Cyclic open transition state

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. 

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. 

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. 

NMR studies of polymers made with deuterated monomers provide additional information on the cyclic isotactic transition state. Miyazawa and Ideyuchi (97) have shown that the isotactic polymerization of propylene takes place with cis opening of the olefinic double bond. This shows that the 4-membered cyclic transition occurs with reaction of the new monomer on the front side of the propagating ion as illustrated in Fig. 12. 

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. 

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. 

The transmetallation step (iii) is certainly the most enigmatic part of the catalytic cycle. Generally, it is assumed to be rate limiting, and several mechanisms are proposed depending on the solvent. An open transition state with inversion of the stereochemistry would arise with polar solvents which are able to stabilize the transient partial charges , whereas a cyclic transition state with retention of the stereochemistry would arise in less polar solvents. It should be noted that the nature of the ligands on the palladium may influence dramatically the kinetics of the transmetallation step. A 1000-fold rate enhancement was observed when replacing triphenylphosphine by tri(2-furyl)phosphine . However, the dissociative or associative nature of the substitution on the palladium is stiU under discussion . ... 

The computational support for Felkin s torsional strain model and its success in interpretation of experimental diastereoselectivities has led to its widespread adoption. It appears to be the preeminent open transition state involved in reductions when chelation is not important. Complementary selectivity observed in reductions that do involve chelation may be understood in terms of Cram s cyclic model. 

In accord with its crowded cyclic transition state, the basic pathway has a very high selectivity for oxidation of primary OH groups, whereas the slower acid pathway, with the more open transition state, has lower selectivity, oxidising secondary alcohols only modestly slower than primary ones. 

In a landmark study of Mukaiyama aldol addition reactions, Heathcock proposed that the observed stereochemical outcome of the products in the Lewis acid-mediated addition of silyl ketene acetals to aldehydes was consistent with extended, open transition-state structures [38a, 38b]. This analysis has gained wide acceptance as a consequence of its predictive power. Alternative models involving cyclic, closed structures have also been postulated, in particular, the latter have been invoked with increasing regularity in the analyses of catalytic, enantioselective aldol addition reactions [7,30b,39a,39b. ... 

These results are interpreted as shown in Figure 6.79. The formation of 6.92 takes place via a cyclic transition state Cj Si. Chelate 6.91 is disrupted in order to allow the coordination of the aldehyde to the boron atom. As usual, steric interactions are minimized in the favored transition state. In the presence of excess boron triflate or of another Lewis acid which can activate the aldehyde carbonyl group, the boron chelate is no longer disrupted. Two acyclic transition-state models, A Re and A Si, can be envisioned according to the nature of the Lewis acid [106], Open transition states are also proposed for the reactions of 6.91 with CF3CHO, which does not require electrophilic assistance [1261]. 

Recent comprehensive studies by Espinet et al. on the Stille reaction and related transmetalation reactions revealed the mechanistic features of transmetalation of organostannanes with Pd complexes, which is a key step in the Pd-catalyzed coupling of organic halides or triflates with organostannanes [109,110]. The reaction can follow two basically different pathways involving a cyclic or an open transition state in the transmetalation step (Scheme 5.15). 

The open transition state operates in cases where no bridging groups are available on the coordination sphere of Pd(ll) to produce a cyclic intermediate [227]. The... 

As the accompanying electrostatic potential maps also show, the carbon-halogen bond to the more substituted carbon of the halonium ion is longer than the bond to the less substituted carbon. This difference in bond lengths in the cyclic intermediate state means that the ring-opening transition state can be reached more easily by attack at the more substituted carbon. 

With allyltin derivatives a change of the relative configurations at the newly formed stereogenic centers is observed when the reaction, which is rather slow without a catalyst, is performed in the presence of BFs, apparently as a consequence of the now open transition state with BFj activation of the carbonyl group and the reaction not going via a cyclic, six-membered transition state as is usual. 

There are several mechanistic modes for the allymetallation of aldehydes (/) The reaction may proceed via open transition states, this would amount to a monocyclic situation on ring closure of 1, cf. 3. Alternatively, the reaction may proceed via cyclic transition states, in which the metal coordinates to the aldehyde function. On cyclization of 1 this would amount to bicyclic transition states 4. 

The high practical value of this reaction rests in the fact that the relative and absolute configurations of products 22-25 are independent of the E/Z geometry of silyl enol ether. -and Z-isomers of substrate 20 give the same yn-product 24 with >95 % e.e. This outcome is explained by the intermediary formation of an open transition state since the dominant interaction between groups R and R precludes the route to the anti-isomer via the cyclic transition state [13]. 

A completely different rationale for the stereochemical outcome of aldol additions relies on open-transition-state models. These involve anti-periplanar orientation of enolate and carbonyl group, in contrast with their syn-clinal conformation assumed in the six-membered cyclic transition states. Open-transition-state structures have been proposed to offer a rationale for those aldol additions that give predominantly syn products, irrespective of enolate geometry [90]. This outcome has been observed in aldol reactions of tin and zirconium enoiates and of naked enoiates generated from enolsilanes by treatment with tris(diethylamino)sulfonium difluoro-methylsiliconate [70]. As shown in Scheme 1.12, the driving force for the... 

Remarkably high stereoselectivity is obtained by means of the sodium enolate of a-N,N-dibenzylamino-substituted ketone 51, a counter-ion not very frequently used in stereoselective aldol additions. In this instance, however, the sodium enolate turned out to be more efficient than the lithium analog. The predominant formation of the main diastereomeric product 52a rather than 52b is explained by an open transition state, assumed to be strongly favored over the cyclic transition state, when the more ionic sodium enolate is used rather than the corresponding lithium reagent (Eq. (24)) [103]. 

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