APPLICATION OF A FERROCENE-BASED PALLADACYCLE
PRECATALYST TO ENANTIONSELECTIVE ARYL-ARYL
KUMADA COUPLING
GROUP 7
ARTICLE # 2
REVIEWED BY
MOHAMMED SHEHU
202214340
&
YAHUZA NANTOMAH ABDULAI
202214280
OUTLINE OF PRESENTATION
• Introduction to Kumada coupling
• Parameters that affect Kumada coupling
• Aim and key objectives of the study
• Justification and relevance of the study
• Research hypothesis
• Synthetic techniques adopted in the research
• Results and Discussion
• Conclusion
1
INTRODUCTION
• Kumada coupling
Ease in reactivity of R-X
Aryl iodides give high yields under mild conditions
Con: Not economical
Fig 2-Standard mechanism for palladium-catalyzed CC cross-coupling reactions.
2
Electron counting is key!
3
INTRODUCTION
Factors that affect reaction rate, yield, and stereochemistry
of Kumada Coupling products
• Organohalide (ArX >RX)
• Grignard reagent (RMgX > ArMgX)
• Palladium catalyst (Palladacycles for enantioselectivity)
• Solvent, temperature, time.
• Substituents on ArX –EWG
• Ligands (Phosphine ligands-BINAP, Chiral (S)-N,N-Dimethyl-1 [(R)-2(diphenylphosphino)ferrocenyl] ethylamine [(S)-(R)-PPFA]), USED HERE!
• Sterics
4
AIM OF STUDY
Main aim: Enantioselective synthesis of a biaryl product through Kumada
coupling using a ferrocene based palladacycle as a precatalyst.
5
RELEVANCE OF THE RESEARCH
• Coupling reactions are widely applied in C-C bond formation.
• Need for efficient and cheap enantioselective methods in biaryl
couplings.
• Enantioselectivity is relevant to the Pharmaceutical and Agrochemical
industries.
6
BACKGROUND AND RESEARCH HYPOTHESIS
• Successful synthesis of P-N ligated Pd(0) complex using a planar
chiral palladacycle (Arthur et al., 2020).
• Application of the catalytically active chiral P-N ligated/Pd(0)
complex in asymmetric allylic alkylation (Arthur et al., 2020)
• In light of these outcomes, the authors hypothesized that Planar chiral
palladacycle could be used as a precatalyst in enantioselective aryl
aryl cross coupling.
7
METHODOLOGY
Scheme 1. Racemic Coupling, Salt of
Pd(II) onlyI.ArBr, ArMgBr2, Pd(PPh3)2Cl2,THF,70°C
II. ArI, same conditions
Scheme 2. Incorporation of
chiral ligands-PPFA derivatives
(Arthurs et al., 2022)
8
METHODOLOGY
(Arthurs et al., 2020)
Scheme 4. Ferrocene-based palladacycle
precatalyst synthesis and cross-coupling
Scheme 3. Previous work and extrapolation to recent
studies
(Arthurs et al., 2022)
9
SUMMARY OF METHODOLOGY
1
Racemic Coupling, Salt of Pd(II) only-
I.ArBr, ArMgBr2, 2.5% mol Pd(PPh3)2Cl2,THF,70°C
II. ArI, same conditions
3
2
Coupling with PPFA/Pd(II) complex
(Preformed)
5% L, 70°C, 48 hrs, 1 eq ArMgBr2
I. 96 hrs, 2 eq ArMgBr2
4
Coupling with Pd(0) source and PPFA (in situ)
I. 5% Pd2(dba)3, 10% PPFA , THF, 24 hrs. II.
48 hrs III. 72 hrs
5
Coupling PPFA related ligands
I. 5% Pd2(dba)3, 10% PPCA
II. 5% preformed PCCA complex
III. P-stereogenic PPFA derivatives
(R,Sp,Sphos)-13 and (R,Sp,Rphos)14 and (R,Sp)-15
Synthesis of deutrated version of S9 , deutration
monitored by 1HNMR, e.e by Chiral HPLC
10
RESULTS AND DISCUSSIONS
11
RESULTS AND DISCUSSIONS
12
WHAT IS OUTSTANDING ABOUT THIS
WORK?
• Successful application of the ferrocene-based palladacycle as a precatalyst
for in situ generation of active Pd(0) complex.
• Achieved high enantioselectivity.
• The precatalyst can easily be synthesized from commercially available N,
N-dimethylaminomethylferrocene in a single step.
• Precatalyst Relevant for asymmetric synthesis.
13
CONCLUSION AND FUTURE PERSPECTIVES
• Successful synthesis of a Sa –configured cross-coupled product in 80% e.e
using a chiral PPFA ligand.
• In situ generation of active catalytic Pd complex using an (Sp)-configured
dimeric palladacycle as a precatalyst.
• The in situ generated catalyst was applied in aryl-aryl Kumada coupling
reaction yielding 71% e.e cross-coupled product.
• This technique could be a useful tool for other asymmetric crosscoupling procedures.
• % e.e can be improved
14
REFERENCES
• Arthurs, R. A., Hughes, D. L., & Richards, C. J. (2022). Application of a Ferrocene-Based Palladacycle Precatalyst to Enantioselective ArylAryl Kumada Coupling. European Journal of Inorganic Chemistry, 2022(9), 4–8. https://doi.org/10.1002/ejic.202101077
•
Arthurs, R. A., Dean, A. C., Hughes, D. L., & Richards, C. J. (2021). Copper(I) Complexes of P-Stereogenic Josiphos and Related Ligands. European
Journal of Organic Chemistry, 2021(18), 2719–2725. https://doi.org/10.1002/ejoc.202100146
•
Arthurs, R. A., Hughes, D. L., & Richards, C. J. (2020). Planar chiral palladacycle precatalysts for asymmetric synthesis. Organic and Biomolecular
Chemistry, 18(28), 5466–5472. https://doi.org/10.1039/d0ob01331e
•
Arthurs, R. A., Hughes, D. L., & Richards, C. J. (2019). Ferrocenyloxazoline-Derived Planar Chiral Palladacycles: C-H Activation, Transmetalation, and
Reversal of Diastereoselectivity. Organometallics, 38(21), 4271–4279. https://doi.org/10.1021/acs.organomet.9b00551
•
Arthurs, R. A., Horton, P. N., Coles, S. J., & Richards, C. J. (2018). Stereoselective and Stereospecific Reactions of Cobalt Sandwich Complexes:
Synthesis of a New Class of Single Enantiomer Bulky Planar Chiral P−N and P−P Ligands. Chemistry - A European Journal, 24(17), 4310–4319.
https://doi.org/10.1002/chem.201705113
•
Richards, C. J., & Arthurs, R. A. (2017). Catalyst Optimisation for Asymmetric Synthesis by Ligand Chirality Element Addition: A Perspective on
Stereochemical Cooperativity. Chemistry - A European Journal, 23(48), 11460–11478. https://doi.org/10.1002/chem.201700926
•
Hayashi, T., Konishi, M., Fukushima, M., Mise, T., Kagotani, M., Tajika, M., & Kumada, M. (1982). Asymmetric synthesis catalyzed by chiral
ferrocenylphosphine-transition metal complexes. 2. Nickel- and palladium-catalyzed asymmetric Grignard cross-coupling. Journal of the American
Chemical Society, 104(1), 180–186. https://doi.org/10.1021/ja00365a033
15
THANKS FOR LISTENING