Trimethylsilyl‐Protected Alkynes as Selective Cross‐Coupling Partners in Titanium‐Catalyzed [2+2+1] Pyrrole Synthesis

• Published in: Angewandte Chemie International Edition Vol. 57; no. 21; pp. 6090 - 6094
• Main Authors: Chiu, Hsin‐Chun, Tonks, Ian A.
• Format: Journal Article
• Language: English
• Published: WEINHEIM Wiley 22.05.2018; Wiley Subscription Services, Inc
• Edition: International ed. in English
• Subjects: Alkynes; Alkynes - chemistry; Catalysis; Chemical reactions; Chemical synthesis; Chemistry; Chemistry, Multidisciplinary; Coupling; cycloaddition; Cycloaddition Reaction; Molecular Structure; multicomponent reactions; Physical Sciences; Pyrroles; Pyrroles - chemical synthesis; Pyrroles - chemistry; Science & Technology; Titanium; Titanium - chemistry; Trimethylsilyl Compounds - chemistry; multicomponent reactions; PAUSON-KHAND REACTION; HYDROBORATION; titanium; REGIOSELECTIVE REACTIONS; alkynes; HYPERVALENT SILOXANE DERIVATIVES; COMPLEXES; CASCADE; HYDROAMINATION; pyrroles; cycloaddition; BICYCLIZATION; CYCLIZATION; ACCESS
• ISSN: 1433-7851; 1521-3773
• DOI: 10.1002/anie.201800595

Trimethylsilyl (TMS)‐protected alkynes served as selective alkyne cross‐coupling partners in titanium‐catalyzed [2+2+1] pyrrole synthesis. Reactions of TMS‐protected alkynes with internal alkynes and azobenzene under the catalysis of titanium imido complexes yielded pentasubstituted 2‐TMS‐pyrroles with greater than 90 % selectivity over the other nine possible pyrrole products. The steric and electronic effects of the TMS group were both identified to play key roles in this highly selective pyrrole synthesis. This strategy provides a convenient method to synthesize multisubstituted pyrroles as well as an entry point for further pyrrole diversification through facile modification of the resulting 2‐silyl pyrrole products, as demonstrated through a short formal synthesis of the marine natural product lamellarin R. E Pluribus Unum: The use of trialkylsilyl‐protected alkynes as substrates enabled highly chemo‐ and regioselective reactions in titanium‐catalyzed [2+2+1] multicomponent pyrrole synthesis (see scheme). The resulting pentasubstituted 2‐silyl pyrroles were formed with high selectivity over the other nine possible pyrrole products.