William H. Myers

Polarization of the Pyridine Ring: Highly Functionalized Piperidines from Tungsten−Pyridine Complex

The N-acetylpyridinium complex of {TpW(NO)(PMe3)} undergoes regio- and stereoselective reactions with a broad range of common organic nucleophiles, providing a family of 1,2-dihydropyridine (DHP) complexes of the form TpW(NO)(PMe3)(3,4-η(2)-DHP). The present study explores the elaboration of these systems into novel piperidines. The addition of an acid to the DHP complexes generates highly asymmetric π-allyl complexes that in turn react with a second nucleophile at either C3 or C5. The subsequent oxidative decomplexation of these materials yields several piperidinamides with unconventional substitution patterns.

Coordination Chemistry of 4-Methyl-2,6,7-trioxa-1-phosphabicyclo[2,2,1]heptane: Preparation and Characterization of Ru(II) Complexes

The complexes TpRu[P(OCH(2))(2)(OCCH(3)](PPh(3))Cl (2) [Tp = hydridotris(pyrazolyl)borate; P(OCH(2))(2)(OCCH(3)) (1) = (4-methyl-2,6,7-trioxa-1-phosphabicyclo[2,2,1]heptane] and TpRu(L)(PPh(3))Cl [L = P(OCH(2))(3)CEt (3), PMe(3) (4) or P(OMe)(3) (5)], (η(6)-C(6)H(6))Ru(L)Cl(2) [L = PPh(3) (6), P(OMe)(3) (7), PMe(3) (8), P(OCH(2))(3)CEt (9), CO (10) or P(OCH(2))(2)(OCCH(3)) (11)] and (η(6)-p-cymene)Ru(L)Cl(2) [L = P(OCH(2))(3)CEt (12), P(OCH(2))(2)(OCCH(3))P(OCH(2))(2)(OCCH(3)) (13), P(OMe)(3) (14) or PPh(3) (15)] have been synthesized, isolated, and characterized by NMR spectroscopy, cyclic voltammetry, mass spectrometry, and, for some complexes, single crystal X-ray diffraction. Data from cyclic voltammetry and solid-state structures have been used to compare the properties of (1) with other phosphorus-based ligands as well as carbon monoxide. Data from the solid-state structures of Ru(II) complexes show that P(OCH(2))(2)(OCCH(3)) has a cone angle of 104°. Cyclic voltammetry data reveal that the Ru(II) complexes bearing P(OCH(2))(2)(OCCH(3)) have more positive Ru(III/II) redox potentials than analogous complexes with the other phosphorus ligands; however, the Ru(III/II) potential for (η(6)-C(6)H(6))Ru[P(OCH(2))(2)(OCCH(3))]Cl(2) is more negative compared to the Ru(III/II) potential for the CO complex (η(6)-C(6)H(6))Ru(CO)Cl(2). For the Ru(II) complexes studied herein, these data are consistent with the overall donor ability of 1 being less than other common phosphines (e.g., PMe(3) or PPh(3)) or phosphites [e.g., P(OCH(2))(3)CEt or P(OMe)(3)] but greater than carbon monoxide.

[4 + 2] Cyclocondensation Reactions of Tungsten–Dihydropyridine Complexes and the Generation of Tri- and Tetrasubstituted Piperidines

A new method for the preparation of functionalized piperidines is described in which various dihydropyridine (DHP) complexes of {TpW(NO)(PMe(3))} that are derived from pyridine-borane undergo [4 + 2] cyclocondensation with enones, enals, nitrosobenzene, and several isocyanates to form [2.2.2] bicyclic species. In several cases the diazabicyclooctene products derived from DHP complexes and isocyanates can be further elaborated into novel syn-2,5-disubstituted and 2,3,6-trisubstituted piperidinamides.

Efficient Synthesis of an η2-Pyridine Complex and a Preliminary Investigation of the Bound Heterocycle’s Reactivity

Pyridine borane is combined with TpW(NO)(PMe(3))(eta(2)-benzene) to form a complex of the heterocycle, which upon treatment with acetone and acid yields the pyridinium complex [TpW(NO)(PMe(3))(eta(2)-pyH(+))]OTf. Deprotonation in the presence of acetic anhydride delivers the N-acetylpyridinium complex as a 10:1 mixture of coordination diastereomers. This acylpyridinium resists reaction with water or oxygen but readily reacts with acetone, pyrrole, indole, or acrolein and a weak base to stereoselectively form 1,2-dihydropyridine complexes. Treatment of the indole-derived analogue with CuBr(2) results in liberation of 3-(pyridin-2-yl)-1H-indole.

Hydrophenylation of ethylene using a cationic Ru(II) catalyst: comparison to a neutral Ru(II) catalyst

Charge neutral Ru(II) complexes of the type TpRu(L)(NCMe)Ph [Tp = hydridotris(pyrazolyl)borate; L = CO, PMe3, P(OCH2)3CEt or P(OCH2)2(OCCH3)] have been previously reported to catalyze the hydrophenylation of ethylene (Organometallics, 2012, 31, 6851–6860). However, catalyst longevity for the TpRu(L)(NCMe)Ph complexes is inhibited by competitive ethylene C–H activation. For example, ethylene C–H activation limits catalysis using TpRu(P(OCH2)3CEt)(NCMe)Ph to a maximum of 20 turnover numbers for conversion of benzene and ethylene to ethylbenzene. In contrast, reaction of the cationic Ru(II) complex [(HC(pz5)3)Ru(P(OCH2)3CEt)(NCMe)Ph][BAr′4] [HC(pz5)3 = tris(5-methyl-pyrazolyl)methane; BAr′4 = tetrakis[3,5-bis(trifluoromethyl)phenyl]borate] (0.025 mol% relative to benzene) in benzene with C2H4 (15 psi) at 90 °C gives 565 turnover numbers of ethylbenzene after 131 hours. The production of 565 turnovers of ethylbenzene corresponds to an approximate one-pass 95% yield with ethylene is the limiting reagent and is a 28-fold improvement compared to the charge neutral catalyst TpRu(P(OCH2)3CEt)(NCMe)Ph. Under identical conditions, the activity of [(HC(pz5)3)Ru(P(OCH2)3CEt)(NCMe)Ph][BAr′4] is only 1.3 times less than TpRu(P(OCH2)3CEt)(NCMe)Ph, but the increased stability of the cationic Ru(II) catalyst allows reactivity at much higher temperatures (up to 175 °C) and significantly enhanced rates.

Synthesis of 1-Oxadecalins from Anisole Promoted by Tungsten

The complex TpW(NO)(PMe3)(eta(2)-anisole) is combined with acrolein or methyl vinyl ketone and various nucleophiles to generate novel chromen complexes. These complexes may be further elaborated by protonation and nucleophilic addition to generate chroman analogues with increased saturation and stereocenters. Treatment with various oxidants effects the decomplexation of the chromen.

Stereoselective Umpolung Tandem Addition of Heteroatoms to Phenol

Upon coordination to {TpW(PMe3)(NO)}, phenol tautomerizes to a cyclohexadienone (a 2H-phenol). The uncoordinated, nonaromatic double bond of this ligand undergoes stepwise addition of electrophiles followed by nucleophiles to produce 4,5-disubstituted cyclohexenone complexes. The metal stabilizes the intermediate cationic ligand and sterically blocks one face of the ligand, resulting in a high degree of stereo- and regiocontrol. These substituted cyclohexenones are readily liberated from the metal by oxidative decomplexation.

Synthesis of a Lactone Diastereomer of the Cembranolide Uprolide D

A convergent stereoselective synthesis of a C1/C14 bis-epimer of uprolide D is described in which an intramolecular Barbier-type reaction was employed for macrocyclization with concomitant introduction of the C1 and C14 stereocenters of a fused α-methylene lactone ring through an anti-Felkin-Anh transition state. Unlike previous examples of allyl chromium additions, none of the Felkin-Anh derived adduct could be detected.

Exploring the Original Proposed Biosynthesis of (+)-Symbioimine: Remote Exocyclic Stereocontrol in a Type I IMDA Reaction

The originally proposed biosynthesis of (+)-symbioimine was explored, resulting in the successful intramolecular Diels-Alder (IMDA) cyclization of an appropriate (E,E,E)-1,7,9-decatrien-3-one. In contrast to the originally proposed biosynthesis, the IMDA reaction appears to proceed via an endo transition state. Remarkably, a single exocyclic stereogenic center effectively controls the pi-facial selectivity affording a highly diastereoselective cycloaddition.

Novel Cyclization Reactions for η2-Furan Complexes

Abstract A series of complexes has been prepared of the form [Os(NH3)5(4,5-η2-L)]2+ where L=furan and various 2-alkylated furans. Electrophilic addition to C(3) results in an unstable reaction intermediate, a 4,5-η2-3H-furanium species, that leads to several novel cyclization reactions with tethered nucleophiles to form new heterocycles.