Careful choice of the N-protecting group provides crucial conformational control, allowing ring-closure to the indole 3-position in the late stages of the synthesis of ajmaline alkaloids; the choice of protecting group and reducing agent can also provide access to either the natural or epi configuration at the indole 2-position. (C) 2013 Elsevier Ltd. All rights reserved.

Whilst cis:trans selectivity of about 4:1 can be obtained from Pictet–Spengler reactions between tryptophan methyl esters and aldehydes using conditions of kinetic control, much higher cis selectivity (>95:5) can be obtained when both the tryptophan derivative and the aldehyde possess a suitable π-system; preliminary results on the scope and limitations of this exceptional stereocontrol are presented in this Letter.