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Indole–Indole Ullmann Cross‐Coupling for C Ar –N Bond Formation: Total Synthesis of (–)‐Aspergilazine A
Author(s) -
Alonso Iago,
Alvarez Rosana,
de Lera Ángel R.
Publication year - 2017
Publication title -
european journal of organic chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.825
H-Index - 155
eISSN - 1099-0690
pISSN - 1434-193X
DOI - 10.1002/ejoc.201700842
Subject(s) - indole test , chemistry , negishi coupling , ullmann reaction , stereochemistry , amide , tryptophan , coupling reaction , copper , medicinal chemistry , catalysis , combinatorial chemistry , organic chemistry , amino acid , biochemistry
The copper‐catalyzed cross‐coupling reaction of indole and protected haloindoles (X = Br, I) by using CuI, N , N′ ‐dimethylethylenediamine, and K 2 CO 3 in dioxane at 130 °C afforded the corresponding bis‐indole products in generally high yields. Starting from the N1′–C6 bis‐indole positional isomer obtained by C Ar –N Ullmann coupling, a new synthesis of (–)‐aspergilazine A was completed. A bidirectional Negishi‐catalyzed cross‐coupling of the C3,C3′‐diiodo N1′–C6 bis‐indole derivative was used to construct the corresponding bis‐tryptophan. Amide formation with l ‐proline and thermally induced deprotection/cyclization completed the diketopiperazine units of (–)‐aspergilazine A.