The domino cycloaddition/N-acyliminium ion cyclization cascade

A Review on Recent Developments in Syntheses of the Post-Secodine Indole Alkaloids. Part I: The Primary Alkaloid Types

“…Thus, while the lactam 229a and amide 229b yielded only the unwanted tetracycles 231 and amide 229c gave rise to a mixture of 230c (23%) and 231c (20%), the same reaction of the amine 229d led exclusively to the desired amine 230d (54%). Encouraged by these results, the authors addressed the synthesis of (±)-20-desethylibophyllidine 68,69 (140). The crucial indole formation from amine ketone 229e, accesible from O-methyltyramine in three steps (54% overall), proceeded as expected and gave the tetracyclic indole 230e as a mixture of sulfur isomers (60% yield), which was carbamoylated with Mander's reagent (78%).…”

“…This protocol was used by Bonjoch et al as a final step in their synthesis of (±)-desethylibophyllidine 58,68,69 (140), Scheme 22 (cf. Chapter 3.1.4).…”

“…The Barcelona group have reported on two alternative syntheses of (±)-20-desethylibophyllidine (140), which are based on transannular cyclisations of the medium-sized intermediates (referred to as "a criss-cross-type annulation"), Scheme 22 57,58 . The synthesis commences with the quaternisation of 4-(dimethoxymethyl)pyridine with tryptophyl bromide.…”

“…An efficient radical approach to the synthesis of the spirocyclic indoline 382 was reported by French authors 140 The Grignard reagent derived from bromide 384 was converted in 5 steps to cyclohexenone 385. The Luche reduction then provided alcohol 386a with high diastereoselectivity (95:5); whereas its actual stereochemistry was not known, it was shown later that its epimer 386b obtained by the Mitsunobu protocol (100%) gave much better yield in a radical cyclisation (vide infra).…”

Synthesis of isoquinolines through the coupling of Fischer carbene complexes with o-alkynylpyridine carbonyl derivatives

“…Heterocyclic o-quinodimethanes and their stable analogs have been utilized in this regard [32][33][34][35][36]. On the other hand, the use of heteroaromatic isobenzofurans [37][38][39] as dienes is emerging as a powerful alternative to the above method. Furo [3,4-c]pyridine intermediate is one of the interesting member of the heteroaromatic isobenzofurans and important building block for the synthesis of isoquinoline derivatives such as heterocyclic analogues of 1-arylnaphthalene lignans [32].…”