Iron(II) complexes of sterically bulky alpha-ketocarboxylates. structural models for alpha-ketoacid-dependent nonheme iron halogenases.

Reaction of the sterically hindered alpha-ketocarboxylate 2,6-di(mesityl)benzoylformate (MesBF) with the iron(II) complexes LFeCl 2 [L = N, N, N', N'-tetramethylpropylenediamine (Me 4pda) or 6,6'-dimethyl-2,2'-bipyridine (dmby)] yielded LFe(Cl)(MesBF) ( 1 or 2). X-ray crystal structures of these complexes showed that they closely model the active site structure of the nonheme iron halogenase enzyme SyrB2. A similar synthetic procedure using benzoylformate with L = dmby yielded (dmby)Fe[(O 2CC(O)Ph)] 2 ( 3) instead, demonstrating the need for the sterically hindered alpha-ketocarboxylate to assemble the halogenase model compounds. In order to make reactivity comparisons among the structurally related iron(II) complexes of benzoylformates of varying steric properties, the complexes [LFe(O 2CC(O)Ar)] n ( 4- 6) were prepared, where L' = tris(pyridylmethyl)amine (tpa) and Ar = 2,6-dimesitylphenyl, 2,6-di p-tolylphenyl, or 2,4,6-trimethylphenyl, respectively. X-ray structures for the latter two cases ( 5 and 6) revealed dinuclear topologies ( n = 2), but UV-vis and (1)H NMR spectroscopy indicated that all three complexes dissociated in varying degrees to monomers in CH 2Cl 2 solution. Although compounds 1- 6 were oxidized by O 2, oxidative decarboxylation of the alpha-ketocarboxylate ligand(s) only occurred for 3. These results indicate that the steric hindrance useful for structural modeling of the halogenase active site prohibits functional mimicry of the enzyme.

Self-assembly of the 2-His-1-carboxylate facial triad in mononuclear iron(II) and zinc(II) models of metalloenzyme active sites.

A synthetic strategy involving the use of sterically hindered N-donor and terphenylcarboxylate ligands has been used to prepare complexes of iron(II) and zinc(II) that feature N2(carboxylate) donors. X-ray crystallographic and NMR data show that the 2-His-1-carboxylate facial triad found in metalloenzyme active sites is closely modeled by the mononuclear complexes. In addition, by virtue of the flexibility of the ligands used, the geometries and coordination environments of the complexes display carboxylate binding mode differences such as those seen in the enzymes.

A transition-metal-catalyzed enediyne cycloaromatization.

The pentamethylcyclopentadienyl iron cation, generated from [(eta5-C5Me5)Fe(NCMe)3]PF6, triggers the room temperature cycloaromatization of acyclic and alicyclic enediynes, in the presence of either 1,4-cyclohexadiene or terpinene as the hydrogen-atom donor, to give metal-arene products in good to excellent yields. Photolysis of the metal-arene complexes liberates the arene from the metal in excellent yield. The first demonstration of a transition-metal-catalyzed cycloaromatization of conjugated enediynes has been achieved under photochemical conditions utilizing either [(eta5-C5Me5)Fe(NCMe)3]PF6 or [(eta5-C5Me5)Fe(eta6-1,2-(Prn)2C6H4)]PF6 as the catalyst precursor. The use of a metal and light has led to a convenient method for cycloaromatization of a trans-enediyne.

An eta(6)-dienyne transition-metal complex.

The ruthenium complexes, [(eta5-C5R5)Ru(CH3CN)3]PF6 (1-Cp*, R = Me; 1-Cp, R = H), underwent reaction with both 1-(2-chloro-1-methylvinyl)-2-pentynyl-(Z)-cyclopentene (6-Z) and 1-(2-chloro-1-methylvinyl)-2-pentynyl-(E)-cyclopentene (6-E) to give (eta5-C5R5)Ru[eta6-(5-chloro-4-methyl-6-propylindan)]PF6 (7-Cp*, R = Me; 7-Cp, R = H). In a similar fashion, reaction of 1-Cp and 1-Cp* with 1-isopropenyl-2-pent-1-ynylcyclopentene (8) led to the formation of (eta5-C5R5)Ru(eta6-4-methyl-6-propylindan)]PF6 (9-Cp*, R = Me; 9-Cp, R = H). The reaction of 1-Cp* with 8 at -60 degrees C in CDCl3 solution led to observation of the eta6-dienyne complex, (eta5-C5Me5)Ru[eta6-(1-isopropenyl-2-pent-1-ynylcyclopentene)]PF6 (10), by 1H NMR spectroscopy. Complexes 7-Cp and 10 were characterized by X-ray crystallographic analysis.

Ruthenium-mediated cycloaromatization of acyclic enediynes and dienynes at ambient temperature.

The ruthenium(II) cation, [Cp*Ru(NCMe)3]OTf (4), triggers the Bergman cycloaromatization of acyclic endiynes at room temperature in THF solvent. Treatment of 1,2-di(1-alkynynyl)cyclopentenes (13-Me, alkynyl = propynyl; 13-Prn, alkynyl = pentynyl; 13-Bui, alkynyl = 4-methyl-pent-1-ynyl) with 4 in THF solvent at room temperature gives rise to the ruthenium arene complexes: [Cp*Ru{(3a,4,5,6,7,7a-eta)-2,3-dihydro-5,6-dialkyl-1H-indene}]OTf (15-Me, alkyl = methyl, 64% yield; 15-Prn, alkyl = n-propyl, 73% yield; 15-Bui, alkyl = 4-methyl-1-pentynyl, 88% yield). In a similar fashion, the room-temperature reaction of 4 with 1-ethynyl-2-(1-propynyl)cyclopentene (11) and [2-(1-propynyl)-1-cyclopenten-1-yl]trimethylsilane (14) leads to the formation of [Cp*Ru{(3a,4,5,6,7,7a-eta)-2,3-dihydro-5-methyl-1H-indene}]OTf (12, 92% yield) and [Cp*Ru{(3a,4,5,6,7,7a-eta)-2,3-dihydro-6-methyl-1H-inden-5-yl)trimethylsilane}]OTf (16, 77% yield), respectively. The bis(TMS)-substituted enediyne (1-cyclopentene-1,2-diyldi-2,1-ethynediyl)bis(trimethylsilane) (9-TMS) and 4 underwent reaction at 100 degrees C to give [Cp*Ru{(3a,4,5,6,7,7a-eta)-2,3-dihydro-1H-inden-5-yl)trimethylsilane}]OTf (10, 69% yield). Deuterium-labeling studies rule out a mechanism that involves a ruthenium-vinylidene intermediate, and provide support for the involvement of a p-benzyne intermediate. In a similar fashion, complex 4 is shown to trigger the cycloaromatization of the conjugated dienyne, 1-ethenyl-2-(1-pentynyl)cyclopentene (19), at room temperature in chloroform-d1 solvent to give [Cp*Ru{(3a,4,5,6,7,7a-eta)-2,3-dihydro-5-(1-propyl)-1H-indene}]OTf (20, 96% yield), with no deuterium enrichment. In the absence of ruthenium the thermal cyclization reactions of unsubstituted acyclic enediynes (Bergman cycloaromatization) and acyclic conjugated dienynes (Hopf cyclization) typically require elevated temperatures (150-250 degrees C). Complexes 10 and 15-Prn were characterized structurally by X-ray crystallography.