Homologation at C5a in the A-Ring

When diketone 55 was reduced to hydroxyl ketone 56, an interesting change occurred in the H NMR that gave us significant insight into for our proposed conformations of these systems. A selected region of the H NMR for compounds 2 and 56 is shown in Fig. 8.9. 

We first examined ketone 48 and hydroxy ketone 56 because (1) no reduction of C5a-carbonyl in 48 occurred when using L-Selectride to reduce the C3-ketone and (2) NaBH4 did not touch the C5a-carbonyl group in hydroxy ketone 56. By using minimized Spartan model of vinylogous ester 48 and the X-ray structure of hydroxy ketone 56, we found unique conformational elements (Fig. 8.10) in addition to fully validating the aforementioned NMR analysis of possible positions for H8a when C8a is ip2-hybridzied and H7 when C8a is sp3-hybridized. In 48, 

We were mesmerized by the X-ray structure of hydroxy ketone 56 with its AB-ring junction being both. -hybridized, revealing a very different conformation from that of 48. The structure showed near-perfect chairs for the m-fused l-a /-decalinic. With this conformational preference, the p-Me group is pseudo-equatorial with the a-Me group now being pseudo-axial position. We believe this new a-Me orientation is responsible for the fact that the C5a-carbonyl is not reduced by NaBFLt it is sterically inaccessible, even by a nucleophile as small as a hydride. 

Interestingly, we were intrigued by the ESI mass spectrum of the compound, as the observed base peak consisted of [M-S02+Na]+. This led us to explore a thermal retro-Diels-Alder reaction that could afford the desired enone 69. It is noteworthy that the chemistry of cyclic enol-sulfites would appear to be an under-explored area with a few references reporting their isolation being found [57]. At last, we were also able to prepare epoxy ketone 70 from 69 in three steps, albeit epoxidation did not take place unless the TES group was removed. Spartan models reaffirmed our initial conformational assessment of enone 69 and epoxy ketone 70, which contain sp3-hybridized C8a and s/r-hybridized C8b (p s e u d o-. v/r - h y b r i d i zed C8b for 70) at the AB-ring junction (Fig. 8.12) and displayed the desired twisted-boat conformation in A-ring. 

---