Rhodium-catalysed enantioselective 1,4-conjugate additions to the phenyl backbone of indole Mark Power 1 , Dr Katrina Mackey 1 , Dr Douglas P. Kjell 2 and Dr Gerard P. McGlacken 1,3 1 School of Chemistry, University College Cork, Ireland, 2 Eli Lilly & Company, Indianapolis, USA 3 Synthesis & Solid State Pharmaceutical Centre (SSPC), University College Cork, Ireland The rhodium-catalysed 1,4-addition of aryl boronic acids to enones is a very useful methodology, especially when carried out in an asymmetric fashion. 1,2 While the range of Michael-acceptor-type substrates is large and versatile, the use of heterocyclic aryl boronic acids is rarely observed with only the occasional example of furan, thiophene or more recently pyridine being used in these reactions. 3 The functionalisation of indole is well documented at the C2/3 position, due to the innate reactivity of these positions on the pyrrole-type ring. 4 However, substitution of the phenyl backbone of indole is much less common and is to date, an unreported process for conjugate additions. Employing a rhodium catalyst and a cheap, easily accessible chiral ligand we have managed to perform conjugate additions to the carbocyclic backbone of indole in er s up to 97:3 and yields up to 86%. The reaction is performed at a mild temperature in an aqueous media. Not only have we designed a protocol to efficiently access novel indole-based structures, we have done so in an asymmetric fashion, obtaining high yields and in an aqueous solvent at room temperature. This methodology herein enables access to a new realm of chemical space for drug discovery given the ubiquity of the indole moiety as a pharmacophore. References 1. Org. Lett . 2014 , 16 , 5212-5215 2. Tetrahedron Asymmetry 2016 , 27 , 513-588
3. ACS Catal . 2022 , 12 , 2434-2440 4. RSC Adv . 2018 , 8 , 12069-12103
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