Premium
Thermal Isomerization of Isoborneols and Dehydroisoborneols to New Chiral Building Blocks in Terpenoid Synthesis
Author(s) -
Rüedi Georg,
Hansen HansJürgen
Publication year - 2004
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.200490179
Subject(s) - chemistry , diradical , isomerization , regioselectivity , stereocenter , intramolecular force , flash vacuum pyrolysis , acetophenone , stereochemistry , alkene , medicinal chemistry , organic chemistry , singlet state , enantioselective synthesis , pyrolysis , catalysis , physics , nuclear physics , excited state
The substituted isoborneols 1a – 1g and 5,6‐dehydroisoborneols 6a – 6c , readily prepared in excellent yields from (+)‐camphor and (+)‐5,6‐dehydrocamphor ( 2 ) by aryl, vinyl, or alkyl Grignard addition in the presence of stoichiometric amounts of CeCl 3 , were thermally isomerized in a flow reactor system under DGPTI (dynamic gas‐phase thermo‐isomerization) conditions at temperatures between 480 and 630° to give the enantiomerically pure monocyclic carbonyl compounds 7a – 7d, 19a , b, 23 , and 24 . In all cases, product formation proceeded highly regio‐ as well as stereoselectively. The absolute configurations of the new stereogenic centers were determined by 1 H‐NOE measurements. DGPTI of the aryl substrates 1a – 1d is proposed to effect initial cleavage of the weakest single bond in the molecule under formation of a diradical intermediate state followed by intramolecular H‐abstraction to afford the acetophenone derivatives 7a – 7d . This reaction path was further supported by a 2 H‐labeling study showing the OH group to be the exclusive H‐source. In contrast, DGPTI of the vinyl substrates 1e and 6b allowed concerted retro ‐ene and oxy‐ Cope rearrangements. In the case of 5,6‐dehydro‐2‐phenylisoborneol ( 6a ), concomitant diradical and retro‐Diels – Alder reaction pathways could be observed. In addition, a new route to (+)‐ trans ‐ α ‐campholanic acid ( 9 ) and (+)‐ trans ‐ α ‐dihydrocampholytic acid ( 14 ) is presented by regioselective Baeyer – Villiger oxidation and subsequent hydrolysis of 7c and 7d , respectively.