Publications

The exceptionally π-basic metal fragments {MoTp(NO)(DMAP)} and {WTp(NO)(PMe₃)} (Tp = tris(pyrazolyl)borate; DMAP = 4-(N,N-dimethylamino)pyridine) form thermally stable η²-coordinated complexes with a variety of electron-deficient arenes. The tolerance of substituted arenes with fluorine-containing electron withdrawing groups (EWG; −F, −CF₃, −SF₅) is examined for both the molybdenum and tungsten systems. When the EWG contains a π bond (nitriles, aldehydes, ketones, ester), η² coordination occurs predominantly on the nonaromatic functional group. However, complexation of the tungsten complex with trimethyl orthobenzoate (PhC(OMe)₃) followed by hydrolysis allows access to an η²-coordinated arene with an ester substituent. In general, the tungsten system tolerates sulfur-based withdrawing groups well (e.g., PhSO₂Ph, MeSO₂Ph), and the integration of multiple electron-withdrawing groups on a benzene ring further enhances the π-back-bonding interaction between the metal and aromatic ligand. While the molybdenum system did not form stable η²-arene complexes with the sulfones or ortho esters, it was capable of forming rare examples of stable η²-coordinated arene complexes with a range of fluorinated benzenes (e.g., fluorobenzene, difluorobenzenes). In contrast to what has been observed for the tungsten system, these complexes formed without interference of C–H or C–F insertion.

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%.