Enyne Metathesis Approach towards the Cyclopentane Motif of Jatrophane Diterpenes

Abstract

A short and efficient synthesis of the cyclopentane moiety of the jatrophane diterpene Pl-3 has been developed. The route features an enyne metathesis reaction, and a stereoselective palladium-catalyzed reductive epoxide opening as key steps.

Construction of the Bicyclic Carbon Framework of Euphosalicin

“…Thus, the secondary alcohol was smoothly protected as its TBS ether, and the subsequent reductive opening of the allylic epoxide 31 was carried out following a protocol developed by Rinner et al (Scheme 5). 7 Using their optimized conditions, the desired secondary alcohol 32 was isolated as a single diastereomer in 82% yield. For the remaining two steps toward the first building block, the vinyl group was ozonolyzed to give the β-hydroxy aldehyde 33.…”

“…After the cleavage of the acetonide in 10 , the obtained diol 20 was treated with the Grubbs second generation catalyst ( Scheme 4 ). 7 Even though TLC control showed that the cyclic compound 21 was the main product of the reaction, all attempts to subject the crude reaction mixture to chromatography, in the presence of air, resulted in a substantial loss of material and 21 was isolated in only 27% yield. It has been conceivable that the ruthenium, forming stable complexes with the hydroxyl groups in close proximity, had been responsible for the degradation of the product.…”

“…1 H NMR (400 MHz, CDCl 3 ): δ 6.51 (t, J = 1.6 Hz, 1H), 5.93 (dd, J = 1.7, 1.1 Hz, 1H), 5.91−5.78 (m, 1H), 5.18−5.08 (m, 2H), 4.26 (dddd, J = 7.7, 6.2, 3.3, 1.6 Hz, 1H), 4.02 (dd, J = 10.9, 2.0 Hz, 1H), 3.18 (d, J = 7. 7 Compound 53. The aldehyde 6 (60 mg, 119 μmol, 1 equiv) and the vinyl iodide 50 (72 mg, 155 μmol, 1.3 equiv) were dissolved in dry ether (2 mL), and the resulting clear solution was cooled to −80 °C.…”

“…The 13-membered macrocycle was envisaged to be prepared via a late stage ring closing metathesis (RCM) of the triene 3 , which could be prepared by the addition of the deprotonated dithiane 5 to the ketone 4 . , The synthesis of 4 was planned to be accomplished by the coupling of the aldehyde 6 with the vinyl iodide 7 (after a metal–halogen exchange). This aldehyde 6 was intended to arise from the cyclopentane derivative 8 , which in turn could be constructed via a ring-closing enyne metathesis of the intermediate 10 . The enantioselective introduction of the 1,2-diol moiety in 10 was expected to be feasible via a Sharpless dihydroxylation; the required enyne system in 11 was traced back to the commercially available 3-butyn-1-ol ( 12 ).…”

“…This aldehyde 6 was intended to arise from the cyclopentane derivative 8 , which in turn could be constructed via a ring-closing enyne metathesis of the intermediate 10 . 7 The enantioselective introduction of the 1,2-diol moiety in 10 was expected to be feasible via a Sharpless dihydroxylation; the required enyne system in 11 was traced back to the commercially available 3-butyn-1-ol ( 12 ).…”