Cycloadditions hydroamination

The metallocene complex 27 containing a M=X double bond undergoes overall [2 + 2] cycloaddition with an internal alkynes to give heterometallacyclobutenes (28) [77], A formal [2 + 2] cycloaddition of CpjZr (=N Bu)(thf) with imine affords a 2,4-diazametallacyclobutane, whose further reaction with imines results in an imine metathesis reaction [78] azametallacyclobutene is an intermediate in the Cp2Zr(NHR)2-assisted hydroamination of alkynes and allene [79],... 

Scheme 10 [2 + 2] Cycloaddition mechanism for alkyne hydroamination catalysis...

The reaction involves initial formation of the zirconium-imido species, followed by [2-1-2] cycloaddition with the C—C unsaturation (Scheme 13). This is consistent with the observation that bis(amidate) complexes do not mediate hydroamination with secondary amine containing substrates. The cyclic transition state of the intramolecular reaction determines the regioselectivity of the reaction followed by successive protonation of the intermediate metallacycle and release of product to regenerate the catalyticaUy active imido species. 

Addition and cycloaddition. Styrenes are transformed into benzylatnine derivatives by hydroamination with TsNH2/" More unusual is the regioselective addition of arenes across the triple bond of an alkynylarene, as catalyzed by FeCls. ... 

Synthesis of saturated heterocycles via metal-catalyzed formal cycloaddition reactions that generate a C—N or C—O bond 13THC(32)225. Synthesis of saturated heterocycles via metal-catalyzed alkene carboami-nation, carboalkoxylation diamination, aminoalkoxylation, dialkoxyla-tion hydroamination or hydroalkoxylation reactions 13THC(32)1, 13THC(32)39, 13THC(32)109. 

Cycloadditions are among the more common reactions of imido and 0x0 groups in catalytic transformations. Both [2+2] cycloadditions and [3+2] cycloadditions are well established. The [2+2] cycloaddition chemistry occurs during hydroaminations of alkynes, allenes, and strained olefins catalyzed by imido compounds. - The [3+2] cycloaddition reactions appear to occur during dihydroxylation and aminohydroxylation of olefins catalyzed by osmium complexes. ... 

The first hydroaminations by this mechanism were reported by Bergman with zircono-cene complexes and by Livinghouse with monocyclopentadienyl titanium and zirconium complexes. Bergman reported the intermolecular addition of a hindered aniline to an alkyne. The hindrance of the aniline was important to prevent formation of stable dimeric complexes containing bridging imido groups. Livinghouse reported intramolecular reactions that occurred at lower temperatures over shorter times. The intramolecularity of this process allows the [2+2] cycloaddition of the imido complex with the alkyne to be faster than the dimerization. 

Examples of the [2+2] cycloadditions and the mechanisms of these processes were presented in detail in Chapter 13 on complexes containing metal-ligand multiple bonds. In short, coordination of the alkyne or allene precedes the [2+2] cycloaddition. This cycloaddition is thermodynamically favorable for aikynes and allenes, but is thermodynamically disfavorable for reactions of alkenes. Studies on the regioselectivity of the stoichiometric [2+2] cycloaddition and of the regioselectivity of zirconocene-catalyzed hydroamination revealed that the [2+2] process is reversible during the hydroaminations catalyzed by zir-conocene complexes. Moreover, it has been shown that addition of an alkyne to an isolated zirconocene azametallacyclobutene leads to exchange. 

The hydroamination of olefins has been shown to occur by the sequence of oxidative addition, migratory insertion, and reductive elimination in only one case. Because amines are nucleophilic, pathways are available for the additions of amines to olefins and alkynes that are unavailable for the additions of HCN, silanes, and boranes. For example, hydroaminations catalyzed by late transition metals are thought to occur in many cases by nucleophilic attack on coordinated alkenes and alkynes or by nucleophilic attack on ir-allyl, iT-benzyl, or TT-arene complexes. Hydroaminations catalyzed by lanthanide and actinide complexes occur by insertion of an olefin into a metal-amide bond. Finally, hydroamination catalyzed by dP group 4 metals have been shown to occur through imido complexes. In this case, a [2+2] cycloaddition forms the C-N bond, and protonolysis of the resulting metallacycle releases the organic product. 

Scheme 15.3 General alkyne hydroamination reaction with Zr catalyst (top) and general [2+2] cycloaddition catalytic cycle (bottom).

Interestingly, the Schafer group [34] has established that group 4 complexes can indeed be used for the intermolecular hydroamination of alkynes with secondary amines consistent with a shift in mechanism from the established [2+2] cycloaddition pathway. Specifically, a Zr ureate catalyst 5 has been developed to realize this shift in mechanism. For example, entry 20 shows that morpholine can be used at elevated temperatures to give enamine products that can be characterized in situ. Using the ureate catalyst 5, mechanistic analyses [35] and subsequent computational investigations [36] support a proton-assisted C-N bond formation (see later discussion). 

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