

Enantioselective vinylogous-Mukaiyama-type dearomatisation by anion-binding catalysis.

The first enantioselective vinylogous Mukaiyama-type dearomatisation of heteroarenes under anion-binding catalysis is presented. A recyclable tetrakistriazole catalyst was used for the enantiocontrol of the remote vinylogous active position of silyl dienol ethers. This approach provided chiral heterocycles bearing α,ß-unsaturated chains with complete regioselectivity and excellent enantioselectivities (up to 97.5 : 2.5 e.r.).

Asymmetric vinylogous Mukaiyama aldol reaction of isatins under bifunctional organocatalysis: enantioselective synthesis of substituted 3-hydroxy-2-oxindoles.

A highly enantioselective organocatalytic vinylogous Mukaiyama aldol reaction of silyloxy dienes and isatins under bifunctional organocatalysis is presented. Substituted 3-hydroxy-2-oxindoles are synthesised in good yields and enantioselectivities. These synthetic intermediates are used for the construction of more complex molecules with biological properties such as the formal synthesis of a CB2 agonist presented.