Transition state carbonyl addition

Figure 8.4. Optimal structure of the transition state for addition of an X -substituted nucleophile to a carbonyl group according to orbital interaction considerations.

Karabatsos87 introduced a variant of Cram s model based on the following assumptions (1) the transition states for addition to carbonyls are reactant-like (2) the reactive conformations are then the most stable ones, which have a neighboring o bond eclipsing the carbonyl group (cf. p. 188) and (3) the nucleophile approaches from the less hindered side. Assumption (2) is questionable even in the reactant-like transition state, the stable and reactive conformations may be completely different. Karabatsos s model was the first to draw attention on the importance of conformational factors in asymmetric induction. 

Comparison of reaction rates and selectivities for BF3-promoted additions of crotyl tributylstannanes to aldehydes revealed that the trans crotyl isomer reacts faster and is more yn-selective than the cis isomer (Table 8) [18]. It is proposed that the synclinal transition state arrangement for the frans-crotylstannane is stabilized by a favorable interaction between the LUMO of the carbonyl oxygen and the allylic tin sigma HOMO. The analogous transition state for addition of the dx-crotylstannane is destabilized by unfavorable steric interactions (Fig. 3). 

By far the most important type of reaction of Grignard reagents is the family of reactions involving addition to carbonyl groups. The transition state for addition of Grignard reagents is often represented as a cyclic array containing the carbonyl and... 

With the use of In(OTf)3, Loh et al. further reported that two equivalents of aldehydes could react with alkenes to form tetrahydropyran rings [204]. The reaction proceeded through an initial carbonyl-ene reaction that generated the intermediate homoallylic alcohol, followed by a (2,5) oxonium-ene cyclization (Figure 8.90). The stereochemical pref erence was attributed to the favored adoption of an all-equatorial six-membered chair-like cyclic transition state. In addition to the tandem reaction, the authors had also carried out only the cyclization step with the same condition using aldehydes and homoallylic alcohols, giving similar end results. This work was further applied to the assembly of the tetrahydropyran core of zampanolide and dactylolide [205]. 

Cyanohydrins are formed by nucleophilic addition of HCN to the carbonyl group of an aldehyde or a ketone Cycloadd ition (Section 10 12) Addition such as the Diels-Alder reaction in which a ring is formed via a cyclic transition state... 

In this section we turn to a consideration of the experimental side of condensation kinetics. The kind of ab links which have been most extensively studied are ester and amide groups, although numerous additional systems could also be cited. In many of these the carbonyl group is present and is believed to play an important role in stabilizing the actual chemical transition state involved in the reactions. The situation can be represented by the following schematic reaction ... 

Various structural factors have been considered in interpreting this result The most generally satisfactory approach is based on a transition>state model, advanced by Felkin and co-woricers, in which the largest group is oriented perpendiculariy to the carbonyl group. Nucleophilic addition to the carbonyl groi occurs from the opposite side. ... 

The fundamental mechanistic concept by which the stereochemical course of the aldol addition under conditions of kinetic control has been analyzed involves a cyclic transition state in which both the carbonyl and enolate oxygens are coordinated to a Lewis... 

Finally, examine transition states for cyanide addition cyanide+formaldehyde, cyanide+acetone, cyanide+ benzophenone) What relationship, if any, is there between the length of the forming CC bond and the various carbonyl properties determined above Try to rationalize what you find, and see if there are other structural variations that can be correlated with carbonyl reactivity. 

Upon addition of a base—triethylamine is often used—the sulfonium salt 7 is deprotonated to give a sulfonium ylide 8. The latter decomposes into the carbonyl compound 2 and dimethyl sulfide 9 through /3-elimination via a cyclic transition state. 

The transition state for the nucleophilic addition reaction to a carbonyl compound is essentially reactant-hke , rather than product-like . 

With a-alkyl-substituted chiral carbonyl compounds bearing an alkoxy group in the -position, the diastereoselectivity of nucleophilic addition reactions is influenced not only by steric factors, which can be described by the models of Cram and Felkin (see Section 1.3.1.1.), but also by a possible coordination of the nucleophile counterion with the /J-oxygen atom. Thus, coordination of the metal cation with the carbonyl oxygen and the /J-alkoxy substituent leads to a chelated transition state 1 which implies attack of the nucleophile from the least hindered side, opposite to the pseudoequatorial substituent R1. Therefore, the anb-diastereomer 2 should be formed in excess. With respect to the stereogenic center in the a-position, the predominant formation of the anft-diastereomer means that anti-Cram selectivity has occurred. 

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