Sharpless epoxidation & suzuki coupling

SHARPLESS EPOXIDATION & SUZUKI COUPLING

Dr. Amit G.Nerkar,Associate Professor,

Post Graduate Dept. of Pharmaceutical Chemistry,

Smt.Kashibai Navale College of Pharmacy, Kondhwa (Bk), Pune-48

SUZUKI COUPLING

REACTION :

MECHANISM :

L

L

L

L

R2

L

L

X

Pd"R2

L

L

O'Bu

Pd"R2

R1

L

L

R2_R1

R2

R

O'Bu

R

B-

R

R

O'BuBuO B-

R2_X

OXIDATIVE ADDITION

BR

R'

R

TRANSMETALATIONMX

MO'Bu

REDUCTIVE ELIMINATION

Pd

Pd

THECATALYTIC

CYCLE

MO'Bu

MECHANISM :Pd0

R2_Pd"_XR2_Pd"_R1

R2_Pd"_OtBu

R1_R2R2_X

NaOtBu

NaX

B OtBuR1

Y

Y Na+

NaOtBu

B

Y

Y

R1

B OtBuBuOt

Y

Y Na+

1

2

3

4

6

7

5

9

8

SUZUKICOUPLING

OTHER CATALYST USED :

• NICKEL ON CHARCOAL• RHODIUM CATALYST• SILVER OXIDE MEDIATED

PALLADIUM CATALYST• TRI-TERT BUTYL PHOSPHINE

ADVANTAGES :

• Mild reaction conditions• Availability of boronic acids• Boronic acids –less toxic• stereo selectivity• Removal of byproducts

DISADVANTAGES :

• Reaction of aryl halides• Self coupling products• Formation of phosphine bound

aryls• Racemisation of optically active

compound• Aldol condensation

APPLICATION :

+

B(OH)2

Aryl halide Phenyl boronic acid

R

R

Cl

Na2CO3

Pd

60 min.1350cM.W.

PRODUCT71%YIELD

• Recent Literature•

Alkyl-Alkyl Suzuki Cross-Couplings of Unactivated Secondary Alkyl Halides at Room TemperatureB. Saito, G. C. Fu, J. Am. Chem. Soc., 2007, 129, 9602-9603.

•Boronic Acids: New Coupling Partners in Room-Temperature Suzuki Reactions of Alkyl Bromides. Crystallographic Characterization of an Oxidative-Addition Adduct Generated under Remarkably Mild ConditionsJ. H. Kirchhoff, M. R. Netherton, I. D. Hill, G. C. Fu, J. Am. Chem. Soc., 2002, 124, 13662-13663.

•Tetraphosphine/palladium catalysed Suzuki cross-coupling reactions of aryl halides with alkylboronic acidsI. Kondolff, H. Doucet, M. Santelli, Tetrahedron, 2004, 60, 3813-3818.

•Pd(N,N-Dimethyl β-alaninate)2 as a High-Turnover-Number, Phosphine-Free Catalyst for the Suzuki ReactionX. Cui, T. Qin, J.-R. Wang, L. Liu, Q.-X. Guo, Synthesis, 2007, 393-399.

•Guanidine/Pd(OAc)2-Catalyzed Room Temperature Suzuki Cross-Coupling Reaction in Aqueous Media under Aerobic ConditionsS. Li, Y. Lin, J. Cao, S. Zhang, J. Org. Chem., 2007, 72, 4067-4072.

•Biphenylene-Substituted Ruthenocenylphosphine for Suzuki-Miyaura Coupling of Aryl ChloridesT. Hoshi, T. Nakazawa, I. Saitoh, Y. Mori, T. Suzuki, J.-i. Sakai, H. Hagiwara, S. Akai, Org. Lett., 2008, 10, 2063-2066

IMPROVEMENTS :

• Development of catalyst facilitating coupling of unreactive aryl halides

• Use of aryl, alkyl trifluroboronates in place of boronic acids