Jane Panteleev

Addition of arylboronic acids to arylpropargyl alcohols en route to indenes and quinolines.

A regio- and stereoselective rhodium-catalyzed synthesis of trisubstituted allylic alcohols is described. The utility of these synthons is demonstrated in a convenient synthesis of indenes and quinolines.

C−H Bond Functionalization in the Synthesis of Fused 1,2,3-Triazoles

A highly modular approach to fused 1,2,3-triazoles has been developed featuring a one-pot procedure combining copper(I) catalyzed azide-alkyne cycloaddition and palladium-catalyzed C-H bond functionalization. A class of structurally unique heterocycles was synthesized in good yields.

Intramolecular Aryne–Ene Reaction: Synthetic and Mechanistic Studies

Although the chemistry of arynes is well developed, some challenges still remain. The ene reaction of arynes has not gained widespread use in synthesis as a result of poor yields and selectivity. A general, high yielding and selective intramolecular aryne-ene reaction is described providing various benzofused carbo- and heterocycles. Mechanistic data is presented, and a rationale for the resulting stereochemistry is discussed.

Multicomponent-multicatalyst reactions (MC)(2)R: efficient dibenzazepine synthesis.

A Rh(I)/Pd(0) catalyst system was applied to the multicomponent synthesis of aza-dibenzazepines from vinylpyridines, arylboronic acids, and amines in a domino process with no intermediate isolation or purification.

Metal-ligand binding interactions in rhodium/palladium-catalyzed synthesis of dihydroquinolines.

A domino Rh- and Pd-catalyzed synthesis of dihydroquinolines is disclosed. Two metals and two ligands are placed in one reaction vessel along with the two reactive reagents to afford selective sequential coupling despite the potential for side reactions. In this report, we describe mechanistic investigations attempting to discern the catalyst-ligand interactions occurring in this domino reaction. Through these studies, the reactivity and relative catalyst ligand loadings were successfully tuned to efficiently access the heterocyclic products.

In Situ Generation of Difluoromethyl Diazomethane. Synthesis of Pyrazoles

Significance: Incorporation of fluorine in pharmaceutical or agrochemical targets is often advantageous for modulation of physicochemical and biological properties. Thus, development of new strategies to incorporate fluorinated motifs is valuable to several industries. Mykhailiuk reports the generation of difluoromethyl diazomethane, followed by its subsequent cycloaddition with alkynes. In situ generation of trifluoromethyl diazomethane was initially described in a protocol which has enabled safe application of this intermediate in synthesis of diverse motifs (B. Morandi, E. M. Carreira Angew. Chem. Int. Ed. 2010, 49, 938). The method, however, was not applicable to the formation of difluoromethyl diazomethane. In the current work, the author describes a solution to this problem, wherein utilization of t-BuONO in non-aqueous media furnishes the desired intermediate. A related publication from the same laboratory describes the use of substituted difluoromethyl diazomethanes (RF2C–CN2; R ≠ H) in a domino reaction with alkynes forming similar pyrazole products. The method utilizes NaNO2 as an oxidant in an aqueous reaction, but cannot be used to efficiently access difluoromethyl substituted pyrazoles (P. K. Mykhailiuk Org. Biomol. Chem. 2015, 13, 3438). Comment: The generated difluoromethyl diazomethane was utilized in a one-pot [3+2] cycloaddition with alkynes to furnish substituted pyrazoles. As is typical with cycloadditions, alkynes bearing more electron-withdrawing substituents led to product formation in higher yields. The regioselectivity of the cycloaddition was generally high with only the electronically favored products being observed in most cases. Notably, the protocol was amenable to scale synthesis (1.5 gram). The structure of the final products was unambiguously confirmed by single-crystal X-ray crystallography. Further studies on the synthetic applications of this protocol may establish this intermediate as a useful addition to the currently available approaches of incorporating difluoromethyl substituents.