19689-18-0Relevant articles and documents
Dramatic Concentration Depedence of Stereochemistry in the Wittig Reaction. Examination of the Lithium Salt Effect
Reitz, Allen B.,Nortey, Samuel O.,Jordan, Alfonzo D.,Mutter, Martin S.,Maryanoff, Bruce E.
, p. 3302 - 3308 (1986)
The stereochemistry for Wittig reactions of butylidenetriphenylphosphorane (1) with benzaldehyde and hexanal was examined in detail with regard to concentration effects.For the reaction of 1 and benzaldehyde in the presence of LiBr, the proportion of trans-oxaphosphetane (measured by low-temperature 31P NMR) and (E)-alkene increased with respect to increasing reaction concentration in THF, approaching limiting values in a hyperbolic manner.Stereochemical drift, i.e., exaggerated production of (E)-alkene relative to trans-oxaphosphetane intermediate, was also concentration dependent, being more pronounced at higher concentrations.Experiments with varying amounts of lithium cation, and with NaBr instead of LiBr, demonstrated that this phenomenon is associated with the concentration of Li ion, which is increasingly sequestered by the THF solvent at higher dilution.In Me2SO, the dependence of alkene stereochemistry on concentration was greatly attenuated.In toluene, the concentration effect was inverted to some extent; more (E)-alkene was formed at higher dilution ( no betaines were observed by 31P NMR at low temperature).The reaction of 1 with hexanal in THF, in the presence of LiBr, exhibited a concentration depedence similar to that observed for the reaction with benzaldehyde ( at the oxaphosphetane stage).The rates of the lithium-dependent ("catalyzed") and lithium-independent ("uncatalyzed") reactions in the original carbon-carbon bond-forming step are ranked relative to each other, based on their concentration dependence in THF.For 1 and benzaldehyde in THF (with LiBr present), the catalyzed (k'') and uncatalyzed (k') rates constant have the following relative order: k1'' = 5.2 and k2'' = 2.5 mol-2*dm6*s-1; k1' = 1.0 and k2' -1*dm3*s-1 (see Scheme I and Appendix).Thus, at the representative concentrations of 0.05, 0.20, and 0.50 M, the original carbon-carbon bond-forming step in this Wittig reaction is 27percent, 61percent, and 79percent lithium catalyzed, respectively.
Catalytic asymmetric carbong-carbon bond formation via allylic alkylations with organolithium compounds
Perez, Manuel,Fananas-Mastral, Martin,Bos, Pieter H.,Rudolph, Alena,Harutyunyan, Syuzanna R.,Feringa, Ben L.
experimental part, p. 377 - 381 (2012/01/06)
Carbon-carbon bond formation is the basis for the biogenesis of nature's essential molecules. Consequently, it lies at the heart of the chemical sciences. Chiral catalysts have been developed for asymmetric C-C bond formation to yield single enantiomers from several organometallic reagents. Remarkably, for extremely reactive organolithium compounds, which are among the most broadly used reagents in chemical synthesis, a general catalytic methodology for enantioselective C-C formation has proven elusive, until now. Here, we report a copper-based chiral catalytic system that allows carbon-carbon bond formation via allylic alkylation with alkyllithium reagents, with extremely high enantioselectivities and able to tolerate several functional groups. We have found that both the solvent used and the structure of the active chiral catalyst are the most critical factors in achieving successful asymmetric catalysis with alkyllithium reagents. The active form of the chiral catalyst has been identified through spectroscopic studies as a diphosphine copper monoalkyl species.
Synthesis of Farnesol Analogues through Cu(I)-Mediated Displacements of Allylic THP Ethers by Grignard Reagents
Mechelke, Mark F.,Wiemer, David F.
, p. 4821 - 4829 (2007/10/03)
The synthesis of a family of farnesol analogues, incorporating aromatic rings, has been achieved in high yields through the development of a regioselective coupling of allylic tetrahydropyranyl ethers with organometallic reagents. The allylic THP group is displaced readily by Grignard reagents in the presence of Cu(I) halides but is stable in the absence of added copper. Thus, an allylic THP group can fulfill its traditional role as a protecting group or serve as a leaving group depending on reaction conditions. An improved synthesis of (2E,6E)-10,11-dihydrofarnesol also has been accomplished using this methodology, and some preliminary studies on the reactivity and regioselectivity of THP ether displacements were conducted. The farnesol analogues reported herein may be useful probes of the importance of nonbonding interactions in enzymatic recognition of the farnesyl chain and allow development of more potent competitive inhibitors of enzymes such as farnesyl protein transferase.
