134876-96-3Relevant articles and documents
Total Synthesis of Putative Chagosensine
Heinrich, Marc,Murphy, John J.,Ilg, Marina K.,Letort, Aurélien,Flasz, Jakub,Philipps, Petra,Fürstner, Alois
, p. 13575 - 13581 (2018)
The marine macrolide chagosensine is the only natural product known to date that embodies a Z,Z-configured chloro-1,3-diene unit. This distinguishing substructure was prepared by a sequence of palladium-catalyzed 1,2-distannation of an alkyne precursor, regioselective Stille cross-coupling at the terminus of the resulting bisstannyl alkene with an elaborated alkenyl iodide, followed by chloro-destannation of the remaining internal site. The preparation of the required substrates centered on cobalt-catalyzed oxidative cyclization reactions of hydroxylated olefin precursors, which allowed the 2,5-trans-disubstituted tetrahydrofuran rings, embedded into each building block, to be formed with excellent selectivity. The highly strained macrolactone could ultimately be closed under forcing Yamaguchi conditions. Comparison of the spectral data of the synthetic sample with those of authentic chagosensine methyl ester confirmed that the structure of this intriguing compound has been mis-assigned by the isolation team.
Chagosensine: A Riddle Wrapped in a Mystery Inside an Enigma
Fürstner, Alois,Flasz, Jakub T.,Heinrich, Marc,Ilg, Marina K.,Letort, Aurélien,Murphy, John J.,Philipps, Petra
supporting information, p. 6409 - 6422 (2020/04/27)
The marine macrolide chagosensine is supposedly distinguished by a (Z,Z)-configured 1,3-chlorodiene contained within a highly strained 16-membered lactone ring, which also incorporates two trans-2,5-disubstituted tetrahydrofuran (THF) rings; this array is unique. After our initial synthesis campaign had shown that the originally proposed structure is incorrect, the published data set was critically revisited to identify potential mis-assignments. The "northern" THF ring and the anti-configured diol in the "southern" sector both seemed to be sites of concern, thus making it plausible that a panel of eight diastereomeric chagosensine-like compounds would allow the puzzle to be solved. To meet the challenge, the preparation of the required building blocks was optimized, and a convergent strategy for their assembly was developed. A key role was played by the cobalt-catalyzed oxidative cyclization of alken-5-ol derivatives ("Mukaiyama cyclization"), which is shown to be exquisitely chemoselective for terminal alkenes, leaving even terminal alkynes (and other sites of unsaturation) untouched. Likewise, a palladium-catalyzed alkyne alkoxycarbonylation reaction with formation of an α-methylene-?-lactone proved instrumental, which had not found application in natural product synthesis before. Further enabling steps were a nickel-catalyzed "Tamaru-type" homocrotylation, stereodivergent aldehyde homologations, radical hydroindation, and palladium-catalyzed alkyne-1,2-bis-stannation. The different building blocks were assembled in a serial fashion to give the idiosyncratic chlorodienes by an unprecedented site-selective Stille coupling followed by copper-mediated tin/chlorine exchange. The macrolactones were closed under forcing Yamaguchi conditions, and the resulting products were elaborated into the targeted compound library. Yet, only one of the eight diastereomers turned out to be stable in the solvent mixture that had been used to analyze the natural product; all other isomers were prone to ring opening and/or ring expansion. In addition to this stability issue, our self-consistent data set suggests that chagosensine has almost certainly little to do with the structure originally proposed by the isolation team.
Cyclopentyl methyl ether-NH4X: A novel solvent/catalyst system for low impact acetalization reactions
Azzena, Ugo,Carraro, Massimo,Mamuye, Ashenafi Damtew,Murgia, Irene,Pisano, Luisa,Zedde, Giuseppe
supporting information, p. 3281 - 3284 (2015/06/25)
Cyclopentyl methyl ether, a low impact ether forming a positive azeotrope with water, was successfully employed as a solvent in the synthesis of 1,3-dioxanes and 1,3-dioxolanes carried out under Dean-Stark conditions by the acetalization of aliphatic and aromatic aldehydes or ketones, employing ammonium salts as environmentally friendly acidic catalysts.
