Widenhoefer

Research

Welcome to the Widenhoefer group web page. Research in the Widenhoefer group is directed toward the development and mechanistic analysis of new organotransition metal-catalyzed transformations for application in the synthesisof functionalized organic molecules. In particular, our group has a long-standing interest in the functionalization of C–C multiple bonds with carbon and heteroatom nucleophiles catalyzed by electrophilic late transition metal complexes, with a recent focus on the synthetic and mechanistic aspect of gold(I) π-activation catalysis. Specific projects currently under investigation in our group include:

Catalytic Hydroamination of Alkenes and Allenes

The addition of the N–H bond of an amine or carboxamide derivative across a C–C multiple bond (hydroamination) represents a highly expedient and atom economical approach to the synthesis of aliphatic and allylic amine derivatives. Despite prolonged effort, many challenges persist in the area of catalytic hydroamination, including intermolecular and/or enantioselective transformations and hydroamination methods that utilizes basic, alkyl amines as nucleophiles. Over the past several years, we have made significant contributions to many of the extant limitations associated with catalytic hydroamination. As examples, we have recently reported gold-catalyzed methods for the regioselective intermolecular hydroamination of unactivated 1-alkenes with cyclic ureas (Scheme 1) and the enantioselective, intermolecular hydroamination of chiral, racemic allenes (Scheme 2). We have also applied gold- and platinum-catalyzed hydroamination to the synthesis of nitrogen heterocycles, such as our recent example of gold-catalyzed intramolecular dihydroamination of allenes to form bicyclic imidazolidin-2-ones (Scheme 3).

 

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Gold(I)-Catalyzed Amination of Underivatized Allylic Alcohols

The transition metal-catalyzed amination of allylic esters and carbonates represents one of the most well established routes to the synthesis of allylic amines. With the potential to condense synthetic sequences and reduce waste streams, there has been considerable interest in the dehydrative amination of underivatized allylic alcohols as more atom economical and more environmentally benign alternatives. Although a number of methods have been developed, the regiospecific amination of allylic alcohols remains problematic, presumably due to the intermediacy of π-allyl complexes or allylic carbocations. We have developed a family of highly regio- and stereospecific gold(I)-catalyzed protocols for the dehydrative amination of allylic alcohols, including the intermolecular amination of allylic alcohols with ureas, the intramolecular amination of allylic alcohols with alkyl amines (Scheme 4), and the enantioselective amination of allylic alcohols with carbamates that formed nitrogen heterocycles with up to 94% ee (Scheme 5).

 

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Synthesis and Study of Cationic Gold π-Complexes

In recent years, application of soluble gold(I) complexes as catalysts for the functionalization of C–C multiple bonds has received considerable attention. Mechanisms involving complexation of the C–C multiple bond to gold followed by outer-sphere addition of the nucleophile on the gold(I) π-complex are often invoked for these transformations. However, until recently little was known regarding the structures, reactivity, and behavior of these key gold π-complexes. In response to this limitation, we have synthesized a family of cationic, two-coordinate gold(I) complexes that contain a π-alkene, allene, 1,3-diene, or alkyne ligand in conjunction with an electron-rich, sterically hindered supporting ligand such as an N-heterocyclic carbene (Figure 1). We have isolated many of these complexes and we have studied their structures in the solid state employing X-ray crystallography. Likewise, we have investigated the ligand binding properties, intermolecular ligand exchange behavior, and intramolecular fluxional behavior of the complexes employing variable temperature NMR spectroscopy.

 

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Evaluating the Catalytic Relevance of Bis(gold) Complexes

Building from our work in the area of cationic gold π-complexes, we have likewise synthesized a number of neutral gold π-complexes, investigated the aggregation behavior of these complexes to form the corresponding bis(gold) π-complexes, and we have evaluated the catalytic relevance of both types of complexes. In one study, we have shown that gold π-(terminal alkyne) complexes undergo rearrangement and aggregation well below room temperature to form dinuclear gold σ,π-acetylide complexes with concomitant release of strong Brønsted acid (Scheme 6). While the gold complex is quite stable, the strong Brønsted acid may affect the reactivity of such solutions. In a second study, we (in collaboration with the Gagné group at UNC) have shown that both mono(gold) and bis(gold) vinyl complexes are catalytically relevant in the gold(I)-catalyzed hydroalkoxylation of π-allenyl alcohols and that the bis(gold) vinyl complex functions as off-cycle catalyst reservoir rather than an on-cycle resting state (Scheme 7).

 

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