Enantioselective Synthesis of Chiral Medium-Sized Cyclic Compounds via Tandem Cycloaddition/Cope Rearrangement Strategy

Abstract

The nine-membered ring-bearing bicyclo[5.2.2]­tetrahydrooxonines frameworks have enantioselectively been constructed via a tandem [3 + 2] cycloaddition/Cope rearrangement reaction of vinylethylene carbonates (VECs) with coumalates or pyrones. Under mild conditions, palladium-catalyzed asymmetric tandem reaction of various substituted VECs and coumalates or pyrones proceeds smoothly to produce the corresponding medium-sized heterocyclic compounds in high yields with very high enantioselectivities. Moreover, the reaction on the gram scale and further diverse transformations of the products were workable. The reaction mechanism was investigated through control experiments and DFT calculations, which show the reaction proceeds via a tandem [3 + 2] cycloaddition/Cope rearrangement pathway rather than via a [5 + 4] cycloaddition pathway.

An Update of Transition Metal-Catalyzed Decarboxylative Transformations of Cyclic Carbonates and Carbamates

“…With the introduction of coumalates as acceptors, the Guo group realized the chiral synthesis of nine-membered ethers with excellent enantioselectivities (mostly > 99% ee) through a tandem [3 + 2] cycloaddition followed by Cope rearrangement (Scheme 6b). The mechanism was further confirmed by DFT calculations [32]. In addition to these aforementioned [3 + 2] annulations, the decarboxylative formation of medium-membered heterocycles through a Pd-catalyzed [5 + n] annulation has been achieved by different research groups (Scheme 7) [33][34][35][36][37][38].…”

“…With the introduction of coumalates as acceptors, the Guo group realized the chiral synthesis of nine-membered ethers with excellent enantioselectivities (mostly > 99% ee) through a tandem [3 + 2] cycloaddition followed by Cope rearrangement (Scheme 6b). The mechanism was further confirmed by DFT calculations [32]. More recently, a palladium and squaramide co-catalyzed decarboxylative [3 + 2] cyclization of VCCs and β-nitroolefins was achieved by the Zhang group (Scheme 6a) [30].…”

2‐Pyrone – A Privileged Heterocycle and Widespread Motif in Nature

“…A recent example was disclosed by Guo et al with the enantioselective synthesis of medium-sized bicyclic compounds 272 via tandem [3 + 2]-cycloaddition of vinyl ethylene carbonates 269 and pyrones 270, followed by a Cope rearrangement of intermediate 271 (Scheme 54). [109] Based on control experiments and detailed computational studies, the product formation via a direct [5 + 4]-cycloaddition pathway was excluded.…”

“…Tandem [3 + 2]-cycloaddition/Cope rearrangement of pyrones 270. [109] Scheme 55. [4 + 3]-cycloaddition of pyrones 273 and imine esters 274.…”

The bio-based methyl coumalate involved Morita–Baylis–Hillman reaction

“…ring opening and decarboxylation). [40][41] Moreover, dienolates generated from 1,6addition are, theoretically, weaker nucleophiles than regular enolates. The delocalization of negative charge on an extra π bond confers greater thermodynamic stability.…”