Lewis acid complexes conformation

FIGURE 5. Important conformations of Lewis acid complexed aldehydes... 

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. 

In 1997, the first truly catalytic enantioselective Mannich reactions of imines with silicon enolates using a novel zirconium catalyst was reported [9, 10]. To solve the above problems, various metal salts were first screened in achiral reactions of imines with silylated nucleophiles, and then, a chiral Lewis acid based on Zr(IV) was designed. On the other hand, as for the problem of the conformation of the imine-Lewis acid complex, utilization of a bidentate chelation was planned imines prepared from 2-aminophenol were used [(Eq. (1)]. This moiety was readily removed after reactions under oxidative conditions. Imines derived from heterocyclic aldehydes worked well in this reaction, and good to high yields and enantiomeric excesses were attained. As for aliphatic aldehydes, similarly high levels of enantiomeric excesses were also obtained by using the imines prepared from the aldehydes and 2-amino-3-methylphenol. The present Mannich reactions were applied to the synthesis of chiral (3-amino alcohols from a-alkoxy enolates and imines [11], and anti-cc-methyl-p-amino acid derivatives from propionate enolates and imines [12] via diastereo- and enantioselective processes [(Eq. (2)]. Moreover, this catalyst system can be utilized in Mannich reactions using hydrazone derivatives [13] [(Eq. (3)] as well as the aza-Diels-Alder reaction [14-16], Strecker reaction [17-19], allylation of imines [20], etc. 

Lewis et al. examined the photocycloaddition of 9-methoxycar-bonylphenanthrene with 2,3-dimethyl-2-butene in the absence or presence of a Lewis acid [213], The conformations of the free and complexed molecules in the ground states have been investigated by means of NMR and Gaussian 88 calculations. In the absence of a Lewis acid, a second unidentified adduct and the photodimer are observed as well as the cycloadduct at the 9,10-position (Scheme 41). In the presence of a Lewis acid, neither the second adduct nor the photodimer is detected, and the yield of the photocycloadduct is inferior to that obtained in the absence of Lewis acid. From the fluorescence quenching experiments, it seems likely that the photocycloaddition occurs via a triplet mechanism, whereas the photocycloaddition of their Lewis acid complexes occurs via a singlet mechanism (Table 2). 

Interestingly, the Diels-Alder reaction of the acrylate of o-pantolactone and cyclopentadiene in the presence of 2 equiv. MAD results in high diastereoselectivity which is the opposite of that encountered with ordinary Lewis acids. The low-temperature NMR spectrum of the Lewis acid complex of the acrylate of D-pantolactone showed that an ordinary Lewis acid such as SnCU forms the chelate complex [O] (Sch. 132). In the 1 1 acrylate-MAD complex, structure [P], although predominant, seems to be in equilibrium with the minor complex [Q] with s-cis conformation this... 

Aluminmn catalysts derived from the three BINOL derivatives outlined in Table 14 have been used in the asymmetric cycloaddition of the A-crotyloxazolidinone 175 and cyclopentadiene. These reactions are slower and require the use of stoichiometric amounts of catalyst. Although the dienophiles 175 are bidentate and should lead to a more conformationally restrained dienophile-Lewis acid complex, asymmetric induction is quite low. 

NMR spectroscopy of Lewis acids complexed widi a,p-unsaturated carbmyls has shed light on their structure and conformational preferences. Low temperature H and C NMR spectra of BF3/2-cyclo-hexenone indicated slow exchange at -80 C. A mixture of syn and anti complexes was detected but the anti preference seemed to increase with increasing bulk at the a-carbon. 

In agreement with ab initio predictions, Lewis acid complexation with a,p-unsaturated carbonyls seems to encourage adoption of the s-trans conformation. In the complexes of conjugated esters and ketones the gearing effect discussed previously may be responsible for the abundance of the (Z)-syn-s-trans conformation. 

Model B describes the case in which a chelating group is present in the dienophile, as shown in Figure 40. In contrast to model A, the Lewis acid complex is now anti-s-cis, although the (Z)-ester conformation is still intact. The s-cis conformation is also observed in two crystal structures of chelated complexes, although one of these (c/. Figure 25) is somewhat unusual. "... 

It has bmn noted that although the linear geometry is consistently predicted for cationic Lewis acid carbonyl complexes in ab initio calculations, extrapolation of these results to neutral Lewis acid complexes may not be justified. Semiempirical MNDO calculations predicted the bent conformation as the lowest energy structure for neutral Lewis acidic derivatives of beryllium, boron and aluminum complexed with trans-2,3-dimethylcyclopropanone, whereas linear structures were predicted for the cationic complexes of beryllium and aluminum (Table I). ... 

This phenomenon was rationalized by arguing that the C=0 dipole moment is decreased upon Lewis acid complexation, thereby reducing dipole-induced dipole stabilization of the lowest energy (methyl) eclipsed conformer. 

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