A General and Efficient Method for the Alkoxycarbonylation of α‐Chloro Ketones

Abstract

The alkoxycarbonylation of a-chloro ketones with carbon monoxide in alcoholic solvents could be optimized to generate b-keto esters in high yields using much lower catalyst loadings than previously reported in the literature. Among the different screened parameters, the nature of the ligand proved to be the most crucial one, the Xantphos ligand affording the highest yields. The scope of the reaction could then be extended to a wide variety of chloro ketones with different types of alcohols.

α‐Oxo‐Ketenimines from Isocyanides and α‐Haloketones: Synthesis and Divergent Reactivity

“…The palladium‐catalyzed carbonylation of α‐haloketones is known and, till now, the scope of this synthetically useful transformation was applied mainly to haloketones lacking the β‐hydrogen because intermediates related to B are known to undergo rapid β‐hydride elimination to enone 21 even under the carefully optimized conditions . The fact that this supposedly facile process, a main concern at the outset of our reaction design, did not take place under our conditions is remarkable.…”

Palladium Nanoparticles Supported on Triphenylphosphine-Functionalized Porous Polymer as an Active and Recyclable Catalyst for the Carbonylation of Chloroacetates

“…Interestingly, some mixed-alkyl malonates were also prepared in excellent yields under the reaction conditions (entries 2-4), although a competing transesterification reaction with the chloroacetate substrate or with the malonate product was possible. Alkoxycarbonylation of α-chloro ketones represents a valuable alternative for the synthesis of the useful β-keto esters [43]. Considering the similar structure of α-chloro ketones and chloroacetates, the alkoxycarbonylation of α-chloro ketones was also tested under the optimal catalytic system.…”

Urea-Catalyzed Functionalization of Unactivated C–H Bonds

“…3,4 While previous studies from our group and others have demonstrated that these species undergo facile C-C bond-forming reactions, all catalytic systems reported thus far have utilized expensive, hygroscopic, and specialized weakly coordinating anion (WCA) salts that are often difficult to functionalize and establish structure-function relationships (Figure 1a). 5 In an effort to identify more easily accessible and modular catalysts for these powerful transformations, we looked towards hydrogen-bonding catalysts, such as thioureas. These readily available and highly tunable scaffolds have found success in promoting the formation of cationic intermediates.…”

“…We began proof-of-concept studies in the context of the C-H insertion reactions of propylated benzosuberonyl triflate 1 (Table 1). 5 We hypothesized that a hydrogen-bonding catalyst could ionize its vinyl triflate, and the ensuing vinyl carbocation would insert into the terminal CH 3 group of the tethered propyl chain to give product 2. Initially, the use of Schreiner's thiourea 3 gave neither conversion to the desired product 2, nor consumption of starting material 1.…”

“…Based on our previous studies, we hypothesized that deprotonation of the urea would yield a lithiate sufficiently Lewis acidic to ionize an enol triflate, revealing the potent vinyl carbocation. 5,10,11 To our delight, we found that the addition of a stoichiometric amount of lithium hexamethyldisilazide (LiHMDS) to this reaction mixture resulted in a high yielding C-H insertion reaction, giving tricycle 2 in 78% yield (entry 2). The urea and squaramide analogs (4 and 5 respectively) of Schreiner's catalyst were also competent catalysts for this transformation, yielding the desired product in 96% and 72% yield, respectively (entries 3 and 4).…”