Publications

The complex MoTp(NO)(DMAP)(η²-naphthalene) (1; DMAP = 4-(dimethylamino)pyridine; Tp = tris(pyrazolyl)borate) is demonstrated to undergo Michael–Michael ring-closure (MIMIRC) reactions promoted by trimethylsilyltriflate. The resulting hexahydrophenanthrenes are formed stereoselectively, with isolation of a single dominant isomer. Combining the MIMIRC sequence with an oxidative decomplexation step, the final tricyclics can be synthesized from the naphthalene complex with overall yields between 19 and 50% (for four steps). This reaction sequence is shown to be capable of producing a steroidal core directly from naphthalene, providing access to a biologically relevant carbon framework.

A method for the resolution of η²-alkene-complex isomers of the type MoTp(NO)(DMAP)(η²-alkene) and WTp(NO)(PMe₃)(η²-alkene) (where Tp = hydridotris(pyrazolyl)borate and DMAP = 4-(dimethylamino)pyridine) has been explored. Alkene and polyene compounds form as a mixture of kinetically trapped isomers. For both types of complexes, it was found that addition of either a fluorinated alcohol or one-electron oxidant reduces the number of isomers in solution. Accelerated ligand exchange was also observed, although these reactions were accompanied by significant decomposition.

The preparation of the complex MoTp(NO)(DMAP)(4,5-η²-(2-trifluoromethyl)pyridine) (DMAP = 4-(dimethylamino)pyridine; Tp = tris(pyrazolyl)borate) is described. The CF₃ substituent is found to preclude κ-N coordination, allowing for direct coordination without protection of the nitrogen. The dihapto-coordinate complex can be isolated as a single diastereomer, methylated, and reacted with a range of nucleophiles. Oxidative decomplexation affords the free dihydropyridines in good yield (75–90%). As a demonstration of synthetic utility, a series of novel bridgehead CF₃-substituted isoquinuclidines was prepared from these decomplexed dihydropyridines.

An oxidant-initiated, substitution process for dihapto-coordinated ligands is described for the {MoTp(NO)(DMAP)} system. Complexes of the form MoTp(NO)(DMAP)(η²-alkene), MoTp(NO)(DMAP)(η²-ketone), and MoTp(NO)(DMAP)(η²-arene) (where Tp = hydridotris(pyrazolyl)borate and DMAP = 4-(dimethylamino)pyridine) undergo an alkene-to-ketone exchange that is catalyzed by the addition of <0.1 equiv of a metallocene oxidant (ferrocenium, permethylferrocenium, or cobaltocenium). A similar acceleration was observed in the presence of the H-bond donor hexafluoroisopropanol (HFIP). From experimental observations, a radical chain propagation mechanism is proposed that is dependent on the equilibrium between dihapto-coordinated (C, O-η²) and monocoordinated (κ-O) isomers and the differing redox characteristics of these two isomeric forms. This concept was then applied to the search of sodium-free reduction conditions for the conversion of MoTp(NO)(DMAP)(I) to various molybdenum(0) complexes of unsaturated ligands, including MoTp(NO)(DMAP)(η²-naphthalene) and MoTp(NO)(DMAP)(α-pinene).

The dihapto-coordination of benzene to the π-basic fragment {TpW(NO)(PMe₃)} (Tp = hydridotris(pyrazolyl)-borate) enhances the basicity of the arene ligand to the point that it can be protonated with a mild Brønsted acid (diphenylammonium triflate; pK_a ∼ 1). The resulting η²-benzenium complex reacts with a wide range of nucleophiles including protected enolates, cyanide, amines, methoxide, and aromatic nucleophiles to form 5-substituted 3,4-η²-1,3-cyclohexadiene complexes in good yield (42–70%). These coordinated dienes were successfully taken through a second protonation and nucleophilic addition with a similar scope of nucleophiles (54–80%). The resulting cis-3,4- and cis-3,6-disubstituted η²-cyclohexene complexes were prepared with high regio- and stereocontrol, as governed by the asymmetric nature of π-allyl intermediates. In some cases, a diene linkage isomerization from 3,4-η² to 1,2-η² could be effected with a redox catalyst, and reactions of the latter species led to cis-3,5-disubstituted cyclohexene products exclusively. Oxidative decomplexation afforded the free cyclohexene products in moderate yield (37–68%). Additionally, when a single enantiomer of the chiral dearomatization agent was used, the elaborated cyclohexenes were able to be synthesized in enantioenriched forms (86–90% enantiomeric excess). Full characterization of 40 new compounds is provided that includes two-dimensional NMR, IR, electrochemical and in some cases crystallographic data.

The preparation and properties of the complex (R_Mo,R)-MoTp(NO)(DMAP)(η²-α-pinene) are described (∼10 g scale; DMAP = 4-(dimethylamino)pyridine; Tp = hydridotris(pyrazolyl)borate). This complex undergoes exchange of the pinene with a wide range of other π ligands including acetone, ethyl acetate, N,N-dimethylformamide, acetonitrile, and naphthalene. Treatment of the α-pinene complex with iodine results in the complex (S)-MoTp(NO)(DMAP)(I), which is recovered in enantioenriched form (er = 99:1; yield >90%; scale 4.6 g). Reduction of this molybdenum(I) precursor results in enantioenriched molybdenum(0) complexes, including (R)-MoTp(NO)(DMAP)(η²-trifluorotoluene). Sequential treatment of this arene complex with acid, a masked enolate, and iodine regenerates MoTp(NO)(DMAP)(I) along with an alkylated 1-(trifluoromethyl)cyclohexa-1,3-diene with an er value as high as 99:1. This process demonstrates the efficient transfer of asymmetry from α-pinene to the diene product. Accompanying studies with (1R)-myrtenal reveal a redox-catalyzed pinene/myrtenal ligand exchange occurring through Mo(I) intermediates.

The effects of an electron-withdrawing group on the organic chemistry of an η²-bound benzene ring are explored using the complex TpW(NO)(PMe₃)(η²-PhCF₃). This trifluorotoluene complex was found to undergo a highly regio- and stereoselective 1,2-addition reaction involving protonation of an ortho carbon followed by addition of a carbon nucleophile. The resulting 1,3-diene complexes can undergo a second protonation and nucleophilic addition with a range of nucleophiles including hydrides, amines, cyanide, and protected enolates. Interestingly, the addition of the second proton and nucleophile occurs in a 1,4-fashion, again with a high degree of regio- and stereocontrol. Oxidation of the metal allows for the isolation of highly substituted trifluoromethylcyclohexenes with as many as four stereocenters set by the metal. The ability to synthesize enantio-enriched organics was also demonstrated for a diene and a trisubstituted cyclohexene. Substitution from an enantio-enriched η²-dimethoxybenzene complex in neat trifluorotoluene yielded enantio-enriched trifluorotoluene complex, which was elaborated into cyclohexadienes and cyclohexenes with ee’s ranging from 92 to 99%.

The preparation of the complexes TpMo(NO)(DMAP)(η²-PhCF₃) (5) and TpMo(NO)(DMAP)(η²-benzene) (3) is described. The CF₃ group is found to stabilize the metal–arene bond strength in 5 by roughly 3 kcal/mol compared to that in 3, allowing the large-scale synthesis and isolation of the trifluorotoluene analogue (5, 37 g, 70%). When a benzene solution of 5 is allowed to stand, clean conversion to the benzene analogue 3 occurs, and this complex may be precipitated from solution upon the addition of pentane and isolated. The trifluorotoluene complex is shown to be a synthetic precursor to functionalized cyclohexadienes: In solution, it selectively protonates at the ortho position, and the resulting η²-arenium species undergoes reactions with nucleophiles at the adjacent meta carbon. Thus, reactions of 5, triflic acid, and either N-methylpyrrole or 1-methoxy-2-methyl-1-(trimethylsilyloxy)-1-propene result in 5-substituted-1,3-cyclohexadienes after removal of the metal.