Investigation of Alkyne Regioselectivity in the Ni‐Catalyzed Benzannulation of Cyclobutenones

Abstract

A Ni-catalyzed benzannulation reaction of cyclobutenones and alkynes provides a rapid synthesis of heavily substituted phenols. The regioselectivity of this reaction can be modulated by variation of substituents on the alkyne. Though the incorporation of Lewis basic donors provides modest selectivities, the use of aryl substituents can provide high levels of regiocontrol. Finally, alkynylboronates derived from alkyl-substituted acetylenes provide both high yields and regioselectivities. This study suggests that alkynes bearing one sp(2) - and one sp(3) -based substituent can undergo benzannulation with high levels of regiocontrol whereby the sp(3) -based group is incorporated ortho-to the phenolic OH.

Cyclobutenones and Benzocyclobutenones: Versatile Synthons in Organic Synthesis

“…Two mechanisms were proposed for this benzannulation reaction (Scheme ) . The first one is initiated by ring opening of the cyclobutenone to form either a metallocyclopentenone or a η 4 ‐vinylketene complex 159 , which would then undergo migratory insertion and reductive elimination to afford the phenol product.…”

“…In 2015, the same group reported ad etailed study of the nickel-catalyzed benzannulation with alkynes bearing aryl substituents( Scheme 52). [59] When norbornadiene was added as ap romoter to enhancet he catalystl ifetime, various alkynes were compatible, giving heavilys ubstituted phenols in good yields, and the regioselectivity was predominantly controlled by the substituents on the alkynes:a na lkyl group tends to be incorporated ortho to the phenol OH moiety,w hereas an aryl group prefers to stay at the meta position. Unlike Liebeskind's work, [57] the presence of heteroatoms only had am arginal effect on the regioselectivity.…”

“…Twom echanisms were proposed for this benzannulation reaction (Scheme 53). [59] The first one is initiated by ring opening of the cyclobutenone to form either am etallocyclopentenone or a h 4 -vinylketene complex 159,w hich would then undergo migratory insertion and reductive elimination to afford the phenol product. The second reactionp athway was initiated by cyclometallation between the carbonyl group and the alkyne to form metallacycle 160.S imilarly to the nickel-catalyzedc yclobutanone activation, [60] subsequent b-carbon elimination and reductive elimination would provide the phenol products.…”

Ruthenium‐ and Rhodium‐Catalyzed Strain‐Driven Cleavage and Reconstruction of the C–C Bond

“…[61] 4.2. Ruthenium-and Rhodium-Catalyzed Ring-Opening Dimerization of Cyclobutenones and the Coupling Reaction with Alkenes [62] A new stereoselective synthesis of 2-pyranones has been developed that proceeds through the ring-opening dimerization of cyclobutenones and is catalyzed by either a ruthenium ([RuCl 2 (CO) 3 ] 2 ) or rhodium ([RhCl(CO) 2 ] 2 ) complex ( Scheme 14).…”

DBU-Catalyzed Michael Reaction of Enones with 1,3-Diketones and the Subsequent Iodine-Mediated Transformation of the Adducts to Polysubstituted Phenols

“…The strategies for their synthesis can be classified as two main types based on the starting materials: (1) Using aromatic precursors including direct conversion of the hydrogen, halo, or amino group on the aromatic ring into hydroxyl group 2 and metalcatalyzed cross-coupling reaction of phenols or halogenated phenols. 3 (2) Using nonaromatic precursors including benzannulation of vinylketenes, 4 furan-tethered or -ketoester-tethered alkynes, 5 cyclopropenes or cyclopropenones, 6 cyclobutenones, 7 and cyclocondensations of enones with substituted acetones. 8 Among these versatile starting materials, enones are readily available as bulk chemicals.…”