Synthesis directed towards trans-clerodanes employing an exo-selective Diels–Alder reaction as a key-step
A potential intermediate in the synthesis of several trans-clerodane natural products has been constructed employing a Diels–Alder reaction as a key-step. Two epimeric exo-adducts were formed in a 4:3 ratio in an EtAlCl2-mediated cycloaddition of O-silylated 2-vinylcyclohex-2-enol and N-tigloylisoxazolidinone. Both isomers were converted to the trans-clerodane intermediate in four steps; reductive removal of the oxazolidinone, followed by O-benzylation, removal of the silyl protecting group, and, finally, a Dess–Martin oxidation of the deprotected alcohol to the corresponding ketone. It was possible to transform both isomers from the cycloaddition into the final target, but the major isomer was converted at greater yields. An interesting discovery made during the work was that the desilylation demanded significantly different conditions depending on which isomer was deprotected. The fact that the cycloaddition not only resulted in an excellent exo-selectivity, but also that the alkene to a large extent approached from the least hindered side, opens the possibility for enantioselective synthesis of the target compound from (R) or (S) diene starting materials in the future.
KeywordsCycloaddition Natural products Oxazolidinone Stereoselective Terpenoid
The Research Council of Norway is gratefully acknowledged for financial support (Grant No. 209330) to JW and for partly financing the NMR instruments used. This work was also partly supported by the Research Council of Norway through the Norwegian NMR Platform, NNP (Grant No. 226244/F50).
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