Cycloisomerization stereoselectivity

Thermal conditions were effective in the stereoselective oxa-ene cycloisomerization of allenylsilanes, furnishing both substituted cyclopentanes and, as in Equation (88), substituted cyclohexanes. 

Kibayashi and co-workers103 implemented the palladium-catalyzed cycloisomerization reaction in a stereoselective total synthesis of enantiomerically pure (+)-streptazolin. The cycloisomerization of enyne 172 to provide diene 173 was remarkably selective when performed in the presence of A,Ar -bis(benzylidene)ethylenediamine (BBEDA) as a ligand and water as a proton source (Scheme 44). 

Mild Ni(0)-catalysed rearrangements of l-acyl-2-vinylcyclopropanes to substituted dihydrofurans have been developed.86 The room temperature isomerizations afford dihydrofuran products in high yield. A highly substituted, stereochemically defined cyclopropane has been employed in the rearrangement to evaluate the reaction mechanism. The Cu(II)-catalysed cycloisomerization of tertiary 5-en-l-yn-3-ols with a 1,2-alkyl shift affords stereoselectively tri- and tetra-cyclic compounds of high molecular complexity (Scheme 29).87 A proposed mechanism has been outlined in which... 

F. E. McDonald and M. Wu, Stereoselective synthesis of L-oliose trisaccharide via iterative alkynol cycloisomerization and acid-catalyzed glycosylation, Org. Lett., 4 (2002) 3979-3981. 

McDonald, F. E. Gleason, M. M. Asymmetric synthesis of nucleosides via molybdenum-catalyzed alkynol cycloisomerization coupled with stereoselective glycosylations of deoxy-furanose glycals and 3-amidofuranose glycals. J. Am. Chem. Soc. 1996, 118, 6648-6659. 

A highly stereoselective kinetic resolution process for Rh-catalyzed enyne cycloisomerization has also been developed by Zhang et al. [41]. This transformation has enabled the highly enantioselective synthesis of polyfunctionalized tetrahydrofurans and lactones with two or three adjacent stereocenters and it is regarded as a major breakthrough in enynes cycloisomerization and in kinetic resolution (Scheme 7). 

The mechanism of these transformations seems to be substrate-dependent and only the cycloisomerization of aryl and primary iodides was thought to proceed as shown in Scheme 31. The stereoselectivity of the isomerization of 110 to 111 is better accommodated with the intermediacy of l-methyl-5-hexenyl radical59. Later, it was proposed that the isomerization of 6 to 109 also proceeds via a radical-mediated atom transfer process initiated by homolytic fragmentation of an ate-complex intermediate 112 (Scheme 32)60. 

Pt(II) to the alkyne of the substrate likely triggers all these events. The cycloisomerization might undergo a metallacyclic intermediate that proceeds to eliminate /3-H. The formation of cyclopropanes is presumably succeeded via alkenyl platinum carbene followed by platina(IV)cyclobutane intermediates. The extension using formal metathesis of the enynes includes two transformations, the formation of 1,3-diene moieties and the stereoselective tetrasubstituted aUcene derivatives via O C allyl shift, both leading to diverse structural motifs and serving as the key step in the total synthesis of bioactive targets (Scheme 83). 

Trost, B.M., Ferreira, E.M. and Gutierrez, A.C. (2008) Ruthenium- and palladium-catalyzed enyne cycloisomerizations differentially stereoselective syntheses of bicyclic structures. Journal of the American Chemical Society, 130,16176-16177 Trost, B.M., Gutierrez, A.C. and Ferreira, E.M. (2010) Differential reactivities of enyne substrates in ruthenium- and palladium-catalyzed cycloisomerizations. Journal of the American Chemical Society, 132, 9206-9218. 

Iridium-catalyzed intramolecular l,n-enyne metathesis has been studied as a unique tool for the synthesis of various types of cyclic compounds. Reactions of this type depend on both the structure of substrates and the nature of catalyst systems used (411). Recently, the cycloisomerization of various 1,6-enynes have been shown to be catalyzed by [Ir(cod)Cl]2/dppf (494). These reactions are highly stereoselective, and generate the (Z)-isomer preferentially over the ( )-isomer (Scheme 63). The proposed mechanism (Scheme 64) involves oxidative cyclization of the enyne at Ir(I) to give the trivalent iridacyclopentene. The intermediate undergoes (3-hydride elimination to give the irida-1,3-diene, which experiences steric repulsion between the metal fragment and the cis substituent on the... 

An enantioselective version of the gold-catalyzed cyclopropanation was reported by Michelet and co-workers. In the presence of [Au2 (/ )-3,5-/-Bu-4-MeO-MeOBIPHEP Cl2] and AgOTf, 3-oxabicyclo[4.1.0]hept-4-ene derivatives were obtained with excellent enantioselectivities (Scheme 4-26). Both electron-rich and electron-poor aryl groups are tolerated under these conditions. Lower reactivities and stereoselectivities were observed in the corresponding platinum- or iliodium-catalyzed cycloisomerizations. ... 

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