The Nature of the Intermediary Ketols in the Robinson Annelation Reaction¹

Synthesis of the Functionalized Tricyclic Skeleton of Guanacastepene A: A Tandem Epoxide-Opening β-Elimination/Knoevenagel Cyclization This work was supported by the National Institutes of Health (HL-25848 and CA-28824). D.S.T. is a Damon Runyon Cancer Research Foundation postdoctoral fellow (DRG-1641). G.B.D. is an NIH postdoctoral fellow (1 F32 NS11150-01). We thank Dr. George Sukenick and Sylvi Rusli (NMR Core Facility, CA-02848) for mass spectral analyses.

“…At this stage, we attempted to employ a Turner–Fujimoto protocol to generate tricycles 15 a and 15 b 14. Unfortunately, after the addition of either methyllithium or ethylmagnesium bromide, we obtained complex mixtures of products that were not resolved by equilibration in refluxing methanolic potassium hydroxide 15. Although the reasons for the failure of these reactions were unclear at the time, subsequent experiments suggest that complications involving C2 may thwart the desired cyclizations.…”

“…In light of the complexities of the multistep Turner–Fujimoto sequence,15 we elected to pursue an alternative route to the tricyclic core through direct Knoevenagel cyclization of the discrete β ‐keto ester precursor 18 (Scheme ). We recognized that the ethyl ester in 18 could also serve as a suitable precursor to the required C15 aldehyde in guanacastepene A ( 1 ).…”

Approaches to the Synthesis of Triterpenoids. II. Some Tetracyclic Precursors Suitable for Conversion into Pentacyclic Triterpenoids

“…Thus, attempts at hydrogenation of 6a in acetic acid -sulfuric acid mixtures led to complex mixtures. In one case a low yield of crystalline material was obtained that appeared from spectral evidence to be a mixture of ketols 9a (12). These observations suggested the use of non-acidic solvents for the hydrogenation and since no hydrogen uptake was observed in boiling ethanol, the use of higher-boiling, nonpolar solvents was investigated.…”

Cd → BCD → Abcd

“…(This ketol mixture was initially formulated as a mixture of 5a-and 5/3-hydroxy compounds, 36. Later work [44] showed this as well as some previous, similar formulations to be incorrect.) For preparative purposes, however, it was not necessary to isolate the tautomeric mixture 33/34.…”