Conformer chiral carbonyls

A homodimer of a tetra-urea calix[4]arene consisting of identical phenolic units A is composed of two enantiomers with C4-symmetry, which results in overall S8-symmetry. Consequently, a heterodimer with a second calixarene consisting of four units B must be chiral, but this chirality is due only to the directionality of the hydrogen-bonded belt or (in other words) to the orientation of the carbonyl groups [42,43]. Rotation around the (four) aryl-NH bonds leads to the opposite enantiomer (conformational chirality). 

The additions of hydride donors to the C=0 double bonds of a-chiral carbonyl compounds take place via transition states whose stereostructures do not reflect the preferred conformations of the substrates. 

After Cram had discovered the selectivities now named after him, he proposed the transition state model for the formation of Cram chelate products that is still valid today. However, his explanation for the preferred formation of Cram products was different from current views. Cram assumed that the transition state for the addition of nucleophiles to a-alkylated carbonyl compounds was so early that he could model it with the carbonyl compound alone. His reasoning was that the preferred conformation of the free a-chiral carbonyl compound defines two sterically differently encumbered half-spaces on both sides of the plane of the C=0 double bond. The nucleophile was believed to approach from the less hindered half-space. 

What does this mean for stereoselectivity Conformations of the chiral carbonyl compound that place an electronegative atom ""Nil perpendicular to the C=C) bond will be more reactive—size... 

In order to explain reactions of chiral alkenes like this, we need to assess which conformations are important, and consider how they will react, just as we have done for chiral carbonyl compounds. Much of the work on alkene conformations was done by K.N. Houk using theoretical computer models, and we will summarize the most important conclusions of these studies. The theoretical studies looked at two model alkenes, shown in the margin. 

The stereochemistry of the reactions of chiral carbonyl compounds with nucleophiles has been a topic of considerable theoretical and synthetic interest since the pioneering study by Cram appeared in 1952. The available predictive models focus entirely on the conformational and stereoelectronic demands of the chiral carbonyl substrate, the implicit assumption being that the relative stabilities of the competing transition states are determined only by stereoelectronics and the minimization of nonbonded interactions between the substituents on the chiral center and the nucleophile. These models totally ignore the possibility, however, that the geometric requirements of the nucleophile may also have an effect on reaction diastereoselectivity. Considerable evidence is now available, particularly in the reactions of Type I (Z)-crotylboronates and Z(0)-metal enolates, that the stereochemistry of the nucleophile is indeed an important issue that must be considered when assessing reaction diastereoselectivity. 

The fragmentation/cyclization ratio is determined by the relative orientation of the respective molecular orbitals, and thus by the conformation of diradical species 2. The quantum yield with respect to formation of the above products is generally low the photochemically initiated 1,5-hydrogen shift from the y-carbon to the carbonyl oxygen is a reversible process, and may as well proceed back to the starting material. This has been shown to be the case with optically active ketones 7, containing a chiral y-carbon center an optically active ketone 7 racemizes upon irradiation to a mixture of 7 and 9 ... 

Figure 8. Equatorial el,e2, e3 and axial al,a2, a3 conformations of the carvone molecule. The asymmetric (chiral) carbon is shaded light gray, the =CH2 carbon in the isopropenyl tail is shaded mid-gray and the carbonyl oxygen atom is shaded dark gray. Taken from Ref. [38].

Results for these CEBEs are presented in Table 1. As can be seen, for the carvone variants I-V the various substitutions have absolutely no effect at the carbonyl C=0 core, and are barely significant at the chiral center that lies between the carbonyl and substituent groups in these molecules. Only upon fluorine substitution at the tail (molecule VI) does the C=0 CEBE shift by one-half of an electronvolt the second F atom substitution adjacent to the C=0 in the difluoro derivative, VII contributes a further 0.6-eV shift. This effect can be rationalized due to the electron-withdrawing power of an F atom. Paradoxically, it is these fluorine-substituted derivatives, VI, VII, that arguably produce b curves most similar to the original carvone conformer, I, yet they are the only ones to produce a perturbation of the ground-state electron density at the C li core. This contributes further evidence to suggest that, at least for the C li... 

Summary of the Relationship between Diastereoselectivity and the Transition Structure. In this section we considered simple diastereoselection in aldol reactions of ketone enolates. Numerous observations on the reactions of enolates of ketones and related compounds are consistent with the general concept of a chairlike TS.35 These reactions show a consistent E - anti Z - syn relationship. Noncyclic TSs have more variable diastereoselectivity. The prediction or interpretation of the specific ratio of syn and anti product from any given reaction requires assessment of several variables (1) What is the stereochemical composition of the enolate (2) Does the Lewis acid promote tight coordination with both the carbonyl and enolate oxygen atoms and thereby favor a cyclic TS (3) Does the TS have a chairlike conformation (4) Are there additional Lewis base coordination sites in either reactant that can lead to reaction through a chelated TS Another factor comes into play if either the aldehyde or the enolate, or both, are chiral. In that case, facial selectivity becomes an issue and this is considered in Section 2.1.5. 

Entry 3 involves another sultam auxiliary. The chirality of the product is consistent with approach of the diene from the re face of a conformation in which the carbonyl oxygen is syn to the sulfonyl group. 

With chiral enol species (/ )-silylketene acetal derived from (1 R,2S)-N-methyl ephedrine-O-propionate, both the aldehyde carbonyl and the ephedrine NMe2 group are expected to bind to TiCU, which usually chelates two electron-donating molecules to form ra-octahedral six-coordinated complexes.25 Conformational freedom is therefore reduced, and the C-C bond formation occurs on the six-coordinated metal in a highly stereoselective manner.18... 

Cadogan and coworkers160 developed a fructose-derived l,3-oxazin-2-one chiral auxiliary which they applied in the Diels-Alder reactions of its iV-enoyl derivatives 246 with cyclopentadiene using diethylaluminum chloride as the Lewis acid catalyst. The reactions afforded mixtures of endo 247 and exo 248 (equation 68). The catalyst binds to the chiral dienophile in a bidentate fashion (co-ordination to both carbonyl groups). As a consequence, the dienophile is constrained to a rigid conformation which accounts for the almost complete diastereofacial selectivities observed. 

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