Endo-/Exo-orientation

Figure 1.24 Minimum-energy preinsertion catalytic intermediates leading to 1,2 and cis-1,4 polymerizations. In particular, (a) absolute minimum-energy intermediate, for which diene and of allyl group present an endo-endo orientation (that is, their concavities are oriented in opposite direction with respect to Cp ligand), can lead to 1,2-unlike or cis-1,4-like insertions, while (b) higher energy intermediate, for which diene and allyl group present an endo-exo orientation (that is, the concavity of allyl is toward Cp whereas diene is in opposite direction) can lead to 1,2-like or cis-1,4-unlike insertions.

In the competing endo/exo orientations, the reaction can reach the exo TS at the cost of an increased repulsion between the reacting centres and a slightly increased deformation of the maleonitrile fragment this cost is partly recovered by new bond formation. Since vicinal interactions are more favourable to the endo than to the exo mode, the endo mode emerges to be favoured also in the absence of further endo-orienting effects. 

Based on the above-mentioned stereochemistry of the allylation reactions, nucleophiles have been classified into Nu (overall retention group) and Nu (overall inversion group) by the following experiments with the cyclic exo- and ent/n-acetales 12 and 13[25], No Pd-catalyzed reaction takes place with the exo-allylic acetate 12, because attack of Pd(0) from the rear side to form Tr-allyl-palladium is sterically difficult. On the other hand, smooth 7r-allylpalladium complex formation should take place with the endo-sWyWc acetate 13. The Nu -type nucleophiles must attack the 7r-allylic ligand from the endo side 14, namely tram to the exo-oriented Pd, but this is difficult. On the other hand, the attack of the Nu -type nucleophiles is directed to the Pd. and subsequent reductive elimination affords the exo products 15. Thus the allylation reaction of 13 takes place with the Nu nucleophiles (PhZnCl, formate, indenide anion) and no reaction with Nu nucleophiles (malonate. secondary amines, LiP(S)Ph2, cyclopentadienide anion). 

In reactions in which methyl acrylate is used as the dienophile (Scheme 6.33), cycloadditions occur with lower levels of enantioselection (23% ee, as compared to 53 % observed for acrolein), but with significantly higher degrees of diastereoselectivity (17 1, endo-.exo). Improved levels of endo selectivity are observed in the case of the methyl ester (Scheme 6.33) this is perhaps because, at least in part, the dienophile p-system is oriented towards the t-butoxy ligand, where the steric influence of the bulky substituent is expected to be more pronounced. As before, formation of the endo isomer may occur to a greater extent, since the transition structure that leads to the exo isomer would involve energetically unfavorable interactions between the diene... 

It is to be noted that the endo addition rule is not as universal as the cis-addition rule. It can be finished by the more general rule according to which the reagents approach each other from the less hindered side. If that side appears to correspond to an exo-orientation, then exoaddition will occur both under and thermodynamic conditions. 

In all the above cases the attack from the less-hindered side (exo-orientation) was preferred and the ratio exo/endo varied from 19 (for a) to 4 (for c). The increase in weight of endo-orientation for c cannot be explained only on secondary overlap interactions. But they are accounted for by decrease of geometrical constraints. The steric requirements of saturated cyclohexane ring are higher than the steric requirements of sp2 carbon atoms in C. 

In the light of the appreciable puckering found in the seven-membered ring of [16], Childs (1984) recalculated the expected chemical shifts for the exo and endo H(8) protons of [12]. He calculated the difference in chemical shift (A6) to be 6.9 ppm which is in good agreement with the observed AS - 5.86 ppm. However, his calculations revealed that both the exo and endo protons are shielded. This surprising result is opposed to the accepted intuitive view that in an aromatic/homoaromatic system protons with the H(8)(exo) orientation should be deshielded and those with the H(8)(cndo) orientation shielded. This result closely parallels the analogous calculated data for the homocyclopropenyl cation [2] (Schindler, 1987). 

In the tetra-bridged phosphocavitands, the preorganized structure is imposed by the fixed boat-chair conformation of the four fused eight-mem-bered rings. Inwards (i) and outwards (o) configurations are defined relatively to the endo and exo orientations of the P=X bonds (X=0, S, electron pair), and six different stereoisomers arise from the equatorial or axial orientation of the substituents on the phosphorus atoms (Scheme 3). 

Metal complexes of bis(oxazoline) ligands are excellent catalysts for the enantioselective Diels-Alder reaction of cyclopentadiene and 3-acryloyl-l,3-oxa-zolidin-2-one. This reaction was most commonly utilized for initial investigation of the catalytic system. The selectivity in this reaction can be twofold. Approach of the dienophile (in this case, 3-acryloyl-l,3-oxazolidin-2-one) can be from the endo or exo face and the orientation of the oxazolidinone ring can lead to formation of either enantiomer R or S) on each face. The ideal catalyst would offer control over both of these factors leading to reaction at exclusively one face (endo or exo) and yielding exclusively one enantiomer. Corey and co-workers first experimented with the use of bis(oxazoline)-metal complexes as catalysts in the Diels-Alder reaction between cyclopentadiene 68 and 3-acryloyl-l,3-oxazolidin-2-one 69 the results are summarized in Table 9.7 (Fig. 9.20). For this reaction, 10 mol% of various iron(III)-phe-box 6 complexes were utilized at a reaction temperature of —50 °C for 2-15 h. The yields of cycloadducts were 85%. The best selectivities were observed when iron(III) chloride was used as the metal source and the reaction was stirred at —50 °C for 15 h. Under these conditions the facial selectivity was determined to be 99 1 (endo/exo) with an endo ee of 84%. 

When subjected to strong bases, gem-dihalocyclopropanes undergo dehydro-halogenations, and cyclopropenes are formed. These are generally unstable under the reaction conditions and participate in further transformations. The most common of these processes is the isomerization of the newly formed double bond from the endo- to the exo-orientation, followed by a second dehydrohalogenation step. The methylenecyclopropenes thus generated are still not stable, and subsequently tend to rearrange to less strained systems. 

If the system in question possesses a CH2 group located above the ring in a similar way to the case of the homotropenylium cation, the shift difference between endo- and exo-orient ed proton should also adopt a maximum value for the homoaromatic system. 

In practice, the adduct with the endo2 configuration usually is the major product. As a general rule, Diels-Alder additions tend to proceed to favor that orientation that corresponds to having the diene double bonds and the unsaturated substituents of the dienophile closest to one another. This means that addition by Equation 13-3 is more favorable than by Equation 13-4, but the degree of endo-exo stereospecificity is not as high as the degree of stereospecificity of suprafacial addition to the diene and dienophile. 

Calculations of the strain energies of the endo and exo forms of the 1-methyl-, 1-fluoro- and 1-chlorosilatranes carried out by the methods of molecular mechanics found these assumptions to be unsound176-180. Even with an additional consideration of the intramolecular electrostatic interactions177-179, employment of the usual force field for tetracoordinate silicon led to potential functions of the endo-exo isomers (equation 44) with a deeper minimum corresponding to the exo form 47, with ouf-orientation of the nitrogen. 

Whereas several X-ray structural analyses prove the endo orientation of the oxygen atom of the oxaziridine ring, the assumption of an exo oriented hydroperoxy group in 83 is based solely on the opposite sense of asymmetric induction observed for 82 and 83. 

These endo-exo preferences are energetically small and are of the order of a kcal mol-1. Consequently, factors such as dipole-dipole,27 electrostatic,28 steric29 and solvent effects27,30 can also influence the stereoselectivity. Secondary orbital interactions may not provide all of the answers, but no other theory can rationalize both the preferential endo orientation of 4 + 2 and 8 + 2 cycloadditions and the exo orientation of 6 + 4 cycloadditions so efficiently. See also Exercise 12. 

Maleic anhydride reacts with cyclopenta-1,3-diene in a Diels-Alder reaction. Since there is a plane of symmetry, the reaction can lead to two achiral compounds, which are diastereomers of each other, containing an endo- or exo-oriented dicarboxylic anhydride group. These differ in absolute and relative configuration at the bond shared by both rings. Under normal conditions the Diels-Alder reaction proceeds stereospecifically to yield preferentially the endo product. Note that in the tricyclic product no trans fusion in the ring system is possible as a consequence of the reaction mechanism. Subsequent reduction of the products therefore affords two diols, which are also diastereomers of each other. These may be separated by chromatography on an achiral stationary phase. 

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