Asymmetric Induction at Remote Quaternary Centers of Cyclohexadienones by Rhodium‐Catalyzed Conjugate Hydrosilylation

Naganawa, Yuki; Kawagishi, Mayu; Ito, Junichi; Nishiyama, Hisao

doi:10.1002/anie.201601636

Cited by 47 publications

(28 citation statements)

References 48 publications

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“…. 32 To a stirred suspension of (methoxymethyl)triphenylphosphonium chloride (5.2 g, 15 mmol) in anhydrous THF (100 mL) at -78, nBuLi (2.5 M in toluene, 6.1 mL) was added dropwise. The resulting red mixture was allowed to stir at -78 ºC for 30 min and at rt for additional 30 min.…”

Section: -(Methoxymethylene)chromane (65)mentioning

confidence: 99%

Structure–Activity Relationship Studies of a Novel Class of Transmission Blocking Antimalarials Targeting Male Gametes

et al. 2019

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Malaria is still a leading cause of mortality among children in the developing world, and despite the immense progress made in reducing the global burden, further efforts are needed if eradication is to be achieved. In this context, targeting transmission is widely recognized as a necessary intervention towards that goal. After carrying out a screen to discover new transmission-blocking agents, herein we report our medicinal chemistry efforts to study the potential of the most robust hit, DDD01035881, as a male-gamete targeted compound. We reveal key structural features for the activity of this series and identify analogues with greater potency and improved metabolic 2 stability. We believe this study lays the groundwork for further development of this series as a transmission blocking agent. 3 130±30 6 128±10 34 > 1000 35 785±48 36 > 25000 37 > 10000 38 196±19 39 83±13 40 364±47 41 79±18 42 > 25000 43 > 25000 44 > 25000 45 > 25000 a Biological evaluation was carried out using the DGFA under the specific "add-in" format. Compounds were incubated at variable concentrations with fresh gametocytes, and their ability to impair exflagellation of male gametes determined. Values below 1 µM are expressed as the mean±SEM obtained from between three and eight biological replicates, each carried out in at least duplicate. All synthesised analogues resulted in a significant loss of activity, with the exception of fluorinated derivatives 38-41 (Table 2). Compounds 39 and 41 even show a slight improvement in potency over 6. Once again, these results suggest the binding site of this series within the target(s) to be reasonably confined. Indeed, in contrast to other substituents, fluorine is very similar in size to hydrogen, which could explain why analogues 38-41 retain activity. It should be highlighted that fluorine is widely used within drug discovery to improve permeability by increasing lipophilicity and to address pharmacokinetic issues such as oxidative metabolism, 21 the latter being interesting in the context of this work (vide infra).

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Section: -(Methoxymethylene)chromane (65)mentioning

confidence: 99%

Structure–Activity Relationship Studies of a Novel Class of Transmission Blocking Antimalarials Targeting Male Gametes

et al. 2019

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“…However, the research on NHC pincer complexes with both unsymmetrical and chiral parameters has been less explored . Anionic bis(oxazolinyl)phenyl (Phebox, A ) moieties have been widely utilized as chiral ligand precursors, which could coordinate with multiple metals to achieve ample asymmetrical transformations . In 2015, the Shi group reported NHC-oxazoline CCN pincer complexes ( B ), which were utilized to support Au metal in cycloaddition/oxidation reactions of enyones with alkenes .…”

Section: Introductionmentioning

confidence: 99%

Synthesis, Characterization, and Catalytic Studies of Unsymmetrical Chiral NCC Pincer Pd(II) and Ni(II) Complexes Bearing (Imidazolinyl)aryl NHC Ligands

et al. 2018

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A series of palladium(II) and nickel(II) complexes based on unsymmetrical chiral (imidazolinyl)aryl NHC ligands are reported. The new ligand presursors 3a−g were prepared from commercially available 3-bromobenzoic acid, in which the carboxyl and bromo functionalities were converted to chiral imidazoline and NHC moieties, respectively, in three steps. Treatment of 3a−g with Pd(OAc) 2 in dimethylacetamide in the presence of NaOAc, followed by addition of LiCl, gave the seven palladium(II) pincer complexes 4a−g via direct aryl C−H activation. Likewise, the six nickel(II) pincer complexes 5a−f were obtained by reacting 3a−f with anhydrous NiCl 2 . All of the ligand precursors and pincer complexes are bench-stable and were fully characterized. The absolute configurations of palladium complexes 4a,c and 5e were further determined by X-ray diffraction. Finally, Pd pincer complex catalyzed asymmetric Friedel−Crafts alkylation and aza-Morita−Baylis−Hillman reactions were briefly assessed.

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“…Spirocyclic cyclohexadienones were found to perform better in this process giving the enantioenriched products in up to 99% yield and with 93% ee with most examples giving high levels of enantioselectivity >80% ee . 509 …”

Section: Bis(oxazoline) Ligandsmentioning

confidence: 99%

Further Developments and Applications of Oxazoline-Containing Ligands in Asymmetric Catalysis

et al. 2021

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The chiral oxazoline motif is present in many ligands that have been extensively applied in a series of important metal-catalyzed enantioselective reactions. This Review aims to provide a comprehensive overview of the most significant applications of oxazoline-containing ligands reported in the literature starting from 2009 until the end of 2018. The ligands are classified not by the reaction to which their metal complexes have been applied but by the nature of the denticity, chirality, and donor atoms involved. As a result, the continued development of ligand architectural design from mono(oxazolines), to bis(oxazolines), to tris(oxazolines) and tetra(oxazolines) and variations thereof can be more easily monitored by the reader. In addition, the key transition states of selected asymmetric transformations will be given to illustrate the features that give rise to high levels of asymmetric induction. As a further aid to the reader, we summarize the majority of schemes with representative examples that highlight the variation in % yields and % ee s for carefully selected substrates. This Review should be of particular interest to the experts in the field but also serve as a useful starting point to new researchers in this area. It is hoped that this Review will stimulate both the development/design of new ligands and their applications in novel metal-catalyzed asymmetric transformations.

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Asymmetric Induction at Remote Quaternary Centers of Cyclohexadienones by Rhodium‐Catalyzed Conjugate Hydrosilylation

Cited by 47 publications

References 48 publications

Structure–Activity Relationship Studies of a Novel Class of Transmission Blocking Antimalarials Targeting Male Gametes

Structure–Activity Relationship Studies of a Novel Class of Transmission Blocking Antimalarials Targeting Male Gametes

Synthesis, Characterization, and Catalytic Studies of Unsymmetrical Chiral NCC Pincer Pd(II) and Ni(II) Complexes Bearing (Imidazolinyl)aryl NHC Ligands

Further Developments and Applications of Oxazoline-Containing Ligands in Asymmetric Catalysis

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