Conformational asymmetric induction

Although increases in the acidity of the aqueous solution were found not to impact on product stereoselectivity, salt effects can prove beneficial (5), presumably as a consequence of the increased internal pressure brought about in the system. The sense of asymmetric induction conforms to operation of the illustrated Cram-like transition state (Scheme 1). This working model is consistent with the nondirective effects brought on by the sterically bulky a-oxy (OBn, OTBS), a-thia (PhS, MeS), and a-amino (BnaN, isoindolyl) groups (9). Under the latter circumstances, chelation is not observed and ir-facial discrimination is achieved instead via Felkin-Anh transition states under the steric control of the substituents. The dimethylamino... 

It is interesting to speculate that asymmetric induction may be the consequence of the exo anomeric effect, a stereoelectronic effect that favors the conformation 5 that places the aglycone O-C bond antiperiplanar to the pyran C(1) —C(2) bond7fi. Related asymmetric induction has also been observed in aldehyde addition reactions of the related, but racemic, pinacol (Z)-y-(tetrahydropyranyloxy)allylboronate49. As indicated in the examples above, however, the level of diastereoselectivity is modest and the only application in asymmetric synthesis is Wuts exo-brevicomin synthesis75. 

Phenyllithium and phenylcopper boron trifluoride yield different diastereomers of the reaction products, i.c., the sense of asymmetric induction is a function of the metal. These results are rationalized on the basis of antiperiplanar 6 and synperiplanar 8 reactive enoate conformations for additions of the copper and lithium reagents, respectively. 

The sense of the asymmetric induction at the /J-carbon of 10 is opposite to that of 7, indicating that 10 reacts with the Gilman reagents in a conformation where the carbonyl is s-trans to the a,(i double bond to avoid steric repulsion of the a-substituent and the camphor residue. 

The asymmetric induction that has been observed in this reaction can be explained in terms of the model shown in Scheme 9. In the most stable conformation the appropriately positioned phenyl group shields selectively the Re,Re face of the chromadiene by 7r,7r-orbital overlap forcing the nucleophile to attack preferentially on the opposite side. 

Six-Membered Ring (exo-Cyclic). The diastereoselective alkylation reactions of exo-cyclic enolates involving 1,2-asymmetric inductions are anti-inductions. In Scheme 2-2, there are two possible enolate chair conformations in which the two possible transition-state geometries lead to the major diaster-eomer 9e (where the substituent takes the equatorial orientation). However, for the case in which R = methyl and X = alkoxyl or alkyl, one would expect the... 

A mechanism for the asymmetric induction for Pd-catalyzed allylic alkylations using chiral ligands such as 23 was proposed on the basis of stereochemical results and the X-ray structure of the intermediate Pd complex 24 <2004T2155>. The enantioselectivity of the alkylations, an example of which is shown in Equation (8), was rationalized by a conformational equilibrium that favored one of two possible 7i-allylpalladium complexes due to steric interference between the aryl substituent on the sulfmyl group of 24 and the phenyl of the 7i-allyl system. 

Also, in 1890 Fischer had proven that the reduction of fructose with sodium amalgam yields a mixture of mannitol and sorbitol and pointed out that this conformed with the van t HofF-Le Bel theory (19). It seems, therefore, that the idea of asymmetric induction was clearly in a state of incubation prior to his publication of the relative configurations of the sugars in 1891. 

Reduction of phenyl trifluoromethyl ketone by 119 generally leads to the (S)-carbinol (Table 15, entry 28). One would expect that conformational changes in the favored transition states would occur. However, the degree of asymmetric induction in these cases is quite low, and the (/ )-carbinol was in fact formed in toluene at 110°C (Table 15, entry 29), suggesting a rather delicate balance of competing interactions. 

As we have seen, one of the main reasons why reactions in crystals lead to high levels of asymmetric induction is that the constituent molecules can be organized in homochiral fixed conformations and intermolecular orientations that are predisposed to formation of a single product enantiomer. With this in mind, it was natural to seek other ways of preorganizing molecules in restricted environments for the purpose of asymmetric synthesis, and one approach that has shown a good deal of promise is the use of chirally modified zeohtes. The great majority of this work has been carried out by Ramamurthy and coworkers at Tulane University [23], and a brief summary is given below. 

To this point, all the examples presented have been ones in which the origin of the asymmetric induction has been unimolecular in nature, that is, the molecules adopt homochiral conformations in the solid state that favor the formation of one enantiomer over the other, usually through the close intramolecular approach of reactive centers bimolecular crystal packing effects appear to play little or no role in governing the stereochemical outcome of such reactions. This raises the interesting question of whether the soUd-state ionic chiral auxiUary approach to asymmetric synthesis could be made to work for conformationally unbiased reactants, i.e., those possessing symmetrical, conformationally locked structures. Two such cases are presented and discussed below. 

Davies, Renaud, and Sibi independently reported the chiral relay approach to control the enhanced steric extension inside a substrate to achieve increased asymmetric induction. However, as our study proves, the asymmetric activation of a tropos catalyst clearly differs from the chiral relay approach, in which substrate conformational control is utilized, since asymmetric activation controls the chiral environment of a tropos catalyst by the addition of a chiral external source (a chiral activator). 

The authors propose a working model relying on the commonly accepted mechanism for BV reactions (Fig. 13, a). Thus the sense of asymmetric induction is determined by the conformation of the Criegee intermediate, which is dictated by the chiral environment created by the catalyst. However, an alternative noncova-lent, bifunctional mechanism may be considered (Fig. 13, b) [80], This work... 

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