Los días 8 y 9 de octubre de 2014, la Fundación Ramón Areces acogió el Simposio Internacional 'Química: respuestas para una vida mejor', organizado en colaboración con la Fundación General CSIC. Su finalidad fue ofrecer a los participantes una visión atractiva de la química moderna que sirva de base al desarrollo de nuevas respuestas para una sociedad en rápida evolución.

1. Photochemical Organocatalytic Processes
Paolo Melchiorre
ICREA Research Professor
Institute of Chemical Research of Catalonia (ICIQ)
Tarragona – SPAIN
pmelchiorre@iciq.es
25th Fundación Ramón Areces Scientific Symposium
Chemistry: answers for a better world
Química: respuestas para un mundo mejor
Madrid – 8 October 2014

2. Asymmetric Aminocatalysis
The work-horses of enantioselective organocatalysis
D. Seebach et al., Helvetica Chim. Acta 2008, 91, 1999-2034
Revolutionizing the way to Asymmetrically Functionalize Carbonyl Compounds

3. Enamine Catalysis
Iminium-Ion Catalysis
Activation Modes in Aminocatalysis
B. List, R. A. Lerner, C. F. Barbas III, J. Am. Chem. Soc. 2000, 122, 2395-2396
K. A. Ahrendt, C. J. Borths, D.W. C. MacMillan, J. Am. Chem. Soc. 2000, 122, 4243-4244

4. Vinylogous Reactivity in Aminocatalysis
Our contributions:
PNAS 2010, 107, 20642
Angew. Chem. Int. Ed. 2010, 49, 9685
J. Am. Chem. Soc. 2011, 133, 15212
Org. Lett. 2013, 15, 220
Our contributions:
Angew. Chem. Int. Ed. 2012, 51, 6439
Angew. Chem. Int. Ed. 2013, 52, 5360
Angew. Chem. Int. Ed. 2013, 52, 10780
Angew. Chem. Int. Ed. 2014, 53, 2997
Fuson RC (1935) The Principle of Vinylogy Chem. Rev. 16: 1–27.
The transmission of electronic effects through a conjugated p-system

5. … and some unexpected results
R. M. Roberts, Wiley-VCH (1989)

6. N. Vignola, B. List, J. Am. Chem. Soc. 2004, 126, 450–451
Intramolecular SN2 type Reaction
a-Alkylation of Aldehydes

7. a-Alkylation of Aldehydes
N. Vignola, B. List, J. Am. Chem. Soc. 2004, 126, 450–451
Intramolecular SN2 type Reaction
INTER-molecular a-Alkylation:
The Holy Grail of Asymmetric Aminocatalysis
Highlight article:
P. Melchiorre, ACIE 2009, 48, 1360

8. Radical Reactivity
D. A. Nicewicz, D. W. C. MacMillan, Science 2008, 322, 77
Photoredox-Organocatalysis
Representative examples

9. Merging Photoredox- and Amino-Catalysis
a-functionalized product

10. Merging Photoredox- and Amino-Catalysis
g-functionalized product

11. Vinylogous Reactivity in Radical Pathways
Photocatalyst time
g-functionalized product
conv.
R’Br
ee
Fluorescein 48 h 100 50 %
[Ru(bpy)3]Cl2 45 h 88 64 %
Rhodamine B 40 h 75 66 %
Rhodamine B 14 h 100 64 %

12. Vinylogous Reactivity in Radical Pathways
Photocatalyst time
g-functionalized product
conv.
R’Br
ee
Fluorescein 48 h 100 50 %
[Ru(bpy)3]Cl2 45 h 88 64 %
Rhodamine B 40 h 75 66 %
Rhodamine B 14 h 100 64 %

13. Vinylogous Reactivity in Radical Pathways
Elena Arceo

14. Elena Arceo
Vinylogous Reactivity in Radical Pathways
Control Experiment
The reaction works without any Photo-redox catalyst!

15. Elena Arceo
Vinylogous Reactivity in Radical Pathways
Control Experiment
The reaction works without any Photo-redox catalyst!

16. Further Control Experiments
Elena Arceo

17. Light-driven a-Alkylation

18. Igor Jurberg
with E. Arceo, I. Jurberg, A. Alvarez
Nature Chemistry, 2013, 5, 750

19. Expanding the Scope
Igor Jurberg
Elena Arceo
Benzylation
Benzoylation
Alkylation
with E. Arceo, I. Jurberg, A. Alvarez
Nature Chemistry, 2013, 5, 750-756

20. entry alkyl-bromide product
9
10*†
11*
12*
The Scope
a
entry alkyl-bromide product entry alkyl-bromide product
1 5
2 6
3 7
4 8
*Reaction catalysed by amine 1b (20 mol%). †Reaction performed under natural sunlight irradiation on the roof-top of the ICIQ, Tarragona (Spain), in a
partially cloudy day (10/10/2012, from 9 a.m. till 18 p.m.).
with E. Arceo, I. Jurberg, A. Alvarez
Nature Chemistry, 2013, 5, 750-756

21. The Mechanism
Thermal Reactivity
Photochemical Reactivity
Established tools
for thermal reactions
EDA complexes and Charge Transfer theory
R. S. Mulliken, J. Phys. Chem. 1952, 56, 801.

22. Abs.
0,7
0,6
0,5
0,4
0,3
0,2
0,1
0
2a:1b:3a (15:1:1)
2a:1b (15:1)
3a
2a
2a:3a (15:1:1)
2a:(15:1)
3a
2a
400 500 600 700
2a:1b:3a
(15:1:1)
2a:1b
(15:1)
1b:3a
(1:1)
2a 3a
[3a] = 0.2 M
Donor-Acceptor Complex
EDA complexes and Charge Transfer theory
R. S. Mulliken, J. Phys. Chem. 1952, 56, 801.

23. Donor-Acceptor Complex
aldehyde:1b: 3a
(3: 0.2: 1)
aldehyde:1b:3a
(3:0.2:1)
3a
aldehyde: 1b
(3:0.2)
[3a] = 0.5 M
nm nm
4
3,5
3
2,5
Abs.
Abs.
a
Abs.
2
1,5
1
0,5
0
3a
aldehyde:1b
(3:0.2)
390 490 590 690 790
aldehyde:1b: 3g
(3: 0.2: 1)
aldehyde: 1b
(3:0.2)
3g
[3g] = 0.5 M
2a:1b:3g (15:1:1)
3g
2a:1b (15:1)
2a:1b:3h (15:1:1)
3h
2a:1b (15:1)
Abs.
[3g] = 0.2 M [3h] = 0.2 M
b
100
EDA complexes and Charge Transfer theory
R. S. Mulliken, J. Phys. Chem. 1952, 56, 801.

24. An Alternative Path: Chain Mechanism
same pathway
as in Fig. 1
a
b
A plausible Kornblum-Russell alkylation pathway via a radical chain SRN1 mechanism
Kornblum, N. Substitution reactions which proceed via radical anion intermediate.
Angew. Chem. Int. Ed. Engl. 14, 734–745 (1975)

25. An Alternative Path: Chain Mechanism
same pathway
as in Fig. 1
a
b
A quantum yield (Φ) of 25 was determined ( = 450 nm)

26. Expanding the Concept
Asymmetric Catalysis of Photochemical Reactions
Ana Bahamonde
with A. Bahamonde, E. Arceo,
Chem. Sci. 2014, 5, 2438-2442

27. Scope
Photochemical Organocatalytic Asymmetric a-Benzylation of Ketones
with A. Bahamonde, E. Arceo,
Chem. Sci. 2014, 5, 2438-2442

28. Scope
Photochemical Organocatalytic Asymmetric a-Phenacylation of Ketones
with A. Bahamonde, E. Arceo,
Chem. Sci. 2014, 5, 2438-2442

29. Moving forward
EDA Complex Activation Strategy
a general mode of molecule activation?

30. EDA Complex Activation as a General Strategy?
Cantacuzène, D.; Wakeselman, C.; Dorme R. J. C. S. Perkin I 1977, 1365

31. Another Unexpected Result…
Giulia Bergonzini
Manuel Nappi

32. Another Unexpected Result…
Giulia Bergonzini
Manuel Nappi

33. with M. Nappi, G. Bergonzini
Angew. Chem. Int. Ed. 2014, 53, 4921-4925

34. Photochemical Aromatic Perfluoroalkylation
EDA Complex Activation
0,9
0,8
0,7
0,6
0,5
0,4
0,3
0,2
0,1
0
360 410 460 510 560
Absorbance (a.u.)
Wavelength (nm)

35. Mechanistic Insights
The reaction is quenched when performed:
• In the dark
• In the air
• In the presence of TEMPO
The use of a cut-off filter at 385 nm did not significantly alter the reaction efficiency
A quantum yield (Φ) of 3.8 was determined ( = 400 nm)
with M. Nappi, G. Bergonzini
Angew. Chem. Int. Ed. 2014, 53, 4921-4925

36. Mechanistic Insights
Taft reactivity resonance
parameter (R) = - 0,40
homolytic aromatic substitution (HAS) pathway
with M. Nappi, G. Bergonzini
Angew. Chem. Int. Ed. 2014, 53, 4921-4925

37. Enantioselective Variant
with Łukasz Wozniak and John Murphy
unpublished results
Łukasz Wozniak John Murphy

38. Enantioselective Variant
with Łukasz Wozniak and John Murphy
unpublished results
Łukasz Wozniak John Murphy

39. Enantioselective Variant
with Łukasz Wozniak and John Murphy
unpublished results
Łukasz Wozniak John Murphy

40. Enantioselective Variant
with Łukasz Wozniak and John Murphy
unpublished results
Łukasz Wozniak John Murphy

41. Enantioselective Variant
with Łukasz Wozniak and John Murphy
unpublished results
Łukasz Wozniak John Murphy

42. Enantioselective Variant
with Łukasz Wozniak and John Murphy
unpublished results
Łukasz Wozniak John Murphy

43. Enantioselective Variant
with Łukasz Wozniak and John Murphy
unpublished results
Łukasz Wozniak John Murphy

44. Enantioselective Variant
with Łukasz Wozniak and John Murphy
unpublished results
Łukasz Wozniak John Murphy

45. EDA Complex Activation
EDA associations of indoles in biological systems: a) A. Szent-Györgyi, I. Senberg, Proc. Natl. Acad. Sci. U.S.A. 1960,
46, 1334; b) A. Szent-Györgyi, I. Senberg, J. McLaughlin, Proc. Natl. Acad. Sci. U.S.A. 1961, 47, 1089;

46. Photochemical Alkylation of Indoles via EDA Activation
with S. Kandukuri, A. Bahamonde, I. Chatterjee, and Igor D. Jurberg
unpublished results

47. Indoles & EDA Complex
Albert Szent-Györgyi (1893-1986)
Nobel Prize in Physiology or Medicine 1937
for his discoveries in connection with the biological
combustion processes, with special reference to
vitamin C and the catalysis of fumaric acid
EDA associations of indoles in biological systems: a) A. Szent-Györgyi, I. Senberg, Proc. Natl. Acad. Sci. U.S.A. 1960,
46, 1334; b) A. Szent-Györgyi, I. Senberg, J. McLaughlin, Proc. Natl. Acad. Sci. U.S.A. 1961, 47, 1089;

48. with S. Kandukuri, A. Bahamonde, I. Chatterjee, and Igor D. Jurberg
unpublished results

49. Photochemical Alkylation of Indoles via EDA Activation
with S. Kandukuri, A. Bahamonde, I. Chatterjee, and Igor D. Jurberg
unpublished results
A quantum yield (Φ) of 0.2 was determined ( = 450 nm)

50. X-Ray Characterization of the EDA Complex
Interplanar distance of 3.33 Å.
considerably less than the van der Waals
separation for aromatic molecules (3.40 Å)
Special thanks to Eduardo C. Escudero-Adán and the X-Ray ICIQ Unit
Dr Sandeep Kandukuri

51. X-Ray Characterization of the EDA Complex
Dr Sandeep Kandukuri
Special thanks to Eduardo C. Escudero-Adán and the X-Ray ICIQ Unit

52. The Pioneers: a kind of acknowledgement
Robert S. Mulliken (1896-1986) Giacomo Ciamician (1857-1922)
‘The Photochemistry of the Future’
Science 1912, 36, 385–394
“… and if in a distant future the supply of coal
becomes completely exhausted, civilization will
not be checked by that, for life and civilization
will continue as long as the sun shines!”
Nobel Prize in Chemistry 1966
for his fundamental work concerning
chemical bonds and the electronic structure
of molecules by the molecular orbital method
“If I have seen further, it is by standing on the shoulders of Giants”
Sir Isaac Newton (1676)

53. Historical Reasons
On the roof of the Chemistry Dept in Bologna (Italy)
Ciamician, G.
‘The Photochemistry of the Future’
Science 36, 385–394 (1912).
“..and if in a distant future the supply of coal becomes
completely exhausted, civilization will not be checked by that,
for life and civilization will continue as long as the sun shines!”
Giacomo Ciamician (1857-1922)
“G. Ciamician” Chemistry Dept
University of Bologna
PhD to PM in 2002

54. Chemistry on the Roof
in a partially cloudy day
98% yield – 92% ee

55. Funds
Acknowledgments
Assistance:
Dr. Lorna Piazzi
Past members:
Giulia Bergonzini
Carlo Cassani
Elisa Montroni
Rodrigo Cesar
Giulio Volpin
Michele Retini
Dr. Yankai Liu
Dr. Ana Álvarez
Dr. A. Moran
Dr. Indra Chatterjee
The Research Group
Present members:
Dr. Elena Arceo
Dr. Charlie Verrier
Dr. John Murphy
Dr. Nora Hofmann
Dr. Sandeep Kandukuri
Ana Bahamonde
David Bastida
Giacomo Filippini
Xin Huang
Manuel Nappi
Mattia Silvi
Łukas Wozniak
Xu Tian