Palladium‐Catalyzed Asymmetric [8+2] Dipolar Cycloadditions of Vinyl Carbamates and Photogenerated Ketenes

Abstract

Higher-order cycloadditions, particularly [8+2] cycloadditions, are a straightforward and efficient strategy for constructing significant medium-sized architectures. Typically, configuration-restrained conjugated systems are utilized as 8pcomponents for higher-order concerted cycloadditions. However, for this reason, 10-membered monocyclic skeletons have never been constructed via catalytic asymmetric [8+2] cycloaddition with high peri-and stereoselectivity. Here, we accomplished an enantioselective [8+2] dipolar cycloaddition via the merger of visible-light activation and asymmetric palladium catalysis. This protocol provides a new route to 10membered monocyclic architectures bearing chiral quaternary stereocenters with high chemo-, peri-, and enantioselectivity. The success of this strategy relied on the facile in situ generation of Pd-containing 1,8-dipoles and their enantioselective trapping by ketene dipolarophiles, which were formed in situ via a photo-Wolff rearrangement. Over the past six decades, the importance of higher-order cycloadditions for the construction of medium-sized heterocyclic skeletons has been demonstrated. [1] In this context, since the first work from Doering and Wiley in 1960, [2] a variety of [8+2] cycloadditions have been developed. [3] These transformations usually require configurationrestrained, conjugated 8p-components [4-6] to reduce the reaction complexity and entropic barriers, i.e., to disfavour intramolecular cyclizations and facilitate the periselectivity.

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

“…In 2020, Lu and coworkers developed an enantioselective [8+2] dipolar cycloadditions of 6‐vinyl‐1,3‐oxazinan‐2‐ones 99 and ketenes 48 via the merger of visible‐light activation and asymmetric palladium catalysis (Scheme 51, top) [36] . In this work, the substituent on N atom of 99 had a great influence on the periselectivity.…”

Construction of Chiral Cyclic Compounds Enabled by Enantioselective Photocatalysis

“…(43b) closed the ring and gave cyclobutyl iminium ions (43c) which could further release the desirable products (39) and finish a catalytic cycle. Bach et al found a co-catalytic system with ruthenium catalyst (Ru(bpz) 3 (PF 6 ) 2 ) and a chiral secondary amine catalyst (44) to synthesize cyclobutanecarbaldehydes (45) from α,β-unsaturated aldehydes (46) and olefins (47) upon the irradiation of visible light (λ = 458 nm) in moderate to good yields and enantioselectivity (49-74% yield, 83-96% er) (Scheme 11) [21]. A variety of substituents such as bromo, chloro, trifluoromethyl, methoxy, pinacolatoboryl, and acetoxy groups at the aryl moiety of α,β-unsaturated aldehydes are reliable substrates.…”

“…In 2020, Xiao et al reported palladium-catalyzed asymmetric [8+2] dipolar cycloadditions. In the presence of a chiral ligand (164) and Pd 2 (dba) 3 •CHCl 3 , vinyl carbamates (165) could react with photogenerated ketenes (166) to deliver 10-membered cycloadducts (167) upon the diffraction of blue LED light in excellent yields and enantioselectivity (up to 97% yield, up to 97% ee) (Scheme 36) [46]. A variety of vinyl carbamates bearing different aryl groups could afford desired cycloadducts with high er, and unsaturated vinyl group substituted with vinyl carbamate could be well tolerated in asymmetric [8+2] cycloaddition.…”

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

“…The Xiao group constructed medium-sized rings by utilizing asymmetric [8 + 2] dipolar cycloadditions with palladium catalysis in combination with chiral ligands and visible light activation. [35] In the first step, diazoketones upon illumination release N 2 forming ketenes, then the reaction mixture is transferred to the solution of Pd catalyst and ligand 24 a. Formation of enantioenriched 10-membered monocyclic compounds takes place with high periselectivity (Scheme 28).…”