Syn addition process

As for additions of allylic Grignard reagents, the relative reactivity order of the olefins appears to be 1-alkenes < styrene < 1,3-butadiene < ethylene and a,oi-or a,/3-disubstituted alkenes do not react94. However, strained alkenes such as cyclopropenes constitute an exception. Indeed, dicrotylzinc smoothly reacted with 3,3-dimethylcyclopropene and afforded the dicyclopropylzinc reagent 130 resulting from a syn addition process (equation 62)93. 

Besides the activation of the olefinic partner by a metal, the unfavorable thermodynamics associated with the addition of an enolate to a carbon—carbon multiple bond could be overwhelmed by using a strained alkene such as a cyclopropene derivative286. Indeed, Nakamura and workers demonstrated that the butylzinc enolate derived from A-methyl-5-valerolactam (447) smoothly reacted with the cyclopropenone ketal 78 and subsequent deuterolysis led to the -substituted cyclopropanone ketal 448, indicating that the carbometallation involved a syn addition process. Moreover, a high level of diastereoselectivity at the newly formed carbon—carbon bond was observed (de = 97%) (equation 191). The butylzinc enolates derived from other amides, lactams, esters and hydrazones also add successfully to the strained cyclopropenone ketal 78. Moreover, the cyclopropylzincs generated are stable and no rearrangements to the more stable zinc enolates occur after the addition. 

Stereochemistry. There are ample experimental indications that both hydropalladation (pattern 5) and carbopalladation (pattern 8) as well as their microscopic reversals (patterns 15 and 18) are, at least in the great majority of cases, strict syn addition processes, as predicted by the concerted mechanism shown in Scheme 8. In the hydropalladation and carobpalladation reactions of alkynes, the stereochemical course of the reactions is readily seen and unmistakable. However, clear-cut and explicit demonstration of the... 

In general, the initial interaction between a palladium compound, a nucleophile X and an alkene can proceed via two different pathways, which may be competing with each other (Figure 4.1)[1]. One consists of a jtnucleophilic attack from X via the uncomplexed face of the alkene, leading to an overall awti-process. Alternatively, X may be coordinated to palladium prior to the alkene coordination, resulting in an overall syn-addition process. 

Fink and coworkers showed, however, that the ethanol addition to the stericaUy highly hindered silacyclobutadiene 296 is a stereospecific syn addition process. When 296 is... 

AdES) mechanism with a transition state resembling (320), the latter dominating at high Cl concentrations and giving the trans addition product (321). Products from attack of the acetic acid solvent are also obtained. Cyclohexene reacts similarly, though slower by both mechanisms. Addition of HCl to l-phenyl-4-t-butylcyclohexene has yielded two crystalline geometrical cis- and /m/w-isomers. The stereochemistry of addition was determined by the use of deuteriated cyclohexene (322) and the isolation of (323) as the major product implies a syn addition process since this is the less-stable... 

The data given for 315Z and 315T indicate a syn-addition process for this cycliza-tion, which is explained by a conformational change in the intermediate cation. 

Intermolecular alkene insertion into the Pd-N bond was shown to be a syn-addition process as well (Scheme 12) [42,47]. Amido complexes of palladium were found to coordinate alkene, undergo migratory insertion and finally to form enamine product after (3-hydrogen elimination. Experimental evidence for the ethylene amido intermediate and for yw-addition process was obtained by NMR spectroscopy, including deuterium labeling study. The rate constant of the decay of observed intermediate complexes leading to the formation of the enamine corresponded to AG of 17 kcal/mol (8.7 x 10 " s -40 "C) [42]. 

The term syn addition describes the stereochemistry of reactions such as this m which two atoms or groups add to the same face of a double bond When atoms or groups add to opposite faces of the double bond the process is called anti addition... 

Overall the reaction leads to syn addition of H and OH to the double bond This fact has an important bearing on the mechanism of the process... 

The stereochemistry of both chlorination and bromination of several cyclic and acyclic dienes has been determined. The results show that bromination is often stereo-specifically anti for the 1,2-addition process, whereas syn addition is preferred for 1,4-addition. Comparable results for chlorination show much less stereospeciftcity. It appears that chlorination proceeds primarily through ion-pair intermediates, whereas in bromina-hon a stereospecific anfi-l,2-addition may compete with a process involving a carbocation mtermediate. The latter can presumably give syn or anti product. 

These observations must be taken into account when considering the mechanism of halogen addition. They force the conclusion that a simple one-step bond-switching process of the following type cannot be conect. A process of this type requires syn addition it is not consistent with the anti addition that we actually see. 

The stereochemical preference (for syn addition) can now also be understood. The step above represents a concerted process. Both BH2 and H are adding simultaneously, so they must end up on the same face of the alkene. In other words, the reaction must be a syn addition. 

It is this first step that allows us to understand why the reaction follows a syn addition. In this step, osminm tetroxide (OSO4) adds across the alkene in a concerted process. In other words, both oxygen atoms attach to the alkene simnltaneonsly. This effectively adds two gronps across the same face of the alkene. 

Two issues are of essential for predicting the structure of 1,3-DCA products (1) What is the regiochemistry and (2) What is the stereochemistry Many specific examples demonstrate that 1,3-dipolar cycloaddition is a stereospecific syn addition with respect to the dipolarophile, as expected for a concerted process. 

It has been demonstrated that ionic intermediates are not involved in the epoxidation reaction. The reaction rate is not very sensitive to solvent polarity.71 Stereospecific syn addition is consistently observed. The oxidation is therefore believed to be a concerted process. A representation of the transition structure is shown below. 

The involvement of ion pairs in the addition process has also been related to the stereochemical behavior. The remarkable difference in configuration between the rearranged chlorides and acetates has been rationalized, as shown in equation 113, on the basis of a syn internal attack of Cl- on ion c and anti external attack of AcOH from the solvent pool. 

When they subjected the allenylzinc reagent to the Hoffmann test for configurational stability,29 Poisson, Chemla and Normant found that at — 50 °C, racemization does not occur at a significant rate (equation 36)30,31. Accordingly, when the racemic allenylzinc reagent was added slowly to the /V-benzy limine of (R)-mandehc aldehyde at — 50 °C, a 1 1 mixture of the anti,syn and anti,anti adducts was isolated in 65% yield. However, when the addition process was reversed, a 3 1 mixture favoring the matched anti,anti adduct was formed in 53% yield, suggestive of a partial kinetic resolution. 

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