Dehydration reactions in polyfunctional natural products

• Published in: Natural product reports 2020-08, Vol.37 (8), p.143-164
• Main Authors: Hjerrild, Per, Tørring, Thomas, Poulsen, Thomas B
• Format: Article
• Language: English
• Subjects: Alcohol; Alcohols; Biological activity; Chemical reactions; Chemists; Dehydration; Functional groups; Natural products; State-of-the-art reviews; Substrates
• ISSN: 0265-0568; 1460-4752
• DOI: 10.1039/d0np00009d

Covering: up to 2020 In this review, we present state of the art methods for performing dehydration reactions in alcohol substrates to deliver alkene products. The dehydration of alcohols typically proceeds through activation of the alcoholic moiety to a nucleofugal species followed by a subsequent elimination step. While the alcohol is a quintessential functional group, selective dehydration of alcohols in complex molecular scaffolds has not been harnessed to allow molecular diversification strategies. We present the perspective of utilizing complex molecular compounds containing alcoholic functionalities to generate novel molecular constructs that impose on chemical space of characterized bioactivity. Nature inspires the direct and selective dehydration of alcohols in complex molecules and demonstrates a potential that has not yet been realized by chemical methodology. We present challenging substrates for direct and selective dehydration reactions and argue that chemical methodology solving the challenges presented will be valued by synthetic and natural product chemists alike. Here, we review methods for chemical dehydration of alcohols to alkenes and discuss the potential of late-stage functionalization by direct, site- and chemo-selective dehydration of complex molecular substrates.