A new and direct approach to functionalized biaryl α-ketophosphonic acids via aqueous Suzuki coupling on solid support (original) (raw)
Related papers
Catalysis Letters, 2021
The iridium-catalyzed C-H borylation of diethyl phenylphosphonate results in nonselective mono and bisborylation to afford a near statistical mixture of 3-, 3,5- and 4-boryl substituted aryl phosphonates whereas 3-substituted aryl phosphonates undergo highly regioselective C-H borylation to afford the corresponding meta-phosphonate substituted arylboronic esters as the sole product; the resulting boronic esters were used as nucleophilic reagents in a subsequent palladium-catalyzed Suzuki–Miyaura cross-coupling to generate a range of biarylmonophosphonates. Gratifyingly, the Suzuki–Miyaura cross-coupling can be conducted without purifying the boronic ester which greatly simplifies the synthetic procedure. Graphical Abstract
Suzuki-Miyaura mediated biphenyl synthesis: a spotlight on the boronate coupling partner
2011
Suzuki-Miyaura Mediated Biphenyl Synthesis: A Spotlight on the Boronate Coupling Partner The biaryl motif is found in many natural and synthetic products that display a wide range of biological activities. This explains why biphenyls are widely encountered in medicinal chemistry as a privileged scaffold. The palladium-catalysed Suzuki-Miyaura (SM) coupling is one of the most important and efficient strategies for the synthesis of symmetrical and unsymmetrical biaryl compounds; the arylboronic acid or ester is a key partner in this coupling reaction. This work presents the synthesis of a library of new molecules containing the biphenyl scaffold; o-, m-and p-(bromomethyl)phenylboronic acid pinacol esters, 2a-c, were selected as coupling partners. Nucleophilic substitution of the bromide was carried out with amine, thiol, alcohol or phenol nucleophiles. Supported reagents and microwave assisted organic synthesis conditions were employed to enhance this chemistry and made it amenable to parallel synthesis. The resulting arylboronates were used in SM coupling reactions in order to obtain a range of biphenyls. The use of Boc-piperazine as a nucleophile in the S N 2 reaction, with 2a-c, and 1-bromo-, 2-, 3-or 4-nitrobenzene or 2-bromo-5-nitropyridine as aryl halides in the SM coupling reaction, allowed two other points of functionalisation to be added to the biaryl motif. The conditions for the SM coupling of mercaptomethylphenylboronic esters and orthosubstituted methylphenylboronic esters were optimised in order to broaden the scope of the biaryl library. Phosphines were found to be good nucleophiles in the S N 2 reaction with 2a-c. A Wittig reaction was performed with the resulting phosphonium arylboronates in order to synthesise arylboronic esters containing an alkene function prior the reduction of the resulting double bond of the stilbene derivatives and realising a SM coupling to synthesise arylethylbiphenyls. The stilbene derivatives were also synthesised by using the olefin cross-metathesis reaction of 4-vinylphenylboronic acid pinacol ester. A solid state crystallographic study was undertaken on a small library of methylbiphenylamides to compare the crystal structures of isomers or biphenyls with different functional groups.
New strategy for the synthesis of functionalized phosphonic acids
Heteroatom Chemistry, 1997
Various approaches leading to mono-, di-and poly-functionalized phosphonates as well as phosphoryl heterocycles were reported for the systematic study of relationship between chemical structure and biological activities of this most important class of organophosphorus compounds.
An alternative C–P cross-coupling route for the synthesis of novel V-shaped aryldiphosphonic acids
Beilstein Journal of Organic Chemistry
The synthesis of phosphonate esters is a topic of interest for various fields, including the preparation of phosphonic acids to be employed as organic linkers for the construction of metal phosphonate materials. We report an alternative method that requires no solvent and involves a different order of addition of reactants to perform the transition-metal-catalyzed C–P cross-coupling reaction, often referred to as the Tavs reaction, employing NiCl2 as a pre-catalyst in the phosphonylation of aryl bromide substrates using triisopropyl phosphite. This new method was employed in the synthesis of three novel aryl diphosphonate esters which were subsequently transformed to phosphonic acids through silylation and hydrolysis.
Catalysts
The enantiomerically pure ligand BisNap-Phos was obtained in a straightforward sequence of reactions beginning with inexpensive starting materials under the readily affordable conditions in high overall yield. An asymmetric BisNap-Phos-palladium complex-catalyzed Suzuki–Miyaura coupling leading to axially chiral biaryl compounds was described. The reactions were carried out under mild conditions in aqueous and organic media. A series of atropisomeric biaryls were synthesized with excellent yields and high enantioselectivities (up to 86% ee). The methodology provides an efficient and practical strategy for the synthesis of novel multifunctionalized axially chiral biaryl compounds under mild environmentally friendly and easily affordable conditions.