Ligand strategies for green chemistry: Catalysts for amide reduction and hydroamination

This thesis describes the synthesis of a new class of mixed monoanionic cyclopentadienyl-bis(oxazoline) ligands and synthesis of new metal complexes. Two achiral ligands were synthesized: H3CC(C5H5)(OxMe2)2 (H{BoMCp}; OxMe2 = 4,4-dimethyl-2-oxazoline) and H3CC(C5HMe4)(OxMe2)2 (H{BoMCptet}). The chiral analogs were also prepared, H3CC(C5H5)(OxiPr)2 (H{BoPCp}, OxiPr = 4S-isopropyl-2-oxazoline) and H3CC(C5HMe4)(OxiPr)2 (H{BoPCptet}). These ligands support a wide variety of metals, including magnesium, zinc, titanium, and zirconium. {BoMCp}MgCH3, {BoMCptet}MgCH3, {BoPCp}MgCH3, and {BoPCptet}MgCH3 show excellent reactivity for catalyzing the hydroboration of ketones using pinacolborane. {BoMCp}Zr(NMe2)3, {BoMCp}MgCH3, and {BoMCptet}MgCH3 are also efficient catalysts for the hydroamination of aminoalkenes. This thesis also describes the catalytic reduction of amides to amines using pinacolborane as the reductant and catalytic amounts of [Mg]. ToMMgMe (ToM = tris(4,4-dimethyl-oxazolinyl)phenylborate is found to show excellent catalytic activity for the reduction of secondary and tertiary amides. Last, pyrene is functionalized with tertiary amine groups following a simple synthetic route from commercially available pyrene precursors. These pyrene compounds, including N-ethyl-N-(pyren-4-ylmethyl)ethanamine, N,N-diethyl-4-(pyren-4-yl)butanamine, and N,N-bis(pyren-4-ylmethyl)ethanamine were prepared to be adsorbed onto multi-walled carbon nanotubes as a catalyst

Magnesium-Catalyzed Mild Reduction of Tertiary and Secondary Amides to Amines

The first example of a catalytic hydroboration of amides for their deoxygenation to amines is reported. This transformation employs an earth-abundant magnesium-based catalyst. Tertiary and secondary amides are reduced to amines at room temperature in the presence of pinacolborane (HBpin) and catalytic amounts of ToMMgMe (ToM = tris(4,4-dimethyl-2-oxazolinyl)phenylborate). Catalyst initiation and speciation is complex in this system, as revealed by the effects of concentration and order of addition of the substrate and HBpin in the catalytic experiments. ToMMgH2Bpin, formed from ToMMgMe and HBpin, is ruled out as a possible catalytically relevant species by its reaction with N,N-dimethylbenzamide, which gives Me2NBpin and PhBpin through C–N and C–C bond cleavage pathways, respectively. In that reaction, the catalytic product benzyldimethylamine is formed in only low yield. Alternatively, the reaction of ToMMgMe and N,N-dimethylbenzamide slowly gives decomposition of ToMMgMe over 24 h, and this interaction is also ruled out as a catalytically relevant step. Together, these data suggest that catalytic activation of ToMMgMe requires both HBpin and amide, and ToMMgH2Bpin is not a catalytic intermediate. With information on catalyst activation in hand, tertiary amides are selectively reduced to amines in good yield when catalytic amounts of ToMMgMe are added to a mixture of amide and excess HBpin. In addition, secondary amides are reduced in the presence of 10 mol % ToMMgMe and 4 equiv of HBpin. Functional groups such as cyano, nitro, and azo remain intact under the mild reaction conditions. In addition, kinetic experiments and competition experiments indicate that B–H addition to amide C═O is fast, even faster than addition to ester C═O, and requires participation of the catalyst, whereas the turnover-limiting step of the catalyst is deoxygenation

Ligand strategies for green chemistry: Catalysts for amide reduction and hydroamination

This thesis describes the synthesis of a new class of mixed monoanionic cyclopentadienyl-bis(oxazoline) ligands and synthesis of new metal complexes. Two achiral ligands were synthesized: H3CC(C5H5)(OxMe2)2 (H{BoMCp}; OxMe2 = 4,4-dimethyl-2-oxazoline) and H3CC(C5HMe4)(OxMe2)2 (H{BoMCptet}). The chiral analogs were also prepared, H3CC(C5H5)(OxiPr)2 (H{BoPCp}, OxiPr = 4S-isopropyl-2-oxazoline) and H3CC(C5HMe4)(OxiPr)2 (H{BoPCptet}). These ligands support a wide variety of metals, including magnesium, zinc, titanium, and zirconium. {BoMCp}MgCH3, {BoMCptet}MgCH3, {BoPCp}MgCH3, and {BoPCptet}MgCH3 show excellent reactivity for catalyzing the hydroboration of ketones using pinacolborane. {BoMCp}Zr(NMe2)3, {BoMCp}MgCH3, and {BoMCptet}MgCH3 are also efficient catalysts for the hydroamination of aminoalkenes. This thesis also describes the catalytic reduction of amides to amines using pinacolborane as the reductant and catalytic amounts of [Mg]. ToMMgMe (ToM = tris(4,4-dimethyl-oxazolinyl)phenylborate is found to show excellent catalytic activity for the reduction of secondary and tertiary amides. Last, pyrene is functionalized with tertiary amine groups following a simple synthetic route from commercially available pyrene precursors. These pyrene compounds, including N-ethyl-N-(pyren-4-ylmethyl)ethanamine, N,N-diethyl-4-(pyren-4-yl)butanamine, and N,N-bis(pyren-4-ylmethyl)ethanamine were prepared to be adsorbed onto multi-walled carbon nanotubes as a catalyst.</p

Magnesium-Catalyzed Mild Reduction of Tertiary and Secondary Amides to Amines

The first example of a catalytic hydroboration of amides for their deoxygenation to amines is reported. This transformation employs an earth-abundant magnesium-based catalyst. Tertiary and secondary amides are reduced to amines at room temperature in the presence of pinacolborane (HBpin) and catalytic amounts of ToMMgMe (ToM = tris(4,4-dimethyl-2-oxazolinyl)phenylborate). Catalyst initiation and speciation is complex in this system, as revealed by the effects of concentration and order of addition of the substrate and HBpin in the catalytic experiments. ToMMgH2Bpin, formed from ToMMgMe and HBpin, is ruled out as a possible catalytically relevant species by its reaction with N,N-dimethylbenzamide, which gives Me2NBpin and PhBpin through C–N and C–C bond cleavage pathways, respectively. In that reaction, the catalytic product benzyldimethylamine is formed in only low yield. Alternatively, the reaction of ToMMgMe and N,N-dimethylbenzamide slowly gives decomposition of ToMMgMe over 24 h, and this interaction is also ruled out as a catalytically relevant step. Together, these data suggest that catalytic activation of ToMMgMe requires both HBpin and amide, and ToMMgH2Bpin is not a catalytic intermediate. With information on catalyst activation in hand, tertiary amides are selectively reduced to amines in good yield when catalytic amounts of ToMMgMe are added to a mixture of amide and excess HBpin. In addition, secondary amides are reduced in the presence of 10 mol % ToMMgMe and 4 equiv of HBpin. Functional groups such as cyano, nitro, and azo remain intact under the mild reaction conditions. In addition, kinetic experiments and competition experiments indicate that B–H addition to amide C═O is fast, even faster than addition to ester C═O, and requires participation of the catalyst, whereas the turnover-limiting step of the catalyst is deoxygenation.Reprinted (adapted) with permission from ACS Catalysis 5 (2015): 4219, doi:10.1021/acscatal.5b01038. Copyright 2015 American Chemical Society.</p

Piano-Stool Lutetium Amido and Imido Compounds Supported by a Constrained Bis(oxazoline)cyclopentadienyl Ligand

{BoMCptet}Lu(CH2Ph)2 (1; BoMCptet = MeC(OxMe2)2C5Me4; OxMe2 = 4,4-dimethyl-2-oxazoline) was prepared in 95% yield from the reaction of BoMCptetH and Lu(CH2Ph)3THF3. Compound1 reacts with 1 or 2 equiv of H2NCH2R (R = C6H5, 1-C10H7) to give the corresponding imido complexes [{BoMCptet}LuNCH2R]2 (R = C6H5 (2a), 1-C10H7 (2b)) or amido complexes {BoMCptet}Lu(NHCH2R)2 (R = C6H5 (3a), 1-C10H7 (3b)). Once isolated, the imido species are insoluble in nonprotic organic solvents. Crystallographic characterization reveals dimeric [{BoMCptet}LuNCH2(1-C10H7)]2 in the solid state. The reaction of 1 and NH3B(C6F5)3 affords crystallographically characterized {BoMCptet}Lu{NHB(C6F5)2}C6F5. This species is proposed to form via a transient lutetium imido, which undergoes C6F5 migration to the lutetium center.Reprinted (adapted) with permission from Inorganic Chemistry 54 (2015): 6938, doi:10.1021/acs.inorgchem.5b00927 . Copyright 2015 American Chemical Society.</p

Piano-Stool Lutetium Amido and Imido Compounds Supported by a Constrained Bis(oxazoline)cyclopentadienyl Ligand

{Bo^MCp^tet}­Lu­(CH₂Ph)₂ (<b>1</b>; Bo^MCp^tet = MeC­(Ox^Me2)₂C₅Me₄; Ox^Me2 = 4,4-dimethyl-2-oxazoline) was prepared in 95% yield from the reaction of Bo^MCp^tetH and Lu­(CH₂Ph)₃THF₃. Compound <b>1</b> reacts with 1 or 2 equiv of H₂NCH₂R (R = C₆H₅, 1-C₁₀H₇) to give the corresponding imido complexes [{Bo^MCp^tet}­LuNCH₂R]₂ (R = C₆H₅ (<b>2a</b>), 1-C₁₀H₇ (<b>2b</b>)) or amido complexes {Bo^MCp^tet}­Lu­(NHCH₂R)₂ (R = C₆H₅ (<b>3a</b>), 1-C₁₀H₇ (<b>3b</b>)). Once isolated, the imido species are insoluble in nonprotic organic solvents. Crystallographic characterization reveals dimeric [{Bo^MCp^tet}­LuNCH₂(1-C₁₀H₇)]₂ in the solid state. The reaction of <b>1</b> and NH₃B­(C₆F₅)₃ affords crystallographically characterized {Bo^MCp^tet}­Lu­{NHB­(C₆F₅)₂}­C₆F₅. This species is proposed to form via a transient lutetium imido, which undergoes C₆F₅ migration to the lutetium center

Cyclopentadienyl-bis(oxazoline) Magnesium and Zirconium Complexes in Aminoalkene Hydroaminations

A new class of cyclopentadiene-bis(oxazoline) compounds and their piano-stool-type organometallic complexes have been prepared as catalysts for hydroamination of aminoalkenes. The two compounds MeC(OxMe2)2C5H5 (BoMCpH; OxMe2 = 4,4-dimethyl-2-oxazoline) and MeC(OxMe2)2C5Me4H (BoMCptetH) are synthesized from C5R4HI (R = H, Me) and MeC(OxMe2)2Li. These cyclopentadiene-bis(oxazolines) are converted into ligands that support a variety of metal centers in piano-stool-type geometries, and here we report the preparation of Mg, Tl, Ti, and Zr compounds. BoMCpH and BoMCptetH react with MgMe2(O2C4H8)2 to give the magnesium methyl complexes {BoMCp}MgMe and {BoMCptet}MgMe. BoMCpH and BoMCptetH are converted to BoMCpTl and BoMCptetTl by reaction with TlOEt. The thallium derivatives react with TiCl3(THF)3 to provide [{BoMCp}TiCl(μ-Cl)]2 and [{BoMCptet}TiCl(μ-Cl)]2, the former of which is crystallographically characterized as a dimeric species. BoMCpH and Zr(NMe2)4 react to eliminate dimethylamine and afford {BoMCp}Zr(NMe2)3, which is crystallographically characterized as a monomeric four-legged piano-stool compound. {BoMCp}Zr(NMe2)3, {BoMCp}MgMe, and {BoMCptet}MgMe are efficient catalysts for the hydroamination/cyclization of aminoalkenes under mild conditions.This is an article from the journal Organometallics 34 (2015): 5566, doi: 10.1021/acs.organomet.5b00771. Posted with permission.</p

Cyclopentadienyl-bis(oxazoline) Magnesium and Zirconium Complexes in Aminoalkene Hydroaminations

A new class of cyclopentadiene-bis­(oxazoline) compounds and their piano-stool-type organometallic complexes have been prepared as catalysts for hydroamination of aminoalkenes. The two compounds MeC­(Ox^Me2)₂C₅H₅ (Bo^MCpH; Ox^Me2 = 4,4-dimethyl-2-oxazoline) and MeC­(Ox^Me2)₂C₅Me₄H (Bo^MCp^tetH) are synthesized from C₅R₄HI (R = H, Me) and MeC­(Ox^Me2)₂Li. These cyclopentadiene-bis­(oxazolines) are converted into ligands that support a variety of metal centers in piano-stool-type geometries, and here we report the preparation of Mg, Tl, Ti, and Zr compounds. Bo^MCpH and Bo^MCp^tetH react with MgMe₂(O₂C₄H₈)₂ to give the magnesium methyl complexes {Bo^MCp}­MgMe and {Bo^MCp^tet}­MgMe. Bo^MCpH and Bo^MCp^tetH are converted to Bo^MCpTl and Bo^MCp^tetTl by reaction with TlOEt. The thallium derivatives react with TiCl₃(THF)₃ to provide [{Bo^MCp}­TiCl­(μ-Cl)]₂ and [{Bo^MCp^tet}­TiCl­(μ-Cl)]₂, the former of which is crystallographically characterized as a dimeric species. Bo^MCpH and Zr­(NMe₂)₄ react to eliminate dimethylamine and afford {Bo^MCp}­Zr­(NMe₂)₃, which is crystallographically characterized as a monomeric four-legged piano-stool compound. {Bo^MCp}­Zr­(NMe₂)₃, {Bo^MCp}­MgMe, and {Bo^MCp^tet}­MgMe are efficient catalysts for the hydroamination/cyclization of aminoalkenes under mild conditions

Cyclopentadienyl-bis(oxazoline) Magnesium and Zirconium Complexes in Aminoalkene Hydroaminations

A new class of cyclopentadiene-bis­(oxazoline) compounds and their piano-stool-type organometallic complexes have been prepared as catalysts for hydroamination of aminoalkenes. The two compounds MeC­(Ox^Me2)₂C₅H₅ (Bo^MCpH; Ox^Me2 = 4,4-dimethyl-2-oxazoline) and MeC­(Ox^Me2)₂C₅Me₄H (Bo^MCp^tetH) are synthesized from C₅R₄HI (R = H, Me) and MeC­(Ox^Me2)₂Li. These cyclopentadiene-bis­(oxazolines) are converted into ligands that support a variety of metal centers in piano-stool-type geometries, and here we report the preparation of Mg, Tl, Ti, and Zr compounds. Bo^MCpH and Bo^MCp^tetH react with MgMe₂(O₂C₄H₈)₂ to give the magnesium methyl complexes {Bo^MCp}­MgMe and {Bo^MCp^tet}­MgMe. Bo^MCpH and Bo^MCp^tetH are converted to Bo^MCpTl and Bo^MCp^tetTl by reaction with TlOEt. The thallium derivatives react with TiCl₃(THF)₃ to provide [{Bo^MCp}­TiCl­(μ-Cl)]₂ and [{Bo^MCp^tet}­TiCl­(μ-Cl)]₂, the former of which is crystallographically characterized as a dimeric species. Bo^MCpH and Zr­(NMe₂)₄ react to eliminate dimethylamine and afford {Bo^MCp}­Zr­(NMe₂)₃, which is crystallographically characterized as a monomeric four-legged piano-stool compound. {Bo^MCp}­Zr­(NMe₂)₃, {Bo^MCp}­MgMe, and {Bo^MCp^tet}­MgMe are efficient catalysts for the hydroamination/cyclization of aminoalkenes under mild conditions