Green synthesis of (R)-3-hydroxy-decanoic acid and analogs from levoglucosenone: a novel access to the fatty acid moiety of rhamnolipids.

Rhamnolipids (RLs) are highly valuable molecules in the cosmetic, pharmaceutic, and agricultural sectors with outstanding biosurfactant properties. In agriculture, due to their potential to artificially stimulate the natural immune system of crops (also known as elicitation), they could represent a critical substitute to conventional pesticides. However, their current synthesis methods are complex and not aligned with green chemistry principles, posing a challenge for their industrial applications. In addition, their bioproduction is cumbersome with reproducibility issues and expensive downstream processing. This work offers a more straightforward and green access to RLs, crucial to decipher their mechanisms of action and design novel potent and eco-friendly elicitors. To achieve this, we propose an efficient seven-step synthetic pathway toward (R)-3-hydroxyfatty acid chains present in RLs, starting from cellulose-derived levoglucosenone, with Michael addition, Baeyer-Villiger oxidation, Bernet-Vasella reaction, and cross-metathesis homologation as key steps. This method allowed the production of (R)-3-hydroxyfatty acid chains and derivatives with an overall yield ranging from 24% to 36%.

Formation of C(sp(3))-C(sp(3)) Bonds by Palladium Catalyzed Cross-Coupling of α-Diazoketones and Allylboronic Acids.

Palladium catalyzed cross-coupling of allylboronic acids with α-diazoketones was studied. The reaction selectively affords the linear allylic product. The reaction proceeds with formation of a new C(sp(3))-C(sp(3)) bond. The reaction was performed without an external oxidant, likely without the Pd-catalyst undergoing redox reactions.

Copper-Catalyzed Cross-Coupling of Allylboronic Acids with α-Diazoketones.

Copper-catalyzed cross-coupling of substituted allylboronic acids with α-diazoketones was studied. This allylation reaction is highly regioselective, providing the branched allylic product. The process involves creation of a new C(sp(3))-C(sp(3)) bond by retaining the keto functional group of the α-diazoketone precursor.

Recent Progress toward the Introduction of Functionalized Difluoromethylated Building Blocks onto C(sp(2) ) and C(sp) Centers.

Fluorine chemistry is a field undergoing tremendous expansion. Although much attention has been paid to the introduction of the fluorine atom and the CF3 group, less interest has been devoted to the introduction of functionalized fluorinated building blocks, in sharp contrast with the high versatility of the fluorinated products. In this Minireview, the most relevant methods for the introduction of difluoromethylated building blocks are summarized. Access to difluoromethylated arenes, alkenes, and alkynes is highlighted and special attention is paid to explanation of the reaction mechanism.

Copper-catalyzed direct C-2 difluoromethylation of furans and benzofurans: access to C-2 CF2H derivatives.

We report herein the first copper-catalyzed C-2 difluoromethylation of furans and benzofurans. The developed methodology allows the selective introduction of the CF2CO2Et moiety at C-2 using CuI as a catalyst. This process was applied to a broad range of furans and benzofurans, giving the functionalized products in moderate to good yields. The resulting products were then decarboxylated to afford the highly valuable C-2-CF2H-substituted furans and benzofurans in good yields.

Copper-catalyzed olefinic C-H difluoroacetylation of enamides.

Copper-catalyzed olefinic difluoroacetylation of enamides via direct C-H bond functionalization using BrCF2CO2Et is reported for the first time. It constitutes an efficient radical-free method for the regioselective synthesis of ß-difluoroester substituted enamides which exhibits broad substrate scope, and thus demonstrates its potent application in a late stage fluorination strategy.

Copper catalyzed ß-difluoroacetylation of dihydropyrans and glycals by means of direct C-H functionalization.

A copper catalyzed direct functionalization of dihydropyrans and glycals has been developed. This method affords a new and straightforward access to C-2-CF2 dihydropyrans and glycosides in a single step starting from readily available starting materials. This new copper based catalytic system, probably involving a Cu(III) species as supported by experiments, allows the formation of the valuable fluorinated glycosides in good yields.

Copper-catalyzed direct arylation of cyclic enamides using diaryliodonium salts.

A convenient method for the copper(II)-catalyzed direct arylation of cyclic and nonaromatic enamides using diaryliodonium salts has been developed. The reaction demonstrates large functional group tolerance, good yields, and total regioselectivity with a C(3)-functionalization. The synthetic potential of this coupling was explored by using a range of readily accessible diaryliodonium salts and enamides.

Indium-promoted Reformatsky reaction: a straightforward access to ß-amino and ß-hydroxy α,α-difluoro carbonyl compounds.

A versatile and practical methodology to access ß-amino and ß-hydroxy α,α-difluoro carbonyl compounds using indium metal is described. This methodology has been successfully applied to a broad range of substrates including aldehydes, ketones, and imines, affording the corresponding and highly valuable gem-difluoro esters. The wide substrate scope highlights the chemoselectivity of the process.