1. Université de Montréal
Clémentine Minozzi
Université de Montréal
Literature Meeting
April 5th 2017

2. About Prof. Morandi Academic Background
BSc ETH Zurich in Biology
MSc ETH Zurich in Chemical Biology  
Dr Sc. ETH Zurich in Organic Chemistry (with Prof. Carreira)
Career
PDF in Organometallic Chemistry with Prof. Grubbs
Independent Max Planck Research Group Leader
Research interest
Shuttle Catalysis
Aliphatic C–O Bond Activation
Direct Catalytic Synthesis of Unprotected Amines
This graph was taken from a recent review on named cross-coupling reactions and illustrates the growth in the number of publications associated with these reactions over the past 30 years.
In all of the publications published since the early nineties, one reaction that caught our eye was the Sonogashira cross-coupling, which has become the third most widely used named cross-coupling in diverse field of applications.
Publications : Since 2014, published 12 papers (28 in total)
1 Science
2 ACIE
1 Org. Lett.
2 Chem. Eur. J.
3 ACS Catal.
1 Chem. Comm.
1 Synlett

3. Synthetic Versatility of Nitriles
This graph was taken from a recent review on named cross-coupling reactions and illustrates the growth in the number of publications associated with these reactions over the past 30 years.
In all of the publications published since the early nineties, one reaction that caught our eye was the Sonogashira cross-coupling, which has become the third most widely used named cross-coupling in diverse field of applications.
Pollak, P.; Romeder, G.; Hagedorn, F.; Gelbke, H. in Nitriles. Ullman’s encyclopedia of industrial chemistry, 5th copl. Rev. ed., Vol. A17, Wiley-VCH, Weinheim, 1985, pp

4. Hydrocyanation of Alkenes
Hydrocyanation definition : Hydrocyanation is the process in which HCN is added across the double bond of an alkene to form a nitrile
Hydrocyanation of alkenes
No regio- nor stereoselectivity
Toxycity of HCN
Huthmacher, K.; Krill, S. in Applied Homogeneous Catalysis with Organometallic Compounds,
2nd ed.; Cornils, B., Hermann, W. A., Eds.; Wiley-VCH: Weinheim,
The first report dealing with a homogeneously catalyzed HCN addition to nonfunctionalized alkenes in 1954
Use of [Co2(CO)8] as a precatalyst
This graph was taken from a recent review on named cross-coupling reactions and illustrates the growth in the number of publications associated with these reactions over the past 30 years.
In all of the publications published since the early nineties, one reaction that caught our eye was the Sonogashira cross-coupling, which has become the third most widely used named cross-coupling in diverse field of applications.
P. Arthur Jr. , D. C. England, B. C. Pratt, G. M. Whitman, J. Am. Chem. Soc. 1954, 76, 5364.

5. Hydrocyanation of Alkenes
The DuPont Adiponitrile process
Adiponitrile is a precursor of hexamethylenediamine necessary for the synthesis of Nylon
Tolman developed important concept in catalysis
This graph was taken from a recent review on named cross-coupling reactions and illustrates the growth in the number of publications associated with these reactions over the past 30 years.
In all of the publications published since the early nineties, one reaction that caught our eye was the Sonogashira cross-coupling, which has become the third most widely used named cross-coupling in diverse field of applications.
C. A. Tolman, Chem. Rev. 1977, 77, 313
L. Bini, C. Müller, D. Vogt, ChemCatChem 2010; 2, 590–608

6. Use of Ni(0) and Lewis Acids
Nickel-Catalyzed Carbocyanation of Alkynes
Acceleration of the oxidative addition of C-CN bond
Positive effect on the reductive elimination
EDG ligand = essential to form an electron-rich nickel center
This graph was taken from a recent review on named cross-coupling reactions and illustrates the growth in the number of publications associated with these reactions over the past 30 years.
In all of the publications published since the early nineties, one reaction that caught our eye was the Sonogashira cross-coupling, which has become the third most widely used named cross-coupling in diverse field of applications.
Y. Nakao, A. Yada, S. Ebata, T. Hiyama, J. Am. Chem. Soc , 2428–2429

7. Postulated Mechanism with Lewis Acids
This graph was taken from a recent review on named cross-coupling reactions and illustrates the growth in the number of publications associated with these reactions over the past 30 years.
In all of the publications published since the early nineties, one reaction that caught our eye was the Sonogashira cross-coupling, which has become the third most widely used named cross-coupling in diverse field of applications.
Steric repulsion leads the regioselectivity
Y. Nakao, A. Yada, S. Ebata, T. Hiyama, J. Am. Chem. Soc , 2428–2429

8. Importance of Bulky Ligands
𝜋-acceptor character of the ligand increases the stability of the Ni(0) complexes
Steric factor of ligands L are defined by Tolman cone angle :
Complex with small ligands ( θ= 109°) = do not dissociate
Chelate effect of bidentate ligands contributes to the complex stability
This graph was taken from a recent review on named cross-coupling reactions and illustrates the growth in the number of publications associated with these reactions over the past 30 years.
In all of the publications published since the early nineties, one reaction that caught our eye was the Sonogashira cross-coupling, which has become the third most widely used named cross-coupling in diverse field of applications.
C. A. Tolman, J. Am. Chem. Soc. 1970, 92, 2953
W. Goertz, P. C. J. Kamer, P. W. N. M. van Leeuwen, D. Vogt, Chem. Eur. J. 2001, 7, 1614.

9. Importance of Bulky Ligands
Cat.
% Nitrile
% 3PN
Turnover 1 61 52
1430 2 79 69 35
This graph was taken from a recent review on named cross-coupling reactions and illustrates the growth in the number of publications associated with these reactions over the past 30 years.
In all of the publications published since the early nineties, one reaction that caught our eye was the Sonogashira cross-coupling, which has become the third most widely used named cross-coupling in diverse field of applications.
Bulky bidentate ligands are more active and efficient
M. J. Baker, K. N. Harrison, A. G. Orpen, P. G. Pringle, G. Shaw, J. Chem. Soc. Chem. Commun. 1991, 803
L. Bini, C. Müller, D. Vogt, ChemCatChem 2010; 2, 590–608

10. Hydrogen Cyanide Colorless liquid, very volatile
Boiling point is 26 °C
Explosive in air from a concentration of ppm (5,6%)
This graph was taken from a recent review on named cross-coupling reactions and illustrates the growth in the number of publications associated with these reactions over the past 30 years.
In all of the publications published since the early nineties, one reaction that caught our eye was the Sonogashira cross-coupling, which has become the third most widely used named cross-coupling in diverse field of applications.
Inhalation of large amounts of cyanide causes immediate unconsciousness, convulsions, and death from respiratory arrest within 1–15 min.
G. Romeder, Hydrogen Cyanide. e-EROS Encyclopedia of Reagents for Organic Synthesis 2001

11. Xianjie Fang, Peng Yu and Bill Morandi. Science 2016, 351, 832-836
This Paper
Catalytic Transfer Hydrocyanation (forward reaction)
Catalytic Retro-Hydrocyanation (reverse reaction)
This graph was taken from a recent review on named cross-coupling reactions and illustrates the growth in the number of publications associated with these reactions over the past 30 years.
In all of the publications published since the early nineties, one reaction that caught our eye was the Sonogashira cross-coupling, which has become the third most widely used named cross-coupling in diverse field of applications.
Xianjie Fang, Peng Yu and Bill Morandi. Science 2016, 351,

12. Xianjie Fang, Peng Yu and Bill Morandi. Science 2016, 351, 832-836.
This Paper
Remaining challenges
Overcome the toxicity involved with the use of HCN
Accessibility of forward and reverse hydrocyanation
Shift the equilibrium of the reaction selectively
Strategy
This graph was taken from a recent review on named cross-coupling reactions and illustrates the growth in the number of publications associated with these reactions over the past 30 years.
In all of the publications published since the early nineties, one reaction that caught our eye was the Sonogashira cross-coupling, which has become the third most widely used named cross-coupling in diverse field of applications.
HCN-free Ni-catalyzed reaction
Use of Ni(0) : very active species in the oxidative addition of polar bonds
Use of a Lewis acid as co-catalyst
Xianjie Fang, Peng Yu and Bill Morandi. Science 2016, 351,

13. Xianjie Fang, Peng Yu and Bill Morandi. Science 2016, 351, 832-836.
Proposed Mechanism
This graph was taken from a recent review on named cross-coupling reactions and illustrates the growth in the number of publications associated with these reactions over the past 30 years.
In all of the publications published since the early nineties, one reaction that caught our eye was the Sonogashira cross-coupling, which has become the third most widely used named cross-coupling in diverse field of applications.
Xianjie Fang, Peng Yu and Bill Morandi. Science 2016, 351,

14. Thermodynamic Challenges
Studies of driving force of hydrocyanation
This graph was taken from a recent review on named cross-coupling reactions and illustrates the growth in the number of publications associated with these reactions over the past 30 years.
In all of the publications published since the early nineties, one reaction that caught our eye was the Sonogashira cross-coupling, which has become the third most widely used named cross-coupling in diverse field of applications.
Formation of gaseous disubstituted alkene
Studies of driving force of retro-hydrocyanation

15. Scope of Hydrocyanation
Aromatic compounds:
This graph was taken from a recent review on named cross-coupling reactions and illustrates the growth in the number of publications associated with these reactions over the past 30 years.
In all of the publications published since the early nineties, one reaction that caught our eye was the Sonogashira cross-coupling, which has become the third most widely used named cross-coupling in diverse field of applications.
Styrene derivatives give generally good yields of linear (Anti-Markovnikov) products
Xianjie Fang, Peng Yu and Bill Morandi. Science 2016, 351,

16. Scope of Hydrocyanation
Aliphatic compounds:
Compatible with a range of functional groups : F, Cl, ether, ester, ketone, silyl, OBn
Heterocyclic compounds:
This graph was taken from a recent review on named cross-coupling reactions and illustrates the growth in the number of publications associated with these reactions over the past 30 years.
In all of the publications published since the early nineties, one reaction that caught our eye was the Sonogashira cross-coupling, which has become the third most widely used named cross-coupling in diverse field of applications.
Xianjie Fang, Peng Yu and Bill Morandi. Science 2016, 351,

17. End of the scope and limitations
Drug precursor and natural compounds:
Limitations of the reactions:
This graph was taken from a recent review on named cross-coupling reactions and illustrates the growth in the number of publications associated with these reactions over the past 30 years.
In all of the publications published since the early nineties, one reaction that caught our eye was the Sonogashira cross-coupling, which has become the third most widely used named cross-coupling in diverse field of applications.
Does not tolerate unprotected alcohols and dienes
Xianjie Fang, Peng Yu and Bill Morandi. Science 2016, 351,

18. Scope of Retro-Hydrocyanation
Styrene synthesis:
This graph was taken from a recent review on named cross-coupling reactions and illustrates the growth in the number of publications associated with these reactions over the past 30 years.
In all of the publications published since the early nineties, one reaction that caught our eye was the Sonogashira cross-coupling, which has become the third most widely used named cross-coupling in diverse field of applications.
Xianjie Fang, Peng Yu and Bill Morandi. Science 2016, 351,

19. Scope of Retro-Hydrocyanation
Aliphatic:
Terpene Derivatives:
This graph was taken from a recent review on named cross-coupling reactions and illustrates the growth in the number of publications associated with these reactions over the past 30 years.
In all of the publications published since the early nineties, one reaction that caught our eye was the Sonogashira cross-coupling, which has become the third most widely used named cross-coupling in diverse field of applications.
Xianjie Fang, Peng Yu and Bill Morandi. Science 2016, 351,

20. Scope of Retro-Hydrocyanation
Construction of aromatic rings from dienes:
This graph was taken from a recent review on named cross-coupling reactions and illustrates the growth in the number of publications associated with these reactions over the past 30 years.
In all of the publications published since the early nineties, one reaction that caught our eye was the Sonogashira cross-coupling, which has become the third most widely used named cross-coupling in diverse field of applications.
Installation of a chiral quaternary vinyl group:
Xianjie Fang, Peng Yu and Bill Morandi. Science 2016, 351,

21. Conclusions
Mechanistic studies confirm the transfer of CN and D between the two substrates
Indicates that it is a syn addition mechanism
Catalytic transfer hydrocyanation with catalytic system of Ni(0)/ Lewis Acid
Catalytic retro hydrocyanation
HCN-free reaction
Method compatible with a large scope
Good regioselectivity
This graph was taken from a recent review on named cross-coupling reactions and illustrates the growth in the number of publications associated with these reactions over the past 30 years.
In all of the publications published since the early nineties, one reaction that caught our eye was the Sonogashira cross-coupling, which has become the third most widely used named cross-coupling in diverse field of applications.
Weaknesses:
Unprotected alcohols and dienes are unreactive under optimized conditions

22. Thank you For Your Attention
This graph was taken from a recent review on named cross-coupling reactions and illustrates the growth in the number of publications associated with these reactions over the past 30 years.
In all of the publications published since the early nineties, one reaction that caught our eye was the Sonogashira cross-coupling, which has become the third most widely used named cross-coupling in diverse field of applications.