Open transition state model

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. 

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. 

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... 

FIGURE 12. Closed and open transition state models for the aldol reaction of a Z(O) enolate (R2 = R5 = H)... 

Reactions of chiral allenes proceed with a preference for the formation of the syn diastereomer. The stereochemical outcome of these reactions can be rationalized by invoking an open transition state model for the addition reactions (Figure 12), which depicts an antiperiplanar orientation of the chiral allenylsi-lane to the aldehyde carbonyl. In this model, steric repulsion between the allenyl methyl and the aldehyde substituent is most likely responsible for the destabilization of transition state (B), which leads to the anti (minor) stereoisomer. This destabilizing interaction is minimized in transition state (A). Table 5 illustrates representative examples and summarizes the scope of the regiocontrolled synthesis of homopropargylic alcohols using allenylsilanes. 

Figure 15 Open transition state models for intermolecular additions of C(3)-substituted allylsilanes...

The mechanism of the Mukaiyama aldol reaction largely depends on the reaction conditions, substrates, and Lewis acids. Linder the classical conditions, where TiCl4 is used in equimolar quantities, it was shown that the Lewis acid activates the aldehyde component by coordination followed by rapid carbon-carbon bond formation. Silyl transfer may occur in an intra- or intermolecular fashion. The stereochemical outcome of the reaction is generally explained by the open transition state model, and it is based on steric- and dipolar effects. " For Z-enol silanes, transition states A, D, and F are close in energy. When substituent R is small and R is large, transition state A is the most favored and it leads to the formation of the anf/-diastereomer. In contrast, when R is bulky and R is small, transition state D is favored giving the syn-diastereomer as the major product. When the aldehyde is capable of chelation, the reaction yields the syn product, presumably via transition state h. ... 

The asymmetric total syntheses of mtamycin B and oligomycin C was accomplished by J.S. Panek et al. In the synthesis of the C3-C17 subunit, they utilized a Mukaiyama aldol reaction to establish the C12-C13 stereocenters. During their studies, they surveyed a variety of Lewis acids and examined different trialkyl silyl groups in the silyl enol ether component. They found that the use of BFs OEta and the sterically bulky TBS group was ideal with respect to the level of diastereoselectivity. The stereochemical outcome was rationalized by the open transition state model, where the orientation of the reacting species was anti to each other, and the absolute stereochemistry was determined by the chiral aldehyde leading to the anti diastereomeric Felkin aldol product. 

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... 

Formation of syn aldols irrespective of enolate geometry. Open-transition-state models. 

In general, diastereomeric ratios in the range of 90 10 are reached. Based on the assumption that the enolate 81 is cis configured with chelation of titanium, an open transition state model 84 was proposed in order to rationalize the anti-selectivity [44a]. Not surprisingly, lower stereoselectivity was observed for the problematic acetate case (cf. Section 4.3), as illustrated by the alkylation of Af-acyl thiazolidinethione 80b that yielded the products 83 with just one stereogenic center in fi-carbonyl position (Scheme 4.15) [44b]. 

Scheme 4.32 Noyori s open transition state models 156 and 157 of the aldol addition. Independence of syn-aldol configuration from enolate configuration.

Despite the similarity of the structures of the silicon enolates 186 and 189 and essentially identical reaction conditions, the rationale for the stereochemical outcome, offered by the authors, is completely opposite the predominant approach of silyl ketene acetal 186 to isobutyraldehyde was assumed to occur through a Zimmerman-Traxler-llke transition state 192 where the titanium salt is embedded in the cycle. On the contrary, an open transition state model 193 was proposed for the Mukalyama reaction of silicon enolates 189. Both models of intuitive character give an explanation for the favored topicity the attack of the enolate to the Si-face of the aldehydes. Thus, the fact that ti-configured aldols are formed diastereoselectlvely Is in accordance with the tr ws-enolate/ nti-aldol correlation predicted by the Zimmerman-Traxler model, but an open model might be suitable to explain the stereochemical outcome as well. Both the Helmchen and the Oppolzer auxiliary were applied as acetates to give cx-unbranched-fi-hydroxycarboxylic acids. 

Scheme 4.59 Kobayashi s vinylogous Mukaiyama aldol reactions of silicon dienolates 252 and 255. Open transition state models 257 and 258 for rationalizing the stereochemical outcome.

Due to the high crystallinity of the sultam auxiliary, however, the aldol adducts 278 were obtained as nearly pure diastereomers after flash chromatography and recrystallization. The cleavage from the auxiliary by means of lithium hydroxide and hydrogen peroxide yielded the corresponding p-hydroxycarboxylic acids. The stereochemical outcome was rationalized by postulating an open transition state model 277, wherein the front side is shielded by the sulfonyl moiety so that the... 

The additions of chiral nonracemic allenylmetal reagents to chiral a-methyl propanal derivatives have been proven useful for the assembly of polypropionate fragments. These reagents rely on allene chirality to favor one of the two possible diastereomeric transition states in the addition and, thus, differ in a fundamental way from the aforementioned methods in which a chiral auxiliary or catalyst provides the control element. For example, a chiral allenylstannane 246 is added to a chiral aldehyde (S)-230, derived from the Roche ester, in the presence of various Lewis acid promoters to afford any of the four diastereo-mers with excellent diastereo- and enantioselectivity, depending on the reaction conditions. Representative results are depicted in Scheme 10.48. From the stereocontrol point of view, these transformations follow Cram-fike open transition state models without or with chelation, respectively. If InBr3, SnCLi, BuaSnCl, or other additives... 

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