Catalytic Enantioselective Mannich-type Reactions of ...ccc.chem.pitt.edu/wipf/Current...
18
Catalytic Enantioselective Mannich-type Reactions of Ketoimines Suto, Y.; Kanai, M.; Shibasaki, M. J. Am. Chem. Soc. ASAP. Zhiyong Wang Wipf Group Current Literature Presentation January 6 th , 2007 Zhiyong Wang @ Wipf Group 1 1/14/2007
Transcript of Catalytic Enantioselective Mannich-type Reactions of ...ccc.chem.pitt.edu/wipf/Current...
Catalytic Enantioselective Mannich-type Reactions ofKetoimines
Suto, Y.; Kanai, M.; Shibasaki, M. J. Am. Chem. Soc. ASAP.
Zhiyong WangWipf Group
Current Literature PresentationJanuary 6th, 2007
Zhiyong Wang @ Wipf Group 1 1/14/2007
β-Amino Acid-Containing Natural Products
Liu, M., Sibi, M. P. Tetrahedron 2002, 58, 7991-8035.
Zhiyong Wang @ Wipf Group 2 1/14/2007
Traditional Stereoselective Approachesto Synthesize β-Amino Acids
Homologation of α-amino acids
Enzymatic resolution of β-amino acids
Curtius rearrangement
Conjugate addition of a nitrogen nucleophile to α,β-unsaturated esters or imides
Hydrogenation
Amino hydroxylation and β-lactam synthesis
Addition of enolates (or equivalents) to imines-indirect Mannich reaction
Liu, M., Sibi, M. P. Tetrahedron 2002, 58, 7991-8035.
Zhiyong Wang @ Wipf Group 3 1/14/2007
Curtius Rearrangement
Sibi, M. P., Deshpande, P, K. J. Chem. Soc., Perkin Trans. 1 2000, 1461-1466.
Zhiyong Wang @ Wipf Group 4 1/14/2007
Zhu, G.; Chen, Z.; Zhang, X. J. Org. Chem. 1999, 64, 6907-6910.
Catalytic Hydrogenation
*(a) NH4OAc, MeOH, rt; (b) Ac2O, py, THF, reflux.
Zhiyong Wang @ Wipf Group 5 1/14/2007
Conjugate Addition
Sibi, M. P. et al. J. Am. Chem. Soc. 1998, 120, 6615.
Zhiyong Wang @ Wipf Group 6 1/14/2007
Hodous, B. L.; Fu, G. C. J. Am. Chem. Soc. 2002, 124, 1578-1579.
From β-Lactam
Zhiyong Wang @ Wipf Group 7 1/14/2007
Asymmetric Addition of Enolates to Imines
Davis, F. A.; Szewczyk, J. M.; Reddy, R. E. J. Org. Chem.1996, 61, 2222–2225.Tang, T. P.; Ellman, J. A. J. Org. Chem. 1999, 64, 12–13.
Zhiyong Wang @ Wipf Group 8 1/14/2007
Hamda, T.; Kobayashi, M. S. J. Am. Chem. Soc. 2004, 126, 7768-7769.
Catalytic Asymmetric Mannich Reaction-Aldimine
Zhiyong Wang @ Wipf Group 9 1/14/2007
Mannich Reaction with Ketoimines - Challenges
Low reactivity of ketoimines
Ketoimine-enamine isomerization
Differentiation of the two substituents on the prochiral carbon
N
R1
R2
R3HN
R1
R2
R3B-
Zhiyong Wang @ Wipf Group 10 1/14/2007
Current Paper: Catalytic Asymmetric MannichReaction with Ketoimines
Suto, Y.; Kanai, M.; Shibasaki, M. J. Am. Chem. Soc. ASAP.
Zhiyong Wang @ Wipf Group 11 1/14/2007
Proposed Reaction Mechanism
Zhiyong Wang @ Wipf Group 12 1/14/2007
Effects of N-Phosphinoyl Moiety
Zhiyong Wang @ Wipf Group 13 1/14/2007
Optimization for Aromatic Ketoimines
Zhiyong Wang @ Wipf Group 14 1/14/2007
Optimization for Aliphatic Ketoimines
Zhiyong Wang @ Wipf Group 15 1/14/2007
Reaction Scope
aCondition A: 3 = 2 equiv, ligand = 6,additive = (EtO)2Si(OAc)2 (1 equiv).Condition B: 2 = 4 equiv, ligand =DuPHOS (7 or 8), additive = (EtO)3SiF (1.2equiv). bIsolated yield. cDetermined bychiral HPLC. D4 equiv of 3 were used.eLigand = 7. fLigand = 8. gAbsoluteconfiguration was determined to be (S).
Zhiyong Wang @ Wipf Group 16 1/14/2007
Conversion to β,β-Disubstituted Amino Acid
Zhiyong Wang @ Wipf Group 17 1/14/2007
Summary
The first catalytic enantioselective Mannich reaction of simple
ketoimines is developed, providing a general way to synthesize
chiral β,β-disubstituted amino acids.
Excellent enantioselectivity is achieved with aromatic ketoimines.
Further ligand optimization is need to improve the enantioselectivity
of aliphatic ketoimines.
Zhiyong Wang @ Wipf Group 18 1/14/2007
![Enantioselective vinylogous Michael addition of γ ... · Enantioselective vinylogous Michael addition of γ-butenolide to 2-iminochromenes Vijay Gupta and Ravi P Singh*[a] Department](https://static.fdocument.org/doc/165x107/5f03db6b7e708231d40b1b41/enantioselective-vinylogous-michael-addition-of-enantioselective-vinylogous.jpg)
