|
In organic chemistry, the Cieplak effect is a predictive model that explains why nucleophiles preferentially add to one face of a carbonyl over another. Proposed by Andrzej Stanislaw Cieplak in 1980, it explains anomalous results that other models of the time, such as the Cram and Felkin-Anh models, can't justify. In the Cieplak model, electrons from a neighboring bond delocalize into the forming carbon-nucleophile (C-Nuc) bond, lowering the energy of the transition state and accelerating the rate of reaction.〔Cieplak, A. S. J. Am. Chem. Soc. 1981, 103, 4540〕 Whichever bond can best donate its electrons into the C-Nuc bond determines which face of the carbonyl the nucleophile will add to. The nucleophile may be a number of reagents, most commonly organometallic or reducing agents. The Cieplak effect is subtle, and often competes with sterics, solvent effects, counterion complexation of the carbonyl oxygen, and other effects to determine product distribution. == Background == The Cieplak effect relies on the stabilizing interaction of mixing full and empty orbitals to delocalize electrons, known as hyperconjugation.〔Alabugin, I. V.; Gilmore, K. M.; Peterson, P. W. WIREs Comput. Mol. Sci. 2011, 1, 109〕 When the highest occupied molecular orbital (HOMO) of one system and the lowest unoccupied molecular orbital (LUMO) of another system have comparable energies and spatial overlap, the electrons can delocalize and sink into a lower energy level. Often, the HOMO of a system is a full σ (bonding) orbital and the LUMO is an empty σ * (antibonding) orbital. This mixing is a stabilizing interaction and has been widely used to explain such phenomena as the anomeric effect. A common requirement of hyperconjugation is that the bonds donating and accepting electron density are antiperiplanar to each other, to allow for maximum orbital overlap. center The Cieplak effect uses hyperconjugation to explain the face-selective addition of nucleophiles to carbonyl carbons. Specifically, donation into the low-lying σ *C-Nuc bond by antiperiplanar electron-donating substituents is the stabilizing interaction which lowers the transition state energy of one stereospecific reaction pathway and thus increases the rate of attack from one side. In the simplest model, a conformationally constrained cyclohexanone is reduced to the corresponding alcohol. Reducing agents add a hydride to the carbonyl carbon via attack along the Burgi-Dunitz angle, which can come from the top along a pseudo-axial trajectory or from below, along a pseudo-equatorial trajectory. It has long been known that large reducing agents add hydride to the equatorial position to avoid steric interactions with axial hydrogens on the ring. Small hydride sources, however, add hydride to an axial position for reasons which are still disputed.〔Eliel, E. L.; Senda, Y. Tetrahedron 1970, 26, 2411〕 center The Cieplak effect explains this phenomenon by postulating that hyperconjugation of the forming σ *C-H orbital with geometrically aligned σ orbitals is the stabilizing interaction that controls stereoselectivity. In an equatorial approach, the bonds that are geometrically aligned antiperiplanar to the forming C-H bond are the C-C bonds of the ring, so they donate electron density to σ *C-H. In an axial approach, the neighboring axial C-H bonds are aligned antiperiplanar to the forming C-H bond, so they donate electron density to σ *C-H. Because C-H bonds are better electron donors than C-C bonds, they are better able to participate in this stabilizing interaction and so this pathway is favored.〔 center 抄文引用元・出典: フリー百科事典『 ウィキペディア（Wikipedia）』 ■ウィキペディアで「Cieplak Effect」の詳細全文を読む スポンサード リンク
|
