Transition-metal Catalyzed Intramolecular Amination of the

C(sp3)-H Bonds

Reporter: Ying Chen March 2nd, 2014

http://www.chem.psu.edu/directory/guc11

Research Interests: Analytical Fluorescence Imaging of Protein Trafficking in Live Cells Organic Synthetic and Biological Studies of Carbohydrates and Peptides Biological Chemical Biology of Carbohydrates and Peptides Materials and Nanoscience Nano Material for Molecular Imaging in Live Cells

2

http://www.chem.psu.edu/directory/specialties/analyticalhttp://www.chem.psu.edu/directory/specialties/organichttp://www.chem.psu.edu/directory/specialties/biologicalhttp://www.chem.psu.edu/directory/specialties/biologicalhttp://www.chem.psu.edu/directory/specialties/materials-and-nanosciencehttp://www.chem.psu.edu/directory/specialties/materials-and-nanoscience

Syntheses of Azetidines via Intramolecular Amination of C(sp3)-H at ɤ Position

J. AM. CHEM. SOC. 2005,127, 13154-13155 3

4

Syntheses of Pyrrolidines via Intramolecular Amination of C(sp3)-H at δ Position

5

Syntheses of Indolines via Intramolecular Amination of C(sp2)-H at δ Position

Substrate Deuteration Studies

Reactivities of different C(sp3)−H bonds: Primary γ-C−H > primary δ-C−H > secondary and tertiary γ-C−H bonds 6

Use of a Readily Removable Auxiliary Group for the Synthesis of Pyrrolidones by the Palladium-Catalyzed Intramolecular Amination of Unactivatedg C(sp3)-H Bonds

Angew. Chem. Int. Ed.2013, 52, 1 – 6

Gang He, Shu-Yu Zhang, William A. Nack, Qiong Li, and Gong Chen

7

B. V. S. Reddy, L. R. Reddy, E. J. Corey, Org. Lett.2006, 8, 3391.

N-Phth

AQ

Original Proposal

8

Intramolecular amination of ɤ C(sp3)-H bonds via a six-membered palladacycle

9

Both AQ- and PM- directed intramolecular ɤ-C(sp3)-H amination reactions proceeded well if the kinetic inertness of the initial ɤ-C-H palladation could be overcome effectively. 10

Application

Removal of the auxiliary group

11

第2弾

Angew. Chem. Int. Ed.2014, 53,1–5

12

The first copper-catalyzed intramolecular C (sp3)-H [and C (sp2)-H] amidation using bidentate DG

The reaction proceeded at a terminal methyl group, as well as at the internal benzylic position of an alkyl chain.

C(sp3)-H C(sp2)-H

terminal methyl benzylic position

13

The proposed mechanism

14

Deuterium-labeling experiment

The kinetic isotope effect value was 2.6, thus supporting our notion that C-H bond activation is the rate-determining step.

C (sp2)-H selective reaction pathway

15