Literature Seminar
2010.5.26 Yao Du (D2)1Construction of C-C or C-N Bond via C-H Activation~Chemistry of Yong-Qiang Tu~Contents:

1. Yong-Qiang Tu's Profile
2. Latest Work of Professor Tu
2-1. C-H Activation by Cu
2-2. C-H Activation by Rh (Pd)2-3. C-H Activation by Fe

1. Yong-Qiang Tu's Profile
Education & Work experience:
1958

Born in Guizhou Province, China

1978-1982

B.S. Organic Chemistry
Lanzhou University, China

1982-1985

M.S. Organic Chemistry
Lanzhou University, China

1985-1989

Ph.D. Organic Chemistry
Lanzhou University, China

1993-1995Post-Doctoral Fellow
Queensland University, Australia; Advisor: Prof . W. Kitching
Visiting Professor
Bielef eld University, Germany

1995-Professor of Chemistry
Lanzhou University, China

2001-

Director of State Key Lab of Applied Organic Chemistry
Lanzhou University, China

Research Interest:
1.
Synthetic studies of the biologically active marine natural products
2.
Tandem reaction and its application to total synthesis of bioactive alkaloids
3.
Studies on the construction of C-C or C-N bond via the C-H activation (since 2005)
Awards & Honors:
1.
1992 Chinese Chemical Society Prize f or Young Chemist
2.
1993 2nd Prize of Progress in Science and Technology, by the Education Council of China
3.
2000 Outstanding Youth Scholarship Award, by Qiu Shi Science & Technology Foundation,Hong Kong, P. R. China
4.
2002 1st Prize of Progress in Science and Technology, by the Gansu Province
5.
2005 Lilly Scientific Excellence Award in China, by Eli Lilly & Company
6.
2006 1st Natural Science Prize, by Gansu Province
7.
2009 Member of the Chinese Academy of Sciences2. Latest Work of Professor Tu
2-1. C-H Activation by Cu
Microwave-Promoted Three-Component Coupling of Aldehyde, Alkyne, and Amine
via C-H Activation Catalyzed by Copper in Water
Lei Shi, Yong-Qiang Tu*, Min Wang, Fu-Min Zhang, and Chun-An Fan,Org. Lett., 2004, 6, 1001.
Advantages:(i) Microwave (MW)-promoted, in water---Green chemistry!
(ii) It required only the cheaper CuI as catalyst without Au, Ag, or other additives.
(iii) It was applicable to a broader substrate scope(both aromatic and aliphatic aldehydes and secondary amines).
(iv) It proceeded faster and gave good to high yield, and its experimental process was simple and easy.

Details of the process:-In 2003, the team developed a MW-promoted coupling reaction of aromatic halides and amines.
(Tu et al. Org. Lett. 2003, 5, 3515.)-Although several methods f or construction of such units in water were reported, some required
expensive Au or Ag as catalyst, while some were limited to only one kind of aldehyde or the aromatic
aldehyde and primary amine.
-For the aldehyde substrate scope, morpholine and phenylacetylene were used as model substrates(entries 1-13).
-For the amine substrate scope, benzaldehyde and phenylacetylene were used as model substrates(entries 14-22).
-For the alkyne substrate scope, benzaldehyde and morpholine were used as model substrates(entries 23-25).
-They f ound MW irradation was necessary, because without MW, the coupling under heating required
more than 5 days.
Preparation of CuI

2

ProcedureAr, sealed

3

microwave irradation,
1 min

CuI (15 mol %)aldehyde (1 eq)
amine (1.3 eq)
alkyne (1.6 eq)
H2O (0.67 M)

cooled to rt......
cooled to lower temp. repeat irradating
and coolingquenched by Et2O, NH4Cl

in ice water, 5 min

2-2. C-H Activation by Rh (Pd)
2-2-1. A Reaction for sp3-sp3 C-C Bond Formation via Cooperation ofLewis Acid-Promoted/Rh-Catalyzed C-H Bond Activation
Lei Shi, Yong-Qiang Tu*, Min Wang, Fu-Min Zhang, Chun-An Fan, Yu-Ming Zhao, and Wu-Jiong Xia
J . Am. Chem. Soc. 2005, 127, 10836-10837.
They were expired by the landmark report of the ruthenium
catalyzed hydroarylation of alkenes by Murai and coworkers.
Murai, S. et al. Nature 1993, 366, 529-531.

4

Procedureolef ine (1 eq)
alcohol (10 eq)
RhCl(PPh3)3 ( 2 mol %)BuBr (0.5 eq)
BF3 OEt2 (2.5 eq)
toluenedropwise
55 oC, 6 hAr

Mechanism supporting experiments:
RhCl3/BF3OEt2/toluene could make the reaction occur.
---> The formation of Rh(III) intermediates.
Addition of PPh3 (0.05 equiv) could prevent the reaction.
--->The presence of PPh3 could prohibit the ligand
dissociation and exchange.
The crossover experiment was performed using styrene and a 1:1
mixture of deuterated and undeuterated alcohols (Scheme 2).
--->A possible radical reaction mechanism was involved, which
would lead to a statistical distribution of the labels in theproducts.
The addition of radical scavenger (1,4-benzoquinone, TEMPO, andquenched by Et2O, NaHCO3

55 oC, efficiently stirredg ( ,q,,FeCl3) in the system of ethanol with styrene prohibited the reaction.
--->The presence of a radical reaction mechanism was furtherconfirmed.
4-phenylbutan-2-one could not have been observed in the crosscoupling of ethanol and styrene (entry 1, Table 1).
--->The reaction could not undergo the reaction mechanism asreported in the hydroacylation of olefins with alcohols:
first hydrogen transfer from alcohol to f orm aldehyde.
When acetaldehyde was used in place of the primary alcohol,
the reaction could not proceed under the same condition.
--->The f irst hydrogen transfer f rom alcohol to f orm aldehyde
was not the proper mechanism.

2-2-2. Palladium-Catalyzed/Lewis Acid-Promoted Alkene Dimerization
and Cross-Coupling with Alcohols via C-H Bond Activation
Yi-Jun Jiang, Yong-Qiang Tu*, En Zhang, Shu-Yu Zhang, Ke Cao, and Lei Shi,Adv. Synth. Catal. 2008, 350, 552.

A supporting experiment using the isolated alkene 5562-2-3. Cross-Coupling Reaction between Alcohols through sp3 C-H Activation
Catalyzed by a Ruthenium/Lewis Acid System
Shu-Yu Zhang, Yong-Qiang Tu*, Chun-An Fan, Yi-Jun Jiang, Lei Shi, Ke Cao, and En Zhang,
Chem. Eur. J . 2008, 14, 10201.
Equation 1.

7

Transfer Hydrogenative Coupling
R1
D

R2OH

D(H)

DR1

O

D(H)

DO

ML
DD(H)

R2

R3

D

R1
R2

R1OH

R3

R2

R3

ML
R3

Oxidation-Hydroacylation-Reduction
R2

R3

R2

oxidation

reduction

DDDDR
D(H)

R1 OO

R1R2R1 OHOH

R1R2R3Dhydroacylation

ODR1 M
R2R3R1ODM
R2R3R3

82-2-4. A Direct C-C Cross-Coupling of Alcohols at the b-Position with Aldehydes under
Co-Promotion of Tris(triphenylphosphine)-rhodium Chloride/Boron Trifuoride Etherate
Shu-Yu Zhang, Yong-Qiang Tu*, Chun-An Fan, Yi-Jun Jiang, Lei Shi, and Ke Cao,Adv. Synth. Catal. 2008, 350, 2189.

9Prins-type cyclization

2-3. C-H Activation by Fe
Iron-Catalyzed C(sp3)-C(sp3) Bond Formation through C(sp3)-H Functionalization:
A Cross-Coupling Reaction of Alcohols with Alkenes
Shu-Yu Zhang, Yong-Qiang Tu*, Chun-An Fan, Fu-Min Zhang, and Lei ShiAngew. Chem. Int. Ed. 2009, 48, 8761.

-Several ligands such as TMEDA, NEt3 and DACH, as well assome additives such as LiCl, KCl, CuI, CuCl2, CuBr2, Cu(OAc)2,CuO, Cu2O, NiCl2 6H2O, and CoCl2 6H2O were tested,
but no significant improvement of the yield was observed.
-The above non-iron additives alone, in the absence of FeCl3, did
not promote this cross-coupling reaction.

10

PhO
Ph
Scheme 2'+H Ph

standardreaction
conditions

no reaction

no C1- or C3-deuterium products