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

Abstract

The scope of chemoselective β-hydride elimination in the context of arylation/alkenylation of homoenolates from cyclopropanol precursors using organoboronic reagents as transmetalation coupling partners was examined. The reaction optimization paradigm revealed a simple ligand-free Pd(II) catalytic system to be most efficient under open air conditions. The preparative scope, which was investigated with 48 examples, supported the applicability of this reaction to a wide range of substrates tolerating a variety of functional groups while delivering β-substituted enone and dienone derivatives in 62−95% yields.

Synthetic Access to α-Oxoketene Aminals by the Nucleophilic Addition of Enol Silane-Derived Palladium(II) Enolates to Carbodiimides

“…The enhanced productivity profile observed with DMSO compared to other solvents alludes to the possibility that DMSO can play an extended role beyond its usual function as a reaction medium by functioning as a Pd­(II)-coordinating ligand. This observation is consistent with the literature precedent of a Pd­(II)/DMSO combination as an efficient catalytic system that has promoted a wide range of synthetic transformations. − The reaction temperature was found to be optimal at 60 °C since either the elevation of the temperature to 80–100 °C or lowering to RT resulted in a suppression of product formation, with the observation of lower yields ranging from 20 to 47% (Table , entries 10–12).…”

Electrophilic Hydrazination of Cyclopropanols Using Azodicarboxylates via Copper(II) Catalysis: An Umpolung Strategy to Access β-Hydrazino Ketone Motifs

“…The initial reaction protocols, which were designed to study the effectiveness of a free-radical pathway for the cross-coupling of 1a and 2a , gave the desired product 3a in 13–15% yield in the presence of silver salts and K 2 S 2 O 8 (entries 1–2). We have previously demonstrated the utility of Pd­(OAc) 2 catalyst in the construction of C–C bonds from the cross-coupling reaction of cyclopropanols and organoboronic acids to derive β-aryl ketones and chalcones. , This literature precedent prompted us to replace silver salts with Pd­(OAc) 2 , which translated into an improved yield of 3a to 43% in DMSO as the solvent (entry 3). An attempt to further improve the yield with Pd­(OAc) 2 by adding CuCl (2.5 equiv) as the additive and bis­(diphenylphosphino)­ethane (DPPE; 0.2 equiv) as the chelating ligand resulted in a considerably improved yield of 96% (entry 4).…”

“…We have previously demonstrated the utility of Pd(OAc) 2 catalyst in the construction of C−C bonds from the cross-coupling reaction of cyclopropanols and organoboronic acids to derive β-aryl ketones and chalcones. 15,16 This literature precedent prompted us to replace silver salts with Pd(OAc) 2 , which translated into an improved yield of 3a to 43% in DMSO as the solvent (entry 3). An attempt to further improve the yield with Pd(OAc) 2 by adding CuCl (2.5 equiv) as the additive and bis-(diphenylphosphino)ethane (DPPE; 0.2 equiv) as the chelating ligand resulted in a considerably improved yield of These results imply that the metal β-homoenolate pathway more effectively promotes the Csp 3 -N bond formation between 1a and 2a than the catalysis involving a β-keto radical mechanism.…”

“…The limited number of methodologies that have been made available to construct C–N bonds from cyclopropanol substrates inspired us to examine the scope of diversification of amine coupling partners, as part of our recent interest in exploiting cyclopropanols as versatile three-carbon building blocks. − In this context, it is noteworthy to mention the ease of synthesis of cyclopropanol substrates from a range of commercially available or readily accessible starting materials (e.g., carboxylic esters, conjugated ketones/esters, enolizable aldehydes/ketones, ketones bearing leaving groups at α-position, alkenes, and carbenoids). − The Kulinkovich reaction serves as the most common tool to prepare cyclopropanols in one step from carboxylic esters in the presence of a Grignard reagent bearing a hydrogen atom at the β-position and titanium­(IV) alkoxide, while the Simmons–Smith cyclopropanation of enol ethers is another methodology that is frequently employed.…”

Examining the Scope of Deriving β-Aryl Enones from Enol Silanes as Ketone Equivalents via Pd(II)-Mediated Sequential Dehydrosilylation and Arylation

“…Taking into account the enormous potential of β-aryl enones or chalcones as privileged structures in the design and development of new therapeutic candidates, there remains an ever-expanding scope for the development of new methodologies to provide synthetic access to these building blocks. ,, We have recently reported synthetic methodologies to derive β-aryl/alkenyl enones or their saturated counterparts, β-aryl/alkenyl ethyl ketones (for example, chalcones and dihydrochalcones) from allyl alcohols and cyclopropanols as readily available starting materials by arylation and alkenylation with arylboronic and alkenylboronic acids (or esters), respectively, using modular Pd­(II) catalytic systems. − The salient feature of these protocols was the exploitation of organoboronic acids or esters as powerful arylating or alkenylating agents that offer multiple advantages, including (a) commercial availability, (b) ease of synthesis, (c) relatively low toxicity, (d) high stability to air and moisture, and (e) facile tendency to undergo transmetallation with transition-metal complexes. , Importantly, the direct C–H borylation of arenes, heteroarenes, and alkenes under either transition-metal-catalyzed or metal-free conditions has significantly expanded the synthetic scope of organoboronic reagents. − …”