Insertion processes regioselectivity

A related situation is found in the case of P-substituted cycloketones here, the electronic difference between the two a-carbons is almost insignificant, resulting in unselective migration upon chemical oxidation. BVMOs have a particularly different behavior, as they can influence the stereo- and/or regioselectivity of the biooxidation. In the latter case, the distribution of proximal and distal lactones is affected by directing the oxygen insertion process either into the bond close or remote to the position of the P-substituent. Consequently, a regioisomeric excess (re) can be defined for this biotransformation, similar to enantiomeric excess or diastereomeric excess values [143]. 

The subsequent step is the propene insertion process. Grima et al. [54] analyzed the [2 -I- 2] addition process for the propene insertion into the Co-H bond by means of CNDO/2 method. They proposed that the origin of the regioselectivity was due to the electrostatic dipole-dipole interaction between Co-H and C=C favoring the linear product, and the disfavored branched product was due to the higher energy required to inverse the olefinic dipole for the proper interaction. However, this interpretation is not supported by the high-level calculations as indicated below. 

B3LYP calculatimis showed that the insertion processes, which can lead to both the linear propyl (IL) and branched isopropyl (IB) complexes, have nearly the same activation free energies (25.8 and 26.5 kJ/mol) and reaction free energies (—4.5 and —4.1 kJ/mol). These results indicated that the insertion process does not determine the regioselectivity, in contrast with the proposal by Grima et al. [54]. On the other hand, the rather low activation barriers and much less exergonic properties suggested that the insertion processes are reversible. This explains the observed isomerization between internal and terminal olefins in experiment reasonably. 

This branched regioselectivity in these cases results from the greater stability of the branched alkyl complex when the alkyl group bears an electron-withdrawing substituent on the a-carbon. This regioselectivity was discussed in Chapter 10 on insertion processes. The high selectivity for formation of branched products from the hydroformylation of vinylarenes results from the formation of an iri -benzyl intermediate, - - as discussed in Chapter 10. The formation of these chiral, branched products has been a particular focal point for the development of enantioselective hydroformylation. 

The formation of the tricarbonylchromium-complexed fulvene 81 from the 3-dimethylamino-3-(2 -trimethylsilyloxy-2 -propyl)propenylidene complex 80 and 1-pentyne also constitutes a formal [3+2] cycloaddition, although the mechanism is still obscure (Scheme 17) [76]. The rf-complex 81 must arise after an initial alkyne insertion, followed by cyclization, 1,2-shift of the dimethylamino group, and subsequent elimination of the trimethylsilyloxy moiety. Particularly conspicuous here are the alkyne insertion with opposite regioselectivity as compared to that in the Dotz reaction, and the migration of the dimethylamino functionality, which must occur by an intra- or intermo-lecular process. The mode of formation of the cyclopenta[Z ]pyran by-product 82 will be discussed in the next section. 

The reaction of alkenylcarbene complexes and alkynes in the presence of Ni(0) leads to cycloheptatriene derivatives in a process which can be considered as a [3C+2S+2S] cycloaddition reaction [125]. As shown in Scheme 77, two molecules of the alkyne and one molecule of the carbene complex are involved in the formation of the cycloheptatriene. This reaction is supposed to proceed through the initial formation of a nickel alkenylcarbene complex. A subsequent double regioselective alkyne insertion produces a new nickel carbene complex, which evolves by an intramolecular cycloprop anation reaction to form a nor-caradiene intermediate. These species easily isomerise to the observed cycloheptatriene derivatives (Scheme 77). 

Microwave-assisted Heck reaction of (hetero)aryl bromides with N,N-dimethyl-2-[(2-phenylvinyl)oxy]ethanamine, using Herrmann s palladacycle as a precatalyst, yielded the corresponding /3-(hetero)arylated Heck products in a good EjZ selectivity (Scheme 79) [90]. The a/yd-regioselectivity can be explained by the chelation control in the insertion step. This selectivity is better than 10/90 when no severe steric hindrance is introduced in the (hetero)aryl bromides. The process does not require an inert atmosphere. There is evidence that a Pd(0)/Pd(II)- and not Pd(II)/Pd(IV)-based catalytic cycle is involved. Similarly, other j6-amino-substituted vinyl ethers such as... 

The poor regioselectivity of alkyne insertion in our polycychc aromatic hydrocarbon synthesis (Scheme 17) suggested to us that perhaps the palladium intermediate in that process was actually undergoing migration from one aromatic ring to the other, perhaps by a Pd(IV) hydride intermediate, to establish an equilibrium mixture of two regioisomeric arylpalladium intermediates under our reaction conditions (Scheme 18). This, indeed, appears to be true as... 

A recent approach used by Heimbach regards each C—C coupling process as a heteroring closure to which Woodward-Hoffmann rules can be applied. Regioselectivity in cyclooligomerization can be predicted on the basis of the least electron density in the LUMO of the double-bond carbon atoms of an inserting olefin (6). 

However, with substrates prone to form carbocations, complete hydride abstraction from the alkane, followed by electrophilic attack of the carbocation on the metal-bound, newly formed alkyl ligand might be a more realistic picture of this process (Figure 3.38). The regioselectivity of C-H insertion reactions of electrophilic transition metal carbene complexes also supports the idea of a carbocation-like transition state or intermediate. 

In basic medium the catalytic species was postulated to be a Ru-dihydride complex. In this case, the regioselectivity was determined by the proton-transfer step (65). The complete catalytic cycle in basic medium is depicted in Scheme 14. First the phosphine dissociation generating a vacant site for the substrate coordination takes place. Next step is the insertion of the substrate into the Ru-H bond (inner-sphere mechanism) followed by water coordination in order to occupy the vacant site. This step has the highest relative energy barrier for the overall process. To generate the final product this intermediate must be somehow protonated however, in basic medium there are no easily available protons in solution. Thus, bulk water molecules are the only proton source. The transfer of a proton from a water molecule to the C=C bond requires at least 36.6 kcal mol-1, which is much more than the highest barrier found for C=0 hydrogenation... 

In the process of olefin insertion, also known as carbometalation, the 1,2 migratory insertion of the coordinated carbon-carbon multiple bond into the metal-carbon bond results in the formation of a metal-alkyl or metal-alkenyl complex. The reaction, in which the bond order of the inserted C-C bond is decreased by one unit, proceeds stereoselectively ( -addition) and usually also regioselectively (the more bulky metal is preferentially attached to the less substituted carbon atom. The willingness of alkenes and alkynes to undergo carbometalation is usually in correlation with the ease of their coordination to the metal centre. In the process of insertion a vacant coordination site is also produced on the metal, where further reagents might be attached. Of the metals covered in this book palladium is by far the most frequently utilized in such transformations. 

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