Stereoselective Synthesis of Medium-Sized Cyclic Ethers by Sequential Ring-Closing Metathesis and Tsuji-Trost Allylation.

Fully functionalized medium-sized cyclic ethers, of the type found in fused polyether natural products, have been prepared by sequential ring-closing diene metathesis, conversion of the resulting cyclic enone into an allylic enol carbonate, and Tsuji-Trost allylation using a chiral palladium complex. Very high levels of diastereocontrol, favoring the diastereomer in which there is a cis relationship between the allyl group at C-2 of the medium-ring ether and the substituent at C-7/C-8, are obtained in cases where catalyst control and substrate control are matched.

Copper-Mediated Introduction of the CF2 PO(OEt)2 Motif: Scope and Limitations.

Herein, a general procedure to access CF2 PO(OEt)2 -containing molecules is reported. The reagent CuCF2 PO(OEt)2 is accessible by a simple protocol and a broad range of substrates can be functionalised. The procedure allows the conversion of aryl diazonium salts, as well as aryl, heteroaryl, vinyl and alkynyl iodonium salts, into the corresponding fluorinated molecules at room temperature. Mechanistic studies were performed to gain a better understanding of the reaction pathway. Under similar conditions, vinyl and aryl iodides, allyl halides, and benzyl bromides were also functionalised, and the scope and limitations of the reaction were studied. Finally, the procedure was extended to disulfides to offer new access to SCF2 PO(OEt)2 -containing molecules.

Copper Salt-Controlled Divergent Reactivity of [Cu]CF2 PO(OEt)2 with α-Diazocarbonyl Derivatives.

Herein, we report a copper salt-controlled divergent reactivity toward α-diazocarbonyl compounds. By a simple change of the copper counteranion under identical reaction conditions, the reported method allowed an easy access to either (Z)-α-fluorovinylphosphonate or alkyl-SCF2 PO(OEt)2 derivatives in good yields. Mechanistic studies were performed and suggested two different pathways to explain the formation of these products.

An Electrophilic Reagent for the Direct Introduction of the SCF2 PO(OEt)2 Group to Molecules.

An unprecedented electrophilic difluoromethylthiolating reagent (MesNHSCF2 PO(OEt)2 ) was designed. Under mild and metal-free conditions, this new reagent reacted with various nucleophiles, thus offering an efficient and operationally simple tool for the construction of C-SCF2 PO(OR)2 , N-SCF2 PO(OR)2 , and S-SCF2 PO(OR)2 bonds. Finally, thanks to this new methodology, the synthesis of the non-stereoidal anti-inflammatory diflumidone was achieved.

New Prospects toward the Synthesis of Difluoromethylated Phosphate Mimics.

The difluoromethyl phosphonate motif plays a crucial role in the development of bioactive molecules as it is considered as a phosphate bioisoster. Since 2010, a renewal of interest to enlarge the panel of reactions to access these difluoromethylated phosphonate-containing molecules has been witnessed. This Concept article charts the recent progress that has been made.

Copper-Mediated Formation of Aryl, Heteroaryl, Vinyl and Alkynyl Difluoromethylphosphonates: A General Approach to Fluorinated Phosphate Mimics.

A general and efficient access to aryl, heteroaryl, vinyl and alkynyl difluoromethylphosphonates is described. The developed methodology using TMSCF2PO(OEt)2, iodonium salts and a copper salt provided a straightforward manifold to reach these highly relevant products. The reaction proved to be highly functional group tolerant and proceeded under mild conditions, giving the corresponding products in good to excellent yields. This method represents the first general synthetic route to this important class of fluorinated scaffolds, which are well-recognized as in vivo stable phosphate surrogates.

A convergent synthesis of the fully elaborated macrocyclic core of TMC-95A.

A concise and straightforward synthesis of the fully elaborated macrocyclic core of TMC-95A is reported. A highly efficient organocatalyzed aldolization between isatin and dihydroxyacetone derivatives and formation of the biaryl subunit with concomitant macrocyclization are the characteristic features of this synthesis.

Copper-catalyzed coupling of 1,1-dibromo-1-alkenes with phenols: a general, modular, and efficient synthesis of ynol ethers, bromo enol ethers, and ketene acetals.

An efficient and general copper-catalyzed method is reported for the synthesis of phenol-derived 1-bromoenol ethers, ynol ethers, and ketene acetals by chemodivergent copper-catalyzed cross-coupling between readily available 1,1-dibromo-1-alkenes and phenols.

Approach to the hyacinthacines: first non-chiral pool synthesis of (+)-hyacinthacine A1.

The first non-chiral pool total synthesis of (+)-hyacinthacine A(1) is described. This synthesis is based on an effective [2 + 2] cycloaddition of dichloroketene to a Stericol-based enol ether, a diastereoselective dihydroxylation, and an efficient Tamao-Fleming oxidation.