Conformational transmission

An example of this effect, called conformational transmission, is found in ergost-7-en-3-one (5) and cholest-6-en-3-one (6), where 6 condenses with benzaldehyde 15 times faster than 5. The reaction site in both cases is the earbonyl group, and the rate increases because moving the double bond from the 7 to the 6 position causes a change in conformation at the carbonyl group (the difference in the side chain at C-17 does not affect the rate). 

Compounds 28 and 29 are pentacoordinated models of the activated state of 3, 5 -cyclic adenosine monophosphate (cAMP), which plays a dominant role as second messenger in cell metabolism regulation69. A conformational transmission effect found by dynamic H and 13C NMR70 results in 51% of trans position for the Oa) and 0(2) atoms, but only when... 

The origin of the observed 1,4-asymmetric induction in Michael reactions of chiral imines (Scheme 28) has been rationalized by conformational transmission of chirality. Thus, the phenethylamine auxiliary forces the cyclohexene part of the intermediate enamine into a half-chair conformation (140) that is 0.8 kcal mol-1 lower in energy than (141). Axial attack as shown then leads to the major product the energy difference between (140) and (141) roughly correlates with the observed diastereoselectivity ( 9 l).105... 

The interdependence of these conformational states and the possibility of transmission of conformational modification through a series of interdependent conformational states led to the definition of the gear-effect a conformational transmission, which is caused by interaction between polyhedral substituents and which depends on their polyhedral shapes. As a corollary of this definition, it was possible to outline the difference between the gear-effect and the classical buttressing effect (76JA2847). The two effects depend on different modes of minimization of the steric strain introduced by two... 

If the double bond is at a ring junction, the ring with the double bond, as well as the fused ring, will both suffer distortion. Such a conformational transmission appears important in interpreting and predicting the outcome of some addition reactions, including the osmylation reaction46 74. 

Studies in the field of tetracyclic and pentacycMc triterpenes [gsa] show that the dissociation constants for C 3)-cyanohydrins vary with structural changes even in rings C and D. A comparison with kinetic data for formation of 2-benzylidene derivatives of the same ketones cf. p. 178) indicates that the effect is largely one of conformational transmission. 

Robinson and Whalley [195] interpreted the mechanism of conformational transmission in two ways. Inspection of a Dreiding model reveals that a change from to hybridisation at C(2) is accompanied by a slight flattening of the... 

A substituent in the steroid molecule can influence reactions at remote centres in three distinct ways, which may be classified as (i) inductive effects (2) electrostatic field effects and (3) conformational transmission. It is difficult to disentangle these effects completely, for all are likely to be operative to some extent, even though for a partioolar reaction one or another may be dominant. The limited number of detailed investigations so far reported make it unwise to generalise at present. 

An example of conformational transmission of relatively short range illustrates its mode of action. The D-homo 17a-methyl-i 7-ketone (2) may be equilibrated with base to give... 

Variations in the magnitudes of Cotton effects associated with the 4-en-3-one system in a series of C(17)-substituted oestr-4-en-3-ones have been attributed to conformational transmission the C(17)-substituents are thought to influence the geometry of the molecule, and as a consequence the chirality of the enone chromophore. In view of the discussion above (see also below), it seems probable that the electronic character of C(17)-substituents should also be taken into account in assessing their effects, but the separation of electronic and conformational effects in such a situation is notoriously difficult. 

Lucero, M. J., Houk, K. N. Conformational Transmission of Chirality The Origin of 1,4-Asymmetric Induction in Michael Reactions of Chiral Imines. J. Am. Chem. Soc. 1997, 119, 826-827. 

Steroid Properties and Reactions (Chapter 1).— The application of modem computing techniques to valence-force calculations marks a new phase in the conformational analysis of steroids. This approach brings within reach the accurate specification of preferred conformations, and the evaluation of conformational energies and conformational transmission effects and thus promises to complement the chemical and physical techniques used hitherto. The introduction of lanthanide shift reagents in n.m.r. spectroscopy promises to be particularly valuable in the analysis of steroids since it overcomes to a large extent a major limitation, namely the near-equivalence of many protons attached to the steroid nucleus. Further useful advances in applying solvent shifts... 

The flattening of ring a in a 4,4-dimethyl-5a-androstan-3-one, inferred from spectroscopic data, is confirmed by X-ray crystallography. Distortion arises mainly from rotation about the C(4)-C(5) bond, and is markedly less in the corresponding 19-nor-compound. The reality of conformational transmission is evident from different conformations of ring d in the 10)3-H and 10/ -methyl compounds. Ring d approximates to a half-chair, distorted either towards a C-14 envelope, or towards a C-13 envelope, respectively. 

The alternative explanation of zwitterionic hexaco-ordinated intermediates (or transition states) to account for the faster pseudorotation rates with X=0, appears to be negated by studies of pseudorotational barriers in (16ab). In these molecules, no conformational transmission effect is possible but the presence of the tetrahydrofuran oxygen atoms would permit a zwitterionic T.S. to accelerate ligand reorganization. In fact the pseudorotational barriers for (16a) and (16b) at 55.2 and 71.9 kjmol respectively, are in excellent agreement with those found for (11a) and (11c) where no hexaco-ordinate species are possible along the isomerisation pathway. 

Although interest in pn-bonded compounds continues at a high level the pace of advance seems to be slackening, perhaps reflecting that the most interesting chemistry in this area has now been revealed. The year has seen a further consolidation of knowledge in the area of hypervalent phosphorus chemistry and the principles established in this area have expanded further into the chemistry of As, Sb, Bi and Si. Notable contributions have appeared on the importance of the conformational transmissions effect to ligand... 

The relative rates of basic methanolysis of the stereoisomers of 631 was attributed to the participation of pentacoordinate intermediates in which the six-membered ring takes up the equatorial-equatorial position and in which that from the equatorial isomer would have an electronic interaction between ring oxygen and oxygen of the exocyclic P—OPh bond implied by structure 632. A conformational transmission effect was proposed to account for the hydrolyses of the diphenylphosphinic esters 633 (X, Y = O or... 

The equilibrium between 2)6,3i5-disubstituted 5a- and 5)5-6-ketones (12) shows a surprising and unexplained dependence upon the nature of the C-17 substituent. The presence of an axial 2) -substituent destabilizes the 5a-isomer, shifting the equilibrium towards the 5jS-isomer where the 2)5,10/5 diaxial interaction is relieved. The influence of the C-17 substituent on the equilibrium varied, over a series of eight different compounds, between the extremes represented by 5 5a ratios of 0.13 (17/5-OH) and 7.06 (17/5-COMe). Steric effects, conformational transmission, and inductive and electrostatic field effects are each discussed and dismissed as being incapable of providing an adequate explanation of the data. 

Esters, Ethers, and Related Derivatives of Alcohols.— The mode of transmission of the effect of remote substituents upon reaction rates and equilibria has been discussed previously under three headings, viz. inductive effects, electrostatic field effects, and conformational transmission.A new survey,quoting over 50 references, covers most of the main studies in this field, and suggests direct interactions as a fourth class. Rates of acetylation of 3j3-hydroxy-A"-steroids variously substituted at C-17 show only small variations, which did not permit of any mechanistic interpretation. The formation of 17a,20- and 20,21-cyclic carbonates and their use as protecting groups for diols have been investigated. ... 

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