Asymmetric Induction in 8π Electrocyclizations. Design of a Removable Chiral Auxiliary

Abstract

The pseudo C2 symmetric trans diphenyl oxazoline group acts as an effective chiral auxiliary in the 8π, 6π tandem electrocyclization of a substituted tetraene 1-carboxylic acid. Assignment of absolute stereochemistry to the [4.2.0] bicyclooctadiene product supports a model in which both s-cis and s-trans conformations favor the transition states with the same helical twist. This assignment prefaces the development of analogs of SNF4435 C and D. These natural products demonstrate activity as androgen receptor antagonists and as multidrug resistance (mdr) reversal agents.

Mechanism and Stereoselectivity of a Dual Amino-Catalyzed Robinson Annulation: Rare Duumvirate Stereocontrol

“…Consistent with our findings, high-accuracy calculations by other groups have shown that monosubstitution at the 3 position of a triene by an amine results in negligible rate enhancement . In addition, the remoteness of the catalyst sulfonamide side chain from the forming C–C bond in this transition state precludes stereocontrol, also rendering this mechanism unlikely . Thus, this mechanism does not display the level of reactivity or stereocontrol that is observed in the reaction.…”

Synthesis of the C1–C12 Fragment of Calyculin C

“…Unfortunately, compound 18 showed a tendency to undergo spontaneous cyclization to give compound 19 during column chromatography or on standing in solution at room temperature. This type of Pd-catalyzed cyclization of conjugated tetraenes has been reported by Parker, 36 Trauner 37 and Baldwin. 38 Finally, the bromotetraene 18 was subjected to a Negishi cross-coupling using ZnMe 2 and [Pd(t-Bu 3 P) 2 ] 39 to give tetraene 20.…”

Total Synthesis of Kingianin A

“…The synthesis of a mixture of the two racemic bicyclooctadienes 2 and 3 by the now classical Stille coupling/electrocyclization cascade method 6 , 7 and the separation of the two racemic compounds were reported by Moses et al 8 These authors dubbed isomer 2 “prekingianin A.” (−)-Kingianin A is the homodimer of monomer 2 ; kingianin D is the heterodimer of monomer 2 and monomer ent 2 (see Table 1). …”

“…Each of the kingianins AÀF (1, Figure 2) appears to be a DielsÀAlder adduct derived from two molecules of the purported biogenetic precursors: the enantiomers of endo 5 amide 2 and those of its exo isomer 3 (Figure 3). The synthesis of a mixture of the two racemic bicyclooctadienes 2 and 3 by the now classical Stille coupling/electrocyclization cascade method 6,7 and the separation of the two racemic compounds were reported by Moses et al 8 These authors dubbed isomer 2 "pre-kingianin A." (À)-Kingianin A is the homodimer of monomer 2; kingianin D is the heterodimer of monomer 2 and monomer ent 2 (see Table 1).…”