Au-catalyzed hydrofluorination reactions of a range of functionalized alkynes are reported. In the presence of an appropriate directing group, localized with particular spacing from the pendant alkyne, regioselective and predictable conversion of the alkyne to the Z-vinyl fluoride may be achieved. In selected cases, yields and selectivities are excellent. Additional experiments with two directing groups installed have established some initial principles with respect to a hierarchy of directing groups and their capacity for influencing hydrofluorination regioselectivity.Fluorine is an element of special interest in organic chemistry. Its electronegativity, highest of all the known elements, contributes to its special properties, which include formation of strong bonds to carbon, 1 low atomic polarizability, 2 and strong inductive characteristics. 3 The field of medicinal chemistry has especially benefited from the development of chemical techniques for incorporating fluorine into organic molecules. Fluorine is now routinely introduced to impart metabolic stability to medicinal compounds. 4 Coupled with its electronegativity, fluorine's small size has made it an attractive choice for isosteric substitutions of hydrogen or In light of the importance of fluoroalkenes, many efforts towards efficient regio-and stereoselective syntheses of these moieties have been reported. 7 Of these, we were especially intrigued by a methodology developed by Sadighi and coworkers employing a Au(I) catalyst 8 to add HF across an alkyne. 9 Using Et 3 N•3HF as a nucleophilic fluorine source, KHSO 4 as an additive, and various co-catalysts, trans-hydrofluorination was achieved in good yields (Scheme 1). Modest regioselectivity for alkyl/aryl alkyne substrates was improved by adding electron-withdrawing groups to the aromatic ring substituents. Although other alkyne hydrohalogenations using Au-catalysis have been reported, these reactions utilize electrophilically activated halogens, for the most part excluding fluorine. 10 Also, the substrate scope of these reactions has been limited to propargyl acetates.Given our interest in fluoroolefins as mechanistic probes, 6 we sought to expand the methodology for Au-catalyzed nucleophilic fluorination of alkynes by developing new avenues for regiocontrol that would expand both the utility and substrate scope of the reaction. Specifically, we envisioned a classical heteroatom-directed reaction that might confer a high degree of selectivity for a broad range of substrates. 11 Here we report the realization of this design in the carbonyl-directed hydrofluorination of alkynes under Au(I) catalysis. We demonstrate that this concept is broadly applicable and engenders regioselectivies that exceed those originally reported for this reaction system. As such, this methodology could facilitate access to new compounds for fundamental research and the development of pharmaceuticals.We commenced our investigations by examining ester 1. We were intrigued to observe that hydrofluorination of this subst...

We report the development of an iron-catalyzed method for the selective oxyfunctionalization of C(sp3)–H bonds in aliphatic amine substrates. This transformation is highly selective for benzylic C–H bonds that are remote (i.e., at least 3-carbons) from the amine functional group. High site selectivity is achieved by in situ protonation of the amine with trifluoroacetic acid, which deactivates more traditionally reactive C–H sites that are α-to nitrogen. The scope and synthetic utility of this method are demonstrated via the synthesis and derivatization of a variety of amine-containing biologically active molecules.

A selective peptide-catalyzed addition of allenic esters to N-acylimines is reported. Tetrasubstituted allenes were achieved with up to 42:1 diastereomeric ratio and 94:6 enantiomeric ratio (up to 99:1 er after recrystallization of the major diastereomer). An exploration of the role of individual amino acids within the peptide was undertaken. The scope of the reaction was explored and revealed heightened reactivity with thioester-containing allenes. A mechanistic framework that may account for the observed reactivity is also described.

We have developed phosphine-catalyzed annulation reactions for the synthesis of highly substituted cyclopentene derivatives from 2-alkynoate and α-keto esters. These transformations involve carbon−carbon bond cleavage of α-keto esters. Preliminary mechanistic studies suggest that, in addition to facilitating carbon−carbon bond formation, the phosphine catalyst plays a role in promoting methanolysis.

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