Toward the Total Synthesis of Vinigrol: Synthesis of epi-C-8-Dihydrovinigrol

Abstract

Two approaches to vinigrol starting from the advanced tricyclic core 7 have been explored using as key intermediates epoxide 12 and diol 17. The preparation of the properly functionalized epoxide 12 has been achieved in a straightforward fashion. However, all attempts to prepare tertiary alcohol 14 by reductive opening of 12 failed. In alternative exploratory efforts to achieve the same goal, allylic alcohols 16 and 29 were prepared by regioselective dehydration of diol 17. Whereas endo-isomer 16 was found to be reluctant to undergo catalytic hydrogenation, the exo counterpart 29 led to the undesired isomer affording after hydrolysis epi-C-8-dihydrovinigrol 32.

Aiming for the Ideal Synthesis

“…The route suffers from four nonstrategic redox reactions and eight functional group interconversions, but only one protecting group manipulation was carried out. These concession steps are opposed by only seven construction steps and three strategic redox reactions, which results in the relatively low ideality of 43%. , Indeed, as will be seen in the following section, our work in the vinigrol arena prompted us to take a step back and question whether there might be a more efficient general strategy for assembling complex terpenes in the laboratory.…”

Special Issue on ‘Recent Advances in Computational Techniques for Biomedical Imaging’ International Journal for Numerical Methods in Engineering (NME)

“…Hanna and co‐workers were the first team to assemble the decahydro‐1,5‐butanonaphthalene skeleton of vinigrol 8a,b. Recently, this group completed the synthesis of epi‐C8‐dihydrovinigrol ( 9 ) using a remarkable oxy‐Cope rearrangement of triene 10 as the key transformation leading to the tricyclic core 8c. Njardarson and co‐workers recently reported an elegant dearomatization/DA reaction cascade to construct the carbocyclic skeleton 11 from simple fragments 12 and 13 9…”

Three‐Membered Heterocycles. Structure and Reactivity

“…For example, 2,6-ditert-butylpyridine was shown to give superior results in the case of certain allyl acetals (e.g., 322, Scheme 2.54) [372]. Bicarbonate [373] and phosphate [374] buffers are also frequently encountered in this context.…”