Mechanochemistry as an emerging tool for molecular synthesis: what can it offer?

Abstract

Mechanochemistry is becoming more widespread as a technique for molecular synthesis with new mechanochemical reactions being discovered at increasing frequency. Whilst mechanochemical methods are solvent free and can therefore lead to improved sustainability metrics, it is more likely that the significant differences between reaction outcomes, reaction selectivities and reduced reaction times will make it a technique of interest to synthetic chemists. Herein, we provide an overview of mechanochemistry reaction examples, with 'direct' comparators to solvent based reactions, which collectively seemingly show that solid state grinding can lead to reduced reaction times, different reaction outcomes in product selectivity and in some instances different reaction products, including products not accessible in solution.

Scheme 1. Examples of equipment used for mechanochemical reactions and key parameters. (a & c) Reproduced with permission from Retsch, (b) reproduced with permission from FormTech Scientific. (d) Reproduced with permission from Prof Stuart James and RSC.

Scheme 2. Formation of Cu–NHC complexes; Lamaty and co-workers.

Scheme 3. Palladacycle synthesis; Ćurić and co-workers.

Scheme 4. C–H amidation of benzamides; Bolm and co-workers.

Scheme 5. Oxidative C–H/C–H coupling; Xu and co-workers.

Scheme 6. Suzuki–Miyaura cross coupling; Su and co-workers.

Scheme 7. Fluorination of 1,3-diketones; Browne and co-workers.

Scheme 8. Enantioselective fluorination of β-ketoesters; Xu and co-workers.

Scheme 9. Proline catalysed enantioselective aldol reaction; Bolm and co-workers.

Scheme 10. N-Alkylation of bridged cyclam and cyclen derivatives; Archibald and coworkers.

Scheme 11. Oxidation of lignin-like methoxylated aromatics; Anastas, Crabtree, Hazari and co-workers.

Scheme 12. Oxidative halogenation of Re(i) complexes; Friščić and co-workers.

Scheme 13. Disulfide metathesis; Friščić and co-workers.

Scheme 14. Synthesis of adamantoid cyclophosphazenes; García and co-workers.

Scheme 15. Nickel catalysed cyclotri/tetra-merisation of alkynes; Guan, Mack and co-workers.

Scheme 16. Palladium catalysed oxidative coupling of indoles and acrylates; Su and co-workers.

Scheme 17. Reaction of anilines with bis(benzotriazolyl)methanethiones and isolation of intermediate; Friščić and co-workers.

Scheme 18. Dimerisation of fullerene; Komatsu and co-workers.

Scheme 19. Fullerene functionalisation; Wang and co-workers.

Scheme 20. Synthesis of N-sulfonylguanidines; Friščić and co-workers.

Scheme 21. Iron catalysed cross dehydrogenative coupling; Su and co-workers.

Scheme 22. Synthesis of unsolvated trisallylaluminium complex; Hanusa and co-workers.

Scheme 23. Synthesis of extended iptycenes; Swager and co-workers.

Joseph L. Howard

Qun Cao

Duncan L. Browne