Total Synthesis of Leucascandrolide A

The Vinylogous Aldol and Related Addition Reactions: Ten Years of Progress

“…The chemistry involved features three sequential vinylogous aldol (or Mannich, vide infra) processes where heterocyclic dienoxy silane synthons TBSOF (157), TBSOT (164), and TBSOP (163) can be installed as wished during the stepwise elongation sequence. As an example, the synthesis of the C12-C25 bis-THF segment of asimicin (202), one of the most potent members of this family, is shown in Scheme 38.…”

1.04 Regio-, Diastereo-, and Enantioselective Addition of Organocopper Reagents onto CO and CN Bonds

“…[63][64][65][66] The mechanism is believed to proceed first through the formation of a CuF(tol-BINAP) precatalyst that is then able to react with the silyl dienolate 101 to form a copper dienolate 102 (observed by IR), which is actually the catalytic species. The copper dienolate is then trapped by the aldehyde to form a copper alkoxide 103 (also observed by IR).…”

The Vinylogous Mukaiyama Aldol Reaction in Natural Product Synthesis

“…Chiral copper(I) complexes are also very efficient catalyst systems, mediating VMARs with cyclic acetoacetate-derived enoxysilanes. Typical examples can be found in the total syntheses of the complex natural products leucascandrolide A (227) (Scheme 2.59)[101,102], amphotericin B (230) (Scheme 2.60)[103], and the three streptogramin antibiotics virginiamycin M 2 (108), madumycin I (233), and griseoviridin (234) (Scheme 2.61)[104].In the total synthesis of leucascandrolide A (227), the opening move of the synthesis was executed according to the Carreira protocol (Scheme 2.59). Thus, Scheme 2.57 Application of the Ti(IV)/Schiff-base-catalyzed vinylogous Mukaiyama aldol reaction in the total synthesis of dihydroxyvitamin D 3 .…”