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Optimising Stereoselectivity in Intramolecular Diels–Alder Reactions of Pentadienyl Acrylates: Synthetic and Computational Investigations into the “Steric Directing Group” Approach
Author(s) -
Cayzer Tory N.,
Wong Leon S.M.,
Turner Peter,
PaddonRow Michael N.,
Sherburn Michael S.
Publication year - 2002
Publication title -
chemistry – a european journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.687
H-Index - 242
eISSN - 1521-3765
pISSN - 0947-6539
DOI - 10.1002/1521-3765(20020201)8:3<739::aid-chem739>3.0.co;2-1
Subject(s) - intramolecular force , steric effects , stereoselectivity , chemistry , substituent , cycloaddition , selectivity , diene , medicinal chemistry , stereochemistry , computational chemistry , organic chemistry , catalysis , natural rubber
Experimental conditions for the intramolecular cycloaddition of four related pentadienyl acrylates 3, 4, 5 and 6 are reported. In contrast with several previous reports, pentadienyl acrylates do undergo synthetically useful intramolecular Diels–Alder reactions: 3, 4, 5 and 6 cyclise at reasonable rates at temperatures of 132–180 °C at atmospheric pressure in moderate to good yields. The stereochemical outcome of each of these reactions was accurately measured and the results are in good agreement with transition structure populations predicted using B3LYP/6‐31+G(d) theory. The parent system 3 cyclises with moderate endo selectivity; the presence of either a C5‐methyl substituent or a C3‐bromine atom results in a slight shift towards the trans ‐fused exo stereoisomer but—overall—a less selective reaction. The presence of both C3‐Br and C5‐CH 3 substituents results in a marked improvement in stereoselectivity with the exo , lk ‐product predominating. Interpretation of B3LYP/6‐31+G(d) transition structures allows insights into the improvement in stereoselectivity obtained by incorporating a removable “steric directing group” into a 5‐methyl‐1,3,8‐nonatriene precursor.