Open transition states

Noyori "Open" Transition State for non-Chelation Control Aldols... 

Non-chelation aldol reactions proceed via an "open" transition state to give syn aldols regardless of enolate geometry. 

Lewis acid promoted condensation of silyl ketene acetals (ester enolate equiv.) with aldehydes proceeds via "open" transition state to give anti aldols starting from either E- or Z- enolates. 

The tris(diethylainino)sulfoiiium difluorotrimethylsiliconate induced aldol addition of enolsi-lancs, which delivers predominantly syw-aldols independent of the cnolate geometry (sec p 1608), calls for another mechanistic model. A.n open transition state model has been proposed which assumes that the naked" ionic oxygens are as far apart as possible28. For (Z)-enolates, one transition state is favored over the diastereomeric orientation due to the avoidance of a repulsive R /CHj interaction. 

In direct contrast, an open transition state is postulated in order to explain the preferred attack of the ketene acetal 6 to the 57-facc of aldehydes, where there is a Lewis acid coordination with... 

Cyclic and open transition state models have been used to explain syn/anti stereoselectivity in these reactions1. The possible transition states (including boat B and chair C transition states) can be deduced from the E/Z geometry of the crotyl reagent and the imine. The postulated cyclic transition states for the preferred E geometry of the imine arc shown below. 

A proposed mechanism (Scheme 5-44) begins with deprotonation of dimethyl phosphite to give an Al-phosphito complex (32) which can react with the aldehyde via either a chelate or open transition state, the latter possibly involving cooperative action of two aluminum centers, consistent with the observation of co-catalysis. Following P-C bond formation, several possible rearrangements could regenerate the achve catalyst and form the product... 

A change in the allyl hapticity (q3 to p1 slippage) leading to the less substituted titanium-carbon o bond accounts for the observed y-regioselectivity. The anti diastereoselectivity stems from a pseudo-equatorial orientation of the aldehyde group. The diastereoselectivity of the reaction can be reversed through the use of a more coordinating cosolvent such as HMPA (Scheme 13.7) [14]. This reversal of anti to syn diastereoselectivity can be rationalized in terms of an open transition state. 

Since dienolates 1 and 2 represent diacetate synthons, the dienolate derived from 6-ethyl-2,2-dimethyldioxinone can be seen as a propionate-acetate syn-thon. The synthesis of the corresponding dienolate provides a mixture of the E and Z enolates in a 3 5 ratio. The reaction with Ti-BINOL complex 5 generates a 5 1 mixture with the syn isomer as the major diastereomer. After separation of the diastereomers, the enantiomeric excess of the syn isomer was determined to be 100%. The anti isomer was formed in 26% ee. The same transformation performed with boron Lewis acid 7 gave the anti isomer as the major compound, but only with 63% ee. The minor syn isomer was produced with 80% ee. The observed selectivity could be rationalized by an open transition state in which minimization of steric hindrance favors transition state C (Fig. 1). In all three... 

According to Heathcock and his associates the configurational dependence on the ratio of Lewis acid to aldehyde must be related to steric effects, and they conclude that the aldols 103 and 102 result from the open transition states A and B, respectively (Scheme 9.33). If the Lewis acid is small, transition state A is preferred because it minimises gauche interactions about the forming bond, but if the Lewis... 

The use of larger counterion (such as K" ) and polar solvents (such as DME) favors an open transition state (PT = phenyltetrazolyl) ... 

Flouk has also considered the alkylation reactions of pyrroles and indoles using the same class of catalyst. The report addresses the fact that while catalyst 12 provides high ees in the alkylation of pyrroles (Scheme 15), the same is not true of indoles and catalyst 21 is required instead (Scheme 16). A thorough examination of the accessible transition states for the reaction of iminium ion 184 with pyrrole and with indole led to the conclusion that the two reactions occur through different transition states. Pyrrole adopts a closed transition state reminiscent of that of the Diels-Alder reaction whereas indole adopts an open transition state (Fig. 19) [233]. 

Using this information in conjunction with a study into the preferred conformations of iminium ions generated from catalysts 12 and 21, Houk suggests that the additional steric bulk of the ferf-butyl group causes the benzyl arm of the catalyst to shield better the Si face of the C=C double bond - a requirement for high ees in an open transition state. For both the Diels-Alder and pyrrole/indole alkylation... 

These observations are explained in terms of a cyclic transition state for the LDA/THF conditions and an open transition state in the presence of an aprotic dipolar solvent. 

The second alternative is the open transition state with the olefin moieties are in an anti arrangement. 

Open transition states have been postulated in the aldol-type additions of ( )- and (Z)-crotyl-stannanes (21/22) to aldehydes. Irrespective of the ( ) or (Z) configuration of the stannane only. yyn-adducts 23/24 are formed. Due to the Lewis acid (LA) complexation of the carbonyl oxygen, a cyclic ( closed ) transition state cannot be adopted. Instead, an open geometry is preferred, in which the methyl and the R group move apart as far as possible to generate the enantiomorphous arrangements 25/2611. 

Stereochemical retention of configuration around the saturated a-carbon can only result from the closed transition state, whereas the open transition state can lead to inversion (10, 193). Configurational inversions occur in many biological substrates, and much future work on biomethylation will likely involve the use of substituted methyl groups and the study of any optical changes that occur. Determination of the relative rates of cleavage for a series of normal and branched alkyl derivatives enables a distinction between retention or inversion in the SK2 (open) pathway (194). 

The transition state is thought to be an open structure. Assuming that a particular silyl enol ether geometry is used, the substituents will tend to occupy opposite faces of the transition state and thus give a particular diastereomer (syn-anti) preferentially. Because of the open transition state geometry, the diastereoselec-tivity is not high. 

An open-transition-state model is proposed for the Darzens condensation of ketones with (—)-8-phenyhnenthyl a-chloroacetate the diastereoselectivity observed is explained in terms of a 71-aryI interaction between the enolate and phenyl moieties.78... 

BIMOLECULAR ELECTROPHILIC SUBSTITUTION via AN OPEN TRANSITION state Se2, Se2(open)... 

Ingold3 has used the term SE2 to describe these bimolecular substitutions which proceed via open transition states (as shown in reaction (4)), but Reutov4 uses the symbol SE2 to describe all bimolecular electrophilic substitutions, including those in which cyclic transition states are formed as well as those in which the transition state is open. More recently, Abraham et at.6 have suggested that bimolecular electrophilic substitutions in which an open transition state is formed could more explicitly be denoted by the term SE2(open). 

As in reaction (4), reactions such as (5) and (6) should lead to retention of configuration at the centre of substitution and to second-order kinetics, first-order in substrate and first-order in electrophile, at least for the case when the two reactants are of the same order in concentration. It is thus not an easy matter to distinguish between bimolecular substitutions involving open transition states and those involving cyclic transition states if retention of configuration is observed. 

Substitution, electrophilic, bimolecular, via an open transition state 1.2 Se2 SE2(open)... 

Tagliavini and co-workers32 wrote a mechanism for reaction (23) which involves coordination of the methanol solvent, S, to the tetraalkyltin, followed by a bimolecular substitution of the adduct by the species Me2SnS32+ through an open transition state, viz. 

In the absence of other information, these results could be interpreted in at least two ways, (/) mechanism SE2(open) obtains in all three reaction media, and the aqueous co-solvent stabilises the open transition state with respect to the reactants, or (u) mechanism SE2(cyclic) obtains in solvent dioxan, and the effect of the co-solvent is to shift the mechanism of reaction towards the SE2(open) mechanism. 

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