the chemistry of prof. paolo melchiorreweb.pkusz.edu.cn/huang/files/2013/04/the-chemistry-of... ·...
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![Page 1: The Chemistry of Prof. Paolo Melchiorreweb.pkusz.edu.cn/huang/files/2013/04/The-Chemistry-of... · 2019-04-02 · 2009-2013, Discovery and mechanistic elucidation of new asymmetric](https://reader034.vdocuments.us/reader034/viewer/2022042306/5ed269984f210d3bba79c4bb/html5/thumbnails/1.jpg)
Supervisor: Prof. Yong Huang
Reporter: Pengfei Yuan
Date: May. 31th, 2017
The Chemistry of Prof. Paolo Melchiorre
Radical Chemistry
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Introduction
Summary
CONTENTSPhotoactivation of EDA Complex
Photoexcitation of Enamines
Phexcitation of Iminium Ions
Other Methods
Acknowledgement04
Curriculum Vitae
Research Interests
Radical Chemistry
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01
02
03
Introduction
Summary
CONTENTSPhotoactivation of EDA Complex
Photoexcitation of Enamines
Phexcitation of Iminium Ions
Other Methods
Acknowledgement04
Curriculum Vitae
Research Interests
Radical Chemistry
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Curriculum Vitae
educational & professional career • 1993-1999, MSc, University of Bologna (Italy);
• 2000-2003, PhD, University of Bologna;
• 2002, Research Period at Centre for Catalysis, University of Århus (DK);
• 2003-2006, Postdoctoral Fellow in Chemistry, University of Bologna;
• 2007-2009, Assistant Professor, University of Bologna;
• 2009 Sept –present, Research Professor, ICIQ – Tarragona (Spain).
Awards & Distinctions
2007 - Recipient of the “G. Ciamician” Gold Medal of the Italian Chemical Society
2008 - Recipient of the Liebig Lectureship awarded by the German Chemical Society
2009 - Thieme Journal Prize
2011 - ERC Starting Grant to carry out the 5-year project “ORGA-NAUT: Exploring
Chemical Reactivity with Organocatalysis”
2013 - JSPS Fellowship under the FY2013 Program for Research in Japan
2014 - Erdtman Lecture 2014 – Stockholm (Sweden)
2015 - Thieme Lecture – DOMINOCAT SYMPOSIUM – Aachen (Germany )
2015 - ERC Consolidator Grant to carry out the 5-year project “CATA-LUX”
2016 - Prize for Scientific Excellence from the Royal Spanish Chemical Society (RSEQ)
Paolo Melchiorre
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Research Interests
2009-2013, Discovery and mechanistic elucidation of new asymmetric organocatalytic processes
and their application in drug discovery research
2013-present, Lie on the discovery and mechanistic elucidation combine new asymmetric
organocatalytic with photochemical processes
P. Melchiorre, Nat. Chem., 2013, 5, 750. 5
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01
02
03
Introduction
Summary
CONTENTSPhotoactivation of EDA Complex
Photoexcitation of Enamines
Phexcitation of Iminium Ions
Other Methods
Acknowledgement04
Curriculum Vitae
Research Interests
Radical Chemistry
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Photoactivation of EDA Complex
P. Melchiorre, Nat. Chem., 2013, 5, 750.
Photochemical activity of EDA (electron donor–acceptor) complexes drive stereoselective
catalytic a-alkylation of aldehydes
*Reaction performed using 1 equiv. NaOAc instead of 2,6-lutidine. 460 nm LED
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Mechanistic investigations
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Mechanistic proposal for asymmetric catalytic photochemical processes
EDA critical factors
1. a weak absorption band lies in
the visible-frequency range
2. the presence of a suitable leaving
group ( LG )
Radical-chain
P. Melchiorre, Nat. Chem., 2013, 5, 750.
Photoactivation of EDA Complex
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Photoactivation of EDA Complex
Evaluating the scope and the strategy’s potential to address synthetically relevant problems
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Enantioselective direct a-alkylation of cyclic ketones by photo-organocatalysis
Concerns:
1. increased steric impediments which significantly limit the use of chiral secondary amine catalysts.
2. the resulting secondary enamine, which should have a suitable ionization potential (IP).
3. Have capable of conferring a high level of stereocontrol during the carbon–carbon bond forming event.
Photoactivation of EDA Complex
P. Melchiorre, Chem. Sci., 2014, 5, 2438.
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h: Reaction performed in the dark. i: Reaction performed in air.
Explorative studies
P. Melchiorre, Chem. Sci., 2014, 5, 2438.
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Scope of the photochemical ketone a-alkylation
Photoactivation of EDA Complex
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Photoactivation of EDA Complex
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Electron Donor–Acceptor Complex that Drives the Photochemical Alkylation of Indoles
P. Melchiorre, Angew. Chem. Int. Ed. 2015, 54, 1485.
Photoactivation of EDA Complex
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Photoactivation of EDA Complex
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Evaluation of the scope of the photochemical indole alkylation strategy
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01
02
03
Introduction
Summary
CONTENTSPhotoactivation of EDA Complex
Photoexcitation of Enamines
Phexcitation of Iminium Ions
Other Methods
Acknowledgement04
Curriculum Vitae
Research Interests
Radical Chemistry
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Enantioselective Organocatalytic Alkylation of Aldehydes and Enals Driven by
the Direct Photoexcitation of Enamines
P. Melchiorre, J. Am. Chem. Soc. 2015, 137, 6120.
d : using a 300 W xenon lamp
Photoactivation of Enamines
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a: Excluding any EDA association in the ground state
b: Absorption band until 415 nm
c: Stern−Volmer quenching Studies revealed that
bromomalonate 1a effectively quenched the excited
state of enamine IV
Mechanistic Investigations
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Proposed Mechanism
P. Melchiorre, J. Am. Chem. Soc. 2015, 137, 6120.
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Substrate Scope
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Enantioselective Formal a-Methylation or Benzylation by Means of Photo-Organocatalysis
P. Melchiorre, Angew. Chem. Int. Ed. 2017, 56, 4447.
Photoactivation of Enamines
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Proposed Mechanism
Epred V/III = -0.95 VEp red 2a = -1.49 V
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Substrate Scope
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01
02
03
Introduction
Summary
CONTENTSPhotoactivation of EDA Complex
Photoexcitation of Enamines
Phexcitation of Iminium Ions
Other Methods
Acknowledgement04
Curriculum Vitae
Research Interests
Radical Chemistry
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26P. Melchiorre, Nature Chem., 2017, DOI: 10.1038/nchem.2748.
Phexcitation of Iminium Ions
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27P. Melchiorre, Nature Chem., 2017, DOI: 10.1038/nchem.2748.
3: electron rich
trimethylsilane reagents
Light excitation of iminium ions enables the enantioselective catalytic β-alkylation of enals
Phexcitation of Iminium Ions
(Ered* (Ib*/Ib·−) = +2.3 V versus Ag/Ag+ in CH3CN)
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Key step of a possible chain propagation manifold
A chain propagation mechanism is unlikely for several reasons:
(i) the already-mentioned poor nucleophilicity of benzyl radicals
(ii) the low tendency of iminium ions to trap radicals
(iii) the endergonic SET in Fig. 2 is highly disfavoured when considering the redox potentials
Figure1
Figure 2
Mechanistic investigation
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Proposed Mechanism
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Substrate Scope
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01
02
03
Introduction
Summary
CONTENTSPhotoactivation of EDA Complex
Photoexcitation of Enamines
Phexcitation of Iminium Ions
Other Methods
Acknowledgement04
Curriculum Vitae
Research Interests
Radical Chemistry
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Other Methods of Photoactivation
Photochemical Direct Perfluoroalkylation of Phenol
P. Melchiorre, Tetrahedron, 2015, 71, 4535.
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Other Methods of Photoactivation
Electron-relay strategy to remove the short-lived α-iminyl radical cation (B) by reduction
P. Melchiorre, Nature 2016, 532, 218.
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01
02
03
Introduction
Summary
CONTENTSPhotoactivation of EDA Complex
Photoexcitation of Enamines
Phexcitation of Iminium Ions
Other Methods
Acknowledgement04
Curriculum Vitae
Research Interests
Radical Chemistry
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Combine organocatalytic with photochemical processes to realize metal-free asymmetric
reaction under mild conditions
Photoactivation of EDA complex
Photoexcitation of Enamines
Photoexcitation of iminium ions
RX radical
Summary
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Acknowledgement
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Thanks for your attention!
Prof. Huang
Dr. Chen
All members here
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