Taxane Synthesis through Intramolecular Pinacol Coupling at C-1−C-2. Construction and Oxidative Transformations of a C-Aromatic Taxane Diene

Abstract

A ten-linear-step construction of C-aromatic taxane diene 14 from ethyl isopropyl ketone, acryloyl chloride, and commercially available 8 is reported. This sequence concludes with an intramolecular pinacol coupling carried out on 13. 14 is oxidized by m-chloroperbenzoic acid and dimethyldioxirane to give 17 through intermediate epoxide 20 and by VO(acac)2−t-BuOOH and Mo(CO)6−t-BuOOH to give 13. 17 is converted efficiently into 22 upon treatment with Mo(CO)6−t-BuOOH, apparently through an unusual equilibration with isomeric 20, which is converted irreversibly to 22. While these oxidative transformations highlight some of the peculiar reactivity patterns characteristic of taxane-related structures, the formation of 14 through an intramolecular pinacol coupling that joins C-1 and C-2 demonstrates the potential of this strategy for stereoselectively delivering advanced taxane synthesis intermediates.

Taxane Synthesis through Intramolecular Pinacol Coupling at C-1−C-2. Highly Oxygenated C-Aromatic Taxanes

“…Following the protocol that had succeeded in the transformation of 1 into 2 , keto aldehyde 3 was exposed to the TiCl 4 −Zn reagent whereupon expected tricycle 4 was formed as the major component of a three-isomer product mixture. The structure of pinacol 4 was confirmed upon its conversion to benzoate 19 , a substance previously prepared and characterized through X-ray crystallography by Nicolaou whose published spectral parameters matched those we observed.…”

“…In the preceding article, we showed that a taxane (cf. taxol 2 ) synthesis strategy having an intramolecular pinacol coupling at C-1−C-2 as the key step could efficiently deliver potential advanced tricyclic intermediates.…”

Progress in the Construction of Cyclooctanoid Systems: New Approaches and Applications to Natural Product Syntheses

“…Swindell and co-workers have investigated in detail the titanium mediated coupling reactions in the context of taxoids employing precursors having rings A and C to construct the central eight-membered ring and identified suitable reagents/conditions for the process. It has been observed that the keto aldehyde 411 is smoothly converted into 412 upon treatment with TiCl/Zn/Py in excellent yield and with high stereoselectivity, placing both of the hydroxyl groups in correct relative stereochemistry, Scheme …”

Asymmetric Total Synthesis of Indole Diterpenes Paspalicine, Paspalinine, and Paspalinine‐13‐ene

“…Unexpectedly, we found that Achmatowicz rearrangement of furfuryl diol 27 was very challenging because our oxone‐halide, N‐bromosuccinimide (NBS), and m ‐chloroperoxylbenzoic acid ( m ‐CPBA) under various conditions caused significant decomposition, probably due to the presence of oxidation‐sensitive indole core [31] . The well‐recognized mild method with VO(acac) 2 / t ‐BuOOH resulted in rather unexpected oxidative cleavage of the vicinal diol in 85 % yield [32] . Fortunately, we found that our newly developed conditions (CeBr 3 cat./H 2 O 2 ) [33] was the only protocol that could effect Achmatowicz rearrangement of 27 (>85 % yield by 1 H NMR of the crude reaction mixture).…”