Remote substituents

The enolization of 5a-3-ketones appears to be cleanly directed to C-2, whereas that of 5j5-3-ketones is less selective. Remote substituents can have a significant effect on the kinetic and thermodynamic enol acetylation of 5j3-steroids. ... 

The structural unit associated with an electronic transition in UV-VIS spectroscopy is called a chromophore. Chemists often refer to model compounds to help interpret UV-VIS spectra. An appropriate model is a simple compound of known structure that incorporates the chromophore suspected of being present in the sfflnple. Because remote substituents do not affect of the chromophore, a strong similarity between the spectrum of the model compound and that of the urrknown can serve to identify the kind of tt electron system present in the sfflnple. There is a substantial body of data concerning the UV-VIS spectra of a great many chromophores, as well as empirical conelations of substituent effects on Such data are helpful when using UV-VIS spectroscopy as a tool for structure determination. 

The stereoselectivity of these intermolecular reactions between 1-alkoxyallylstannanes and aldehydes induced by boron trifluoride-diethyl ether complex is consistent with an open-chain, antiperiplanar transition state. However, for intramolecular reactions, this transition state is inaccessible, and either (Z)-.yyn-products are formed, possibly from a synclinal process105, or 1,3-isomerization competes113. Remote substituents can influence the stereoselectivity of the intramolecular reaction114. 

Most radicals located on saturated bonds are jt-radicals with a planar configuration and may be depicted with the free spin located in a p-orbital (1). Because such radical centers are achiral, stereochemical integrity is lost during radical formation, A new configuration will be assumed (or a previous configuration resumed) only upon reaction. Stereoselectivity in radical reactions is therefore dependent on the environment and on remote substituents. 

The rate of radical addition is most dramatically affected by substituents either at the site of attack or at the radical center. Remote substituents generally have only a small influence on the stereochemistry and regiospecificity of addition unless these groups are very bulky or the geometry of the molecules is constrained (e.g. intramolecular addition - Section 1,2.4). 

In small molecule chemistry it is well established that p- and more remote substituents (Figure 7.2) can have a substantial influence on radical conformation, formation and reactivity. Thus, it should be anticipated that the nature of the penultimate unit of the propagating chain could significantly modify its reactivity towards monomers and other species. However, the magnitude of the effect w ill be dependent on the exact nature of the remote substituent and the reactants. It is... 

These major trends in act can be qualitatively predicted using semi-empirical molecular orbital calculations. However, the methods fail to adequately predict some electronic effects, remote substituent effects and the influence of hydrogen bonding. Higher level ah initio or DFT calculations provide a better indication of trends in these circumstances. 

Ho, T. L. Trough-Bond Modulation of Reaction Centers by Remote Substituents. 155, 81-158 (1990). 

Scheme 39 Influence of a remote substituent on efficiency and stereochemistry of the RCM step in Fiirstner s total synthesis of amphidinolide T4 (199) [98a] and amphidinolide T3 (12-epf-199) [98b]...

The results obtained with the various metathesis substrates depicted in Scheme 44 demonstrate the lack of a stereopredictive model for the RCM-based formation of macrocycles, not only by the strong influence that may be exhibited by remote substituents, but also by the fact that the use of more reactive second-generation catalysts may be unfavorable for the stereochemical outcome of the reaction. Dienes 212a-f illustrate the influence of the substitution pattern. All reactions were performed with Grubbs first-generation catalyst A... 

Scheme 44 Influence of remote substituents in RCM precursors 212 and 213 and of catalyst activity on stereochemistry in salicylihalamide synthesis [103]...

Directing effects have also been attributed to more remote substituents, as, e.g., a urea NH. 

A particularly useful probe of remote-substituent influences is provided by optical rotatory dispersion (ORD),106 the frequency-dependent optical activity of chiral molecules. The quantum-mechanical theory of optical activity, as developed by Rosenfeld,107 establishes that the rotatory strength R0k ol a o —> k spectroscopic transition is proportional to the scalar product of electric dipole (/lei) and magnetic dipole (m,rag) transition amplitudes,... 

In order to activate remote substituent effects in cycloaromatization reactions, two orthogonal re-systems need to find a way to communicate. At first glance, this task... 

In this analysis, the activation barrier for both C1-C6 and C1-C5 cyclizations of enediyne radical-anions can be described as the avoided crossing between the out-of-plane and in-plane MOs (configurations). One-electron reduction populates the out-of-plane LUMO of the enediyne moiety. At the TS (the crossing), the electron is transferred between the orthogonal re-systems to the new (in-plane) LUMO. This effect leads to the accelerated cyclization of radical-anions of benzannelated enediynes, a large sensitivity of this reaction to re-conjugative effects of remote substituents and the fact that this selectivity is inverse compared to that of the Bergman cyclization. Similar electronic effects should apply to the other reductive cyclization reactions that were mentioned in the introduction. 

Stratakis, M., Sofikiti, N., Baskakis, C. and Raptis, C. (2004). Dye-sensitized intrazeolite photooxygenation of 4-substituted cyclohexenes. Remote substituent effects in regioselectivity and diastereoselectivity. Tetrahedron Lett. 45, 5433-5436... 

The stereoselectivity of 1,2-cis glycosylations is improved by anchimeric assistance of remote substituents at C-3, C-4 or C-6 in the glycosyl donors.68... 

The effect of remote substitutents on the complexing ability of crown ethers [256] towards t-butylammonium salts has been studied by Moore et al. (1977). The results (Table 52) show that electron-attracting substituents decrease the stability of the complex. The t-BuNHJ cation is even more sensitive to remote substituent effects than alkali-metal cations. This fact was attributed to the non-polar character of the alkyl group and to the different structure of the... 

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