Shape transition state

The situation with respect to HCN is rather different, because it is no longer vahd to approximate the internal rotational constant, B, as independent of the angle 0. As discussed by Efstathiou et al. [10], the form of the most recent potential energy surface [48, 49] shows that the separation of the H atom from the CN center of mass decreases by about 30% between the HCN configuration and the T-shaped transition state, giving the optimized bending potential energy... 

Another idea, which was originally put forward by Ruzicka (1935) and has ever since provided a common basis for many discussions of reactivity in intramolecular reactions, is that the ring-shaped transition state should be affected by a significant fraction of the strain-energy of the ring being formed. The simplest way to express this idea is by use of (62), where the weighting... 

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

The reaction occurs suprafacially across the allyl unit through a five-membered ring envelope-shaped transition state. The five-membered cychc transition state of [2,3]-sigmatropic rearrangement shows greater conformational flexibility than the six-membered transition state of [3,3]-sigmatropic rearrangements and should therefore be far more susceptible to the effects of stereochemical control by substituents. ... 

TMS enol ether has been shown to rearrange with good enantioselectivity, presumably because the boat-shaped transition state is sterically disfavoured. Rearrangement of the enantiomeric starting material has been used as a key step in a total synthesis of (+)-alline.13... 

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... 

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 activation entropy represents the probability of chain ends coming close enough for reactive interactions. This leads to negative contributions for the entropy owing to the loss of rotational freedom of the chain when the disordered open chain is converted to the ring-shaped transition state. 

Annulation, e.g. 7, 9 and 10, and ring contraction, e.g. 8, can both be used to form the bicyclo[4.1.0]heptane system. Both methods are demonstrated in the formation of The W-shaped transition state required for the ring-closure reaction may require epimerization prior to the 1,3-elimination reaction for the substrates trans- and cis- l. 

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. 

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