Nitrogenation-transmetallation process

Scheme 2.176 Palladium-catalyzed nitrogenation-transmetallation process.

In 1991, a new C-N-C bond formation reaction using a nitrogenation-transmetalation process was described. Ketones and aryl or vinyl halides couple to give divinyl or arylvinyl amines in the presence of the titanium isocyanate complex [3THF MgaClaO TiNCO] and a palladium catalyst, via transmetallation of the titano imine complex with aryl or vinyl palladium bromide. Moderate to good yields of the desired products were observed (Scheme 2.176). 

Examples exist of rearrangements in which a halogen atom migrates from annular nitrogen to carbon, or from one ring carbon to another ( halogen-dance or transmetalation). Such processes occasionally have preparative importance, and they will be covered in the appropriate sections. 

The nickel ) complex of 92 cannot be prepared directly via the template method, but can be prepared by a transmetallation procedure. Synthesis of the macrocycle in the presence of one of the metal ions known to be effective as a template is followed by a metal exchange process in solution to insert the nickel ) ion. This cation exhibits a strong preference for the square planar, square pyramidal, and octahedral geometries 79). Thus the failure of the nickel ) cation to behave as a template ion in the synthesis of 92 is probably due to the disinclination of the metal to accommodate the pentagonal array of donor nitrogen atoms necessary for reaction to occur. 

The transition-metal catalyzed cross-coupling reaction of (hetero)aryl hahdes and triflates with primary and secondary amines or (hetero)aryl amines is know as the Buchwald-Hartwig reaction [144]. Mechanistically, this reaction is related to the crosscoupling reactions outlined thus far (Fig. 4.6). The modification arises at the point of transmetalation. This step in the process is substituted with the coordination of the amine reactant. Deprotonation of the amine nitrogen now precedes the reductive elimination step to generate the aryl amine product. This reaction has foimd utility in the academic setting, for use in natural product total synthesis, and in industry, for the preparation of materials up to the multi-hundred kilogram scale. 

A Vnsh coupling of 24 Hz has been observed by Santiago et in the spectrum of trans-4-terf-butyl-2-(tributylstannane)piperidine but not in that of its cis isomer. In the first case the lone nitrogen pair and the C-Sn bond are eclipsed, in the other antiplanar. The authors also noticed that the tin-lithium transmetallation proceeds very easily for the trans compound, whereas isomer cis does not undergo this process. 

The arylation of aromatic ketones with arylboronates proceeds by an oriho-ruthenation with RuH2(CO)(PPh3)3 as the catalyst [137]. In this transformation, the final C—C bond is formed in a transmetallation-reductive elimination process. In a different reaction, ortHo-arylated compounds are obtained from o-aminoaryl ketones and arylboronates through substitution of the amino function catalyzed by the same Ru(II) complex [138], A nitrogen-directed homocouphng of aromatic compounds takes place with Ru(II) catalysts in the presence of aUylic chlorides or acetates by a mechanism that presumably involves Ru(IV) intermediates [139],... 

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