Four-center addition

Four-centered addition of RCu to an enone was widely discussed in the 1960s (Scheme 10.3a) [51-53], while discussions on six-centered transition states have continued until recent times (Scheme 10.3b) [54]. These mechanisms do not, however, explain the formation of E/Z mixtures of enolate stereoisomers [20, 55] and must now be considered obsolete. 

The mechanism of this reaction is not well understood. It is a kind of three-or four-center addition. Some variations of this mechanism are ... 

In general, the ease of addition of H—X to simple alkenes follows their relative acidity, HI > HBr > HC1, but HF addition is often surprisingly easy. A diversity of mechanisms appear to be involved in these processes, ranging from relatively pure carbocation processes to those more reminiscent of four-center addition. Markovnikov addition is commonly observed when precautions are taken to exclude peroxide or other possible free radical initiators. Though strong acids are involved and rearrangements are not uncommon, the reaction conditions are otherwise quite mild and yields can be high. 

The o-TT switch is simply a four-center addition (elimination) there is a net loss (gain) of a n MO and a gain (loss) of a a MO. Orbital symmetries have been indicated beside reactants and product in (94). ir2(a) X=X X—X... 

Notwithstanding the fact that certain four-center additions to alkenes, e.g. equation (94) or Fig. 22, are forbidden, bromine addition to an alkene does occur. The orbital symmetry arguments which forbid cis addition to isolated bonds favor trans addition in equation (144), in which j = 4, X may be a nucleophile or radical and Y an electrophile or radical. Therefore, additions of molecular bromine or in general X—Y to alkenes, should proceed in at least two steps. Otherwise, separated X and Y, with one electron pair between them, add in concerted fashion to the alkene. Equation (144) is effectively the prototype of numerous ionic and radical a-w exchange reactions. A wealth of information has been recorded in excellent reviews covering special aspects of this general process, e.g. electrophilic additions (de la Mare and Bolton,... 

As a final reaction mechanism catalyzed by water, we consider the hydration/hydrolysis reaction of an imine, CH2NH. The reaction energetics are shown in Fig. 8. As a simple bimolecular reaction, the four-centered addition transition state structures leading to hydration and hydrolysis have high activation barriers. The presence of an additional water molecule, providing six-centered transition state structures, lowers the barrier heights significantly. It should be noted that the hydrated form of the imine is the more stable form of the imine in aqueous solutions, as indicated in Fig. 8. This is also true of formaldehyde, for which the hydrated form, CH2(0H)2, is the more stable. 

The influence of the solvent on the decomposition rate of phenylpentazole (see Table II) supports the one-step four-centered 1,3-flssion of phenylpentazole according to 22. The correlation of the polarity of the transition states of 1,3-additions, which resemble the assumed transition state of the phenylpentazole decomposition (22), andsolvent effects has recently been discussed by Huisgen. ... 

A simplified mechanism for the hydroformylation reaction using the rhodium complex starts by the addition of the olefin to the catalyst (A) to form complex (B). The latter rearranges, probably through a four-centered intermediate, to the alkyl complex (C). A carbon monoxide insertion gives the square-planar complex (D). Successive H2 and CO addition produces the original catalyst and the product ... 

There are some addition reactions where the initial attack is not at one carbon of the double bond, but both carbons are attacked simultaneously. Some of these are four-center mechanisms, which follow this pattern ... 

Hydroboration is a stereospecific syn addition that occurs through a four-center TS with simultaneous bonding to boron and hydrogen. The new C—B and C—H bonds are thus both formed from the same face of the double bond. In molecular orbital terms, the addition is viewed as taking place by interaction of the filled alkene it orbital with the empty p orbital on boron, accompanied by concerted C—H bond formation.158... 

Computational studies of both hydroalumination and carboalumination have indicated a four-center TS for the addition.220 The aluminum reagents, however, have more nucleophilic character than do boranes. Whereas the TS for hydroboration is primarily electrophilic and resembles that for attack of CH3+ on a double bond, the... 

The relative reactivity profile of the simple alkenes toward Wacker oxidation is quite shallow and in the order ethene > propene > 1-butene > Zi-2-butene > Z-2-butene.102 This order indicates that steric factors outweigh electronic effects and is consistent with substantial nucleophilic character in the rate-determining step. (Compare with oxymercuration see Part A, Section 5.8.) The addition step is believed to occur by an internal ligand transfer through a four-center mechanism, leading to syn addition. 

A concerted four-center cis addition leads to (52) and a trans adduct a trans addition, possibly via protonium species, leads to (53) and a cis adduct a stepwise cationic addition leads to (54) and a mixture of cis and trans adducts. Recent studies by Marshall and Wurth strongly indicate that intermediate (54) is correct. Irradiation of octalin (55) in aqueous /-butyl alcohol (DaO)-xylene results in formation of the equatorially deuterated alcohols (56) and (57) and the equatorially deuterated exocyclic olefin (58) ... 

In the second step, the n complex becomes the addition product by passing through a four-center transition state in which the boron atom is partially bonded to the less substituted carbon atom of the double bond. 

Addition takes place through the initial formation of a n complex, which changes into a cyclic four-center transition state with the boron atom adding to the less hindered carbon atom. The dashed bonds in the transition state represent bonds... 

A theoretical study of the reaction mechanism for addition of organozincate complexes to aldehydes was recently performed using density functional theory.298 It has been suggested that the addition takes place through formation of a four-centered transition state and, therefore, it can be considered a typical nucleophilic reaction. 

Aside from two-center (Patterns 1 and 2) and three-center (Patterns 3, 4, 11, and 12) processes, most of the processes shown in Scheme 1.3 are four-center processes involving either addition (Patterns 5—10) or 0-bond metathesis (Pattern 13). In this context, it should be noted that addition is simply a four-center metathesis in which one molecule happens to be multiply-bonded. In addition to these metathetical processes, there is yet another fundamentally important four-center metathetical process termed migratory insertion and deinsertion (Patterns 14 and 15). It should be clear from Patterns 14 and 15 shown in Scheme 1.3 that distinction between insertion and deinsertion is only a relative and semantic issue. In the current discussion, a process involving cleavage of the C—Zr bond is termed migratory insertion, while the reverse process is termed migratory deinsertion. 

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