Synthesis of (S)-(−)-N-acetylcolchinol using intramolecular biaryl oxidative coupling

Abstract

An asymmetric synthesis of the tubulin polymerisation inhibitor (S)-(-)-N-acetylcolchinol is reported based on an intramolecular biaryl oxidative coupling of a 1,3-diarylpropyl acetamide intermediate using phenyliodonium bis(trifluoroacetate) as the final step. Three syntheses of the penultimate 1,3-diarylpropyl acetamide intermediate (S)-(-)-N-[1-[3-(tert-butyldimethylsilyloxy)phenyl)]-3-(3,4,5-trimethoxyphenyl)propyl] acetamide are described which differ in the means by which the stereogenic centre was introduced.

Formal Synthesis of (±)-Allocolchicine Via Gold-Catalysed Direct Arylation: Implication of Aryl Iodine(III) Oxidant in Catalyst Deactivation Pathways

“…Herein, we present further advancement of this goldcatalysed ring-forming process by way of a formal synthesis of (±)-allocolchicine (±)-5 [8][9][10][11], utilising the orthogonality of the process to palladium catalysis to install the requisite ester via carbonylation [12]. The synthesis has revealed a potent mechanism of catalyst deactivation, with substantial implications from this for the requirement of a change in the nature of the oxidant in further developments of the methodology.…”

Reagent-Controlled Lithiation–Borylation

“…Kocienski [14] and Aggarwal [15] showed that the 3-step sequence could be streamlined to a single operation by directly adding a boronic ester to the intermediate chiral organolithium. As outlined in Table 2, a general lithiation-borylation process starts with the asymmetric deprotonation of primary carbamates to give the corresponding enantioenriched organolithiums 12.…”

Hypervalent iodine reagents in the total synthesis of natural products

“…316 The reaction mechanism was thus suggested to proceed via a cation radical rather than through the oxidative coupling mechanism described in Section 2.4. In a synthesis of 1-dearyllamellarin D, Iwao and coworkers reported that a key PIFA-mediated cyclization of a pyrrole-containing phenol ether failed, and instead resulted in a decarbonylative cyclization.…”