Asymmetric Hydroalkoxylation of Non-Activated Alkenes: Titanium-Catalyzed Cycloisomerization of Allylphenols at High Temperatures

• Published in: Angewandte Chemie (International ed.) Vol. 54; no. 13; pp. 4014 - 4017
• Main Authors: Schlüter, Johannes, Blazejak, Max, Boeck, Florian, Hintermann, Lukas
• Format: Journal Article
• Language: English
• Published: Weinheim WILEY-VCH Verlag 23.03.2015; WILEY‐VCH Verlag; Wiley; Wiley Subscription Services, Inc
• Edition: International ed. in English
• Subjects: Alkenes; asymmetric catalysis; Asymmetry; Catalysis; Catalysts; Chemistry; Chemistry, Multidisciplinary; Derivatives; heterocycles; Isomerization; Ligands; microwave chemistry; Phenols; Physical Sciences; Science & Technology; titanium; FUNCTIONALIZATION; ALCOHOL; heterocycles; microwave chemistry; titanium; OLEFINS; asymmetric catalysis; TRIFLIC ACID; HYDROAMINATION; alkenes; INTRAMOLECULAR HYDROALKOXYLATION; HYDROETHERIFICATION
• ISSN: 1433-7851; 1521-3773
• DOI: 10.1002/anie.201409252

The asymmetric catalytic addition of alcohols (phenols) to non‐activated alkenes has been realized through the cycloisomerization of 2‐allylphenols to 2‐methyl‐2,3‐dihydrobenzofurans (2‐methylcoumarans). The reaction was catalyzed by a chiral titanium–carboxylate complex at uncommonly high temperatures for asymmetric catalytic reactions. The catalyst was generated by mixing titanium isopropoxide, the chiral ligand (aS)‐1‐(2‐methoxy‐1‐naphthyl)‐2‐naphthoic acid or its derivatives, and a co‐catalytic amount of water in a ratio of 1:1:1 (5 mol % each). This homogeneous thermal catalysis (HOT‐CAT) gave various (S)‐2‐methylcoumarans with yields of up to 90 % and in up to 85 % ee at 240 °C, and in 87 % ee at 220 °C. Best served hot and fast: The metal‐catalyzed asymmetric hydroalkoxylation of non‐activated alkenes was catalyzed by a chiral titanium–carboxylate complex that requires co‐catalytic amounts of water to reach full activity. This homogeneous thermal catalysis (HOT‐CAT) proceeds at remarkably high temperatures (above 220 °C, typically 240 °C) and produces 2‐methylcoumarans from 2‐allylphenols in up to 90 % yield and 87 % ee.