Selective Palladium‐Catalyzed α,β‐Homodiarylation of Vinyl Esters in Aqueous Medium

Abstract

A palladium‐catalyzed 1,2‐diarylation of vinyl esters with arylboronic acids in water has been developed. This newly elaborated protocol features a good functional group tolerance and provides one‐step access to 1,2‐diarylethanol derivatives under mild reaction conditions. The presented reaction can be carried out in the water at ambient temperature without the addition of any ligands, what makes this procedure environmentally benign. The transformation occurs within a single catalytic cycle and is feasible due to the modification of transition metal catalytic activity through the influence of π‐acceptor olefin (benzoquinone) as well as water as a medium. Moreover, this protocol allows to generate entire compound libraries (highly profitable in medicinal chemistry) and utilizes sustainable arylboronic acids as coupling partners under mild conditions. It is also noted that the structure of boron moiety has a great impact on the reaction selectivity, the usage of sterically hindered esters of arylboronic acids influence the reaction course towards stilbenes.

Promiscuous Lipase-Catalyzed Markovnikov Addition of H-Phosphites to Vinyl Esters for the Synthesis of Cytotoxic α-Acyloxy Phosphonate Derivatives

“…As a continuation of our research on sustainable protocols, [ 50 , 51 , 52 , 53 ] we paid attention to find an environmentally friendly method for desired α-hydroxy phosphonates 1 – 4 [ 16 ] and α-acyloxy phosphonates 5 – 10 ( Figure 2 ).…”

“…Among the derivatives studied, the compounds possessing methyl group at α-position 5 , 6 , 7 , 8, and 9 turned out to be the most active comparing to derivatives with aryl group at α-position ( Figure 2 ). The research results presented are important for understanding the biological properties of tested α-hydroxy phosphonate derivatives as a function of potential new antibiotics and their toxic effects on Gram-negative bacteria in the face of the growing drug resistance pandemic, in reference to our previous works related to the characteristics of the model E.coli K12 and R2-R4 [ 44 , 51 , 52 , 53 , 54 , 55 , 56 , 57 , 58 , 59 , 60 , 61 , 62 , 63 , 64 , 65 ]. Finally, the analyzed α-hydroxy phosphonate derivatives are more cytotoxic in the model bacterial cells than the commonly used antibiotics: ciprofloxacin, bleomycin, and cloxacillin.…”

The Synthesis and Evaluation of Diethyl Benzylphosphonates as Potential Antimicrobial Agents

“…The 1,2-bis(4-((diethoxyphosphoryl)methyl)phenyl)ethyl acetate ( 4 ) can be obtained using known protocols; however, they are non-efficient, and the overall yield of product 4 was 1% ( Scheme 1 A). Thus, we have developed a new approach towards the compound 4 based on our previously developed vinyl esters α,β-homodiarylation method [ 25 ], which improved the yield to 38% ( Scheme 1 B). So far, such benzylphosphonate esters were obtained via coupling of p -hydroxymethylphenylboronic acid with olefin followed by Arbuzov reaction ( Scheme 1 A), but this approach suffers from low yield.…”

Palladium(ii)-catalyzed enantioselective intermolecular oxidative diarylation of internal enamides

“…3 Among these reactions, the Pd-catalyzed oxidative intermolecular alkene dicarbofunctionalization reactions with organometallic reagents have also received considerable attention, in which the σ-alkyl palladium( ii ) intermediate formed through the migratory insertion of alkenes into aryl or vinyl Pd( ii ) is intercepted by another nucleophile. 4–8 The Sigman group developed the 1,2-diarylation of terminal alkenes with organostannanes by the utilization of molecular oxygen as a terminal oxidant (Scheme 1a, top). 5 Apart from molecular oxygen, benzoquinone (BQ) and its derivatives are commonly used as oxidants to participate in Pd( ii )-catalyzed oxidative coupling reactions.…”

“…6 The Larhed group disclosed Pd( ii )-catalyzed oxidative diarylation of terminal vinyl ethers with environmentally benign aryl boronic acid as the nucleophile with benzoquinone (Scheme 1a, bottom). 7 The Pd-catalyzed 1,2-diarylation of internal alkenes was reported by the Mukherjee group in the presence of the radical oxidant TEMPO, where the diastereoselectivity was governed by the glycal substrates (Scheme 1b). 8 However, the asymmetric oxidative intermolecular diarylation of alkenes still remains a daunting challenge.…”