21 research outputs found
Illuminating Lewis acidity strength
In this issue of Chem, Baumgartner, Caputo and co-workers describe a simple naked-eye litmus test for the determination of Lewis acid strength. This technique is based on fluorescence via highly tunable, luminescent phosphole oxide Lewis basic probes
Novel organoalanes in organic synthesis and mechanistic insight in conjugate addition
This thesis describes the development of novel aluminium hydrides (HAlCl2•Ln) and organoalanes(Cl2AlCH=CHR and ClMeAlCH=CHR) for organic synthesis, as well as exploring the mechanism by which copper-catalysed conjugate addition proceed with diethylzinc and triethylaluminium.
In Chapter 1, the mechanism of copper-catalysed conjugate addition of diethylzinc to cyclohexenone and nickelcatalysed 1,2-addition of trimethylaluminium to benzaldehyde has been studied. The kinetic behaviour of the systems allows insight into which metal to ligand ratio provides the fastest rest state structure of the catalyst to enter the rate determining step. The ligand order in these reactions (derived from these ligand optimisation plots) provides information about the molecularity within the transition state.
In Chapter 2, the synthesis of somewhat air-stabilised aluminium hydrides and their subsequent use in palladiumcatalysed cross-coupling is described. Stabilised aluminium hydrides of the type HAlCl2•Ln, [HAl(OtBu)2] and [HAl(NiBu2)]2 were synthesised. The hydroalumination of terminal alkynes was optimal using bis(pentamethylcyclopentdienyl) zirconocene dichloride, resulting in a highly regio- and stereo3 chemical synthesis of alkenylalanes which undergo highly efficient palladium catalysed cross-coupling with a wide range of sp2 electrophiles.
Chapter 3, describes conjugate addition chemistry of ClXAlCH=CHR (X = Cl or Me) under phosphoramidite/ copper(I) conditions (X = Me). Highly enantioselective additions to cyclohexenones (89-98+% ee) were attained. A highly efficient racemic addition of the alkenylalanes (X = Cl) to alkylidene malonates occurs without catalysis.
Finally, Chapter 4 includes all the experimental procedures and the analytical data for the compounds prepared in the subsequent chapters
Streamlined Synthesis of C(sp3)-Rich N-Heterospirocycles Enabled by Visible-Light-Mediated Photocatalysis
We report a general visible-light-mediated strategy that enables the construction of complex C(sp3)-rich N-heterospirocycles from feedstock aliphatic ketones and aldehydes with a broad selection of alkene-containing secondary amines. Key to the success of this approach was the utilization of a highly reducing Ir-photocatalyst and orchestration of the intrinsic reactivities of 1,4-cyclohexadiene and Hantzsch ester. This methodology provides streamlined access to complex C(sp3)-rich N-heterospirocycles displaying structural and functional features relevant to fragment-based lead identification programs.We are grateful to the Gates Cambridge Trust (N.J.F.) and Herchel Smith Scholarship Scheme (A.T.) for studentships, the EPSRC (EP/S020292/1 and EP/N031792/1), Ambitious Leader’s Program, Hokkaido University, Japan (Y.K.), and the Royal Society for a Wolfson Merit Award (M.J.G.). S.M.W. is a Fellow of the AstraZeneca Postdoctoral program. We are grateful to the EPSRC UK National Mass Spectrometry Facility at Swansea University for HRMS analysis
Recommended from our members
Streamlined Synthesis of C(sp3)-Rich N-Heterospirocycles Enabled by Visible-Light-Mediated Photocatalysis
We report a general visible-light-mediated strategy that enables the construction of complex C(sp3)-rich N-heterospirocycles from feedstock aliphatic ketones and aldehydes with a broad selection of alkene-containing secondary amines. Key to the success of this approach was the utilization of a highly reducing Ir-photocatalyst and orchestration of the intrinsic reactivities of 1,4-cyclohexadiene and Hantzsch ester. This methodology provides streamlined access to complex C(sp3)-rich N-heterospirocycles displaying structural and functional features relevant to fragment-based lead identification programs.We are grateful to the Gates Cambridge Trust (N.J.F.) and Herchel Smith Scholarship Scheme (A.T.) for studentships, the EPSRC (EP/S020292/1 and EP/N031792/1), Ambitious Leader’s Program, Hokkaido University, Japan (Y.K.), and the Royal Society for a Wolfson Merit Award (M.J.G.). S.M.W. is a Fellow of the AstraZeneca Postdoctoral program. We are grateful to the EPSRC UK National Mass Spectrometry Facility at Swansea University for HRMS analysis
Mechanistic investigation into the C(sp3)–H acetoxylation of morpholinones
The study of a selective palladium(II)-catalyzed C(sp3
)–H acetoxylation reaction on a class of cyclic alkyl
amines is reported. Computational modelling and kinetic studies were used to provide support for
a mechanism involving selective C–O bond formation from a g-aminoalkyl-Pd(IV) intermediate. The C–O
bond forming step was computed to occur by a dissociative ionization mechanism followed by an SN2
process involving external acetate attack at the C–Pd(IV) bond. This pathway was computed to be of
lowest energy with no competing C–N products observed. Additionally, with a few modifications to
reaction conditions, preliminary studies showed that this process could be rendered enantioselective in
the presence of a non-racemic BINOL-phosphoric acid
Asymmetric ketone hydroboration catalyzed by alkali metal complexes derived from BINOL ligands
The ability of alkali metal complexes featuring functionalized BINOL-derived ligands to catalyze ketone hydroboration reactions was explored. The reduced products were formed in excellent yield and with variable enantioselectivities dependent upon the nature of the ligand and the alkali metal cation
Testing a global standard for quantifying species recovery and assessing conservation impact.
Recognizing the imperative to evaluate species recovery and conservation impact, in 2012 the International Union for Conservation of Nature (IUCN) called for development of a "Green List of Species" (now the IUCN Green Status of Species). A draft Green Status framework for assessing species' progress toward recovery, published in 2018, proposed 2 separate but interlinked components: a standardized method (i.e., measurement against benchmarks of species' viability, functionality, and preimpact distribution) to determine current species recovery status (herein species recovery score) and application of that method to estimate past and potential future impacts of conservation based on 4 metrics (conservation legacy, conservation dependence, conservation gain, and recovery potential). We tested the framework with 181 species representing diverse taxa, life histories, biomes, and IUCN Red List categories (extinction risk). Based on the observed distribution of species' recovery scores, we propose the following species recovery categories: fully recovered, slightly depleted, moderately depleted, largely depleted, critically depleted, extinct in the wild, and indeterminate. Fifty-nine percent of tested species were considered largely or critically depleted. Although there was a negative relationship between extinction risk and species recovery score, variation was considerable. Some species in lower risk categories were assessed as farther from recovery than those at higher risk. This emphasizes that species recovery is conceptually different from extinction risk and reinforces the utility of the IUCN Green Status of Species to more fully understand species conservation status. Although extinction risk did not predict conservation legacy, conservation dependence, or conservation gain, it was positively correlated with recovery potential. Only 1.7% of tested species were categorized as zero across all 4 of these conservation impact metrics, indicating that conservation has, or will, play a role in improving or maintaining species status for the vast majority of these species. Based on our results, we devised an updated assessment framework that introduces the option of using a dynamic baseline to assess future impacts of conservation over the short term to avoid misleading results which were generated in a small number of cases, and redefines short term as 10 years to better align with conservation planning. These changes are reflected in the IUCN Green Status of Species Standard
Novel organoalanes in organic synthesis and mechanistic insight in conjugate addition
This thesis describes the development of novel aluminium hydrides (HAlCl2•Ln) and organoalanes(Cl2AlCH=CHR and ClMeAlCH=CHR) for organic synthesis, as well as exploring the mechanism by which copper-catalysed conjugate addition proceed with diethylzinc and triethylaluminium.
In Chapter 1, the mechanism of copper-catalysed conjugate addition of diethylzinc to cyclohexenone and nickelcatalysed 1,2-addition of trimethylaluminium to benzaldehyde has been studied. The kinetic behaviour of the systems allows insight into which metal to ligand ratio provides the fastest rest state structure of the catalyst to enter the rate determining step. The ligand order in these reactions (derived from these ligand optimisation plots) provides information about the molecularity within the transition state.
In Chapter 2, the synthesis of somewhat air-stabilised aluminium hydrides and their subsequent use in palladiumcatalysed cross-coupling is described. Stabilised aluminium hydrides of the type HAlCl2•Ln, [HAl(OtBu)2] and [HAl(NiBu2)]2 were synthesised. The hydroalumination of terminal alkynes was optimal using bis(pentamethylcyclopentdienyl) zirconocene dichloride, resulting in a highly regio- and stereo3 chemical synthesis of alkenylalanes which undergo highly efficient palladium catalysed cross-coupling with a wide range of sp2 electrophiles.
Chapter 3, describes conjugate addition chemistry of ClXAlCH=CHR (X = Cl or Me) under phosphoramidite/ copper(I) conditions (X = Me). Highly enantioselective additions to cyclohexenones (89-98+% ee) were attained. A highly efficient racemic addition of the alkenylalanes (X = Cl) to alkylidene malonates occurs without catalysis.
Finally, Chapter 4 includes all the experimental procedures and the analytical data for the compounds prepared in the subsequent chapters