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Formation of Cyclic Ketals from Hydroxyalkyl Enol Ethers, a stereoelectronically controlled endo‐trig ‐cyclization process
Author(s) -
Deslongchamps Pierre,
Dory Yves L.,
Li Shigui
Publication year - 1996
Publication title -
helvetica chimica acta
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.74
H-Index - 82
eISSN - 1522-2675
pISSN - 0018-019X
DOI - 10.1002/hlca.19960790106
Subject(s) - chemistry , enol , hydrolysis , stereochemistry , intramolecular force , intermolecular force , medicinal chemistry , radical cyclization , ring (chemistry) , ring strain , catalysis , organic chemistry , molecule
Acid‐catalyzed cyclic ketal formation vs. hydrolysis of a series of hydroxyalkyl cyclic enol ethers in the presence of 1 equiv. of H 2 O, and acid‐catalyzed cyclic‐ketal formation (same ketals as above) vs. methanolysis of a series of mixed pent‐4‐enyl hydroxyalkyl ketals with N ‐bromosuccinimide in the presence of 4 equiv. of MeOH led to the same result: the intramolecular cyclization processes occur at similar rates as the intermolecular H 2 O or MeOH attacks independently of the size of the rings formed (five‐, six‐, or seven‐membered), by cyclizations. These results can be explained by the facts that, due to stereoelectronic effects which impose a torsional strain to the sp 2 hybridized O‐atom, the cyclization activation enthalpy decreases, as the length of the hydroxyalkyl chain increase (ease of cyclization: 7 > 6 > 5), whereas the entropy factor favors the cyclization in the reverse fashion (ease of cyclization: 5 > 6 > 7). The various reaction pathways have been examined using the semi‐empirical Hamiltonian AM1, and the results obtained confirm that large‐ring formation is enthalpically much favored over the cyclization processes leading to small rings (ease of cyclization: 7 > 6 > 5).