Alkenes chiral, conformation

Figure 12-20 Representation of (a) achiral and (b) chiral conformations of frans-cycloalkenes, using frans-cyclooctene as a specific example. For frans-cyclooctene, the achiral state is highly strained because of interference between the inside alkenic hydrogen and the CH2 groups on the other side of the ring. Consequently the mirror-image forms are quite stable. With frans-cyclononene, the planar state is much less strained and, as a result, the optical isomers are much less stable. With frans-cyclodecene, it has not been possible to isolate mirror-image forms because the two forms corresponding to (b) are interconverted through achiral planar conformations corresponding to (a) about 1016 times faster than with frans-cyclooctene.

The concepts learned from the examples in Fig. 3 have been used to develop more complex and efficient systems. The idea of trans-cis isomerization, for instance, has led to the construction of a molecule that may be converted between its states by the use of circularly polarized light (Fig. 4) [23]. The alkene 7 is forced to adopt a chiral conformation as a consequence of its steric requirements, allowing isomerization between the trans- and ds-states (7a and 7b) to be accomplished. The state of the system can be monitored easily by measuring the rotation of linearly polarized light. The construction of these chiroptical molecular switches is of great interest because of their ability to be both written to and read by non-interfering photonic means [24]. 

Where, as with (24) above, both Cp and C are chiral, elimination from the two conformations will lead to different products—the trans-alkene (25) from (24a) and the cis-alkene (26) from (24b). Thus knowing the configuration of the original diastereoisomer (e.g. 24), and establishing the configuration of the geometrical isomeride(s) that is formed, enables us to establish the degree of stereoselectivity of the elimination process. In most simple acyclic cases, ANTI elimination is found to be very much preferred, e.g. in about the simplest system, (26) and (27), that permits of stereochemical distinction ... 

The chiral sites which are able to rationalize the isospecific polymerization of 1-alkenes are also able, in the framework of the mechanism of the chiral orientation of the growing polymer chain, to account for the stereoselective behavior observed for chiral alkenes in the presence of isospecific heterogeneous catalysts.104 In particular, the model proved able to explain the experimental results relative to the first insertion of a chiral alkene into an initial Ti-methyl bond,105 that is, the absence of discrimination between si and re monomer enantiofaces and the presence of diastereoselectivity [preference for S(R) enantiomer upon si (re) insertion]. Upon si (re) coordination of the two enantiomers of 3-methyl-l-pentene to the octahedral model site, it was calculated that low-energy minima only occur when the conformation relative to the single C-C bond adjacent to the double bond, referred to the hydrogen atom bonded to the tertiary carbon atom, is nearly anticlinal minus, A- (anticlinal plus, A+). Thus one can postulate the reactivity only of the A- conformations upon si coordination and of the A+ conformations upon re coordination (Figure 1.16). In other words, upon si coordination, only the synperiplanar methyl conformation would be accessible to the S enantiomer and only the (less populated) synperiplanar ethyl conformation to the R enantiomer this would favor the si attack of the S enantiomer with respect to the same attack of the R enantiomer, independent of the chirality of the catalytic site. This result is in agreement with a previous hypothesis of Zambelli and co-workers based only on the experimental reactivity ratios of the different faces of C-3-branched 1-alkenes.105... 

The use of chiral auxiliaries to induce (or even control) diastereoselectivity in the cycloaddition of nitrile oxides with achiral alkenes to give 5-substituted isoxazolines has been investigated by a number of groups. With chiral acrylates, this led mostly to low or modest diastereoselectivity, which was explained in terms of the conformational flexibility of the vinyl-CO linkage of the ester (Scheme 6.33) (179). In cycloadditions to chiral acrylates (or acrylamides), both the direction of the facial attack of the dipole as well as the conformational preference of the rotamers need to be controlled in order to achieve high diastereoselection. Although the attack from one sector of space may well be directed or hindered by the chiral auxiliary, a low diastereomer ratio would result due to competing attack to the respective 7i-faces of both the s-cis and s-trans rotamers of the acrylate or amide. 

The stereochemistry of 1,3-dipolar cycloadditions of azomethine ylides with alkenes is more complex. In this reaction, up to four new chiral centers can be formed and up to eight different diastereomers may be obtained (Scheme 12.4). There are three different types of diastereoselectivity to be considered, of which the two are connected. First, the relative geometry of the terminal substituents of the azomethine ylide determine whether the products have 2,5-cis or 2,5-trans conformation. Most frequently the azomethine ylide exists in one preferred configuration or it shifts between two different forms. The addition process can proceed in either an endo or an exo fashion, but the possible ( ,Z) interconversion of the azomethine ylide confuses these terms to some extent. The endo-isomers obtained from the ( , )-azomethine ylide are identical to the exo-isomers obtained from the (Z,Z)-isomer. Finally, the azomethine ylide can add to either face of the alkene, which is described as diastereofacial selectivity if one or both of the substrates are chiral or as enantioselectivity if the substrates are achiral. 

Numerous chiral cyclic allyl alcohol derivatives have been used as the chiral alkene part in 1,3-dipolar cycloadditions. In general, the more rigid conformational... 

Alkenyl nitrones, having the alkene connected to the nitrone nitrogen atom, have been used in another approach to intramolecular reactions (231-235). Holmes and co-workers have this method for the synthesis of the alkaloid (—)-indolizidine 209B 137 (210,231). The alkenyl nitrone 134, was obtained from the chiral hydroxylamine 133 and an aldehyde. In the intramolecular 1,3-dipolar cycloaddition, 135 was formed as the only isomer (Scheme 12.45). The diastereofacial selectivity was controlled by the favored conformation of the cyclohexane-like transition state in which the pentyl group was in a pseudoequatorial position, as indicated by 134. Further transformation of 135 led to the desired product 137. 

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