Catalytic Asymmetric Construction of a 1,2,4-Benzotriazepine Skeleton via Diastereo- and Enantioselective Decarboxylative [4 + 3] Cyclization

Abstract

We have developed a protocol for palladium-catalyzed decarboxylative [4 + 3] cycloaddition reactions between 4-vinyl benzoxazinanones and azomethine imines to generate moderate to good yields of structurally diverse 1,2,4-benzotriazepines bearing two stereogenic centers with good to excellent stereoselectivities. This protocol not only addresses the challenge of asymmetrically constructing compounds with a 1,2,4-benzotriazepine skeleton but also demonstrates the utility of decarboxylative cycloadditions for the synthesis of enantioenriched polycyclic compounds.

Recent Advances in Metal‐Catalyzed Decarboxylative Reactions of Vinyl Benzoxazinanones

“…reported decarboxylative [4+3] cycloaddition reactions between 4‐vinyl benzoxazinanones with azomethine imines to generate moderate to good yields of structurally diverse 1,2,4‐benzotriazepines bearing two stereogenic centers with good to excellent stereoselectivities (Scheme 38). [39] Various substituents on the benzene ring of 4‐vinyl benzoxazinanones and azomethine imine were compatible in this reaction. Variation of the arylsulfonyl protecting group of the azomethine imine was also well tolerated.…”

“…In 2019, the Ding and co-workers asymmetric decarboxylative [4 + 2] cycloaddition of 3nitroindoles and vinyl benzoxazinones by the catalysis of the Pd 2 (dba) 3 •CHCl 3 /L13 complex to deliver a series of chiral tetrahydro-5H-indolo [2,3-b] quinolines (39) in high yields and with excellent diastereo-and enantioselectivities (Scheme 15). [18] Various electronwithdrawing and electron-donating substituents at the aryl moiety of vinyl benzoxazinones and 3-nitroindoles substrates were tolerated.…”

Advances in Palladium‐Catalyzed Decarboxylative Cycloadditions of Cyclic Carbonates, Carbamates and Lactones

“…Chiral 1,2,4-benzotriazepine derivatives were prepared by Miao and coworkers via asymmetric decarboxylative [4 + 3] cycloadditions of 108 and azomethine imines 55. [50] Employing spiro-phosphoramidite L27 as the chiral ligand, the reaction proceeded smoothly and produced 1,2,4-benzotriazepine derivatives 138 in moderate to good yields and enantioselectivities with high diastereoselectivities (63-83 % yield, 13 : 1-> 20 : 1 dr, 79-95 % ee) (Scheme 68). Moreover, the corresponding enantiomers of the products 138 could also be obtained legitimately by using enantiomer of L27 as ligand.…”

“…Palladium-catalyzed asymmetric DCs of 4-vinyl benzoxazinones with azomethine imines. [50] nitrogen anion to the central carbon of π-allyl palladium unit gave the palladacyclobutane intermediate 3.2U. Next, 3.2U was captured by the arynes to afford the intermediates 3.2V or 3.2V', thus producing the desired product cis-5,5a,6,10btetrahydroindeno [2,1-b]indoles 141 via reductive elimination (Scheme 69, top).…”

Stereoselective Synthesis of Azacycles Induced by Group 8–11 Late Transition Metals

“…Miao et al applied the same catalyst in combination with SPINOL-derived spiro-phosphoramidite ligand 17 to construct a family of condensed tetracyclic products with a 1,2,4-benzotriazepine skeleton bearing two stereogenic centers. [30] These were created in the reaction of vinyl benzoxazinanones and azomethine imines via decarboxylative [4 + 3] cycloaddition in high yields with excellent stereoselectivities (Scheme 23). On the basis of product absolute configurations and literature precedents, ligands define the direction of palladium coordination in int-6 delivering cis compounds.…”