Story Behind the Well-Developed
Chiral Lewis Acid in Asymmetric
Diels-Alder reaction
Reporter:
Zhang Sulei
Supervisors: Prof. Yang Zhen
Prof. Chen Jiahua
Prof. Tang Yefeng
2015-10-05
1
Contents

Background
 Development of Chiral Lewis Acid Catalyst(CLA) Design
in Asymmetric Diels-alder Reaction

Pioneering Work

Tartaric derived CLA

BINOL/VAPOL derived CLA

Aminoalcohol dericed CLA
 Summary and Acknowledge
2
Background
Asymmetric Diels-Alder reaction
1980-now
1970s
Dienophile
with chiral
auxiliary
Lewis
Acid
catalyzed D-A
Chiral Lewis Acid
Catalyzed D-A
……
3
Contents

Background
 Development of Chiral Lewis Acid Catalyst(CLA) Design
in Asymmetric Diels-alder Reaction

Pioneering Work

Tartaric derived CLA

BINOL/VAPOL derived CLA
 Aminoalcohol dericed CLA
 Summary and Acknowledge
4
CLA in Diels-Alder Reaction

Pioneering Work
 Tartaric derived CLA
 BINOL/VAPOL derived CLA
 Aminoalcohol dericed CLA
5
Pioneering Work
First example
1979, Koga
Steric Interaction
1987, Kaufmann
Steric Interaction
1991, Hawkins
two-point-binding
Hashimoto, S.; Komeshima, N.; Koga, K. J. Chem. Soc., Chem. Commun. 1979, 437.
Bir, G.; Kaufmann, D. Tetrahedron Lett. 1987, 28, 777.
Hawkins, J. M.; Loren, S. J. Am. Chem. Soc. 1991, 113, 7794.
Hawkins, J. M.; Loren, S.; Nambu, M. J. Am. Chem. Soc. 1994, 116, 1657.
6
CLA in Diels-Alder Reaction

Pioneering Work
 Tartaric derived CLA
 BINOL/VAPOL derived CLA
 Aminoalcohol dericed CLA
7
L-Tartaric acid derived CAB
Origin
1988, Yamamoto: Toward simple dienophile
Substrate screening
•
•
Generality
Practicability
Brown, H. C.; Stocky, T. P. J. Am. Chem. Soc. 1977, 99, 8218.
Furuta, K.; Miwa, Y.; Iwanaga, K.; Yamamoto, H. J. J. Am. Chem. Soc. 1988, 110, 6254.
Furuta, K.; Shimizu, S.; Miwa, Y.; Yamamoto, H. J. Org. Chem. 1989, 54, 1481.
8
Mechanistic Analysis
1. Determine the activated face (Adol reaction):
Re-face attack, then Si-face shielding.
2. Detailed 1H NMR (NOE) analysis
3. Detailed 1H NMR (NOE) analysis
π stacking
Ishihara, K.; Gao, Q.; Yamamoto, H. J. Am. Chem. Soc. 1993, 115, 10412.
9
CLA in Diels-Alder Reaction

Pioneering Work
 Tartaric derived CLA
 BINOL/VAPOL derived CLA
 Amino-alcohol derived CLA
10
BINOL/VAPOL-CLA
concave
convex
1993, William D. Wulff
Helmchen, G.; Schmiere, R. Angew. Chem., Int. Ed. Engl. 1981, 20, 205.
Bao J.; Wulff, W. D.; Rheingold A. L., J. Am. Chem. Soc. 1993, 115, 3814.
11
BINOL/VAPOL-CLA
1993, William D. Wulff
•
•
Highest induction
Lowest catalyst loading
Bao J.; Wulff, W. D.; Rheingold A. L., J. Am. Chem. Soc. 1993, 115, 3814.
12
BINOL-Helical CLA
1993, Yamamoto
Effective
hydrogen bond
Helix conformation
Designed helical metal catalysts
New model
Moderate activity
Maruoka, K.; Murase, N.; Yamamoto, H. J. Org. Chem. 1993, 58, 2938.
13
BINOL-BLA
1994, Yamamoto
1st chiral BLA catalyst
• Intramolecular hydrogen bonding interaction
• attractive π-π donor-acceptor interaction
Substrate: α-substituted enals
various dienes.
Ishihara, K.; Yamamoto, H. J. Am. Chem. Soc. 1994, 116, 1561.
14
Mechanism analysis
 Adol reaction: Re-face attack, Si-face shielded
 Hydroxyphenyl:
Hydrogen Bonding
π donor-acceptor interaction
 Abs. config.(S): dienophile s-trans
Ishihara, K.; Yamamoto, H. J. Am. Chem. Soc. 1994, 116, 1561.
15
Mechanism analysis
BLA
Monoether-BLA
Opposite face
selectivity
Ishihara, K.; Yamamoto, H. J. Am. Chem. Soc. 1994, 116, 1561.
16
BINOL-BLA
1996, Yamamoto
2nd chiral BLA catalyst-More practical
More Lewis acidic;
Activate some reaction.
Ishihara, K.; Kurihara, H.; Yamamoto, H. J. Am. Chem. Soc. 1996, 118, 3049.
Ishihara, K.; Kurihara, H.; Matsumoto, M.; Yamamoto, H. J. Am. Chem. Soc. 1998, 120, 6920.
17
Results and Interpretation
Substrate
Assembly Model
Ishihara, K.; Kurihara, H.; Yamamoto, H. J. Am. Chem. Soc. 1996, 118, 3049.
Ishihara, K.; Kurihara, H.; Matsumoto, M.; Yamamoto, H. J. Am. Chem. Soc. 1998, 120, 6920.
18
CLA in Diels-Alder Reaction

Pioneering Work
 Tartaric derived CLA
 BINOL/VAPOL derived CLA
 Amino-alcohol derived CLA
19
Tryptophan-derived oxazaborolidine catalyst
Origin
1991, Corey
Broad application
Diene:
Corey, E. J.; Bakshi, R. K.; Shibata, S. J. Am. Chem. SOC. 1987, 109, 5551。
Corey, E. J.; Loh, T-P. J. Am. Chem. Soc. 1991, 113, 8966.
20
Physical and Chemical studies: Experiment support
 Cat. ID.: 1H NMR, 11B NMR, 13C NMR
 1H 2-D NOESY:
Rigid
Geometry as depicted
Corey, E. J.; Loh, T-P.; Roper, T. D.; Azimioara, M. D.; Noe, M. C. J. Am. Chem. Soc. 1992, 114, 8290.
21
Physical and Chemical studies: Experiment support
210K
> 250K
1. Charge Transfer
2. Indole cis Dienophile
Corey, E. J.; Loh, T-P.; Roper, T. D.; Azimioara, M. D.; Noe, M. C. J. Am. Chem. Soc. 1992, 114, 8290.
22
Physical and Chemical studies: Experiment support
 Both the indole and N-Ts are crucial:
π-donor/acceptor interaction
Fix the position of indole
 Steric repulsion/better overlap: s-cis
Corey, E. J.; Loh, T-P.; Roper, T. D.; Azimioara, M. D.; Noe, M. C. J. Am. Chem. Soc. 1992, 114, 8290.
23
Proline-derived oxazaborolidine catalyst
Origin
1991, Mukaiyama
The HBr salt : crucial for high enantioselectivity
Soai, K.; Ookawa, A.; Kaba, T.; Ogawa, K. J. Am. Chem. Soc. 1987, 109, 7111.
Kobayashi, S.; Murakami, M.; Harada, T.; Mukaiyama, T. Chem. Lett. 1991,1341.
24
Cationic oxazaborinane catalyst
1996, Corey
LA: Cationic oxazaborinane >neutral
3,5-dimethylbenzyl on N is important.
Hayashi, Y.; Rohde, J. J.; Corey, E. J. J. Am. Chem. Soc. 1996, 118, 5502.
25
Cationic oxazaborinane catalyst
N-CH2Ar:
block one face of dienophile;
Limits the rotation of dienophile & N-CH2Ar
Formyl C-H---O: weak hydrogen bond
Supported by X-ray crystal structures
Corey, E. J.; Rohde, J. J.; Fischer, A.; Azimioara, M. D. Tetrahedron Lett. 1997, 38, 33.
Corey, E. J.; Rohde, J. J.; Tetrahedron Lett. 1997, 38, 37.
Corey, E. J.; Barnes-Seeman, D.; Lee, T. W. Tetrahedron Lett. 1997, 38, 1699.
26
Proline derived cationic oxazaborolidine catalyst
2002, Corey
A very strong protic acid is used to create a very strong lewis acid.
Catalyst Screening:
Corey, E. J.; Shibata T.; Lee T. W. J. Am. Chem. Soc. 2002, 124, 3808.
Corey, E. J. Angew. Chem. Int. Ed. 2009, 48, 2100.
27
Proline derived cationic oxazaborolidine catalyst
Substrate expanding:
Ligand can be recovered for use (> 95%) after workup.
Corey, E. J. Angew. Chem. Int. Ed. 2009, 48, 2100.
28
Proline derived cationic oxazaborolidine catalyst
Transition state assembly and Interpretation
Formyl CH----O interaction
α CH----O interaction
Corey, E. J. Angew. Chem. Int. Ed. 2009, 48, 2100.
29
Summary
Design of Chiral Lewis Acid
 Intermolecular (“Strong”):
Covalent bond (Lewis Acid & Base)
 Intermolecular (“weak”):
Dipole-induced dipole interaction;
Hydrogen bonding interaction;
π-donor/acceptor interaction;
π-stacking interaction.
30
Summary
Design of Chiral Lewis Acid
 Intermolecular (“Strong”):
Covalent bond (Lewis Acid & Base)
 Intermolecular (“weak”):
Dipole-induced dipole interaction;
Hydrogen bonding interaction;
π-donor/acceptor interaction;
π-stacking interaction.
31
Acknowledge
 Prof. Yang, Prof. Chen, Prof Tang
 Mr. Youlin, Mr. Luyong, Mr. LiYuanhe
 Mr. LiangXingting, Mr. Niuzhe
 All mates in B630
 All members in our lab
 Everyone here
Thanks
32