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A variety of bis-allylic esters were prepared by vinylmetal addition to cycloalkenones followed by esterification either in situ or in a separate operation. For chiral cyclohexenones, the vinyl additions generally occurred with >10:1 diastereoselectivity. Although in some cases the bis-allylic esters proved to be sensitive to silica gel or other adsorbents, all of the esters examined could be isolated in acceptable purity. The Ireland-Claisen rearrangement of the bis-allylic esters occurred with complete regioselectivity via the exocyclic alkene. The alkene stereochemistry and the stereochemistry at C-2 and C-3 of the pentenoic acid products were consistent with a chairlike transition state in the rearrangement. Substituents at the carbons adjacent to the allylic carbinol carbon (i.e., C-2 or C-6 in cyclohexenone-derived substrates) directed the stereochemical course of the rearrangement. The rearrangements generally proceeded so as to place the larger of the C-2 or C-6 substituents in the pseudoequatorial position with respect to the chairlike transition state. For a bis-allylic ester bearing both a C-2-CH(3) and a C-6-OMEM substituent, the rearrangement product resulted from the nominally smaller OMEM substituent occupying a pseudoequatorial position with respect to the chairlike transition state.

[reaction: see text] The synthesis of an advanced intermediate in the synthesis of the title compound has been achieved. Key steps include an Ireland-Claisen rearrangement to install the C7 tertiary alcohol stereocenter, an SN2' reaction of an alkoxymethyl Cu reagent, and a diastereoselective Re-catalyzed allylic alcohol transposition.

In undergraduate education, a relatively small percentage of students participate in scientific research. Recently educators have suggested that research universities might better serve their undergraduates by establishing stronger connections between teaching and research. Faculty who teach large undergraduate lecture courses and also direct graduate research have the opportunity to increase undergraduate participation in research at an early stage in the students' academic career.In the project detailed herein, 29 student volunteers from second-semester organic chemistry lecture courses at the University of Arkansas participated in a one-afternoon research experience on a natural product synthesis project. Each student spent a few hours in our laboratory and performed one reaction directed toward the total synthesis of the anticancer natural product eleutherobin. The details of the student involvement in the project, progress of the student research efforts (Web version), teaching opportunities derived from the research, and some observations regarding student participation are described.