Abstract
A novel method for C—H functionalization of heteroaromatic rings by using continuous-flow reactors is reported. Direct alkylation reactions were investigated under heterogeneous catalytic conditions using simple transition metal catalysts at elevated temperature and pressure. As a model reaction, the alkylation of indole was attempted using cheap Raney® Nickel catalyst. Alcohols served both as alkylating agent and as reaction media. The targeted 3-alkyl-indoles were obtained in moderate to good yield with reasonable selectivity. Transient protection on the N-atom increased the selectivity up to 80%. The scope and limitations were also investigated. In summary, direct alkylation with alcohols represents a rapid (residence time of <1 min) and traceless process with high atom economy (88–92%, in those cases where transient protection was not applied).
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Sipőcz, T., Lengyel, L., Sipos, G. et al. Regioselective Catalytic Alkylation of N-Heterocycles in Continuous Flow. J Flow Chem 6, 117–122 (2016). https://doi.org/10.1556/1846.2015.00030
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DOI: https://doi.org/10.1556/1846.2015.00030