Boron trichloride, a cheap and commercially available Lewis acid, has been demonstrated to activate alkynes possessing appropriate nucleophiles, facilitating borylative cyclisation. This reaction furnishes polycyclic compounds possessing a new C(sp2)-B bond externally to the newly formed ring (through concomitant C-C and C-B bond formation). The RBCl2 intermediates generated from cyclisation were esterified with pinacol to furnish air/moisture stable boronic esters. This methodology has been applied to the following classes of starting materials: 1,4-disubstituted but-1-ynes (including N- and O- linked analogues), 2-alkynylanisoles, 2-alkynylthioanisoles and 1,2-bis(alkynyl)benzenes. Thus, borylated scaffolds such as dihydronaphthalenes, dihydroquinolines, 2H-chromenes, benzofurans, benzothiophenes, dibenzopentalenes and benzofulvenes have been synthesised. A variety of functionalities (e.g. amines, esters, nitriles) were tolerated by the reaction, with a number of substrates cyclised on either a gram scale, or under ambient conditions, demonstrating the robust nature of this methodology. An oxidation reaction with [Ph3C][BF4] was carried out on some of the borylated dihydronaphthalene compounds to obtain borylated naphthalenes. Suzuki-Miyaura cross-coupling reactions were carried out on certain borylated cycles to furnish new C-C bonds and generate analogues of established pharmaceuticals such as Nafoxidine or Raloxifene, demonstrating the synthetic value of these borylated cycles. Additionally, a one-pot borylative cyclisation/Suzuki-Miyaura cross-coupling reaction was also developed. Throughout this investigation, alternative reactivity has been observed when using BCl3 to activate certain alkynes, including intermolecular 1,2-trans-carboboration and a rare example of N- and O-directed 1,2-trans-haloboration. Additionally, multiple borylative cyclisations have been carried out on an appropriate alkyne to obtain a B-doped polyaromatic hydrocarbon (PAH), which has potential material-based applications.
| Identifer | oai:union.ndltd.org:bl.uk/oai:ethos.bl.uk:748027 |
| Date | January 2017 |
| Creators | Warner, Andrew |
| Contributors | Ingleson, Michael |
| Publisher | University of Manchester |
| Source Sets | Ethos UK |
| Detected Language | English |
| Type | Electronic Thesis or Dissertation |
| Source | https://www.research.manchester.ac.uk/portal/en/theses/borylative-cyclisation-of-alkynes-using-bcl3(7a4e56f3-e8c6-4c68-97ec-4596ef5e0ce2).html |
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