Rhodium-Catalyzed Chemo- and Regioselective Decarboxylative Addition of β-Ketoacids to Allenes: Efficient Construction of Tertiary and Quaternary Carbons Centers
By : Antoine Caron
Literature meeting February 19 th 2014
Li C.; Breit B. J.Am.Chem.Soc. 2014, 136, 862−865
Prof. Bernhard Breit
•Ph.D. at University of Kaiserslautern in 1993•Post-doctoral studies with Trost at Standford•1999-2001 professor of organic chemistry at University of Heidelberg•Since 2001, holds a chair of organic chemistry at the University of Freiburg
His research interests include the developement and exploration of new concepts and methods for organic synthesis and homogeneous catalyst.
Background
Under certain conditions, transition metals produce branched allylic compounds (right)
Liu, W.-B.; Reeves, C. M.; Virgil, S. C.; Stoltz, B. M. J. Am. Chem. Soc. 2013, 135, 10626.Trost M.B. ; Fullerton J. T. J. Am. Chem. Soc.1973, 95, 292–294
Background
Koscher, P.; Lumbroso, A.; Breit, B. J. Am. Chem. Soc. 2011, 133, 20746.
+HO R
O [Rh(COD)Cl2(R-R)-DIOP
Cs2CO3 DCE
O
R
O
Allenes
R3
R4R2
R1R2R1
R3
R4
OHH
H
CH3
H
CH3HO
H
12
3
4H
CH3
HHO
1
2
3 4
S configuration S configuration
12
3
Van' Hoff, J.H.; La chimie dans L'espace, 1885, Bazendijk, RotterdamBurton, B.S.; Pechmann, H.v., Ber, Dtsh, Chem, Ges, 1887, 20, 145-149http://wps.prenhall.com/wps/media/objects/602/616516/Chapter_07.html
Allenes in organic synthesis
Allenes are used in many ways in organic synthesis. These methods are often applied toward making a natural product. They are used as substrates in many well known transformations:
•Diels-Alder reaction
•Pausan-Khand cyclization
O
O
H
Me
Me2AlCl-78°C to -20°C
80%O
Me HO
Min, S.-J.; Jung, M.E., J. Am. Chem. Soc., 2005, 127, 10834-10835
DMPS
H Mo(CO)6DMSO/Toluene
95°C80% E:Z 8:1 O
HDMPS
H
95% ee
R
H
R
H
MLx
MLx
O
HR
H
O
HR
H
Brummond, K.M.; Kerekes, A.D.; Wan, H., J. Org. Chem., 2002, 67, 5156-5163
Shen R.; Chen K.; Deng Q.; Yang J.; Zhang L. Org. Lett. ASAP
Pd-catalyzed tandem coupling isomerization reaction (CIR)
Allenes in natural products
OOH
O
AcOOH
AcOOH OH
O
OO
Fucoxanthin
Peridinin
Carotinoids
CO2HMycomycin
Hoffmann-Röder, A.; Krause, N.; Angew. Chem. Int. Ed.; 2004, 43, 1196-1216
As of 2004, around 150 natural products containing allenes were identified
Synthesis of allene.
•Crabbé Homologation and modification.
•Nucleophilic attack on alkyne
•[2,3] sigmatropic rearrangement
R+ R'CHO
Cu R''2NH R
R'
R'''
LG
R'R'' Nu
R'''
R'
R''
Nu
R'''
OH
R'R''
EDG CO2Me
N2
Rh(II)
R'''
O+
R'R''
H
Rh-EDGMeO2C
R'''
R'
R''
EDG CO2Me
HO
Li Z.; Boyarskikh V.; Hansen H. J.; Autschbach J.; Museav G.D.; Davies L. M. H. J.Am.Chem.Soc. 2012, 134, 15497−1550
Background
S
O
CoA
-O S
O O
CoA
S
O
ACP
-O S
O O
ACP
S
O O
ACP
Acetyl CoA:ACP transacylase
Malonyl CoA:ACP transacylase
3-ketoacyl-ACP synthetase
SH-ACP + CO2
Various fatty acids
R'HO
O
R''R'
O R''
O
[Rh]
R'R''
O
R'
R''
O
[Rh] R'''R''' X
Koscher, P.; Lumbroso, A.; Breit, B. J. Am. Chem. Soc. 2011, 133, 20746.
This paper
R'
R'' +HO R'''
O O x mol% [Rh(cod)Cl]2y mol% ligand
DCE, rt,
O
R'''
R'R''
•The carboxylic acid may initiate the reaction through the formaton of the allyl-Rh intermediate.
•The nucleophilicity of the α carbon would be enhanced.
•CO2 can be eliminated as a traceless directing group.
Optimization of reaction conditions
Scope of regioselective synthesis of tertiary carbon centers
Scope of regioselective synthesis of quaternary carbon centers
Diallylation of acetone-1,3-dicarboxylic acid
Mechanistic studies
2 questions regarding this mechanism :
•Decarboxylation or allylation goes first ?
•Inner-sphere or outer-sphere mechanism ?
Proposed mechanism
O
O O
R
R'
11 =
Conclusions
•They have developed a highly regioselective decarboxylative addition of β-ketoacids to allenesto give γ-δ-unsaturated ketones.
•Quaternary and tertiary carbons centers could be generated in high yield.
•A mild and atom economic method was developed.
•Milder conditions than the enolate allylation under basic conditions.
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