- Title
- In situ epoxide generation by dimethyldioxirane oxidation and the use of epichlorohydrin in the flow synthesis of a library of beta-amino alcohols
- Creator
- Cossar, Peter J.; Baker, Jennifer R.; Cain, Nicholas; McCluskey, Adam
- Relation
- Royal Society Open Science Vol. 5, Issue 4, no. 171190
- Publisher Link
- http://dx.doi.org/10.1098/rsos.171190
- Publisher
- Royal Society Publishing
- Resource Type
- journal article
- Date
- 2018
- Description
- 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.
- Subject
- dimethyl dioxirane; epoxide; flow chemistry; β-amino alcohols; microwave
- Identifier
- http://hdl.handle.net/1959.13/1412601
- Identifier
- uon:36503
- Identifier
- ISSN:2054-5703
- Rights
- © 2018 The Authors. Published by the Royal Society under the terms of the Creative Commons Attribution License http://creativecommons.org/licenses/by/4.0/, which permits unrestricted use, provided the original author and source are credited.
- Language
- eng
- Full Text
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