hydrogen bond catalysis - david a. evansevans.rc.fas.harvard.edu/pdf/smnr_2009_fuller_peter.pdftypes...
Post on 18-Mar-2020
42 Views
Preview:
TRANSCRIPT
Catalysis
OO O+
AlCl3, CH2Cl2
rt, 1.5 min
quantitative
Yates and Eaton (1960)
without AlCl3 ~ 95% conversion after 4800 h (200 d)
Yates, P.; Eaton, P. J. Am. Chem. Soc. 1960, 82, 4436-4437.
OO
O
Prompted an era of intensive research activity on metal-centered Lewis acid catalysis that continues today.
Catalysis
OO O+
AlCl3, CH2Cl2
rt, 1.5 min
quantitative
Yates and Eaton (1960)
without AlCl3 ~ 95% conversion after 4800 h (200 d)
Yates, P.; Eaton, P. J. Am. Chem. Soc. 1960, 82, 4436-4437.
OO
O
Prompted an era of intensive research activity on metal-centered Lewis acid catalysis that continues today.
Wassermann (1942)
O
O
+Phenol or H+ H+ = CH3CO2H, ClCH2CO2H
BrCH2CO2H, Cl3CCO2H
O
O
H
H
> 90%
Wassermann, A. J. Chem. Soc. 1942, 618-621.
Catalysis
OO O+
AlCl3, CH2Cl2
rt, 1.5 min
quantitative
Yates and Eaton (1960)
without AlCl3 ~ 95% conversion after 4800 h (200 d)
Yates, P.; Eaton, P. J. Am. Chem. Soc. 1960, 82, 4436-4437.
OO
O
Prompted an era of intensive research activity on metal-centered Lewis acid catalysis that continues today.
Wassermann (1942)
O
O
+Phenol or H+ H+ = CH3CO2H, ClCH2CO2H
BrCH2CO2H, Cl3CCO2H
O
O
H
H
> 90%
Wassermann, A. J. Chem. Soc. 1942, 618-621.
"Why did the report of Yates and Eaton, and not that of Wassermann, capture the imagination of
the early practitioners of asymmetric catalysis, leading to the current situation where chiral Lewis
acid catalysis, rather than chiral Brønsted acid catalysis, is the dominant strategy for promotion of
enantioselective additions to electrophiles?" Taylor, M. S. and Jacobsen, E. N.
Taylor, M. S.; Jacobsen, E. N. Angew. Chem. Int. Ed. 2006, 45, 1520-1543.
Lewis acid vs. Brønsted acid catalysis
R1
Y
R2
[M]Ln
X
Lewis acid catalysis
Pros:- Highly tunable structures (element, ligand framework, counterion)- Low catalyst loadings- Strong Lewis acid/Lewis base interactions
Cons:- Often generated in situ and employed directly- Often water/moisture sensitive
Pros:
- Moderately tunable (structure of A and pKa)
- Exists as the active catalyst (i.e. no in situ preparation required)
- Water/moisture stable/tolerant
- Potentially recoverable/reuseable
Cons:
- Higher catalyst loadings
Selected references:1. "Metal-Free Organocatalysis Through Explicit Hydrogen Bonding Interactions." Schreiner, P. R. Chem. Soc. Rev. 2003, 32, 289-296.2. "Activation of Carbonyl Compounds by Double Hydrogen Bonding: An Emerging Tool in Asymmetric Catalysis." Pihko, P. M. Angew. Chem. Int. Ed. 2004, 43, 2062-2064.3. "Recent Progress in Chiral Brønsted Acid Catalysis." Akiyama, T.; Itoh, J.; Fuchibe, K. Adv. Synth. Catal. 2006, 348, 999-1010.4. "Asymmetric Catalysis by Chiral Hydrogen-Bond Donors." Taylor, M. S.; Jacobsen, E. N. Angew. Chem. Int. Ed. 2006, 45, 1520-1543.5. "History and Perspective of Chiral Organic Catalysts," in New Frontiers in Asymmetric Catalysis. Lelais, G.; MacMillan, D. W. C. New Jersey: John Wiley & Sons, Inc. 2007.6. "Small-Molecule H-Bond Donors in Asymmetric Catalysis." Doyle, A. G.; Jacobsen, E. N. Chem. Rev. 2007, 107, 5713-5743.7. "Stronger Brønsted Acids." Akiyama, T. Chem. Rev. 2007, 107, 5744-5758.8. "Brønsted Acids," in Acid Catalysis in Modern Organic Synthesis, Vol, 1. Yamamoto, H.; Nakashima, D. Weinheim: Wiley-VCH. 2008.9. "(Thio)urea Organocatalysis-What can be learnt from anion recognition?" Zhang, A.; Schreiner, P. R. Chem. Soc. Rev. 2009, 38, 1187-1198.
R1
Y
R2
Hydrogen bond catalysis
H A
Types of hydrogen bond catalysis
R1
Y
R2
Hydrogen bond catalysis
H A
Specific Acid Catalysis: Reversible protonation of the electrophile in a pre-equilibriumstep prior to nucleophilic attack.
General acid catalysis or Hydrogen bond catalysis: Acid activation of an electrophile,but not full proton transfer.
R1
Y
R2
H A!+!"
type of bonding mostly covalent mostly electrostatic electrostatic
length of H-bond [A] 1.2-1.5 1.5-2.2 2.2-3.2
bond angles [°] 175-180 130-180 90-150
bond energy [kcal/mol-1] 14-40 4-15 <4
example intramolecular NH-H NH-O C in peptide CH donors to N, O
bond in conjugate acid H+ sponge helices and sheets acceptors
Strong Moderate Weak
Properties of hydrogen bonds
interactions we will be discussing today
Connon, S. J. Chem. Eur. J. 2006, 12, 5418-5427.Taylor, M. S.; Jacobsen, E. N. Angew. Chem. Int. Ed. 2006, 45, 1520-1543.
Doyle, A. G.; Jacobsen, E. N. Chem. Rev. 2007, 107, 5713-5743.Akiyama, T. Chem. Rev. 2007, 107, 5744-5758.
R1
Y
R2
Y = O, NR
+ H-A Cat.Nu
R1 R2
HY Nu
R1
YH+
R2
R1
Y
R2
Y = O, NR
+ H-A Cat.Nu
R1 R2
HY Nu
A-
What makes a good hydrogen bond catalyst?
R1
Y
R2
H A!+!"
Desired interaction
1) Modest acidity (pKa ~ 30 - 5)
2) Low dimerization potential
3) Induce directionality within the substrate
What makes a good hydrogen bond catalyst?
R1
Y
R2
H A!+!"
Desired interaction
1) Modest acidity (pKa ~ 30 - 5)
2) Low dimerization potential
3) Induce directionality within the substrate
Some of the more priviledged H-bond catalyst structural motifs:
N N
O
R
N N
S
R
R
R
HH
HH
urea
thiourea
- pKa ~ 26
- high propencity to dimerize
due to oxygens ability to
accept an H-bond, i.e. low
cat. TOF N N
O
R R
HH
N N
O
R R
HH
- pKa ~ 20
- low propencity to dimerize,
i.e. increase in TOF for a wide
range of catalysts
What makes a good hydrogen bond catalyst?
R1
Y
R2
H A!+!"
Desired interaction
1) Modest acidity (pKa ~ 30 - 5)
2) Low dimerization potential
3) Induce directionality within the substrate
Some of the more priviledged H-bond catalyst structural motifs:
N N
O
R
N N
S
R
R
R
HH
HH
urea
thiourea
- pKa ~ 26
- high propencity to dimerize
due to oxygens ability to
accept an H-bond, i.e. low
cat. TOF N N
O
R R
HH
N N
O
R R
HH
- pKa ~ 20
- low propencity to dimerize,
i.e. increase in TOF for a wide
range of catalysts
OH
OH
ArAr
Ar Ar
O
O
Me
Me
diol
- pKa ~ 20
- structure enforces a
single H-bond activation
mode (more later)
OH OH - pKa ~ 18
- structure enforces a
double H-bond activation
mode
- One of the earliest H-bond
catalysts investigatedbisphenol
What makes a good hydrogen bond catalyst?
R1
Y
R2
H A!+!"
Desired interaction
1) Modest acidity (pKa ~ 30 - 5)
2) Low dimerization potential
3) Induce directionality within the substrate
Some of the more priviledged H-bond catalyst structural motifs:
N N
O
R
N N
S
R
R
R
HH
HH
urea
thiourea
- pKa ~ 26
- high propencity to dimerize
due to oxygens ability to
accept an H-bond, i.e. low
cat. TOF N N
O
R R
HH
N N
O
R R
HH
- pKa ~ 20
- low propencity to dimerize,
i.e. increase in TOF for a wide
range of catalysts
OH
OH
ArAr
Ar Ar
O
O
Me
Me
diol
- pKa ~ 20
- structure enforces a
single H-bond activation
mode (more later)
OH OH - pKa ~ 18
- structure enforces a
double H-bond activation
mode
- One of the earliest H-bond
catalysts investigatedbisphenol
N
N
OH
OH - pKa ~ 18, 25
- bifunctional capability
- tunable
What makes a good hydrogen bond catalyst?
R1
Y
R2
H A!+!"
Desired interaction
1) Modest acidity (pKa ~ 30 - 5)
2) Low dimerization potential
3) Induce directionality within the substrate
Some of the more priviledged H-bond catalyst structural motifs:
N N
O
R
N N
S
R
R
R
HH
HH
urea
thiourea
- pKa ~ 26
- high propencity to dimerize
due to oxygens ability to
accept an H-bond, i.e. low
cat. TOF N N
O
R R
HH
N N
O
R R
HH
- pKa ~ 20
- low propencity to dimerize,
i.e. increase in TOF for a wide
range of catalysts
OH
OH
ArAr
Ar Ar
O
O
Me
Me
diol
- pKa ~ 20
- structure enforces a
single H-bond activation
mode (more later)
OH OH - pKa ~ 18
- structure enforces a
double H-bond activation
mode
- One of the earliest H-bond
catalysts investigatedbisphenol
N
N
OH
OH - pKa ~ 18, 25
- bifunctional capability
- tunable
N
N
N+ArAr
H H
guanidinium
- pKa ~ 15 (?)
- low propencity to dimerize
- borderline between specific
and/or general acid catalysis
What makes a good hydrogen bond catalyst?
R1
Y
R2
H A!+!"
Desired interaction
1) Modest acidity (pKa ~ 30 - 5)
2) Low dimerization potential
3) Induce directionality within the substrate
Some of the more priviledged H-bond catalyst structural motifs:
N N
O
R
N N
S
R
R
R
HH
HH
urea
thiourea
- pKa ~ 26
- high propencity to dimerize
due to oxygens ability to
accept an H-bond, i.e. low
cat. TOF N N
O
R R
HH
N N
O
R R
HH
- pKa ~ 20
- low propencity to dimerize,
i.e. increase in TOF for a wide
range of catalysts
OH
OH
ArAr
Ar Ar
O
O
Me
Me
diol
- pKa ~ 20
- structure enforces a
single H-bond activation
mode (more later)
OH OH - pKa ~ 18
- structure enforces a
double H-bond activation
mode
- One of the earliest H-bond
catalysts investigatedbisphenol
N
N
OH
OH - pKa ~ 18, 25
- bifunctional capability
- tunable
N
N
N+ArAr
H H
guanidinium
- pKa ~ 15 (?)
- low propencity to dimerize
- borderline between specific
and/or general acid catalysis
Connon, S. J. Chem. Eur. J. 2006, 12, 5418-5427.
Taylor, M. S.; Jacobsen, E. N. Angew. Chem. Int. Ed. 2006, 45, 1520-1543.
Doyle, A. G.; Jacobsen, E. N. Chem. Rev. 2007, 107, 5713-5743.
Akiyama, T. Chem. Rev. 2007, 107, 5744-5758.
Bordwell pKaTable
Ar
Ar
O
O
PO
OH
phosphoric acid
- pKa ~ 1
- largely accepted as a
specific acid catalyst
R1
Y
R2
single hydrogen bonding
H A
The three distinct modes of hydrogen bond catalysis will be discussed:
R1
YH
R2
double hydrogen bonding
H
AA
R1
YH
R2
H
AA chiralscaffold
B
H
X
bifunctional catalysis
Hydrogen bond catalysis
Related topics beyond the scope of this seminar include:
- Hydrogen bonding in biological systems (serine proteases, aldolases)- Enantioselective protonation- Hydrogen bonding phase transfer catalysis- Enamine catalysis (that use H-bonding as a stereochemical control element)
e.g., diols, bisphenols, hydroxy acids e.g., ureas, thioureas, guanidinium and amidinium ions, lactams
e.g., thioureas, cinchona alkaloids,phosphoric acids
ArAr
OHOH
ArAr
O
OH
OH
OH
Ar
Ar
OH
Rawal, Yamamoto
Yamamoto
Schaus
N
O
NH
X
NH
R1
R2
tBu
N
ArJacobsen
X = O, S
N
N
N+ArAr
H H
Corey
Ar
ON
H
NH2+
Göbel
N
O
NH
S
NH
R1
Bn
tBu
NH2
Jacobsen
N
N
R
OH
Wynberg
Ar
Ar
Akiyama
O
O
PO
OH
Catalysis by single hydrogen bond activation
Rawal: H-Bond catalyzed Hetero-Diels-Alder reaction (2000)
NMe2
TBSO
CHO
OMe
+solvent
O
TBSO
NMe2
Ar
dielectric relativeentry solvent constant rate
1 THF 7.6 12 benzene 2.3 1.33 acetonitrile 37.5 3.04 chloroform 4.8 305 tBuOH 10.9 2806 iPrOH 18.3 630
Reaction rate does not correlate with dielectric constant. Thus, the increase in rate could arise from a C-H---O H-bond.
~100%
Catalysis by single hydrogen bond activation
Rawal: H-Bond catalyzed Hetero-Diels-Alder reaction (2000)
NMe2
TBSO
CHO
OMe
+solvent
O
TBSO
NMe2
Ar
dielectric relativeentry solvent constant rate
1 THF 7.6 12 benzene 2.3 1.33 acetonitrile 37.5 3.04 chloroform 4.8 305 tBuOH 10.9 2806 iPrOH 18.3 630
Reaction rate does not correlate with dielectric constant. Thus, the increase in rate could arise from a C-H---O H-bond.
~100%
NMe2
TBSO
+
O
H R
OH
OH
ArAr
Ar Ar
O
O
Me
Me
1 (0.2 equiv)
Toluene, -40 °C, 24 h
1 =
Ar = 1-naphthyl
O
TBSO
NMe2
RAcCl, CH2Cl2
-78 °C, 15 min O
O R
R = aromatic, aliphatic
52 - 97% yield; 92 - 98% ee
Huang, Y.; Rawal, V. H. Org. Lett. 2000, 2, 3321-3325.Huang, Y.; Rawal, V. H. J. Am. Chem. Soc. 2002, 124, 9662-9663.
Huang, Y.; Unni, A. K.; Thadani, A. N.; Rawal, V. H. Nature, 2003, 424, 146.
Rawal: Enantioselective H-Bond catalyzed Hetero-Diels-Alder reaction (2003)
Catalysis by single hydrogen bond activation
Rawal: Enantioselective H-Bond catalyzed all carbon Diels-Alder reaction (2004)
NMe2
TBSO
+
OH
OH
ArAr
Ar Ar
O
O
Me
Me
1 (0.2 equiv)
Toluene, - 80 °C, 48 h
1 =
Ar = 1-naphthyl
TBSO
NMe2
HF/CH3CN
-78 °C to rt, 1 h
O
R = aliphatic
77 - 85% yield; 86 - 92% ee
R
O
H CHOR
RCHO
1) LiAlH4, Et2O- 78 °C to rt, 2 h
2) HF/CH3CN0 °C to rt, 30 min
O
R
OH
77 - 83% yield; 86 - 92% eeWhen R is large (i.e. > H), high enantioselectivity is observed
Catalysis by single hydrogen bond activation
Rawal: Enantioselective H-Bond catalyzed all carbon Diels-Alder reaction (2004)
NMe2
TBSO
+
OH
OH
ArAr
Ar Ar
O
O
Me
Me
1 (0.2 equiv)
Toluene, - 80 °C, 48 h
1 =
Ar = 1-naphthyl
TBSO
NMe2
HF/CH3CN
-78 °C to rt, 1 h
O
R = aliphatic
77 - 85% yield; 86 - 92% ee
R
O
H CHOR
RCHO
1) LiAlH4, Et2O- 78 °C to rt, 2 h
2) HF/CH3CN0 °C to rt, 30 min
O
R
OH
77 - 83% yield; 86 - 92% eeWhen R is large (i.e. > H), high enantioselectivity is observed
Rawal/Yamamoto: H-Bond catalyzed enantioselective Hetero-Diels-Alder reaction (2005)
NMe2
TBSO
+
O
H R 2 (0.2 equiv)
Toluene, -40 °C, 24 hor -80°C, 48 h
2 = Ar = 1-F-3,5-Et2C6H2
O
TBSO
NMe2
AcCl, CH2Cl2
-78 °C, 15 min O
O
R = aromatic, aliphatic
>70% yield; ~95% ee
ArAr
OHOH
ArAr
RR
Thadani, A. N.; Stankovich, A. R.; Rawal, V. H. Proc. Natl. Acad. Sci. USA 2004, 101, 5846-5850.Unni, A. K.; Takenaka, N.; Yamamoto, H.; Rawal, V. H. J. Am. Chem. Soc. 2005, 127, 1336-1337.
Mechanism and stereochemical model
OH
OH
PhPh
Ph Ph
O
O
Me
Me1 =
TADDOL: Over 35 crystal structures of various derivatives of 1 are known (as of 2001).
O OH
OO
Ph
Ph
Ph
H
Ph
HH
Preferred conformations are due to the intramolecular nature of the H-bond that is reinforced by the geminal substitution (Thorpe-Ingold effect).
ArAr
OHOH
ArAr
2 =
Mechanism and stereochemical model
OH
OH
PhPh
Ph Ph
O
O
Me
Me1 =
TADDOL: Over 35 crystal structures of various derivatives of 1 are known (as of 2001).
O OH
OO
Ph
Ph
Ph
H
Ph
HH
Preferred conformations are due to the intramolecular nature of the H-bond that is reinforced by the geminal substitution (Thorpe-Ingold effect).
ArAr
OHOH
ArAr
2 =
Proposed stereochemical model
O O
H
O
O
H
H
H O
H
R
NMe2
TBSO
+ R
O
H
O
RCHO
Seebach, D.; Beck, A. K.; Heckel, A. Angew. Chem. Int. Ed. 2001, 40, 92-138.
Thadani, A. N.; Stankovic, A. R.; Rawal, V. H. Proc. Natl. Acad. Sci. USA 2004, 101, 5846-5850.
Unni, A. K.; Takenaka, N.; Yamamoto, H.; Rawal, V. H. J. Am. Chem. Soc. 2005, 127, 1336-1337.
intramolecularH-bond intermolecular
H-bond
!-! interaction
Catalysis by single hydrogen bond activation
- Despite the modest strength of singly H-bonded complex, significant rate accelerations and enantioselectivities canbe obtained.
- Selectivities are potentially reinforced by non-bonding interactions in the transition state.
- Catalyst turnover continues to be a problem.
Catalysis by double hydrogen bond activation
- Despite the modest strength of singly H-bonded complex, significant rate accelerations and enantioselectivities canbe obtained.
- Selectivities are potentially reinforced by non-bonding interactions in the transition state.
- Catalyst turnover continues to be a problem.
R1
YH
R2
double hydrogen bonding
H
AA
- A much more intensely studied area of research.
- Contributors include:
Jacobsen, Bach, Corey, Göbel, Mikami, Johnston,
Catalysis by double hydrogen bond activation
Jacobsen: Thio-urea catalyzed enantioselective addition to imines
N
HR1+ HCN
1) 1 (1 mol%), PhMe- 65 °C, 20 h
2) TFAA R1 CN
NF3C
O
100% conv. 98% ee
N
HAr
BocOTBS
OiPr+
1) 1 (5 mol%), PhMe- 40 °C, 48 h
2) TFA, 2 minAr
O
OiPr
NHBoc
96% conv. 97% ee
1 =
NNH
O
NH
SMe
Ph
N
HO
tBu OCOtBu
tBu
R1 = aryl or alkyl
Catalysis by double hydrogen bond activation
Jacobsen: Thio-urea catalyzed enantioselective addition to imines
N
HR1+ HCN
1) 1 (1 mol%), PhMe- 65 °C, 20 h
2) TFAA R1 CN
NF3C
O
100% conv. 98% ee
N
HAr
BocOTBS
OiPr+
1) 1 (5 mol%), PhMe- 40 °C, 48 h
2) TFA, 2 minAr
O
OiPr
NHBoc
96% conv. 97% ee
1 =
NNH
O
NH
SMe
Ph
N
HO
tBu OCOtBu
tBu
R1 = aryl or alkyl
Mechanistic analysis
- The reaction was found to display first order dependence on catalyst and HCN implying reversible imine-catalyst complexation
- Detailed NMR studies in conjunction with energy minimization (B3LYP) revealed a significant preference for an imine hydrogenbonded to both urea protons in a bridged fashion.
N
HR1
N N
S
N
H H HCNN N
S
H H
N
CNR1
H
+ Cat. 1R1 CN
NF3C
O
TFAA
8.5 kcal/mol 5.0 kcal/mol
Vachal, P.; Jacobsen, E. N. J. Am. Chem. Soc. 2002, 124, 10012-10014.Wenzel, A. G.; Jacobsen, E. N. J. Am. Chem. Soc. 2002, 124, 12964-12965.Wenzel, A. G.; Lalonde, M. P.; Jacobsen, E. N. Synlett, 2003, 12, 1919-1922.
H
R1
R
1) 3A MS or Na2SO4°
2) AcCl (1.0 equiv)2,6-lutidine (1.0 equiv)2 (5-10 mol%), Et2O
-78 °C to -40 °C
2 =
(iBu)2NNH
O
NH
S
N
tBu
Me Ph
Catalysis by double hydrogen bond activation
Jacobsen: Thio-urea catalyzed enantioselective acyl-Mannich reaction and acyl-Pictet-Spengler reactions.
OHCR1+
(1.05 equiv)NH
NH2
R
NH
NAc
R1
65-81% yield; 86-95% eeR1 = alkylR = H, 5-OMe
NH
N
O
HO R
3 (10 mol%), TMSCl
TBDE, -78 °C or -55 °C24 - 72 h
R = H, alkyl, aryl
NH
NO
R
65-94% yield; 88-98% ee
3 =
NNH
O
NH
S
N
tBu
Me Ph
Me
C5H11n
N
1) TrocCl (1.1 equiv)Et2O, 0 °C to rt
2) 2 (10 mol%), Et2O-78 °C to -65 °C
OTBS
OMe+ NTroc
CO2Me
80% yield; 86% ee
R
1) 3A MS or Na2SO4°
2) AcCl (1.0 equiv)2,6-lutidine (1.0 equiv)2 (5-10 mol%), Et2O
-78 °C to -40 °C
2 =
(iBu)2NNH
O
NH
S
N
tBu
Me Ph
Catalysis by double hydrogen bond activation
Jacobsen: Thio-urea catalyzed enantioselective acyl-Mannich reaction and acyl-Pictet-Spengler reactions.
OHCR1+
(1.05 equiv)NH
NH2
R
NH
NAc
R1
65-81% yield; 86-95% eeR1 = alkylR = H, 5-OMe
NH
N
O
HO R
3 (10 mol%), TMSCl
TBDE, -78 °C or -55 °C24 - 72 h
R = H, alkyl, aryl
NH
NO
R
65-94% yield; 88-98% ee
3 =
NNH
O
NH
S
N
tBu
Me Ph
Me
C5H11n
N
1) TrocCl (1.1 equiv)Et2O, 0 °C to rt
2) 2 (10 mol%), Et2O-78 °C to -65 °C
OTBS
OMe+ NTroc
CO2Me
80% yield; 86% ee
Taylor, M. S.; Jacobsen, E. N. J. Am. Chem. Soc. 2004, 126, 10558-10559.Taylor, M. S.; Tokunaga, N.; Jacobsen, E. N. Angew. Chem. Int. Ed. 2005, 44, 6700-6704.
Raheem, I. T.; Thiara, P. S.; Peterson, E. P.; Jacobsen, E. N. J. Am. Chem. Soc. 2007, 129, 13404-13405.
Mechanistic analysis
N+
Troc
Cl-
NH
N+
R
O
Me
Cl-
NH
N+
O
R
Cl-
N
HR
N
HR
Boc
NH
N
O
HO R
3 (10 mol%), TMSCl
TBDE, -78 °C or -55 °C24 - 72 h
R = H, alkyl, aryl
NH
NO
R
65-94% yield; 88-98% ee
3 =
NNH
O
NH
S
N
tBu
Me Ph
Me
C5H11n
Hydrogen bond donor catalysis by anion binding
NH
N
O
RCl
NH
N+
O
R
Cl-
N N
S
H H
Path A
Path B
NH
NO
R
+
NH+
N
R
O
Cl-
Product
NH
N
O
HO R
3 (10 mol%), TMSCl
TBDE, -78 °C or -55 °C24 - 72 h
R = H, alkyl, aryl
NH
NO
R
65-94% yield; 88-98% ee
3 =
NNH
O
NH
S
N
tBu
Me Ph
Me
C5H11n
Hydrogen bond donor catalysis by anion binding
NH
N
O
RCl
NH
N+
O
R
Cl-
N N
S
H H
Path A
Path B
NH
NO
R
+
NH+
N
R
O
Cl-
Product
NH
N
O
HO H
3 (10 mol%), TMSX
TBDE, -55 °Ctime
NH
NO
H
Halide effect
entry X time (h) %conv. %ee
1 Cl 23 80 972 Br 23 82 683 I 23 75 <5
Raheem, I. T.; Thiara, P. S.; Peterson, E. P.; Jacobsen, E. N. J. Am. Chem. Soc. 2007, 129, 13404-13405.
O
OMe
1) BCl3, CH2Cl2, 0 °C to rt
2) 4, (10 mol%), TBME, -78 °COMe
OTMS
R
R
+
R = Me, -(CH2)n-
O
RR
CO2Me
70-95% yield; 88-97% ee
4 =
NNH
O
NH
StBu
1.5 (equiv)
CF3
CF3
Ar
Ar = 4-F-Ph
Hydrogen bond donor catalysis by anion binding
Jacobsen: Enol silane additions to oxocarbenium ions
O+
Cl-
N N
S
H H
O
OMe
1) BCl3, CH2Cl2, 0 °C to rt
2) 4, (10 mol%), TBME, -78 °COMe
OTMS
R
R
+
R = Me, -(CH2)n-
O
RR
CO2Me
70-95% yield; 88-97% ee
4 =
NNH
O
NH
StBu
1.5 (equiv)
CF3
CF3
Ar
Ar = 4-F-Ph
Hydrogen bond donor catalysis by anion binding
Jacobsen: Enol silane additions to oxocarbenium ions
O+
Cl-
N N
S
H H
N
H tBu
Ph2HC
+ HCN 1
Jacobsen ASAP
ON
N
NS Ph
H
H
H
tBuMe
Ph2HC
NC
H
NPh2HC R
ON
N
NS Ph
H
H
H
tBuMe
Ph2HC
NC-
N+Ph2HC R
H
H H
R CN
NHCHPh2
Reisman, S. E.; Doyle, A. G. Jacobsen, E. N. J. Am. Chem. Soc. 2008, 130, 7198-7199.Zuend, S. J.; Jacobsen, E. N. J. Am. Chem. Soc. 2009, ASAP (9/24/09)
- Due to the recent developments/observations concerning anion binding the previously proposed mechanisms of a bifurcated hydrogen bonding association between the imine and thiourea were challenged.
- Further kinetic, computational, and labeling experiments led to the revised mechanistic hypothesis shown.
Catalysis by double hydrogen bond activation
- Significant advances with regard to reaction development and understanding are being made.
- Catalyst loadings are much less and TOF are higher.
Bifunctional catalysis
- Significant advances with regard to reaction development and understanding are being made.
- Catalyst loadings are much less and TOF are higher.
Bifunctional catalysis:
- Just as active of an area of research as double hydrogen bond catalysis.
- Contributors include:
Jacobsen, Deng, Akiyama, Terada, Tsogoeva
Enamine catalysis:
- Contributors include:
List, Barbas III, Yamamoto, among many others
R1
YH
R2
H
AA chiralscaffold
B
H
X
bifunctional catalysis
Bifunctional catalysis
Hajos-Parrish-Eder-Sauer-Wiechert reaction (1971)
O
OMeO
Me
L-proline (3 mol%)
DMF, rt
O
O
Me
OH
O
O
Me
O
Me
N H
O
O
99% yield; 93% ee
N+
NH
H-OTf
YamamotoBarbas
NH
O
NH
OH
Ph
Ph
NH
O
NH
SO2Ar
NH
NH
N
NN
ListAdolfsson
WuYamamoto
Recently developed unnatural proline catalysts
Bifunctional catalysis
Hajos-Parrish-Eder-Sauer-Wiechert reaction (1971)
O
OMeO
Me
L-proline (3 mol%)
DMF, rt
O
O
Me
OH
O
O
Me
O
Me
N H
O
O
99% yield; 93% ee
N+
NH
H-OTf
YamamotoBarbas
NH
O
NH
OH
Ph
Ph
NH
O
NH
SO2Ar
NH
NH
N
NN
ListAdolfsson
WuYamamoto
Recently developed unnatural proline catalysts
Deng: Cinchona alkaloids as bifunctional hydrogen bond catalysts
RNO2
MeO
O O
OMe+
1 (10 mol%), THF
-20 °C, 1.5 - 4 d
(3 equiv)R
NO2
CO2MeMeO2C
71-99% yield; 91-98% ee
N
N
OH
OH
1 =
R = aryl, aliphatic
RNO2 +
1 (10 mol%), THF
-60 to -20 °C, 1.5 - 4 d
(3 equiv)73-95% yield; 92-99% ee 6:1->20:1 dr
R = aryl, aliphatic
O O
OMe
O
NO2
R
CO2Me
Mukherjee, S.; Yang, J. W.; Hoffmann, S.; List, B. Chem. Rev. 2007, 107, 5471-5569.Li, H.; Wang, Y.; Tang, L.; Deng, L. J. Am. Chem. Soc. 2004, 126, 9906-9907.
Li, H.; Wang, Y.; Tang, L.; Wu, F.; Liu, X.; Guo, C.; Foxman, B. M.; Deng, L. Angew. Chem. Int. Ed. 2005, 44, 105-108.
Bifunctional catalysis
Deng: Mechanistic analysis and proposed transition state for enantioselective Michael additions
N
N
OH
OH
1 =PhNO2 +
1 (10 mol%), THF
-60 °C, 1.5 d
(3 equiv)97% yield; >99% ee 96:4 dr
O O
OMe
O
NO2
Ph
CO2Me
PhNO2 +
2 (10 mol%), THF
-60 °C, 1.5 d
(3 equiv)97% yield; >99% ee 97:3 dr
O O
OMe
O
NO2
Ph
CO2MeN
N
OH
2 =O
Me
Bifunctional catalysis
Deng: Mechanistic analysis and proposed transition state for enantioselective Michael additions
N
N
OH
OH
1 =PhNO2 +
1 (10 mol%), THF
-60 °C, 1.5 d
(3 equiv)97% yield; >99% ee 96:4 dr
O O
OMe
O
NO2
Ph
CO2Me
PhNO2 +
2 (10 mol%), THF
-60 °C, 1.5 d
(3 equiv)97% yield; >99% ee 97:3 dr
O O
OMe
O
NO2
Ph
CO2MeN
N
OH
2 =O
Me
N+
O
O-
H
Ph
Catalyst conformation and transition state analysis
N
H
RON
OH
N
H
N
OH
O
Me
N
N
OH
OH
1 = N
N
OH
= 2O
Me
PhNO2 +
O O
OMe OO
MeO
N
O
HHN+
H
H
O
NO2
Ph
CO2Me
- First order with respect to catalsyt, donor, and acceptor
Bifunctional catalysis
Deng: Thio-urea modified cinchona derived catalysts
Ar
NBoc
H RO
O O
OR
1 (20 mol%), Acetone
-60 °C, 1.5 d
(1.5 equiv)81-99% yield; 88-99% ee
+
R = Me, Bn, allyl
Ar
NHBoc
CO2R
CO2R
1 =
N
N
H
MeO
HN
S
HN
Ar
Ar = 3,5-bisCF3Ph-
O
CN
Cl
CN+
1 (10 mol%)
PhMe, rt, 1 h
(3 equiv)
O
CN
CN
Cl
99% yield; 97% ee 10:1 dr
Bifunctional catalysis
Deng: Thio-urea modified cinchona derived catalysts
Ar
NBoc
H RO
O O
OR
1 (20 mol%), Acetone
-60 °C, 1.5 d
(1.5 equiv)81-99% yield; 88-99% ee
+
R = Me, Bn, allyl
Ar
NHBoc
CO2R
CO2R
1 =
N
N
H
MeO
HN
S
HN
Ar
Ar = 3,5-bisCF3Ph-
O
CN
Cl
CN+
1 (10 mol%)
PhMe, rt, 1 h
(3 equiv)
O
CN
CN
Cl
99% yield; 97% ee 10:1 dr
Mechanism and proposed transition state
O
CN
Cl
CN+
N
HNS
N
Ar
ArH
H
N
OH
N
Cl
O
CN
CN
Cl
Song, J.; Deng, L. J. Am. Chem. Soc. 2006, 128, 6048-6049.Wang, B.; Wu, F.; Liu, X.; Deng, L. J. Am. Chem. Soc. 2007, 129, 768-769.
BrØnsted basic functionality
Hydrogen bond activation(s)
Bifunctional catalysis
1 =
N
N
H
MeO
HN
S
HN
Ar
Ar = 3,5-bisCF3Ph-
O
CN
Cl
CN+
1 (10 mol%)
PhMe, rt, 1 h
(3 equiv)
O
CN
CN
Cl
99% yield; 97% ee 10:1 dr
N
N
OH
OH
2 =RNO2 +
2 (10 mol%), THF
-60 to -20 °C, 1.5 - 4 d
(3 equiv)73-95% yield; 92-99% ee 6:1->20:1 dr
R = aryl, aliphatic
O O
OMe
O
NO2
R
CO2Me
Bifunctional catalysis
1 =
N
N
H
MeO
HN
S
HN
Ar
Ar = 3,5-bisCF3Ph-
O
CN
Cl
CN+
1 (10 mol%)
PhMe, rt, 1 h
(3 equiv)
O
CN
CN
Cl
99% yield; 97% ee 10:1 dr
N
N
OH
OH
2 =RNO2 +
2 (10 mol%), THF
-60 to -20 °C, 1.5 - 4 d
(3 equiv)73-95% yield; 92-99% ee 6:1->20:1 dr
R = aryl, aliphatic
O O
OMe
O
NO2
R
CO2Me
- Significant advances with regard to reaction development have/are being made.
- Due to the bifunctional nature of the catalysts, many substrate(s) - catalyst interactions are possible. Consequently,it becomes very difficult to rationalize reactivity and/or stereoselectivity.
- A greater mechanistic understanding of the subtleties of these processes is necessary for advancement.
top related