Reactivation conformation

Step through the sequence of structures depicting rotation about the carbon-carbon bond in the two dibromoethane isomers l,2-dibromo-l,2-diphenylethane A andfi). For each, plot energy (vertical axis) vs. BrCCBr torsion angle (horizontal axis), and identify all minimum-energy structures. Which of these are reactive conformers , that is, conformers which are set up for either syn or anti elimination of HBr Which are non-reactive conformers , that is, which do not meet the requirements for elimination Do the reactive conformers correspond only to syn elimination, only to anti elimination, or are both pathways represented Which alkene would these reactive conformers lead to Are your results consistent with the observation that each isomer of the starting material gives only one alkene Explain. 

Do any or all of the reactive conformations correspond to the lowest-energy conformations What, if anything, does this tell you about the rate of interconversion of conformers relative to the rate of elimination ... 

Another interesting question concerns the rate at which each tosylate undergoes elimination. A tosylate sample contains molecules with several different conformations. The size of each conformer population depends on conformer energy, and the more reactive tosylate will probably be the one with the largest population of reactive conformers, i.e., molecules whose geometries allow anti elimination. Which tosylate, cis or trans, will have a larger population of reactive conformers Explain how you reached this conclusion. 

Wlien tlie diiral molybdenum -K-allyl-substituted enone 147 was treated witli litliium dimetliylciiptate, formation of adduct 148 witli fait selectivity was observed tSdieme 6.29) [69], Interestingly, bigber selectivities were obtained in tlie presetice of boron ttlbuotlde etlierate. It is assumed tliat Lewis acid coordination induces tlie s-trans reactive conformation 149 [64], Consequently, nudeopb de attack anti to tlie molybdetiLim ftagmetit sbould afford tlie major diastereomer 148. 

For acyclic allylic substrates die situation is mote complex, since a larger number of reactive conformations, and betice corcesponding transition states, compete. Hius, mediyl ciimamyl derivatives 163 tX= O.Acj, upon treatment witli litliiiim dimetliylcuprate, mainly gave tlie S 2 substitution product 166 fentry 1, Tab. 6.6 and Sdieme 6.34) [80]. Hie preference for die S 2 product is expected, since de-conjugation of die alkene system is electronically imfavorable. 

N-Benzoyl-Lalanine methyl ester is in turn about eight times more reactive than is its D enantiomer). The open-chain compounds may not bind to the enzyme in the same manner, however, as does the locked substrate. The conformation around the amido bond of the open-chain compounds, for example, can be transoid rather than cisoid (81). In addition, if equatorial 24 is considered to be the reactive conformer for both the Dand L enantiomers, and if the alanine methyl group is attracted to the hydrophobic aromatic binding subsite, then structures 34 and 38 would result. The L enantiomer of N-benzoyl-phenylalanine methyl ester 38 in this representation has approximately the same conformation as equatorial L-24. But attraction of the methyl of the D enantiomer to the location occupied by the methyl group of the L enantiomer causes the carbomethoxy group to move from the position it occupies in D-24. 

Scheme 1-17 Preferred Reactive Conformations for Allylic Alcohols...

The antibody-catalyzed Diels-Alder reaction developed by Schultz utilized a Diel-Alderase enzyme-like catalyst evolved from an antibody-combining site (Eq. 12.13). The idea is that the generation of antibodies to a structure that mimics the transition state for the Diels-Alder reaction should result in an antibody-combining site that lowers the entropy of activation by binding both the diene and dienophile in a reactive conformation. 

Finally a few sentences are deserved for the vast area of DNA photochemistry. Thymine dimerization is the most common photochemical reaction with the quantum yield of formation in isolated DNA of all-thymine oligodeoxynucleotides 2-3% [3], Furthermore, a recent study based on femtosecond time-resolved transient absorption spectroscopy showed that thymine dimers are formed in less than 1 ps when the strand has an appropriate conformation [258], The low quantum yield of the reaction in regular DNA is suggested to be due to the infrequency of these appropriate reactive conformations. 

The rationalization of stereoselectivity is based on two assumptions. (1) The 1-arylthio-1-nitroalkenes adopt a reactive conformation in which the ally lie hydrogen occupies the inside position, minimizing 1,3-allylic strain. (2) The epoxidation reagent can then either coordinate to the ally lie oxygen (in the case of Li), which results in preferential syn epoxidation or in the absence of appropriate cation capable of strong coordination (in the case of K) steric and electronic effects play a large part, which results in preferential anti epoxidation (Scheme 4.7).52... 

Accelerations (or decelerations) imposed by the cycloamyloses on the rate of an intramolecular reaction may be derived from a conformational effect. The rate of an intramolecular reaction depends not only on the proximity of the reactive groups but also on their relative orientation. For example, Bruice and Bradbury (1965) have shown that the rates of formation of cyclic anhydrides from mono esters of 3-substituted glutaric acids depend on the size of the substituent at the 3-position. This observation was interpreted as a change in the ground state population of reactive and non-reactive conformers as the 3-substituents are varied (Scheme IX). Reason-... 

Recently, an example of cycloamylose-induced catalysis has been presented which may be attributed, in part, to a favorable conformational effect. The rates of decarboxylation of several unionized /3-keto acids are accelerated approximately six-fold by cycloheptaamylose (Table XV) (Straub and Bender, 1972). Unlike anionic decarboxylations, the rates of acidic decarboxylations are not highly solvent dependent. Relative to water, for example, the rate of decarboxylation of benzoylacetic acid is accelerated by a maximum of 2.5-fold in mixed 2-propanol-water solutions.6 Thus, if it is assumed that 2-propanol-water solutions accurately simulate the properties of the cycloamylose cavity, the observed rate accelerations cannot be attributed solely to a microsolvent effect. Since decarboxylations of unionized /3-keto acids proceed through a cyclic transition state (Scheme X), Straub and Bender suggested that an additional rate acceleration may be derived from preferential inclusion of the cyclic ground state conformer. This process effectively freezes the substrate in a reactive conformation and, in this case, complements the microsolvent effect. 

Initially, a complex of nitroalkene (42) with LA (A) is reversibly formed. The efficient concentration of the latter is determined by the reaction conditions and the nature of heterodiene (42) and LA. This complex acts as a Michael substrate and adds alkene (43) to give bipolar adduct B, which undergoes cycliza-tion to give cationic intermediate C. The latter eliminates LA to yield target nitronate (35). In the case of nonconcerted cycloaddition, ionic intermediate B can undergo different isomerization reactions, some of which are considered below. The stereoselectivity of the process depends on the reactive conformation... 

The enone system has to preferably adopt an s-cis or s-trans conformation in the transition state. Which one is favored may depend on the nature of the Lewis acid. It is generally accepted that Lewis acid complexation dramatically stabilizes the s-trans conformation204. The s-cis conformation, however, may be the more reactive conformation. The dienophile may react selectively in this conformation, if the s-trans and s-cis conformations are in equilibrium. 

Antibodies also well catalyze the reactions where a molecule should he forced to adopt a particular and reactive conformation, thanks to privileged interactions with the amino acids of the binding site. For example, ahzymes with a ferrochelatase activity, 7G12, force the mesoporphyrin IX ring to adopt a distorted conformation favorable to the insertion of a Cu ion in the center of the macrocycle,thanks to an interaction with the HlOOc methionine which constrains one of the pyrrole rings to be left outside the plane of porphyrin (Figure 24). 

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