Enantioselective Synthesis of cis‐Decalins by Merging the Birch Reduction and Inverse‐Electron‐Demand Diels–Alder Reaction

Abstract

Herein, we show that the combination of the Birch reduction of readily available anisole derivatives and the catalytic asymmetric inverse‐electron‐demand Diels–Alder reaction of 2‐pyrones can serve as a powerful platform for the diverse synthesis of synthetically important cis‐decalin scaffolds. Enabled by a well‐modified chiral bis(oxazoline) ligand/CuII complex, a wide range of polysubstituted cis‐decalin scaffolds with up to six contiguous stereocenters were generated efficiently. The synthetic potential of this method is demonstrated by the concise synthesis of the sesquiterpene (+)‐occidentalol and a key intermediate for seven triterpenes. Mechanistic studies suggest the 1,3‐cyclohexadienes formed in situ are the key intermediates, and efficient kinetic resolution occurs when C2‐ and/or C3‐substituted 1,4‐cyclohexadienes are utilized as substrates. DFT calculations elucidated that the Diels–Alder reaction proceeds in a stepwise fashion and revealed the origins of the stereoselectivities.

Enantioselective synthesis of unsymmetrical α,α-diarylacetates via organocatalyzed formal C–H insertion reactions of sulfoxonium ylides with indoles and pyrroles

“…In recent times, the utilization of London dispersion (LD) interactions has emerged as a fundamental approach in catalyst design. 41–46 Drawing from this concept, we designed and synthesized two new chiral phosphoric acids ( HA-7 and HA-8 ) to enhance LD interactions, with the goal of improving enantioselectivity. However, the achieved enantioselectivity was slightly lower compared to the utilization of HA-6 in the reaction (entries 11–13).…”

“…This involves employing an unconventional and attractive strategy that enhances London dispersion (LD) interactions within the principles of organocatalyst design. 41–46 Additionally, we have achieved the unprecedented organocatalytic asymmetric formal C–H insertion reaction of N–H free pyrrole with excellent stereoselectivity and yield (Fig. 1D).…”

Enantioselective Cross-[4 + 2]-Cycloaddition/Decarboxylation of 2-Pyrones by Cooperative Catalysis of the Pd(0)/NHC Complex and Chiral Phosphoric Acid

“…However, owing to the challenges to simultaneously control the essential periselectivity, regioselectivity, and stereoselectivity, the cross-Diels–Alder reaction often gives a complex mixture of products, thus diminishing its synthetic value dramatically (Scheme A) . Recently, our group has reported peri- and enantioselective cross-Diels–Alder reactions with 3-carboalkoxyl-2-pyrones and cyclic 1,3-dienes by the Lewis acid catalysis and demonstrated their synthetic potential in the synthesis of several biologically important terpenes (Scheme B) . Although synthetically intriguing, these reactions are limited to use cyclic 1,3-dienes as reaction partners.…”

Access to cyclohexadiene and benzofuran derivatives via catalytic arene cyclopropanation of α-cyanodiazocarbonyl compounds

“…In order to expand the synthetic utility of the concept, we designed a new synthetic route to 1,3- or 1,4-cyclohexadienes that have been extensively used as building blocks 18,19 or ligands 20 in various transformations. Prior synthetic efforts towards these types of compounds can be organized into four categories: (1) Birch reduction of benzene; 21 (2) [4 + 2] cycloaddition of 1,3-dienes with activated alkynes; 22 (3) photo- or metal-induced nucleophilic addition to benzene; 23 and (4) oxidative dehydrogenation of cyclohexenes. 24…”