Transition chair-shaped

The structure of the molecule is such that it does not allow the attainment of a chair shaped transition state. 

An aromatic Claisen rearrangement has been used as a key step in a total synthesis of racemic heliannuols C and E.18 A formal synthesis of (-)-perhydrohistrionicotoxin has used Claisen rearrangement of an amino acid ester enolate as the key step, in which almost total chirality transfer was observed from (S, )-oct-3-en-2-ol in the sense predicted by a chair-shaped transition state with chelation control of enolate geometry.19 Treatment of 1-(cyclohex-l-enyl)-6-methoxy-2-propargylindanol derivatives with base... 

Structure B corresponds to the most stable transition state of the Ireland-Claisen rearrangement of Figure 14.49. In this transition state, the substituent at the allylic stereocenter is in a pseudo-equatorial orientation with respect to the chair-shaped skeleton. This is the same preferred geometry as in the case of the most stable transition state B of the Claisen rearrangement of Figure 14.48. The reason for this preference is as before that is, an allylic substituent that is oriented in this way experiences the smallest possible interaction with the chair skeleton. The obvious similarity of the preferred transition state structures of the Ireland-Claisen rearrangements of Figures 14.49 and 14.48 causes the same trans-selectivity. 

This methodology has been applied to the synthesis of an advanced intermediate 211 related to the natural product (—)-a-kainic acid. The required stannane 210 was prepared in several steps from /3-lactam 209. Disappointingly, the major diastereoisomer (with respect to the new stereogenic centre) of the desired pyrrolidine 211 was not the expected one for similar cyclizations and has not the required stereochemistry across C-3 and C-4 for the synthesis of kainic acid (Scheme 56)95. Attempts to alter the stereoselectivity by changing the solvent were unsuccessful. The authors reasoned that if the intramolecular carbolithiation reaction takes place through a six-membered chair-shaped transition state, then different conformations must be preferred for the two different cyclizations leading to the cis-and frans-diastereoisomers of 211. 

The pyrrolizidine nucleus is also affordable by intramolecular carbolithiation reaction starting from stannane 212. After transmetallation, cyclization and trapping with electrophiles the pyrrolizidines 213 were isolated as their picrate salts, as an inseparable (3 1) mixture of diastereoisomers. The preference for a chair-shaped transition state, with a ris-fused l-azabicyclo[3.3.0]octane ring system, suggests that the major diastereoisomer would be the first, though this was not completely ascertained (Scheme 57)96. 

The pyrolyses of esters and xanthates involve six-membered cyclic transition states and these are presumably almost strainless and chair-shaped rather than planar and eclipsed. Thus, they are more realistically regarded as occurring from syn-clinal rather than a syn conformation of the eliminating fragments in the substrate. 

In certain cases, high levels of selectivity in the asymmetric aldol reaction can be achieved in the absence of a metal salt. The amino acid proUne catalyses the aldol reaction of aldehydes or ketones (which are enolizable) with aldehydes (preferably non-enolizable or branched to disfavour enolization) to give p-hydroxy-aldehydes or ketones. For example, use of acetone (present in excess) and isobutyraldehyde gave the (3-hydroxy-ketone 81 (1.88). The reaction involves an enamine intermediate and is thought to proceed via the usual Zimmerman-Traxler chair-shaped transition state. 

The stereoselectivity of this reaction can be explained by invoking a Z-enolate and drawing the six-membered, chair-shaped transition state (see Scheme 1.80). The Z-enolate leads, using this transition state, to the syn aldol product. The chiral auxiliary directs the approach of the aldehyde to the less hindered face of the enolate. To obtain the other syn aldol product, use either the other oxazolidinone auxiliary (53) or use the titanium enolate. In the latter case, the stereoselectivity can be rationalized by co-ordination of titanium to the carbonyl oxygen atom of the oxazolidinone group. 

The Z-a, 3-unsaturated ester 2 is formed from the syn 3-hydroxy selenide by an anti elimination. 0-Mesylation and loss of the leaving group generates the cis episelenonium ion and hence the Z-alkene 2 (see Scheme 2.28). The syn 3-hydroxy selenide is formed by an aldol reaction of the Z-titanium enolate via a chair-shaped transition state (see Section 1.1.3). See S. Nakamura, T. Hayakawa, T. Nishi, Y. Watanabe andT. Torn, Tetrahedron, 57 (2001), 6703. 

Whereas cyclic allyhc alcohols of normal size can only yield (Z)acyclic allylic alcohols preferentially give ( )-isomers. Indeed, the Meerwein-Eschenmoser-Claisen rearrangement is an excellent method for the stereoselective formation of di- and trisubstituted (E)-double bonds in acyclic systems. The high diastereoselectivities observed (dr >95 5) can be explained by invoking a chair shaped transition state 35a or 36a (Scheme 7.15). This minimizes... 

The issue of simple diastereoselectivity arises when both the allyl and vinyl moieties of the ketene N,0-acetal intermediate 2 are substituted at their terminus, leading to vicinal stereocenters in the products (Scheme 7.22). In analogy to the aldol reaction, the stereochemical outcome can be predicted in terms of a Zimmermann-Traxler type chair-shaped transition state. Accordingly, the synlanti ratio of the products depends on double bond geometry. Whereas the geometry of the unsaturated alcohol is pre-determined and usually not subject to equilibration, the geometry of the ketene N,0-acetal moiety depends on the reaction conditions that lead to its in situ formation. 

In the case of substituted ketene N,0-acetals formed through equilibria, for instance under the classical Eschenmoser conditions, the thermodynamically more stable (Z)-ketene N,0-acetal 61a is preferentially formed to avoid aUyUc strain between residue R and the bulky dimethylamine moiety (Scheme 7.22). Invoking a chair-shaped transition state, the anti-isomer is then formed from an (E)-allylic alcohol in the course of the sigmatropic rearrangement. Note that transition states 61a and 61b are diastereomers and not conformational isomers. 

Dienes under thermal conditions undergo [3, 3]-sigmatropic shift known as Cope-rearrangement. Stereochemical outcome of this reaction can be rationalized through chair-shaped transition state as given below ... 

The value of q3 = (6) V2R (R is the CC bond length) is 0.63 A. Under pseudorotation the equatorial boat-shaped structures B (0 = 90°, = 0, 60°, 120°,.. . ) turn into a twist-boat structure TB (0 = 90°, = 30°, 90°,.. . ). The transitions between the chair and twist boat structures involve the intermediate formation of half boat (HB) and half chair (HC) structures. Quantum chemical calculations carried out by Dixon and Komornicki [1990] show that the axial structure C with symmetry D3d is stable. The energies of structures B and TB are 7.9 and 6.8kcal/mol higher than C. The barrier for transition from C to TB is 12.2-12.4 kcal/ mol. Because of the high barriers for pseudorotation, only thermally activated conformational transitions occur in cyclohexane. 

Fig. 5.45 One might have guessed that the chair cyclohexane conformations 1 and I are connected by a boat-shaped intermediate 2. However, this C2v structure shows an imaginary frequency it is a transition state which wants to twist toward 3 (arrows) or 3 (arrows in opposite directions, not shown), which are the actual intermediates (no imaginary frequencies) between 1 and 1. The chair conformation reaches the twist via a half-chair 4...

Another explanation takes into account that boat- and twist-shaped six-membered, closed transition states can successfully compete with the chair model. " Evans et al. pointed out that in a-unsubstituted enolate reactions, missing allyl strain interactions lead to lower selectivity in diastereoselective aldol reactions.Calculations indicate that a twist-boat can easily be formed from the U-configuration of a-unsubstituted enolates. The possible transition state in this case has a geometry like 34 and is favored by the chelating character of the complexation mode for the zinc cation and the outward-pointing substituents of the oxazolidinone moiety. This twist-boat transition state correctly predicts the stereochemical outcome of the reaction. 

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