12 research outputs found
Synthesis and Reactivity of d<sup>0</sup> Alkyl, Silyl, and Hydride Complexes of Titanium and Zirconium Featuring an Aryl-Substituted Tripodal Triamido Ligand Derived from <i>cis,cis</i>-1,3,5-Triaminocyclohexane
No full textZirconium and titanium complexes containing the new chelating triamido ligand [cis,cis-1,3,5-(3,5-tBu2C6H3N)3C6H9]3- (1) are reported. The chloride complexes [cis,cis-1,3,5-(3,5-tBu2C6H3N)3C6H9]TiCl (2) and [cis,cis-1,3,5-(3,5-tBu2C6H3N)3C6H9]ZrCl (3) were prepared by
reaction of TiCl4(THF)2 and ZrCl4, respectively, with [1]Li3 (prepared in situ). The diethyl
ether adduct of 3 (3·OEt2) was crystallographically characterized. The alkyl complexes [cis,cis-1,3,5-(3,5-tBu2C6H3N)3C6H9]ZrCH2SiMe3 (4) and [cis,cis-1,3,5-(3,5-tBu2C6H3N)3C6H9]ZrCH2Ph (5) were prepared by reaction of the triamine ([1]H3) with Zr(CH2SiMe3)4 and Zr(CH2Ph)4,
respectively. The aryl complexes [cis,cis-1,3,5-(3,5-tBu2C6H3N)3C6H9]ZrPh (6) and [cis,cis-1,3,5-(3,5-tBu2C6H3N)3C6H9]ZrMes (7, Mes = 2,4,6-Me3C6H2) were prepared by the reaction
of 3 with PhLi and MesLi, respectively. Similarly, [cis,cis-1,3,5-(3,5-tBu2C6H3N)3C6H9]TiMe
(8) was prepared by the reaction of 2 with MeMgBr. The alkyl and aryl complexes 4−8 did
not react with hydrosilanes to give isolable silyl complexes. The titanium and zirconium
silyl complexes [cis,cis-1,3,5-(3,5-tBu2C6H3N)3C6H9]TiSi(SiMe3)3 (9), [cis,cis-1,3,5-(3,5-tBu2C6H3N)3C6H9]ZrSi(SiMe3)3 (10), [cis,cis-1,3,5-(3,5-tBu2C6H3N)3C6H9]TiSiHMes2 (11), and [cis,cis-1,3,5-(3,5-tBu2C6H3N)3C6H9]ZrSiHMes2(THF) (12) were prepared by the reaction of the
corresponding titanium and zirconium chloride complexes with either KSi(SiMe3)3 or
LiSiHMes2(THF)2. Although the alkyl and aryl complexes 4−8 did not react appreciably
with H2 (1 atm), the silyl complexes 9 and 10 reacted with H2 (1 atm) over the course of only
a few minutes to give d0 hydride products. Hydrogenolysis of 9 yielded the monohydride
complex [cis,cis-1,3,5-(3,5-tBu2C6H3N)3C6H9]TiH (13), which was characterized in solution.
Complex 13 readily inserted 1-hexene to give the hexyl insertion product [cis,cis-1,3,5-(3,5-tBu2C6H3N)3C6H9]TiHex (14). Hydrogenolysis of 10 yielded a mixture of monomeric and
dimeric hydride products, [cis,cis-1,3,5-(3,5-tBu2C6H3N)3C6H9]ZrH (17a) and {[cis,cis-1,3,5-(3,5-tBu2C6H3N)3C6H9]ZrH}2 (17b), both of which were characterized in solution. Upon
addition of 1 equiv of PMe3, a mixture of 17a and 17b reacted to give the adduct [cis,cis-1,3,5-(3,5-tBu2C6H3N)3C6H9]ZrH(PMe3) (15), which binds PMe3 reversibly in solution. In the
presence of 1-hexene, the mixture of 17a and 17b was readily converted to the hexyl insertion
product, [cis,cis-1,3,5-(3,5-tBu2C6H3N)3C6H9]ZrHex (16). The hydride species 13 and 17a/17b undergo H/D exchange with D2 but exhibit low reactivities toward hydrosilanes
Coordination Chemistry and Reactivity of New Zwitterionic Rhodium and Iridium Complexes Featuring the Tripodal Phosphine Ligand [PhB(CH<sub>2</sub>P<sup>i</sup>Pr<sub>2</sub>)<sub>3</sub>]<sup>-</sup>. Activation of H−H, Si−H, and Ligand B−C Bonds
No full textThe synthesis, characterization, and reactivity of zwitterionic rhodium and iridium
complexes containing the tris(phosphino)borate ligand [PhB(CH2PiPr2)3]- ([PhBP3‘]-) are
reported. The allyl complexes [PhBP3‘]IrH(η3-C8H13) (3) and [PhBP3‘]IrH(η3-C3H5) (4) were
prepared by reaction of [PhBP3‘]Li(THF) (2) with the corresponding [(alkene)2IrCl]2 complex.
Complex 3 reacted with secondary silanes (H2SiR2, with R = Et, Ph) to give silyl-capped
trihydride complexes of the type [PhBP3‘]IrH3(SiHR2) (R = Et, 5; Ph, 6) with concomitant
β-hydride elimination of 1,3-cyclooctadiene. Complex 5 underwent H/D exchange with D2 to
incorporate deuterium into both the Ir−H and Si−H positions. The reaction of 5 with 1
equiv of PMe3 resulted in elimination of Et2SiH2 to form the corresponding dihydride complex,
[PhBP3‘]Ir(H)2(PMe3) (7). Complexes of the type [PhBP3‘]Ir(H)2(L) (L = PMe3, 7; PH2Cy, 8;
CO, 9) could also be prepared directly by the reaction of 3 with L. The observed reactivity
of [PhBP3‘]Ir complexes is compared with that of the related [PhB(CH2PPh2)3]- ([PhBP3]-)
species. The Rh(I) complexes [κ2-PhBP3‘]Rh(PMe3)2 (10) and [PhBP3‘]Rh(CO)2 (11) are also
reported. Variable-temperature 1H and 31P NMR experiments did not reveal evidence for
κ2−κ3 interconversion for 10 and 11. However at elevated temperatures 10 was found to
engage in a dynamic equilibrium process involving dissociation of the PMe3 ligands and
reversible migration of a −CH2 group in the ligand backbone from B to Rh. The product of
this migration, (12), was prepared independently by the
reaction of 2 with [RhCl(C2H4)2]2 and was structurally characterized by X-ray crystallography.
Complex 10 reacted with H2 to give the oxidative addition product [PhBP3‘]Rh(H)2(PMe3)
(13). The reaction of 10 with 1 equiv of Ph2SiH2 resulted in loss of a ligand arm to give the
bis(phosphino)borane complex [PhB(CH2PiPr2)2]Rh(H)2(SiHPh2)(PMe3) (14). Complex 11
reacted with H2 in the presence of 1 equiv of Me3NO to give the oxidative addition product
[PhBP3‘]Rh(H)2(CO) (15), with concomitant liberation of Me3N
Coordination Chemistry and Reactivity of New Zwitterionic Rhodium and Iridium Complexes Featuring the Tripodal Phosphine Ligand [PhB(CH<sub>2</sub>P<sup>i</sup>Pr<sub>2</sub>)<sub>3</sub>]<sup>-</sup>. Activation of H−H, Si−H, and Ligand B−C Bonds
No full textThe synthesis, characterization, and reactivity of zwitterionic rhodium and iridium
complexes containing the tris(phosphino)borate ligand [PhB(CH2PiPr2)3]- ([PhBP3‘]-) are
reported. The allyl complexes [PhBP3‘]IrH(η3-C8H13) (3) and [PhBP3‘]IrH(η3-C3H5) (4) were
prepared by reaction of [PhBP3‘]Li(THF) (2) with the corresponding [(alkene)2IrCl]2 complex.
Complex 3 reacted with secondary silanes (H2SiR2, with R = Et, Ph) to give silyl-capped
trihydride complexes of the type [PhBP3‘]IrH3(SiHR2) (R = Et, 5; Ph, 6) with concomitant
β-hydride elimination of 1,3-cyclooctadiene. Complex 5 underwent H/D exchange with D2 to
incorporate deuterium into both the Ir−H and Si−H positions. The reaction of 5 with 1
equiv of PMe3 resulted in elimination of Et2SiH2 to form the corresponding dihydride complex,
[PhBP3‘]Ir(H)2(PMe3) (7). Complexes of the type [PhBP3‘]Ir(H)2(L) (L = PMe3, 7; PH2Cy, 8;
CO, 9) could also be prepared directly by the reaction of 3 with L. The observed reactivity
of [PhBP3‘]Ir complexes is compared with that of the related [PhB(CH2PPh2)3]- ([PhBP3]-)
species. The Rh(I) complexes [κ2-PhBP3‘]Rh(PMe3)2 (10) and [PhBP3‘]Rh(CO)2 (11) are also
reported. Variable-temperature 1H and 31P NMR experiments did not reveal evidence for
κ2−κ3 interconversion for 10 and 11. However at elevated temperatures 10 was found to
engage in a dynamic equilibrium process involving dissociation of the PMe3 ligands and
reversible migration of a −CH2 group in the ligand backbone from B to Rh. The product of
this migration, (12), was prepared independently by the
reaction of 2 with [RhCl(C2H4)2]2 and was structurally characterized by X-ray crystallography.
Complex 10 reacted with H2 to give the oxidative addition product [PhBP3‘]Rh(H)2(PMe3)
(13). The reaction of 10 with 1 equiv of Ph2SiH2 resulted in loss of a ligand arm to give the
bis(phosphino)borane complex [PhB(CH2PiPr2)2]Rh(H)2(SiHPh2)(PMe3) (14). Complex 11
reacted with H2 in the presence of 1 equiv of Me3NO to give the oxidative addition product
[PhBP3‘]Rh(H)2(CO) (15), with concomitant liberation of Me3N
Coordination Chemistry and Reactivity of New Zwitterionic Rhodium and Iridium Complexes Featuring the Tripodal Phosphine Ligand [PhB(CH<sub>2</sub>P<sup>i</sup>Pr<sub>2</sub>)<sub>3</sub>]<sup>-</sup>. Activation of H−H, Si−H, and Ligand B−C Bonds
No full textThe synthesis, characterization, and reactivity of zwitterionic rhodium and iridium
complexes containing the tris(phosphino)borate ligand [PhB(CH2PiPr2)3]- ([PhBP3‘]-) are
reported. The allyl complexes [PhBP3‘]IrH(η3-C8H13) (3) and [PhBP3‘]IrH(η3-C3H5) (4) were
prepared by reaction of [PhBP3‘]Li(THF) (2) with the corresponding [(alkene)2IrCl]2 complex.
Complex 3 reacted with secondary silanes (H2SiR2, with R = Et, Ph) to give silyl-capped
trihydride complexes of the type [PhBP3‘]IrH3(SiHR2) (R = Et, 5; Ph, 6) with concomitant
β-hydride elimination of 1,3-cyclooctadiene. Complex 5 underwent H/D exchange with D2 to
incorporate deuterium into both the Ir−H and Si−H positions. The reaction of 5 with 1
equiv of PMe3 resulted in elimination of Et2SiH2 to form the corresponding dihydride complex,
[PhBP3‘]Ir(H)2(PMe3) (7). Complexes of the type [PhBP3‘]Ir(H)2(L) (L = PMe3, 7; PH2Cy, 8;
CO, 9) could also be prepared directly by the reaction of 3 with L. The observed reactivity
of [PhBP3‘]Ir complexes is compared with that of the related [PhB(CH2PPh2)3]- ([PhBP3]-)
species. The Rh(I) complexes [κ2-PhBP3‘]Rh(PMe3)2 (10) and [PhBP3‘]Rh(CO)2 (11) are also
reported. Variable-temperature 1H and 31P NMR experiments did not reveal evidence for
κ2−κ3 interconversion for 10 and 11. However at elevated temperatures 10 was found to
engage in a dynamic equilibrium process involving dissociation of the PMe3 ligands and
reversible migration of a −CH2 group in the ligand backbone from B to Rh. The product of
this migration, (12), was prepared independently by the
reaction of 2 with [RhCl(C2H4)2]2 and was structurally characterized by X-ray crystallography.
Complex 10 reacted with H2 to give the oxidative addition product [PhBP3‘]Rh(H)2(PMe3)
(13). The reaction of 10 with 1 equiv of Ph2SiH2 resulted in loss of a ligand arm to give the
bis(phosphino)borane complex [PhB(CH2PiPr2)2]Rh(H)2(SiHPh2)(PMe3) (14). Complex 11
reacted with H2 in the presence of 1 equiv of Me3NO to give the oxidative addition product
[PhBP3‘]Rh(H)2(CO) (15), with concomitant liberation of Me3N
The Development of Catalysts for the Monoarylation of Ammonia and Related Challenging Cross-Coupling Reactions
No full textThe use of homogeneous organometallic catalysis for otherwise challenging chemical transformations is a concept that has gained significant interest in recent decades, providing access to a variety of useful chemical products. The catalytic reactivity of transition metals and non-reactive ancillary ligands that bind to the metal center has played an important role in such methods, with notable breakthroughs being Nobel Prize-winning reactions (palladium-catalyzed C-C cross-coupling, 2010). The research compiled in the thesis further develops the themes of ligand design and catalytic applications currently studied in the Stradiotto group. Key ideas throughout the thesis are to establish an understanding of the palladium/Mor-DalPhos catalyst system in ammonia arylation with respect to mechanism and substrate scope, and to expand the reactivity profile of the DalPhos ligand set to more challenging C-N and related cross-coupling processes. The first section describes an examination of the [Pd(cinnamyl)Cl] dimer/Mor-DalPhos catalyst system in C-N cross-coupling employing ammonia to better understand the catalyst formation process and to provide a guide for the development of precatalysts for otherwise challenging room-temperature ammonia monoarylations. Oxidative addition complex [(Mor-DalPhos)Pd(Ph)Cl] proved to be the optimal catalyst for arylation of ammonia at room temperature using aryl halides and tosylates. In the second section, ammonia cross-coupling was extended by applying it in the construction of indole frameworks, for the first time, which gave access to NH-indoles directly from ortho-alkynylbromoarenes. The Pd/JosiPhos was the superior catalyst system in comparison to Pd/Mor-DalPhos for this reaction and further stoichiometric studies revealed the reasons for this may be that the bulky arylalkyne ligand induces loss of ammonia from (Mor-DalPhos)Pd catalytic intermediates, and that catalyst inhibition by the alkyne substrate through irreversible metal binding is also a possible factor prior to the oxidative addition step. The reactivity profile of the DalPhos ligand set was successfully expanded in the third section of the thesis to palladium-catalyzed aminocarbonylation of aryl bromides using a pyridine-derived DalPhos variant (Pyr-DalPhos). Several different aryl and some heteroaryl bromides were accommodated in the coupling reaction with ammonia and carbon monoxide as reagents, providing aryl amide products in synthetically useful yields. The methodology described in the final thesis section demonstrated the use of Mor-DalPhos and [Pd(cinnamyl)Cl] dimer mixtures for gaining access to the first examples of ketone alpha-arylation employing aryl methanesulfonates (mesylates) and expanding the scope of amination reactions involving these non-halide aryl electrophiles to primary alkyl amines for the first time. These transformations featured acetone and methylamine as coupling partners, both of which can be difficult substrates to monoarylate but were found to be coupled with ease in this chemistry
Development of the Interrupted Nazarov Cyclization of Allenyl Vinyl Ketones, with Application to the Total Synthesis of the Cyclooctane Natural Product Roseadione
No full textThe development of the interrupted Nazarov cyclization of allenyl vinyl ketones is presented. The intermediate oxyallyl cation, derived from an allenyl vinyl ketone, may be trapped efficiently by a divergent array of nucleophilic species generating functionalized cyclopent-2-enone products. Allenyl vinyl ketones are also a versatile source of cyclic molecules via a tandem reaction sequence terminated via reaction with acyclic dienes, cyclic dienes, aza-heterocycles, electron-rich alkenes, or styrenes by the formation of an additional ring by a [4 + 3] and/or [3 + 2] cyclization or by the formation of one additional carbon-carbon bond. The bicyclic compounds generated by these processes are densely substituted, and would be difficult to access as succinctly in other ways. The products of these interrupted Nazarov reactions generally reflect excellent regio- and stereoselectivity in the trapping reaction. In some instances, equilibrating conditions were shown to enhance the proportion of one product at the expense of another or to provide a different carbon skeleton. This process appears fairly general, and can be conducted with unsubstituted or alkyl, aromatic, or heteroaromatic allenyl vinyl ketones. The exceptional affinity of allenyl vinyl ketones to undergo interrupted Nazarov reactions is likely a result of the increased longevity of the intermediate oxyallyl cation, due in part to the increased resonance stabilization provided by the allene unit. The high regioselectivity noted in the trapping process was computationally and experimentally confirmed to be a result of a localization of the positive charge in the intermediate oxyallyl cation.
The application of this recently developed methodology towards the synthesis of the natural product (+)-roseadione is also described. The tandem Nazarov/[4 + 3] cascade of allenyl vinyl ketones provides a unique manner in which to access the tricyclic core of this cyclooctanoid natural product, a molecule which, to date, has never been synthesized
Coordinatively and Electronically Unsaturated Zwitterionic Iron Silyl Complexes Featuring the Tripodal Phosphine Ligand [PhB(CH<sub>2</sub>P<sup>i</sup>Pr<sub>2</sub>)<sub>3</sub>]<sup>-</sup>
No full textA series of 14-electron, coordinatively unsaturated Fe(II) silyl complexes featuring the anionic,
tripodal phosphine ligand [PhB(CH2PiPr2)3]- have been
prepared and characterized; preliminary reactivity studies indicate that at least one such complex can undergo
redox processes to generate isolable Fe(I) species with
concomitant loss of the silyl ligand
Synthesis of Bis(phosphino)silyl Pincer-Supported Iron Hydrides for the Catalytic Hydrogenation of Alkenes
No full textThe synthesis and
characterization of Fe pincer complexes supported
by a bis(phosphino)silyl (PSiP) ligand are described. While four-coordinate
species of the type (PSiP)FeX (X = halide) proved challenging to access,
examples of five-coordinate (PSiP)Fe(II) and (PSiP)Fe(I) species were
prepared and crystallographically characterized. In studying the reactivity
of such (PSiP)Fe precursors, a variety of iron hydride species were
observed and characterized, and interconversion among such complexes
facilitated by the coordination of N2 was noted. The structures
and spectroscopic features of several such diamagnetic Fe(II) hydrides
were elucidated, including that of a unique and highly stable η2-(Si–H)Fe(II) dihydride complex. A surrogate for a
low coordinate (PSiP)FeH species in the form of its bis(dinitrogen)
adduct was found to be an effective precatalyst for the direct hydrogenation
of alkenes, including various mono- and disubstituted aliphatic alkenes,
as well as a trisubstituted example. Esters and ethers were found
to be well-tolerated by the catalyst, and alkyne hydrogenation was
also demonstrated
Association between age, deprivation and specific comorbid conditions and the receipt of major surgery in patients with non-small cell lung cancer in England: A population-based study.
No full textINTRODUCTION: We investigated socioeconomic disparities and the role of the main prognostic factors in receiving major surgical treatment in patients with lung cancer in England. METHODS: Our study comprised 31 351 patients diagnosed with non-small cell lung cancer in England in 2012. Data from the national population-based cancer registry were linked to Hospital Episode Statistics and National Lung Cancer Audit data to obtain information on stage, performance status and comorbidities, and to identify patients receiving major surgical treatment. To describe the association between prognostic factors and surgery, we performed two different analyses: one using multivariable logistic regression and one estimating cause-specific hazards for death and surgery. In both analyses, we used multiple imputation to deal with missing data. RESULTS: We showed strong evidence that the comorbidities 'congestive heart failure', 'cerebrovascular disease' and 'chronic obstructive pulmonary disease' reduced the receipt of surgery in early stage patients. We also observed gender differences and substantial age differences in the receipt of surgery. Despite accounting for sex, age at diagnosis, comorbidities, stage at diagnosis, performance status and indication of having had a PET-CT scan, the socioeconomic differences persisted in both analyses: more deprived people had lower odds and lower rates of receiving surgery in early stage lung cancer. DISCUSSION: Comorbidities play an important role in whether patients undergo surgery, but do not completely explain the socioeconomic difference observed in early stage patients. Future work investigating access to and distance from specialist hospitals, as well as patient perceptions and patient choice in receiving surgery, could help disentangle these persistent socioeconomic inequalities
Global surveillance of trends in cancer survival 2000-14 (CONCORD-3): analysis of individual records for 37 513 025 patients diagnosed with one of 18 cancers from 322 population-based registries in 71 countries.
No full textBACKGROUND: In 2015, the second cycle of the CONCORD programme established global surveillance of cancer survival as a metric of the effectiveness of health systems and to inform global policy on cancer control. CONCORD-3 updates the worldwide surveillance of cancer survival to 2014. METHODS: CONCORD-3 includes individual records for 37·5 million patients diagnosed with cancer during the 15-year period 2000-14. Data were provided by 322 population-based cancer registries in 71 countries and territories, 47 of which provided data with 100% population coverage. The study includes 18 cancers or groups of cancers: oesophagus, stomach, colon, rectum, liver, pancreas, lung, breast (women), cervix, ovary, prostate, and melanoma of the skin in adults, and brain tumours, leukaemias, and lymphomas in both adults and children. Standardised quality control procedures were applied; errors were rectified by the registry concerned. We estimated 5-year net survival. Estimates were age-standardised with the International Cancer Survival Standard weights. FINDINGS: For most cancers, 5-year net survival remains among the highest in the world in the USA and Canada, in Australia and New Zealand, and in Finland, Iceland, Norway, and Sweden. For many cancers, Denmark is closing the survival gap with the other Nordic countries. Survival trends are generally increasing, even for some of the more lethal cancers: in some countries, survival has increased by up to 5% for cancers of the liver, pancreas, and lung. For women diagnosed during 2010-14, 5-year survival for breast cancer is now 89·5% in Australia and 90·2% in the USA, but international differences remain very wide, with levels as low as 66·1% in India. For gastrointestinal cancers, the highest levels of 5-year survival are seen in southeast Asia: in South Korea for cancers of the stomach (68·9%), colon (71·8%), and rectum (71·1%); in Japan for oesophageal cancer (36·0%); and in Taiwan for liver cancer (27·9%). By contrast, in the same world region, survival is generally lower than elsewhere for melanoma of the skin (59·9% in South Korea, 52·1% in Taiwan, and 49·6% in China), and for both lymphoid malignancies (52·5%, 50·5%, and 38·3%) and myeloid malignancies (45·9%, 33·4%, and 24·8%). For children diagnosed during 2010-14, 5-year survival for acute lymphoblastic leukaemia ranged from 49·8% in Ecuador to 95·2% in Finland. 5-year survival from brain tumours in children is higher than for adults but the global range is very wide (from 28·9% in Brazil to nearly 80% in Sweden and Denmark). INTERPRETATION: The CONCORD programme enables timely comparisons of the overall effectiveness of health systems in providing care for 18 cancers that collectively represent 75% of all cancers diagnosed worldwide every year. It contributes to the evidence base for global policy on cancer control. Since 2017, the Organisation for Economic Co-operation and Development has used findings from the CONCORD programme as the official benchmark of cancer survival, among their indicators of the quality of health care in 48 countries worldwide. Governments must recognise population-based cancer registries as key policy tools that can be used to evaluate both the impact of cancer prevention strategies and the effectiveness of health systems for all patients diagnosed with cancer. FUNDING: American Cancer Society; Centers for Disease Control and Prevention; Swiss Re; Swiss Cancer Research foundation; Swiss Cancer League; Institut National du Cancer; La Ligue Contre le Cancer; Rossy Family Foundation; US National Cancer Institute; and the Susan G Komen Foundation
