Dominos at zirconium: A cascade of N–N and C–H scissions and C–C and C–N coupling steps in the coordination sphere of zirconium directly converts alkynes and hydrazines into indoles. The reaction pathway differs fundamentally from that of the Fischer indole synthesis.
Reaction of cyclic 1,1′-disubstituted hydrazines
with the
bis(dimethylamido)zirconium complex [Zr{(NXyl)2Npy} (NMe2)2] (1) in
the presence of dmap yielded the hexacoordinate zirconium hydrazinediido
complexes [Zr{(NXyl)2Npy}(NNC9H10)(dmap)2] (2) and [Zr{(NXyl)2Npy}(NNC12H8)(dmap)2] (3). Hydrazinediides are
thought to be key intermediates in the zirconium-catalyzed reaction
of cyclic 1,1′-disubstituted hydrazines and disubstituted alkynes
to yield 1,7-annulated indoles. Their basic structural motif is found
in 5-HT3 receptor antagonists such as Cilansetron.
Reaction of [Zr{(NAr)(2)N(py)}(NMe(2))(2)] (Ar=3,5-xylyl: 2 a, mesityl: 2 b) with one or two molar equivalents of 1,1-diphenylhydrazine gave the mixed amido/hydrazido(1-) complex [Zr{(NMes)(2)N(py)}(HNNPh(2))(NMe(2))] (3), the bis-hydrazido complex [Zr{(NMes)(2)N(py)}(HNNPh(2))(2)] (4), and, in the presence of excess 4-dimethylaminopyridine (DMAP), hexacoordinate hydrazinediidozirconium complexes [Zr{(NXyl)(2)N(py)}(=NN(Me)Ph)(dmap)(2)] (5) and [Zr{(NXyl)(2)N(py)}(=NNPh(2))(dmap)(2)] (6). The reaction of one equivalent of the zirconium-hydrazinediide [Zr{(NTBS)(2)N(py)}(NNPh(2))(py)] (1) with disubstituted alkynes at RT for 16 h led to the formation of seven-membered diazazirconacycles 7 a-7 e in high yields. Similar reactivity was observed by reacting bis-amido complex 2 b with one molar equivalent of the corresponding alkyne and diphenylhydrazine. The formation of the seven-membered zirconacycles implied a key coupling step that involved the alkyne and one of the aryl rings of the diphenylhydrazinediido ligand. In some cases, such as the reaction with 2-butyne, the corresponding metallacycle was only obtained in modest yields (45 % for the reaction with 2-butyne) and a second major product, vinylimido complex 9, was formed in almost equal amounts (42 %) by 1,2-amination (formal insertion of the alkyne). The formation of compounds 7 a and 9 followed in part the same sequence of reaction steps and a key intermediate, an azirinido complex, represented a "bifurcation point" in the reaction network. Reaction of 1.2 equivalents of several diarylhydrazines and various substituted alkynes (1 equiv) at ambient temperature (or at 80 °C) in the presence of 10 mol % [Zr{(NXyl)(2)N(py)}(NMe(2))(2)] (2 a) gave the corresponding indole derivatives. On the other hand, the replacement of 1,1-diarylhydrazines by 1-methyl-1-phenyl hydrazine led to head-to-head cis-1,3-enynes in good yields.
The N-perfluoro-phenylated pyridyldiamine H2N2(PFP)N(py) (1) has been prepared by a palladium-catalyzed coupling of hexafluorobenzene and the diamine (H2NCH2)2C(CH3)(2-C5H4N) using the palladacycle trans-di(μ-acetato)bis[o-(di-o-tolylphosphino)benzyl]palladium(II) as catalyst. Reactions of H2N2(PFP)N(py) and Zr(NMe2)4 at room temperature or 90 °C led to the complexes [(N(PFP)N2(TFAP)N(py))ZrF(NMe2)] (2) and [(N2(TFAP)N(py))ZrF2] (3) in which one or two dimethylamido groups replaced one or two ortho fluorine atoms of the pentafluorophenyl groups in the ligand. Reaction of Me3SiX (X = Cl, I) with [(N2(TFAP)N(py))ZrF2] (3) resulted in the formation of mixed halogenated complexes [(N2(TFAP)N(py))ZrFI] (4) and [(N2(TFAP)N(py))ZrFCl] (5) in which the axially bound fluorido ligand is substituted. Reaction of [(N2(TFAP)N(py))ZrF2] (3) with LiNHNPh2 afforded the monohydrazido(1-) complex [(N2(TFAP)N(py))ZrF(NHNPh2)] (6) which was converted to the dimeric fluoro-potassium bridged hydrazinediido complex [Zr(N2(TFAP)N(py))FNNPh2K]2 (7) using KHMDS. The corresponding reaction with LiHMDS yielded the monomeric, donor free complex [Zr(N2(TFAP)N(py))NNPh2] (8).
Domino‐Spiel an einem Zirconiumatom: Eine Kaskade von N‐N‐ und C‐H‐Bindungsspaltungen sowie C‐C‐ und C‐N‐Kupplungen in der Koordinationssphäre von Zirconium führt zur direkten Umwandlung von Alkinen und Hydrazinen zu Indolen. Der Reaktionsweg unterscheidet sich grundlegend von der Fischer‐Indol‐Reaktion.
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