Utility of Organoboron Reagents in Arylation of Cyclopropanols via Chelated Pd(II) Catalysis: Chemoselective Access to β-Aryl Ketones

Abstract

Organoborane reagents were investigated as coupling partners to cyclopropanol-derived β-ketone enolates in the presence of a chelated Pd(II) catalyst. Efficient coupling of a range of electronically and sterically diverse cyclopropanols and aryl/ alkenyl boronic derivatives (39 examples, 65−94% yield) could be achieved with the generation of synthetically important β-aryl ketone intermediates in a chemoselective fashion. This reactivity paradigm, which broadens the scope of aryl donor partners to homoenolates, allows open-flask conditions, water as a cosolvent, and preparation of halogen-bearing β-aryl ketones that are distinct from previous methods. This chelated Pd(II) catalysis appears to be different from the Pd(0) pathway, as evident from deuterium scrambling studies that could reveal differentiating protonolysis of an α-keto carbopalladium complex in the terminal step.

Orchestrating a β-Hydride Elimination Pathway in Palladium(II)-Catalyzed Arylation/Alkenylation of Cyclopropanols Using Organoboron Reagents

“…As a part of expanding the scope of boronic esters, the alkenyl variants that would be electronically different from aromatic boronic acid/ester reagents were next explored for coupling competency. While the cross-coupling of alkenyl triflates/halides with cyclopropanols has been reported, alkenylboronic esters have rarely been explored in this specific context. ,, Alkenylboronic esters have received significant attention among organic chemists in recent years because of their ready availability associated with facile synthetic methods. , These esters, which have the ability to undergo a variety of synthetic transformations to form C–C, C–O, and C–N bonds, provide ready synthetic access to tri- and tetra-substituted alkenes. We were encouraged by the initial successful attempt of alkenylation of cyclopropanol 1a upon coupling with the tri-substituted olefin-bearing cyclohexenyl boronic ester 8a , which produced the dienone 9a in 81% yield.…”

“…As a part of our recent research efforts to exploit cyclopropanols as a convenient source of three-carbon homoenolate synthons for synthetic manipulation, , we recently reported for the first time that arylboronic acids could effectively serve as the cross-coupling partners for the cyclopropanol-derived metal homoenolates, leading to the synthesis of dihydrochalcones and related analogues in a chemoselective fashion . The absence of a practical methodology to readily transform cyclopropanols into the corresponding β-aryl enones, which was deliberated earlier in the context of Scheme (equations 1–4), inspired us to explore the feasibility of alternative catalytic pathways of Pd­(II)-mediated coupling of cyclopropanols using organoboronic acids as transmetalation reagents. − In contrast to the reported substrate control approaches, our design aspect revolved around a catalyst-driven strategy to selectively effect syn β-H elimination of a β-aryl/alkenyl α-carbopalladium keto complex after the migratory insertion of an aryl/alkenyl group from the metal center into the homoenolate of a cyclopropanol (Figure ).…”

Aryl Pyrazoles from Photocatalytic Cycloadditions of Arenediazonium

“…1-Aryl-1-cyclopropanols could engage in photocatalytic ring-opening to provide a benzoylethyl motif exhibiting 1,3-dipolarophilic reactivity . In the presence of arenediazonium, radical trapping would result in the formation of β-aryl propiophenones via N 2 -elimination or diaryl pyrazoles via N 2 -retentive formal cycloaddition (Scheme ). Our initial investigations of the model reaction between 1-anisyl-1-cyclopropanol ( 1a ) and 4-methoxybenzenediazonium tetrafluoroborate ( 2a ) with the organic photocatalyst eosin Y indeed afforded the pyrazole 3aa in 42% yield as the sole product (Table S1).…”

Metal-Catalyzed Transformations of Cyclopropanols via Homoenolates

“…Recently, Ilangovan and coworkers reported oxidative ring-opening arylation of cyclopropanols with arylboronic acids, which may be complementary to the above-mentioned arylationg using aryl bromdies (Scheme 28). 48 The reaction between 1-substituted cyclopropanols and arylboronic acids proceeded smoothly in the presence of Pd(OAc)2, dppp, and Cu(OAc)2 to afford β-aryl ketones in moderate to good yields. A mechanistic study suggested that the reaction is less likely to involve a palladium homoenolate.…”