Iridium‐Catalyzed Asymmetric Allylic Aromatization Reaction

• Published in: Angewandte Chemie International Edition Vol. 58; no. 31; pp. 10493 - 10499
• Main Authors: Liu, Xi‐Jia, Zheng, Chao, Yang, Yi‐Han, Jin, Shicheng, You, Shu‐Li
• Format: Journal Article
• Language: English
• Published: WEINHEIM Wiley 29.07.2019; Wiley Subscription Services, Inc
• Edition: International ed. in English
• Subjects: allylic compounds; Aromatic compounds; asymmetric catalysis; Chemical reactions; Chemistry; Chemistry, Multidisciplinary; Equivalence; heterocycles; Heterocyclic compounds; Iridium; Nucleophiles; Physical Sciences; Science & Technology; Substitution reactions; synthetic methods; SUBSTITUTION; ENANTIOSELECTIVE SYNTHESIS; SYNERGISTIC IRIDIUM; ALLYLATION; ALPHA-AMINO-ACIDS; asymmetric catalysis; ALKYLATIONS; iridium; heterocycles; allylic compounds; ESTERS; DERIVATIVES; ENE; synthetic methods; DEAROMATIZATION
• ISSN: 1433-7851; 1521-3773
• DOI: 10.1002/anie.201904156

Described herein is an asymmetric allylic aromatization (AAAr) strategy that employs readily accessible equivalents of benzylic nucleophiles in iridium‐catalyzed allylic substitution reactions with the concomitant formation of aromatic rings by aromatization. The optimized reaction conditions involving a catalyst derived from a commercially available iridium precursor and the Carreira ligand are compatible with equivalents of benzylic nucleophiles derived from 4‐ or 5‐methyloxazoles, 5‐methylthiazoles, 4‐ or 5‐methylfurans, 2‐ or 3‐methylbenzofurans, 3‐methylbenzothiophene, 3‐methylindole, 1‐methylnaphthalene, and methylbenzene. This strategy provides straightforward accesses to valuable heterocyclic aromatic compounds, bearing a homobenzylic stereogenic center, in an enantiopure form and would be difficult to access otherwise. The versatility of the reaction was showcased by the further elaboration of the products into useful building blocks and a drug analogue. An asymmetric allylic aromatization (AAAr) strategy employs readily accessible equivalents of benzylic nucleophiles in iridium‐catalyzed allylic substitution reactions with the concomitant formation of aromatic rings. This strategy provides straightforward access to valuable heteroarenes, bearing a homobenzylic stereogenic center, in enantiopure form.