Borylative Cyclisation of Alkynes Using BCl3

Abstract

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.

Date of Award	1 Aug 2017
Original language	English
Awarding Institution	The University of Manchester
Supervisor	Richard Layfield (Supervisor) & Michael Ingleson (Supervisor)