Enantioselective Total Synthesis of Epothilone A Using Multifunctional Asymmetric Catalyses

Abstract

Epothilones (see Scheme 1 for epothilones A (1) and B (2)) show potent antitumor activity by binding and stabilizing microtubules in the same way as taxol, and they are promising drug candidates. Epothilones A and B were isolated from the groups with a dihedral angle of 608 between the two planes and in which both CO groups are cisoid (length of the PtÀPt bond 2.584 ). [7a] Other related, crystallographically characterized dinuclear platinum carbonyl species include [{PtCl(CO)(PtBu 2 Ph)} 2 ] [7b] and [{Pt(C 6 F 5 )(CO)(PPh 3 )} 2 ], [7c] which have dihedral angles of 70.18 and 78.68, and PtÀPt distances of 2.628 and 2.599(), respectively. Preliminary reports have also appeared for [{PtCl(CO)(PPh 3 )} 2 ] [8] and, in all cases, the carbonyl groups are cis and the two phosphanes are trans to the PtÀPt bond.It has been shown that there is no correlation of d(PtÀPt) with 1 J(Pt,Pt') in closely related dinuclear platinum complexes. [8] It is worth noting that 1 J(Pt,Pt') for 1 is 550.9 Hz, while the values for [{PtCl 2 (CO)} 2 ] 2À (5250 Hz) [9] and [{PtCl(CO)(PPh 3 )} 2 ] (760 Hz) [8] are widely different, although other related coupling constants are similar (see Table 1 and refs. [8, 9]).Prolonged evacuation of 1 results in disproportionation and formation of 2 through loss of CO [see Eq. (2)]. In this case, 13 C and 195 Pt NMR measurements on unenriched and 99 % 13 CO-enriched 2 show that there are two magnetically equivalent carbonyl groups per platinum with no 195 PtÀ 195 Pt coupling; 2 is thus a monomer. We presently favor a squareplanar platinum(ii) center with two CO ligands in a cis configuration, consistent with both IR and Raman measurements; the CO stretching frequencies are close to those for cis-[Pt(CO) 2 (SO 3 F) 2 ], [5b] but higher than those for cis-[Pt(CO) 2 Cl 2 ]. [10] It is difficult to be sure whether the other two coordination sites on platinum are occupied by a bidentate SO 4 2À or by two monodentate SO 4 2À /HSO 4 À groups since it is impossible to obtain any useful IR or Raman data in the sulfato region. However, when 1 is in concentrated H 2 SO 4 , it seems more probable that the other two sites are occupied by monodentate HSO 4 À groups as recently found for silver(i). [11] The discovery of 1 suggests that homoleptic cationic carbonyl complexes of late transition metals in low oxidation states can be formed in media which are less acidic than the superacids that have been used previously. We found that this unusual dinuclear platinum carbonyl complex, 1, exhibits high catalytic activity for the carbonylation of olefins; [12] future studies will investigate the detailed reaction mechanism of this catalytic activity and attempts will be made to obtain 1 as a crystalline salt. Experimental SectionStandard canula transfer techniques were used for all sample manipulations. NMR spectra were recorded in D 2 SO 4 at room temperature on a Bruker AMX 200. The 13 C chemical shifts were referenced to external tetramethylsilane (TMS), and 195 Pt chemical shifts were referenced to 42.8 MHz at s...

The Direct Catalytic Asymmetric Mannich Reaction

“…The reactions are catalyzed by heterobimetallic complexes that function as both a Lewis acid and a Brønsted base. Among them, LaLi 3 tris(binaphthoxide) 1 (LLB) was proven to be an effective catalyst in direct asymmetric aldol reactions (Figure ) . On the basis of this research, Shibasaki et al disclosed the first report of a direct catalytic asymmetric Mannich reaction …”

Total Synthesis of the Chlorinated Pentacyclic Indole Alkaloid (+)-Ambiguine G

“…13a − 13c To our knowledge, this epoxyhydrazone-mediated directed introduction of a carbon substituent α to a carbonyl group has not been utilized in natural product synthesis. 16 Conversion of the vinyl-alcohol product 16 to chloro ketone 17 was accomplished using N -chlorosuccinimide and PPh 3 with complete stereoinversion at the chlorine attaching carbon. The stereoretentive chlorination product was not observed.…”