In situ epoxide generation by dimethyldioxirane oxidation and the use of epichlorohydrin in the flow synthesis of a library of β-amino alcohols

Peter J. Cossar, Jennifer R. Baker, Nicholas Cain, Adam McCluskey (Lead / Corresponding author)

Research output: Contribution to journalArticlepeer-review

15 Citations (Scopus)
7 Downloads (Pure)

Abstract

The flow coupling of epichlorohydrin with substituted phenols, while efficient, limits the nature of the epoxide available for the development of focused libraries of β-amino alcohols. This limitation was encountered in the production of analogues of 1-(4-nitrophenoxy)-3-((2-((4-(trifluoromethyl)pyrimidin-2-yl) amino)ethyl)amino)propan-2-ol 1, a potential antibiotic lead. The in situ (flow) generation of dimethyldoxirane (DMDO) and subsequent flow olefin epoxidation abrogates this limitation and afforded facile access to structurally diverse β-amino alcohols. Analogues of 1 were readily accessed either via (i) a flow/microwave hybrid approach, or (ii) a sequential flow approach. Key steps were the in situ generation of DMDO, with olefin epoxidation in typically good yields and a flow-mediated ring opening aminolysis to form an expanded library of β-amino alcohols 1 and 10a–18g, resulting in modest (11a, 21%) to excellent (12g, 80%) yields. Alternatively flow coupling of epichlorohydrin with phenols 4a–4m (22%–89%) and a Bi(OTf)3 catalysed microwave ring opening with amines afforded a select range of β-amino alcohols, but with lower levels of aminolysis regiocontrol than the sequential flow approach.

Original languageEnglish
Article number171190
Number of pages22
JournalRoyal Society Open Science
Volume5
Issue number4
DOIs
Publication statusPublished - 4 Apr 2018

Keywords

  • Dimethyl dioxirane
  • Epoxide
  • Flow chemistry
  • Microwave
  • β-amino alcohols

ASJC Scopus subject areas

  • General

Fingerprint

Dive into the research topics of 'In situ epoxide generation by dimethyldioxirane oxidation and the use of epichlorohydrin in the flow synthesis of a library of β-amino alcohols'. Together they form a unique fingerprint.

Cite this