Upload
dragnerkar
View
2.191
Download
1
Tags:
Embed Size (px)
DESCRIPTION
Useful content for postgraduates students of Pharmaceutical and Medicinal Chemistry and undergraduate students of Organic Chemistry
Citation preview
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