TADDOL‐Promoted Enantioselective Intramolecular Diels–Alder Reactions of 1,7,9‐Decatrien‐3‐ones to Octalin Derivatives

Abstract

The diastereoselective and enantioselective intramolecular Diels–Alder reactions of 1,7,9‐decatrien‐3‐ones to cis‐ or trans‐octalin derivatives were systematically investigated in the presence of different Lewis acids and chiral ligands. The best cis‐selective promoter, consisting of diethylaluminum chloride and (R)‐1,1′‐bi‐2‐naphthol (BINOL), provided an enantiomeric excess (ee) of only 33 %. For the trans‐selective reactions, dichlorotitanium diisopropoxide was the best Lewis acid, and a 2‐naphthyl‐substituted (R,R)‐α,α,α′,α′‐tetraaryl‐1,3‐dioxolane‐4,5‐dimethanol ligand (TADDOL) furnished excellent diastereoselectivities and enantioselectivities in the range of 50–68 %. Subsequent reactions of a typical trans‐octalin derivative led to compounds, which enabled the determination of the absolute configuration of the favored enantiomer and a deduction of the involved reaction mechanism. Interpretation of the NMR shifts of the enantio‐enriched Mosher esters and an X‐ray structure analysis were the keys for this structural assignment. We could demonstrate that Mosher analyses do not necessarily rely on enantiopure samples.