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 synthesis of 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. Specific projects currently under investigation in our group include:

 

  • Multi-State Mechanocatalysis
  • Carbene Transfer Employing Diazirines as Carbene Precursors
  • Study of Gold(I) Vinyl Compounds Undergoing Electrophilic Substitution
  • Synthesis and Study of Cationic Gold π-Complexes
  • Synthesis and Evaluation of Cationic Bis(gold) Complexes

 

Multi-State Mechanocatalysis

Multi-state mechanocatalysts (MMCs) are a new class of polymer-embedded catalysts that funnel mechanical forces to the molecular level used to bias catalysis. In a sense, we pursue the ultimate extension of top-down atomic manipulation—pushing and pulling molecules into the optimal shape for a desired function (catalysis). Rather than manipulating individual atoms with specialized instrumentation, however, our ultimate goal is to develop polymeric platforms within which active, transition-metal (or organic) catalysts are strategically positioned so that when the polymer is stretched or deformed, the distribution of catalyst conformational states is changed. Because polymers can be stretched and deformed both incrementally and reversibly, MMCs offer the potential to tune selectivity and/or reactivity for a desired substrate or product within a single catalytic scaffold. By coupling mechanical force to catalytic systems, we have shown an ability to modulate rates of elementary catalytic steps (oxidative addition and reductive elimination), as well as enantioselectivity, regioselectivity, and chemoselectivity of catalytic reactions. This project is performed in collaboration with the Craig Lab here at Duke.

Carbene Transfer Employing Diazirines as Carbene Precursors

Diazirines are attractive precursors for transition metal-catalyzed carbene transfer with the potential to both mitigate safety concerns and significantly expand the scope of accessible metallocarbenes relative to organic diazo compounds. Although transition metal complexes are known to activate diazirines to form metallocarbene complexes under mild conditions, extensions of this reactivity to include catalytic carbene transfer have not been forthcoming. Recently, we have shown that weakly ligated PtCl2 complexes catalyzed the cyclopropanation of vinyl arenes and 1-aryl-1,3-butadienes using aryl diazirines as carbene precursors. Kinetic studies support a mechanism for diazirine to alkene carbene transfer involving nucleophilic attack of diazirine on a platinum bis(vinyl arene) complex followed by C-N oxidative addition, nitrogen gas extrusion, and addition of vinyl arene across Pt=C bond of the electrophilic carbene complex. This work provides both the groundwork and mechanistic framework for the development of catalysts that display enhanced reactivity and selectivity for cyclopropanation, provide access to additional reaction manifolds such as C-H or X-H insertion, and show ligand-controlled diastereo and enantioselectivity.

 

Study of Gold(I) Vinyl Compounds Undergoing Electrophilic Substitution

Over the past 2 decades, cationic gold(I) catalysis has been a field of increasing interest due to gold’s capacity to functionalize C-C multiple bonds. Gold vinyl complexes are commonly invoked intermediates in gold(I) catalysis, as they are invoked in the addition of carbon and heteroatom nucleophiles to allenes and alkynes, [2+2] cycloaddition of alkynes with alkenes, [2+2+2] cycloadditions of alkynes and oxoalkenes, and dimerization of chloroalkanes. The consumption of these gold vinyl complexes is via electrophilic cleavage, either by protodemetallation or with carbon/heteroatom electrophiles, forming carbon-carbon and carbon-heteroatom bonds. We plan to investigate and observe the consumption of these gold(I) vinyl compounds to further understand their reactivity.

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.

Synthesis and Evaluation of Cationic Bis(gold) Complexes

Despite being invoked as key reactive intermediates within gold(I)-catalyzed reactions, gold(I) allyl, allenyl, and propargyl complexes are not well-characterized. They have been studied computationally and spectroscopically, but there still lacks important experimental characterization. There is also  potential for monomeric gold complexes to form cationic bis gold complexes which could also serve as reactive intermediates or even catalytic sinks. Recently, we have synthesized a variety of gold(I) allyl complexes such as gold(I)-indenyl and cyclopentadienyl complexes and subsequently generated the respective cationic bis gold complexes. Upon studying the solid state of the bis gold complexes using X-ray crystallography, we found that the gold atoms adopt an unprecedented trans configuration about the allyl ligand. In addition, we have evaluated their intramolecular fluxional behavior using variable temperature NMR spectroscopy, tested their binding affinity toward exogenous gold, and analyzed their resistance toward protodeauration.

“Cationic Bis(Gold) Indenyl Complexes,” B. L. Slinger, J. Zhu, R. A. Widenhoefer, ChemPlusChem 2024, 89, e202300691.

“Syntheses and Structures of Cationic Bis(gold) Cyclopentadienyl Complexes,” Slinger, B. L.; Malek, J. C.; Widenhoefer, R. A. Organometallics 2025, 44, 224-235.

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.

 

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