Science of Synthesis

Joule, J. A., Science of Synthesis Knowledge Updates, (2018) 2, 147.

There are hundreds of examples of reactions between 2-(1H-indol-3-yl)ethan-1-amines (tryptamines) and aldehydes producing 2,3,4,9-tetrahydro-1H-pyrido[3,4-b]indoles (e.g., ‌438‌ and ‌439‌). Schemes 163[‌190‌] and 164[‌191‌] detail just two examples, chosen at random, both using tryptamine (‌436‌) itself and an aryl aldehyde in one case and an alkyl aldehyde in the other. The sequence involves formation of an iminium species (e.g., ‌437‌) and then intramolecular electrophilic attack on the indole 2-position (an intramolecular Mannich reaction) and exactly parallels the Pictet–Spengler reaction to prepare 1,2,3,4-tetrahydro­isoquinolines from 2-arylethan-1-amines and aldehydes [see Science of Synthesis, Vol. 15, (Section 15.5.1.1.1.2.3.2)].

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Meeeee 8-Meeeee-8-(eeeeeeee-8-ee)-8M-eeeeee[8,8-e]eeeeee-8-eeeeeeeeeee (‌888‌, M8 = M8 = M8 = M8 = M8 = M8 = M8 = M); Meeeeee Meeeeeeee:[‌888‌]

M eeee ee eeeeeeeee-8-eeeeeeeeeeee (‌888‌, M8 = M8 = M8 = M8 = M; 888 ee, 8 eeee) ee eeeeeee (8 eM) eee eeeee eeee eeeeeeee eee eeeee eeeee ee e eeee ee eeeeeeeeee eeeeee eeeee ‌888‌ (M8 = M8 = M8 = M; 888 ee, 8 eeee) ee eeeeeee (8 eM). MMMM (88 ee, 8.8 eeee) eee eeeee eee eee eeeeeee eee eeeeee ee eeeeee eee eeee eeeeeee eee 8.8 e ee eeee eeeeeeeeeee. M eeeeee eeeeeeeeeee eeeeeeee ee eeeeeee eee eee eeeeeeeee ee eeeeeeeeee. Mee eeeeeeee eee eeeeeeeeeeee eee eee eeeeeeee eee eee eeeeeeeee ee eeeee eeeeee eeeeeeeeeeeeee (MM8Me8) ee eeeeeee eeee eeeeee eeeee; eeeee eeeee: 888 ee (88%); ee 888–888 °M.

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