Regiochemistry of Insertion

This regiochemistry is consistent with the regiochemistry of the hydroesterification and hydrocarboxylation of 1-alkenes that results from 1,2 insertion into a metal-hydride. 1,2-Insertion of propene has also been observed directly during studies on the individual steps of the copolymerization process. One example of the direct observation of this step is shown in Equation 17.69 for a catalyst containing BIMAPHOS.  

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For application in organic synthesis, the regiochemistry of insertion of carbenoids into un-symmetrical zirconacydes needs to be predictable. In the case of insertion into mono- and bicydic zirconacydopentenes where there is an wide variety of metal carbenoids insert selectively into the zirconium—alkyl bond [48,59,86], For more complex systems, the regiocon-trol has only been studied for the insertion of lithium chloroallylides (as in Section 3.3.2) [60]. Representative examples of regiocontrol relating to the insertion of lithium chloroal-lylide are shown in Fig. 3.2. 

The effect of bond polarity on the regiochemistry of insertion may be involved in the case of the Rh complex of equation (53) which adds to acrylonitrile as if it were Rh+—H, in contrast with the Ir complex of equation (54) which appears to add as Ir- —H+. 23 Relatively little is known about the pXa values of metal hydrides.124 In addition to the reactivity properties mentioned above, the M—H bond can also tend towards M+—H or M —H+ character in its ground state structure. This seems to have an influence on spectroscopic (Section 19.4.3), physical (Section 19.4.7) and structural (Section 19.4.2) properties. 

The catalyst system 192/MAO has been used for the synthesis of multi-block propylene-styrene co-polymers. The resulting co-polymers have a propylene content in the range 1-33 mol%, and the molecular masses are in the range d/w = 2100 — 60 000. Lower d/w values were observed for higher propylene content. Interestingly, NMR analysis indicated that the regiochemistry of insertion of the two monomers is opposite. In particular, the iPP blocks are formed by primary insertion of propylene, whereas the iPS blocks are formed by secondary insertion of styrene.1244... 

Klingebiel32 observed a related insertion with the silene 131 (Eq. 47), which gave the product 132 under the thermal conditions of its formation. Surprisingly, the regiochemistry of the C—H addition to the Si=C bond was opposite to the case in Eq. (46). 

We and others have revealed that syndiospecific propylene polymerization is exclusively initiated by 1,2-insertion followed by 2,1-insertion as the principal mode of polymerization [64]. This is the first example of a predominant 2,1-insertion mechanism for chain propagation exhibited by a group 4 metal-based catalyst. The unusual preference for 2,1-regiochemistry displayed by the Ti-FI catalysts compared with the Zr- and Hf-FI catalysts is apparently inconsistent with the crys-tallographically characterized structures, which indicate that the Ti is shielded more by the phenoxy-imine ligands and thus possesses higher steric compression. The reason for the unusual preference in the regiochemistry of Ti-FI catalysts is unclear at the present time. 

Scheme 3.39. Alternative explanation for the regiochemistry of carbenoid insertion.

Presumably, the oxidative cyclization of 3 commences with direct palladation at the a position, forming o-arylpalladium(II) complex 5 in a fashion analogous to a typical electrophilic aromatic substitution (this statement will be useful in predicting the regiochemistry of oxidative additions). Subsequently, in a manner akin to an intramolecular Heck reaction, intermediate 5 undergoes an intramolecular insertion onto the other benzene ring, furnishing 6. (i-Hydride elimination of 6 then results in carbazole 4. 

These results led to the proposal of the following mechanism. Decomplex-ation of the central C2 fragment allows coordination of the alkyne (intermediate 119), which then inserts to form the metallacycle 120. Deinsertion (reductive eliminate of the cobalt moiety allows ring closure to give the cyclohexadienone complex 121, which upon decomplexation yields the desired phenol. The regiochemistry of the alkyne insertion determines the ratio of 116 117 (for simplicity, only the sequence leading to 116 has been shown). 

The established activity of ethereal a-C-H bonds toward carbene and nitrene insertion has evoked new applications for sulfamate oxidation [76-78] In principle, a C-H center to which an alkoxy group is attached should be a preferred site for amination irrespec-hve of the addihonal functionality on the sulfamate ester backbone (Scheme 17.20). Such a group can thus be used to control the regiochemistry of product formation. The N,0-acetal products generated are iminium ion surrogates, which may be coupled to nucleophiles under Lewis acid-promoted conditions [79]. This strategy makes available substituted oxathiazinanes that are otherwise difficult to prepare in acceptable yields through direct C-H amination methods [80]. 

The regiochemistry of the insertion results from a combination of factors which are still being sorted out. It is possible to diink of the carbon attached to palladium as electron rich, and it tends to attack die it system at die least elecd on rich position. Thus alkenes widi electron-withdrawing groups react faster dian alkenes widi electron-donating groups. It is quite paradoxical, however, that alkenes, dienes, and alkynes react much more readily dian carbonyl compounds, even diough the latter are much more elecd on deficient. 

A wide range of substituted isoquinolines (93) have been synthesized via a highly efficient nickel-catalysed annulation of the r-butylimines of 2-iodobenzaldehydes (91) and various alkynes (92) examination of the regiochemistry of the reaction revealed the operation of two different alkyne insertion pathways.119... 

In Bennett and Wenger s study68 of the factors that control the two insertions in the naphthalene forming sequence, they concluded that (1) the regiochemistry of the first insertion step is sterically controlled with the substituted carbon bonding to Ni (e.g., 152 favored over 151) (2) the second insertion occurs between Ni and vinyl rather than Ni and aryl and is sterically controlled with electron-rich alkynes and (3) with electron-deficient alkynes, both steric and electronic factors influence the regiochemistry of the second insertion step. 

Schenck H, Stromberg S, Zetterberg K, Ludwig M, Akermark B, Svensson M, Insertion Aptitudes and Insertion Regiochemistry of Various Alkenes Coordinated to Cationic (-R)(diimine) palladium(II) (R = -CH3, -C6H5) A Theoretical Study, Organometallics, 20,2813—2819 (2001)... 

For example, photocyclization61,78 of compound 49, derived from the phenyl complex la by addition of cyclopentadiene, was shown to afford the 1,2-dioxy naphthalene 50 (Scheme 18).79 Thus, the regiochemistry of this type of ring annulation is complementary to that of the Dotz reaction, which yields 1,4-dioxy compounds. Photocyclization of aminocarbene complex 5180 involves insertion of carbon monoxide and leads to production of an 2-amino-l-oxy naphthalene derivative 52. Regio isomers, e.g., l-amino-2-oxy compounds 54, can be generated thermally by intermediate formation of a ketene imine 53 by addition of an isocyanide to compound 49 79,81,82 (Amino)alkynylcarbene complexes also give [4+2] cycloadducts, but they prove to be much less reactive than the corresponding alkoxycar-bene compounds (Scheme 18).42,83... 

Steric differences have been shown to affect the regio-chemistry of cyclization, as the CO inserts in the a-position of the larger alkynyl snbstitnent. However, theoretical stndies on dicobalt hexacarbonyl alkyne complexes have snggested that electronic differences in alkyne substitnents may also exert control over the regiochemistry of cyclizationd Calculations have also provided information on geometries and configurational stabilities of these complexes. 

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