Catch It If You Can: Copper-Catalyzed (Transfer) Hydrogenation Reactions and Coupling Reactions by Intercepting Reactive Intermediates Thereof

Abstract

The key reactive intermediate of copper(I)-catalyzed alkyne semihydrogenations is a vinylcopper(I) complex. This intermediate can be exploited as a starting point for a variety of trapping reactions. In this manner, an alkyne semihydrogenation can be turned into a dihydrogen­-mediated coupling reaction. Therefore, the development of copper-catalyzed (transfer) hydrogenation reactions is closely intertwined with the corresponding reductive trapping reactions. This short review highlights and conceptualizes the results in this area so far, with H2-mediated carbon–carbon and carbon–heteroatom bond-forming reactions emerging under both a transfer hydrogenation setting as well as with the direct use of H2. In all cases, highly selective catalysts are required that give rise to atom-economic multicomponent coupling reactions with rapidly rising molecular complexity. The coupling reactions are put into perspective by presenting the corresponding (transfer) hydrogenation processes first.1 Introduction: H2-Mediated C–C Bond-Forming Reactions2 Accessing Copper(I) Hydride Complexes as Key Reagents for Coupling Reactions; Requirements for Successful Trapping Reactions 3 Homogeneous Copper-Catalyzed Transfer Hydrogenations4 Trapping of Reactive Intermediates of Alkyne Transfer Semi­hydrogenation Reactions: First Steps Towards Hydrogenative Alkyne Functionalizations 5 Copper(I)-Catalyzed Alkyne Semihydrogenations6 Copper(I)-Catalyzed H2-Mediated Alkyne Functionalizations; Trapping of Reactive Intermediates from Catalytic Hydrogenations6.1 A Detour: Copper(I)-Catalyzed Allylic Reductions, Catalytic Generation of Hydride Nucleophiles from H2 6.2 Trapping with Allylic Electrophiles: A Copper(I)-Catalyzed Hydro­allylation Reaction of Alkynes 6.3 Trapping with Aryl Iodides7 Conclusion

Mechanochemical solid state synthesis of copper(I)/NHC complexes with K3PO4

“…Noteworthy, the complex 5 was never evaluated in this reported reaction. Therefore, 5bm behaves similarly to other copper(I)/NHC complexes in this transformation [ 54 – 60 ]. The catalytic 1,2-reduction of carbonyl compounds is mainstay for copper(I)/NHC complexes [ 61 – 67 ], which is why we also tested 5bm in these transformations: The 1,2-reduction of benzaldehyde ( 14 ) and acetophenone ( 15 ) proceeded with good yields ( Scheme 3c ).…”

Rapid Enantiomeric Excess Measurements of Enantioisotopomers by Molecular Rotational Resonance Spectroscopy

“…Recently, precision deuteration reactions have emerged that incorporate deuterium or hydrogen in a highly controlled fashion across alkene or alkyne functionality in a small molecule (Scheme a). ,− Using transfer hydrodeuteration techniques, our research groups have developed an enantioselective reaction to make enantioisotopomers that are chiral by virtue of deuterium substitution (Scheme b) . Now, enantioisotopomers can be readily accessed in one step from achiral and readily accessible alkene precursors.…”

Precision Deuteration Using Cu-Catalyzed Transfer Hydrodeuteration to Access Small Molecules Deuterated at the Benzylic Position

“…A survey of previously reported [Cu–H]-catalyzed alkyne hydrofunctionalization reactions reveals that aryl- or alkyl-substituted terminal alkynes undergo hydrocupration with anti-Markovnikov regioselectivity as a result of Cu insertion at the less sterically hindered terminal position. − However, the increased steric hindrance of an internal aryl alkyne leads to a modest preference for the product resulting from Cu insertion α to the arene. ,− Prior density functional theory (DFT) calculations suggest that the demanding steric environment of the aryl substituent is counterbalanced by energetic stabilization provided by the overlap of the empty Cu d orbital with the aryl π system when Cu inserts at the α-carbon . With the goal of improving the regioselectivity of alkyne hydrocupration to achieve a minimum 9:1 r.r.…”

“…By doing so, the α- and β-deuterated styrene products E / Z - 2 and E / Z - 3 could be observed, resulting from semireduction of 1 (Scheme ). Given the prevalence of NHC–Cu catalysts in alkyne hydrofunctionalization reactions, ,− the IPr–Cu catalyst was evaluated first and found to be moderately regioselective for alkyne hydrometalation (3.8:1 r.r. ; entry 1).…”