Conformational stereochemical control

The importance of conformational analysis is made evident, for instance, in the total synthesis of reserpine (9) in which Woodward [6] introduced conformational stereochemical control, in two versions thermodynamic control and kinetic control. 

The foregoing stabilizing 1,3-diaxial interaction was shown to have potentially useful applications for stereochemical control of addition reactions56. The /l-trimethylstannyl cyclohexenone ketal 65 affords a nearly 1 1 mixture of isomeric c/s-diols 66 and 67 when hydroxylated with OsC>4 (equation 25). However, the chlorostannane 68 upon hydroxylation with OSO4, then Sn methylation, yields a 94 6 mixture favoring the a,a,-diol 66. Evidently, the conformational change induced by the 1,3-diaxial donor-acceptor... 

The surface complementarity between the quantum activated complex and the catalytic surrounding media is the main idea of the present theory. The oscillating stereochemical control of the synthesis of thermoplastic elastomeric polypropylene recently reported by Coates and Waymouth [208] can be easily interpreted in terms of catalyst changing surface complementarity. Hill and Zhang have discovered a molecular catalyst that experiences a kinetic and thermodynamic drive for its own reassembly and repair under conditions of catalysis [209]. This is basically what an enzyme does when moving from the apo-structure towards the catalytically apt conformation. 

Sometimes, in order to exert the pertinent stereochemical control, instead of inducing a conformational change, it is necessary to resort to a change of... 

Concerted mechanisms have also been considered to justify the high degree of stereoselectivity observed in many instances as, for example, in the cases shown in Scheme 3 [13,18-21], However, the high stereochemical control often observed in many ODPM rearrangements does not necessary imply that the reaction is taking place via concerted mechanisms. A stepwise process is also consistent with the stereochemical outcome of the reaction, where there are conformational or configurational restrictions to rapid C—C rotation. This subject has been extensively discussed and reviewed by Schuster [16]. 

The reaction occurs suprafacially across the allyl unit through a five-membered ring envelope-shaped transition state. The five-membered cychc transition state of [2,3]-sigmatropic rearrangement shows greater conformational flexibility than the six-membered transition state of [3,3]-sigmatropic rearrangements and should therefore be far more susceptible to the effects of stereochemical control by substituents. ... 

The key issue for synthesis of pure stereoisomers, in either racemic or enantiomerically pure form, is that the configuration at newly created chiral centers must be controlled in some way. This may be accomplished in several ways. An existing functional group may control the approach of a reagent by coordination. An existing stereocenter may control reactant conformation, and thereby the direction of approach of a reagent. Whatever the detailed mechanism, the synthetic plan must include the means by which the required stereochemical control is to be achieved. When this cannot be done, the price to be paid is a separation of stereoisomers and the resulting reduction in overall yield. 

This alkynone thermolysis has served as the key step in several natural product syntheses. The considerations that lead to regio- and stereochemical control are illustrated by an elegant synthesis of clovene 725. Thermolysis of the symmetrical alkynone 4 could lead to three different enones, two of which (5 and 6) arc illustrated. In fact, only 8-methyltricyclo[8.3.1.01 5]dodec-3-en-2-one (5) is isolated, in 80% yield. The structure of 5 was confirmed by straightforward conversion to the tricyclic hydrocarbon clovene. The outcome of the thermolysis was anticipated, as it had previously been observed that C-H insertion is most facile when the intermediate alkylidene can achieve coplanarity with the target C-H bond. In this system, such coplanarity is achievable only via the boat conformation of one of the two symmetrical rings. 

Although a disadvantage here, in other cases equilibration to the more stable all-equatorial conformation can be a useful source of stereochemical control. You will very shortly see an example of this. 

The process of enamine alkylation has found widespread application in natural product synthesis188. Since the overall sequence involves the reaction of a nitrogen moiety with a ketone to form a reactive intermediate, modification of the process through the use of chiral enamine seemed ideal for asymmetric induction. Previous attempts to obtain stereochemical control were for a long time unsuccessful, because proper attention had not been directed to the involvement of two reactive conformations, interconvertible... 

To show how ring-closing reactions, particularly those on the side of an already existing ring, can give excellent stereochemical control. And again - the importance of conformation in six-membered rings. 

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