Ethers benzyl alkynyl

Substituted benzyl alkynyl ethers undergo [3,3]-sigmatropic rearrangement/intra-molecular 5-exo-dig cyclization to substimted 2-indanones (Scheme 1). °... 

This protocol recently rose in appeal by the observation of Gau et al. that 4 mol% of cheap [NiCl2(PPh3)2] catalyzes such aryl-alkyne couplings with an even higher efficiency [146]. Moreover, various benzyl bromides as well as bromomethyl-substituted heteroarenes were alkynylated in yields exceeding 90% when diethyl ether was used as the solvent. These nickel-catalyzed benzyl-alkynyl couplings... 

R = alkyl, alkenyl, alkynyl, aryl, acetate, ester, benzyl or silyl ether groups Scheme 6.15 Cleavage of methoxyphenyl methyl (MPM) ethers using clayan. 

The resultant 3-alkynyl-5-bromo-2-pyrones 83 are potent ambident dienes, undergoing cycloadditions with both electron-rich and electron-poor dienophiles. As exemplied in Scheme 24, 3-[(trimethylsilyl)-ethynyl]-5-bromo-2-pyrone 83a underwent efficient cycloaddition with benzyl vinyl ether, as well as with methyl acrylate, to afford the corresponding cycloadducts 84 and 85, respectively. 

For the final part (Scheme 5.3), the 20-carbon chain of fumonisin Bj was coupled from the Uthium acetylide derived from 273 and the Weinreb amide 279 (233). After enantioselective reduction of the alkynyl ketone 281 (234, 235), the C-10 stereochemistiy was set, followed by benzyl ether formation and acid-catalyzed acetonide removal, to provide diol 282 (236). Using tricarballylic acid dibenzyl ester, the two hydroxy groups were esterified (237) and the hydrogenation of the azide, the alkyne, and the benzylic ethers led to the target product, fumonisin Bj (249). The spectroscopic analysis matched with those of commercial fumonisin Bj and further experiments on the synthetic material showed inhibitoiy activity on sphingoUpid biosynthesis. 

The aforementioned methods to construct benzofurans are all achieved by activation of C(sp )-H bond. In 2012, based on the alkynoxy-directed synthesis of 2-methylidene-2H -chromene derivatives [28], Hiyama and coworkers developed a palladium-catalyzed hydrobenzylation of ortho-tolyl alkynyl ethers to construct 2-methylidene-2,3-dihydrobenzofurans via the activation of benzylic C(sp )-H bond [34]. 

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