Premium
TADDOL‐Promoted Enantioselective Intramolecular Diels–Alder Reactions of 1,7,9‐Decatrien‐3‐ones to Octalin Derivatives
Author(s) -
Andrä Michal Sascha,
Thiemermann née Suhrbier Jutta,
Schnaubelt Jürgen,
Lentz Dieter,
Zimmer Reinhold,
Reissig HansUlrich
Publication year - 2017
Publication title -
european journal of organic chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.825
H-Index - 155
eISSN - 1099-0690
pISSN - 1434-193X
DOI - 10.1002/ejoc.201601068
Subject(s) - chemistry , enantiopure drug , enantioselective synthesis , intramolecular force , enantiomer , stereochemistry , absolute configuration , diels–alder reaction , medicinal chemistry , organic chemistry , catalysis
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.