Heteroatom-substituted alkynes in catalysis

We have been exploring the use of heteroatom (N, O, S)-substituted alkynes as enabling tools for reaction discovery and as the basis for rapid entry into heterocyclic structures.


These electron-rich alkynes are superb substrates for in gold catalysis, reacting via gold keteniminium species. These reactive electrophiles can be combined with a variety of nucleophiles to achieve regiospecific addition across the triple bond. We have been particularly interested in their use as precursors to carbenoid reactivity in complexity-building cascade processes, across both intermolecular and intramolecular processes. We have triggered carbenoid formation by oxidation, CH insertion and nitrenoid-based processes. For some key references see:

1,2-N-Migration in a Gold-Catalysed Synthesis of Functionalised Indenes by the 1,1-Carboalkoxylation of Ynamides; H. V. Adcock, T. Langer, P. W. Davies,* Chem. Eur. J. 2014, 20, 7262-7266.

Intermolecular and selective synthesis of 2,4,5-trisubstituted oxazoles by a gold-catalysed formal [3+2] cycloaddition; P. W. Davies,* A. Cremonesi, L. Dumitrescu, Angew. Chem. Int. Ed. 2011, 38, 8931-8935.

Oxidation reactions: In combination with a nucleophilic oxidant, gold catalysed reactions of ynamides can be used to access alpha-amido gold carbene reactivity patterns. Since introducing this reactivity approach with ynamides, we have used it to generate a range of reactions, particularly those giving rapid entry into lactam motifs. For key references see:

A Gold Carbene Manifold to Prepare Fused γ‐Lactams by Oxidative Cyclisation of Ynamides, F. Sanchez-Cantalejo,  J. D. Priest, P. W. Davies,* Chem. Eur. J. 2018, 24, 17215-17219.

Site-specific introduction of gold-carbenoids by intermolecular oxidation of ynamides or ynol ethers; P. W. Davies,* A. Cremonesi, N. Martin, Chem. Commun. 2011, 47, 379-381.

Diverting reaction pathways: By replacing an alkyne with an ynamide we can change the reaction pathways accessed using this to achieve new transformations. By this way we showed the first example of a 1,2-nitrogen migration onto a gold carbene and the generation of sp3-sp3 systems by a formal CH insertion of an ynamide. See:

Gold-catalysed cycloisomerisation of ynamides to access 2,2-disubstituted tetrahydrothiophene motifs, P. Heer Kaur and P. W. Davies* Synlett, 2021, 32, 897-900.

Divergent C-H Insertion-Cyclization Cascades of N-Allyl Ynamides; H. V. Adcock, E. Chatzopoulou, P. W. Davies* Angew. Chem. Int. Ed. 2015, 54, 15525-15529. 

1,2-N-Migration in a Gold-Catalysed Synthesis of Functionalised Indenes by the 1,1-Carboalkoxylation of Ynamides; H. V. Adcock, T. Langer, P. W. Davies,* Chem. Eur. J. 2014, 20, 7262-7266.

Alkynyl thioethers

A growing area of interest in the group concerns the use of sulfur substitution in alkynes. We showed that these species, far from poisoning gold catalysts actually enhance reactivity in some gold catalysed processes and that there is also an intriguing regiocontrolling processes. We are exploring the underlying aspects of this reactivity whilst also exploring the potential to generate efficient new synthetic methods. See:

Gold(I)-Catalyzed Synthesis of 3-Sulfenyl Pyrroles and Indoles by a Regioselective Annulation of Alkynyl Thioethers, P. E. Simm, P. Sekar, J. Richardson, P. W. Davies* ACS Catalysis, 2021, 6357–6362.

Sulfenyl Ynamides in Gold Catalysis: Synthesis of Oxo-functionalised 4-Aminoimidazolyl Fused Compounds by Intermolecular Annulation Reactions, E. M. Arce, S. G. Lamont, P. W. Davies,* Adv. Synth. Catal. 2020, 362, 2503-2509.

Alkynyl thioethers in gold-catalysed annulations to form oxazoles, R. J. Reddy, M. P. Ball-Jones, P. W. Davies,* Angew. Chem. Int. Ed. 2017, 56, 13310-13313.

Alkynyl sulfoxides

We have shown that an alkynyl sulfoxides can be used to access desirable carbene substitution patterns that had proven previously elusive, and used this to access novel bridged bicyclic motifs:

Alkynyl sulfoxides as α-sulfinyl carbene equivalents: Gold-catalysed oxidative cyclopropanation, M. J. Barrett,  G. F. Khan, P. W. Davies,*  R. S. Grainger* Chem. Commun. 2017, 53, 5733-5736.