Competitive Intramolecular Diels - Alder Reactions of bis-α,β-Unsaturated Ester Derivatives of Enzymatically Derived and Enantiopure cis-1,2-Dihydrocatechols. Enantiodivergent Synthesis of Monochiral Bicyclo[2.2.2]oct-2-enes

Abstract

bis-Crotonate and related α,β-unsaturated ester derivatives of readily available and enantiomerically pure cis-1,2-dihydrocatechols engage, upon heating in refluxing toluene, in two competitive intramolecular Diels–Alder reactions to give varying mixtures of chromatographically separable and pseudo-enantiomeric bicyclo[2.2.2]oct-2-enes. Such adducts, many of which have been characterized by single-crystal X-ray analysis, are likely to serve as useful building blocks in natural products synthesis.

Studies on the Photochemical Rearrangements of Enantiomerically Pure, Polysubstituted, and Variously Annulated Bicyclo[2.2.2]octenones

“…The residue thus obtained was subjected to flash column chromatography to give, after concentration of the appropriate fractions ( R f = 0.5 in 1:4 v/v ethyl acetate/40–60 petroleum ether), compound 14 (4.04 g, 81%) as a pale-yellow oil. The spectral data recorded on this material matched those reported previously …”

“…Concentration of fraction A [ R f = 0.2(5) in 1:4 v/v ethyl acetate/40–60 petroleum ether] afforded compound 16 (1.62 g, 40%) as a white, crystalline solid, mp = 45–47 °C. The spectral data recorded on this material matched those reported previously …”

“…Specific Chemical Transformations. (2a′R,3S,4S,4aR)-3,4-Dihydroxy-2b-methylhexahydrocyclopropa[cd]pentalen-2(1H)-one (8). A deoxygenated solution of compound 6 7 (94 mg, 0.56 mmol) and acetophenone (90 μL, 0.77 mmol) in acetone (100 mL) maintained under nitrogen was subjected to irradiation with a Hanovia 450 W medium-pressure mercury-vapor lamp for 2.5 h and then cooled and concentrated under reduced pressure to give a yellow oil.…”

“…The spectral data recorded on this material matched those reported previously. 8 (1S,2R)-3-Methylcyclohexa-3,5-diene-1,2-diyl (2E,2′E)-Bis(4methylpent-2-enoate) (15). A magnetically stirred solution of (1S,2R)-3-methylcyclohexa-3,5-diene-1,2-diol (5) (2.40 g, 19.02 mmol) in dry THF (284 mL) was cooled to −78 °C and then treated, dropwise over 0.5 h, with n-BuLi (12.5 mL of a 1.6 M solution in hexane, 20.0 mmol).…”

“…Establishing the impact of various modes of ring-fusion on the capacity of bicyclo [2.2.2]octenones to engage in oxa-di-π-methane and 1,3-acyl migration reactions was another topic of interest. Therefore, building upon our earlier studies 8 on the assembly of the relevant frameworks through the intramolecular Diels−Alder (IMDA) reactions of crotonate esters derived from cis-1,2-dihydrocatechols, compound 5 was converted (Scheme 3) into the diesters 14 (81%) and 15 (74%) under previously established 8 conditions. When each of compounds 14 and 15 was heated in refluxing toluene they engaged in the two possible modes of cycloaddition and thus giving rise to the corresponding pair of adducts, viz.…”