| A stereo- and regio-controlled enantioselective total synthesis of eunicenone A (I-1) starting from geranylgeraniol (15 steps) is described. The most critical transformation in the synthesis is the highly effective asymmetric Diels-Alder reaction between achiral components 2-bromoacrolein and diene I-30 in the presence of chiral Lewis acid catalyst I-9 to form I-31 (85% yield, 97% ee, >98:2 endo-exo ratio). A general methodology for the preparation of aryldimethylsilyl lithium and cuprate reagents is developed specifically for the synthesis of I-30, although its application can be broadened to include other alkylation and conjugate addition reactions. Other noteworthy steps include mild hydroxy desilylation and selective ketal formation, selective monoepoxidation of a reactive pentaene, novel methoxycarbonylation of a 1,2epoxy-1,3-diene with allylic transposition, and extremely efficient ketal unmasking and glycol cleavage.*.;The first examples of catalytic enantioselective Diels-Alder reactions of cyclopentadiene and alpha,beta-acetylenic aldehydes such as Bu 3SnC≡CCHO (II-12) using chiral oxazaborinane catalyst II-2a/b (80--87% ee) are also described herein along with a proof of absolute stereochemistry. The intrinsic exo selectivity of this reaction and subtle non-bonded interactions between the catalyst-dienophile complex and the approaching cyclopentadiene are believed to be important factors which contribute to the success of this reaction. Tributylstannyl Diels-Alder adduct II-13 is a versatile synthetic intermediate and has been further elaborated by iodo-destannylation and cross coupling reactions.*.;The progress directed toward the total synthesis of clavirolides and clavulactone employing a macrocyclization/ring-enlargement strategy ( III-13 → III-12) is discussed. In addition, evidence indicating the importance of formyl C--H--O hydrogen bond in enantioselective Lewis-acid catalyzed reactions of aldehyde s is reviewed.*.;*Please refer to dissertation for diagrams. |
