Stereochemical predictions

The stereochemical features of the Claisen rearrangement are very similar to those described for the Cope rearrangement, and reliable stereochemical predictions can be made on the basis of the preference for a chairlike transition state. The major product has the -configuration at the newly formed double bond because of the preference for placing the larger substituent in the pseudoequatorial position in the transition state. ... 

In general, stereochemical predictions based on the Alder rule can be made by aligning the diene and dienophile in such a way that the unsaturated substituent on the dienophile overlaps the diene n system. The stereoselectivity predicted by the Alder rule is independent of the requirement for suprafacial-suprafacial cycloaddition, since both the endo and exo transition states meet this requirement. 

Note that the first example bears out the stereochemical prediction made earlier. Only the two isomers shown were formed. In the second example, migration can > continue around the ring. Migrations of this kind are called circumambulatory rearrangements. Such migrations are known for cyclopentadiene, pyrrole, and phosphole derivatives.[1,5] Hydrogen shifts are also known with vinyl aziridines." ... 

The stereochemical predictions for the intramolecular cycloadditions described in Scheme 10 and Eq. (9) in terms of MMX calculations are compared to experimental results in Table 9. The most striking trend from inspection of the data is the predominance of trans cycloadduct. The computed energy difference between the transition states 88 and 89 (Fig. 1) when R = H corresponds to 1.42 kcal/mol. The experimental preference for the trans-cis isomers 72 a and 86 a is correctly predicted by the MMX calculations. It seems reasonable to invoke A strain which is present in the transition state 88 leading to the cis product 71 a to explain the trans over cis preference. Since the substituent R is... 

It may be of interest to note that the stereospecific transformation shown in equation 15 has been cited as the first reported observation of an 1 - 3 chirality transfer. It is evident that on rearrangement of optically active 6d to 7d, the chiral center at C-a is eliminated and a new one created at C-y. The term self-immolative asymmetric synthesis has also been used to describe syntheses of this kind. As pointed out by Hoffmann , quantitative 1 - 3 chirality transfer will follow from the suprafacial - course of rearrangement, provided the reactant has a uniform configuration at the j8, y-double bond. This stereochemical prediction has also been confirmed by the results obtained in several other [2,3]sigmatropic rearrangements, subsequently reported " . 

Using (-)-lOO [46] as a chiral auxiliary tethered to the enolether, one face of the alkene can be specifically blocked by a n-n interaction of the phenyl rest for the [2 r5+2 r ] cycloaddition with a ketene [47], resulting in the highly diastereoselective formation of the cyclobutanone 102 (Scheme 15). The observed regio- and stereoselectivity is in accord with the stereochemical predictions made on the basis of the Woodward-Hoffmann... 

The reaction sequence using l,3-oxathiolan-4-ones77,81 is very similar to the above protocol with l,3-dioxolan-4-ones77. Thus, enolate 17 was transformed into 18 in good yield with excellent diastereoselectivity. In the cases of 18i and 18j there is a second asymmetric center in the enolate which makes stereochemical predictions very difficult. 

The correctness of the stereochemical prediction based on the comparison of the NMR data of each diastereomeric pair could be assessed through this study, furthermore, the observation that the methyl protons and the vinylic proton of the (Ra,Sc)- and of the (Ra,Rc)-diastereomer, respectively, show an NOE signal with the ortho and meta protons of only one binaphthyl moiety clearly indicates that the rotation around the P—N bond is hindered. In this structure the presence of a bulky chlorine substituent in the 8-position may account for the restricted rotation and a similar behavior would be expected for all 8-substituted QUINA-PHOS ligands. 

For molecules containing only one type of metal—ligand bond, the above energy relation is sufficient to enable very accurate stereochemical predictions to be made. 

Making Stereochemical Predictions with the VBSCD Model... 

The state-symmetry correlation also indicates that electrocyclic radical interconversion favors a conrotatory path from the first excited state and a disrotatory path from the second excited state. Because of the proximity of the energy levels and the violations of the noncrossing rule, it is probable that the excited state process will not be highly stereoselective. The same detailed considerations must be applied to the five-atom five-electron system and yield the results given in Table 1. Differences between the stereochemical predictions of Table 1 and those of others (Woodward and Hoffmann, 1965a Fukui and Fujimoto, 1966b Zimmerman, 1966) tend to be limited to the excited-state reactions of odd-atom radicals. 

These results are compatible with stereochemical predictions derived through orbital symmetry theory, assuming a one-step n2s - -n2a addition. But secondary deuterium kinetic isotope effects on the allene plus allene thermal (2+2) cycloaddition seem to require a two-step mechanism with formation of an intermediate 44>, and as Moore and coworkers fully realized 83> stereoselective formation and reactions of 2,2 -biallylene intermediates will equally well account for the product ratios. In their rationale, two allenes approach and distort through simultaneous conrotatory twistings to give the perpendicular 2,2 -biallylene intermediate, which closes to form products in a disrotatory fashion. The experimentally observed stereochemical selectivity is equally compatible with a reversed order of rotatory motions disrotatory joining of two allenic reactants followed by conrotatory closure to create the 1,2-dimethylenecyclobutane products 83>. 

The Nazarov cyclization is an example of a 47r-electrocyclic closure of a pentadienylic cation. The evidence in support of this idea is primarily stereochemical. The basic tenets of the theory of electrocyclic reactions make very clear predictions about the relative configuration of the substituents on the newly formed bond of the five-membered ring. Because the formation of a cyclopentenone often destroys one of the newly created centers, special substrates must be constructed to aUow this relationship to be preserved. Prior to the enunciation of the theory of conservation of orbital symmetry, Deno and Sorensen had observed the facile thermal cyclization of pentadienylic cations and subsequent rearrangements of the resulting cyclopentenyl cations. Unfortunately, these secondary rearrangements thwarted early attempts to verify the stereochemical predictions of orbital symmetry control. Subsequent studies with Ae pentamethyl derivative were successful. - The most convincing evidence for a pericyclic mechanism came from Woodward, Lehr and Kurland, who documented the complementary rotatory pathways for the thermal (conrotatory) and photochemical (disrotatoiy) cyclizations, precisely as predicted by the conservation of orbital symmetry (Scheme 5). 

Although the mechanism of the Mukaiyama reaction is not yet fully understood, several points have now been firmly established (a) a Lewis acid enolate is not involved (b) the Lewis acid activates the carbonyl group for the nucleophilic addition and (c) the Si—O bond is cleaved by nucleophilic attack of the anionic species, generally halide, on silicon. Point (a) has been established by the use of INEPT- Si NMR spectroscopy. Moreover, trichlorotitanium enolates have been synthesized, characterized and shown to give a completely different stereochemical outcome than the TiCU-mediated reactions of silyl enol ethers. Complexes between Lewis acids and carbonyl compounds have been isolated and characterized by X-ray crystallography and recently by NMR spectrometry. On the basis of these observations closed transition structures will not be considered here open transition structures with no intimate involvement between the silyl enol ether and the Lewis acid offer the best rationale for the after the fact interpretation of the stereochemical results and the best model for stereochemical predictions. 

Making stereochemical predictions with the VBSCD model... 

Stereochemical predictions based on the Alder rule are made by aligning the diene and dienophile in such a way that the unsaturated substituent on the dienophile overlaps the diene tt system. 

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