Formal Total Synthesis of Kendomycin by Way of Alkyne Metathesis/Gold Catalysis

Abstract

In an attempt to study the ability of the latest generation of alkyne metathesis catalysts to process sterically hindered substrates, two different routes to the bacterial metabolite kendomycin (1) were explored. Whereas the cyclization of the overcrowded arylalkyne 39 and related substrates turned out to be impractical or even impossible, ring closure of the slightly relaxed diyne 45 was achieved in excellent yield under notably mild conditions with the aid of the molybdenum alkylidyne 2 endowed with triphenylsilanolate ligands. The resulting cycloalkyne 46 was engaged into a gold-catalyzed hydroalkoxylation, which led to benzofuran 47 that had already previously served as a late-stage intermediate en route to 1

A New Method for the Preparation of Non‐Terminal Alkynes: Application to the Total Syntheses of Tulearin A and C

“…[35] Moreover, entry 1 shows that a lactone with a chiral center a to the carbonyl group can be transformed into the corresponding non-terminal alkyne without loss in optical purity; this particular product was of immediate interest for a total synthesis of kendomycin recently completed by our laboratory. [36] For all products derived from five-membered lactone precursors (entries 14-21), the iron catalyzed variant was quintessential for success as it allows competing allene formation to be suppressed. This striking dichotomy of alkyne versus allene formation is apparent from entries 14/15 and 19/20.…”

Progress in the trans-Reduction and trans-Hydrometalation of Internal Alkynes. Applications to Natural Product Synthesis

“…This lactone was subjected to dichloroolefination to provide 192 as the substrate of an iron-catalyzed reductive methylation, which results in ring opening and concomitant formation of the methyl-capped alkyne 193. 70, 119 Oxidation of the released primary alcohol and epimerization of the resulting aldehyde to the thermodynamically more stable trans-configured product gave the required building block 194.…”

The chemistry of the carbon-transition metal double and triple bond: Annual survey covering the year 2014

“…1567) through ring closing alkyne metathesis was a key M a n u s c r i p t 190 step in the total synthesis of the putative structure of mandelalide A (the synthesis includes an acrylate CM step as well) [1329]. Formation of the macrocyclic alkyne enyne 1569 was a key event in the total synthesis of kendomycin [1330]. Construction of a cyclic alkyne-bis(lactone) system was a key event in the synthesis of oxygenated metabolites of n-3 polyunsaturated fatty acids [1331].…”