Nikolaos Papaioannou, M. Fray, Andreas Rennhack
Aug 18, 2020
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0
Influential Citations
5
Citations
Journal
The Journal of organic chemistry
Abstract
The synthesis of a series of 2-amidomethylated pyridines (3-8) was investigated, starting from 4-chloro-3-fluoropyridine. Kinetic deprotonation at -75 oC followed by reaction with DMF gave 2-formyl-4-chloro-3-fluoropyridine 10 regioselectively, which was converted to 2-aminomethyl analogue 1 via sulfinamide 2. Alternatively, Minisci-type amidomethylation under Ag+/persulfate or photo-redox mediated conditions using a series of amino-acid derivatives gave (3-8, 19 and 34) in 30-74% yield and isomer ratios in the range 6.7:1 to >50:1. The latter methods gave similar overall yields to the deprotonation approach, but were shorter and more amenable to scale-up. In particular, N-Boc analogue (8) was obtained in a single step. The amidomethylations of another six 3-fluoropyridines under the photo-redox conditions were briefly examined.