Reporter: Siyu Peng ( 彭思宇 ) Supervisor: Prof. Yong Huang

1. Literature Report Reporter:Siyu Peng( 彭思宇) Supervisor: Prof. Yong Huang

2. Acc. Chem. Res. 2015, 48, 619−627

3. Background: Concept of intermolecular reaction evaluation

4. Background: Comparison of a Traditional Substrate Scope and an Intermolecular Reaction Evaluation

5. Background: Fox: A Rhodium-Catalyzed Cycloaddition Reaction Using an Intermolecular Additive Screen Enthaler: Highlights the Benefits of Evaluating the Stability of an Additive to the Reaction Conditions Stephan: A Preliminary Assessment of Functional Group Tolerance Using Intermolecular Additives J. Am. Chem. Soc. 2009, 131, 1101−1105Catal. Lett. 2011, 141, 833−838Inorg. Chem. 2011, 50, 12338−12348

6. Robustness Screen: General concept of a robustness screen

7. Functional Group Tolerance: Color-coding was used to provide a rapid qualitative assessment red 0−33%; yellow 34−66%; green 67−100%. Selected results from an intermolecular evaluation of additives for a Buchwald−Hartwig amination reaction

8. Functional Group Tolerance: I II III IV V VI The reaction of bifunctional substrates was undertaken to evaluate the screen results

9. Overcoming Reaction Inhibition: Malik Chem. Sci., 2014, 5, 2352–2361 Intermolecular Screen Was Used to Evaluate the Tolerance of Complementary C−H Acetoxylation Protocols to Lewis-Basic Heterocycles

10. Overcoming Reaction Inhibition: Five representative heterocycles from the high-throughput screen were incorporated within substrates that were subjected to Pd(II)-catalyzed allylic C–H acetoxylation. intermolecular screening Validation of the potential predictive qualities of the high-throughput heterocycle screen Chem. Sci., 2014, 5, 2352–2361

11. Overcoming Reaction Inhibition: Strategiesto “block” the basic site Chem. Sci., 2014, 5, 2352–2361

12. Overcoming Reaction Inhibition: Strategiesto “block” the basic site Chem. Sci., 2014, 5, 2352–2361

13. Overcoming Reaction Inhibition: Strategiesto “block” the basic site Chem. Sci., 2014, 5, 2352–2361

14. Stability of Protecting Groups: esp. evaluating protecting group stability for contemporary synthetic methods Evaluating the Stability of up to 12 Different Protecting Groups in a Single Experiment Has Been Demonstrated

15. Stability of Functional Groups: esp. evaluating protecting group stability for contemporary synthetic methods Peters and Fu Light Induced Arylations of Heteroatoms Have Been Evaluated Using an Intermolecular Additive Screen J. Am. Chem. Soc. 2013, 135, 13107–13112 Chem. Sci. 2014, 5, 2831–2835

16. Stability of Functional Groups: esp. evaluating protecting group stability for contemporary synthetic methods Further experiments would be required to identify the disruptive functionality. A Number of Bifunctional Additives Were Screened in the Evaluation of a Copper-Catalyzed Arylation of Sodium Trifluoromethanesulfinate J. Org. Chem.2013, 78, 12194–12201

17. Stability of Functional Groups: esp. evaluating protecting group stability for contemporary synthetic methods Yoshida Additional experiments may be required to identify inhibitory functional groups Evaluation of the Tolerance of Several Additives in a Single Experiment J. Am. Chem. Soc. 2014, 136, 4496–4499

18. Stability of Functional Groups: 1st application of “robustness screen” to organocatalytic and enantioselective reaction Mukherjee Chem. Sci., 2014, 5, 1627–1633

19. Inspiration about the mechanism: A comparison of the influence of basic and acid additives on the functional group tolerance of RhCp*-catalyzed ortho-bromination of benzamides Tetrahedron2013, 69, 7817–7825

20. Summary: Application of Intermolecular screening The value can be derived from both qualitative data and negative results

21. Summary: Application of Intermolecular screening • A defined set of functional groups to test the validation of intermolecular reaction screening; • To prevention from “preselection” of additives that are likely to be tolerated

22. THANK YOU!!!