Elusive 6-exo-Hydroxybicyclo[2.2.2]octan-2-ones from the Corresponding Acetates by Methanolysis in the Presence of CH₃ONa/La(OTf)₃

Abstract

[reaction: see text] A series of 6-exo-acetoxybicyclo[2.2.2]octan-2-ones were converted into the corresponding 6-exo-hydroxybicyclo[2.2.2]octan-2-ones by methanolysis in the presence of CH(3)ONa/La(OTf)(3). Under the given conditions, epimerization at C(6) of the latter led in the least favorable cases only to traces of the more stable 6-endo-hydroxybicyclo[2.2.2]octan-2-ones. This procedure, when combined with the described conversion of easily available 6-endo-hydroxybicyclo[2.2.2]octan-2-ones into the corresponding 6-exo-acetoxy derivatives, provides a convenient route to elusive 6-exo-hydroxybicyclo[2.2.2]octan-2-ones. Applications to total synthesis are shown and envisaged.

(+)-Podocarpic Acid as Chiral Template in the Synthesis of Aphidicolane, Stemodane and Stemarane Diterpenoids †

“…(+)-Podocarpic acid (4) was also converted into (+)-aphidicol-15-ene (36) [51] and into the Stemodia chilensis tetracyclic diterpenoid (+)-19-acetoxystemodan-12-ol (2f) allowing confirmation of the structure attributed to the latter only on the basis of NMR experiments [54]. (+)-Podocarpic acid (4) was then extensively used in the work which led to the synthesis of (+)-stemar-13-ene (57) and (+)-18-deoxystemarin (3b) [55,56,59,60,62]. (+)-Podocarpic acid (4) was also converted into (+)-2-deoxyoryzalexin S (66) [69].…”

“…Later, in view of a methodology [58] by which esters are cleaved in the presence CH 3 ONa/La(OTf) 3 at neutral pH, thus ensuring no epimerization at HO-C(12), the desulphurization/debenzoylation steps could be reversed [59]. Later, in view of a methodology [58] by which esters are cleaved in the presence CH3ONa/La(OTf)3 at neutral pH, thus ensuring no epimerization at HO-C(12), the desulphurization/debenzoylation steps could be reversed [59].…”

“…Later, in view of a methodology [58] by which esters are cleaved in the presence CH3ONa/La(OTf)3 at neutral pH, thus ensuring no epimerization at HO-C(12), the desulphurization/debenzoylation steps could be reversed [59].…”

“…This solution is based on the existing endo/exo equilibrium under acidic conditions between 1-methyl-6-hydroxybicyclo[2.2.2]octan-2-ones (Scheme 12a) and on the acid catalyzed rearrangement of 1-methyl-6-hydroxybicyclo[2.2.2]octan-2-ones to 4-methylbicyclo[3.2.1]oct-3-en-6-ones (Scheme 12b) described in 2005 within the framework of a study on the reactivity of isotwistanes [61]. Later, in view of a methodology [58] by which esters are cleaved in the presence CH3ONa/La(OTf)3 at neutral pH, thus ensuring no epimerization at HO-C(12), the desulphurization/debenzoylation steps could be reversed [59]. Thus a 7:3 endo/exo mixture of hydroxydithioacetals 41, prepared from 33 by the action of 1,2-ethanedithiol in the presence of BF3 Et2O, was submitted to equilibration with TsOH in benzene.…”

Synthesis of (+)‐13‐Stemarene and (+)‐18‐Deoxystemarin: Expeditious Preparation of the Key 6‐exo‐Hydroxybicyclo[2.2.2]octan‐2‐one Ethylene Dithioacetal

“…Compounds 1 and 2b were efficiently prepared from the corresponding 6-exohydroxybicyclo[2.2.2]octan-2-ones 8 and 9b by thioacetalization with 1,2-ethanedithiol in the presence of BF 3 · Et 2 O [2] [6]. Given that 6-exo-hydroxybicyclo[2.2.2]octan-2-ones of the type of 8 and 9b are the minor products (endo/exo 85 : 15) of the intramolecular aldol condensation of a 3-oxocyclohexaneacetaldehyde [7] [8] (Scheme 2), the efficiency of the synthesis of stemarane diterpenoids, by this approach,…”