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

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.