Rhodium(I)‐Catalyzed Intermolecular Aza‐[4+3] Cycloaddition of Vinyl Aziridines and Dienes: Atom‐Economical Synthesis of Enantiomerically Enriched Functionalized Azepines

Abstract

A new synthetic application of vinyl aziridines as N-containing three-atom components in a rhodium-catalyzed [4+3] cycloaddition reaction is described. The reaction proceeds well with various silyl dienol ethers and vinyl aziridines, and enables the efficient synthesis of highly functionalized azepines in an enantioselective manner with net inversion of absolute configuration. The salient features of the transformation include the use of readily available substrates, high selectivity, and mild reaction conditions, as well as the versatile functionalization of the products.

Asymmetric Cyclopropanation and Epoxidation via a Catalytically Formed Chiral Auxiliary

“…The amino alcohol product was detected in the crude mixture, but upon basification, or any attempts of chromatographic separation (for full details see the Supporting Information, section D.6) of the salt 7 , degradation was observed. The products of the decomposition were identified as a mixture of geometrical isomers of enone 8 , presumably formed from a ring opening reaction of 7 [19a,b,h,i] . Interestingly, a thermal ring opening was observed by heating product 3 a in methanol, to give the same enone 8 as a single isomer in 70 % yield.…”

Transition‐Metal‐Catalyzed Cycloaddition Reactions to Access Seven‐Membered Rings

“…In 2017, Zhang and co-workers reported the rhodium-catalyzed intermolecular aza-[4+ +3] cycloaddition of optically pure vinyl aziridines 154 andd ienes 155 to form enantiomericallyenriched functionalized azepines 156 (Scheme 40). [48] Interestingly,t he cyclic silyl enol ether did not give the [4+ +3] cycloaddition, but [3+ +2] annulation. Elaborationo ft he available multi- functional cycloadducts enabled rapid access to aw ide range of structural types, indicating that this approach could find broad application in the synthesis of valuable natural products and pharmaceuticals containing chiral azepine skeletons.T he reactioni nitially proceeds with oxidative addition into vinyl aziridines 154 with the assistance of both the olefin and the nitrogen atom, and leads to the enyl (d + p)rhodium species 157 a.S ubsequently,n ucleophilic attack of the silyl enol ether on the rhodiumc omplex 157 a from the back face mayp roduce the oxoniumi on intermediate 157 b with net inversion of the absolute configurationa nd regeneration of the rhodium catalyst.…”

“…In 2017, Zhang and co‐workers reported the rhodium‐catalyzed intermolecular aza ‐[4+3] cycloaddition of optically pure vinyl aziridines 154 and dienes 155 to form enantiomerically‐enriched functionalized azepines 156 (Scheme 40). [48] Interestingly, the cyclic silyl enol ether did not give the [4+3] cycloaddition, but [3+2] annulation. Elaboration of the available multifunctional cycloadducts enabled rapid access to a wide range of structural types, indicating that this approach could find broad application in the synthesis of valuable natural products and pharmaceuticals containing chiral azepine skeletons.…”

Recent Achievements in the Rhodium‐Catalyzed Concise Construction of Medium N‐Heterocycles, Azepines and Azocines

“…In 2016, Zhang used vinyl aziridine as a new aza‐3 C synthons for the intermolecular aza‐[4+3] cycloaddition reaction, affording to 2,5‐dihydroazepines (Scheme 7). [9] With the use of chiral transfer strategy, highly functionalized azepine architectures were synthesized with great enantioselectivity. The regio‐ and enantioselelctive process is highly efficient, showing great synthetic potentials for the related bioactive molecules delivery.…”