Journal Article

Decarboxylative alkenylation

Knouse, Kyle W., Vokits, Benjamin, Qin, Tian, Wei, Fu-Liang, Bao, Deng-Hui, Eastgate, Martin D., Malins, Lara R., McClymont, Kyle S., Merchant, Rohan R., Zhou, Ting, Shaw, Scott A., Edwards, Jacob T., Baran, Phil S.

2017

Overview

Starting with alkyl carboxylic acids, a simple olefin synthesis using any substitution pattern or geometry, based on amide-bond synthesis with nickel- or iron-based catalysis, is described. Simplified olefin synthesis Olefins are ubiquitous functional groups in organic chemistry and are typically installed in small molecules by the formation of a carbon–carbon double bond. Here, Phil Baran and colleagues report a decarboxylative alkyl-vinyl cross-coupling that offers a cheap and simple route to olefins with defined geometry and substitution pattern. The nickel or iron catalysts extract carbon dioxide from the carboxylic acid, which is activated in a similar way to peptide-bond formation. The alkene is then attached with a vinyl zinc reagent. The authors exemplify their method by preparing more than 60 olefins and synthesizing 16 natural products. One such example offers a short route to macrocyclic polyketides from the commodity chemical diethyl tartrate. Olefin chemistry, through pericyclic reactions, polymerizations, oxidations, or reductions, has an essential role in the manipulation of organic matter 1 . Despite its importance, olefin synthesis still relies largely on chemistry introduced more than three decades ago, with metathesis 2 being the most recent addition. Here we describe a simple method of accessing olefins with any substitution pattern or geometry from one of the most ubiquitous and variegated building blocks of chemistry: alkyl carboxylic acids. The activating principles used in amide-bond synthesis can therefore be used, with nickel- or iron-based catalysis, to extract carbon dioxide from a carboxylic acid and economically replace it with an organozinc-derived olefin on a molar scale. We prepare more than 60 olefins across a range of substrate classes, and the ability to simplify retrosynthetic analysis is exemplified with the preparation of 16 different natural products across 10 different families.

• Publisher: Nature Publishing Group UK,Nature Publishing Group
• Subject: 639/638/403/933 / 639/638/403/977 / 639/638/77/888 / Alkenes / Alkenes - chemical synthesis / Alkenes - chemistry / Alkenes - classification / Amides - chemistry / Biological Products - chemical synthesis / Biological Products - chemistry / Biological Products - classification / Carbon dioxide / Carbon Dioxide - chemistry / Carbon Dioxide - isolation & purification / Carboxylic acids / Carboxylic Acids - chemistry / Catalysis / Chemical properties / Chemical reactions / Chemical synthesis / Chemistry / Humanities and Social Sciences / Hydrocarbons / Iron / Iron - chemistry / letter / Metathesis / multidisciplinary / Natural products / Nickel / Nickel - chemistry / Observations / Organic chemistry / Organic matter / Oxidation-Reduction / Polyketides - chemical synthesis / Polyketides - chemistry / Science / Substrate Specificity / Substrates / Tartrates - chemical synthesis / Tartrates - chemistry / Zinc - chemistry