hydrogen-bond catalysis for reviews see: m. s. taylor, e. n. jacobsen, angew. chem. int. ed. 2006,...
TRANSCRIPT
Hydrogen-Bond Catalysis
For reviews see:
M. S. Taylor, E. N. Jacobsen, Angew. Chem. Int. Ed. 2006, 45, 1520-1543
A. G. Doyle, E. N. Jacobsen, Chem. Rev., 2007, 5713-5743
Nadia Fleary-Roberts03/02/10
• Lewis acids has dominated enantioselective catalysis• acceleration of Diels Alder reaction with AlCl3
•
A brief history…
• Wynberg reported asymmetric conjugate addition reactions with cinchona alkaloids bearing a free hydroxyl group.
Hiemstra H.; Wynberg H., J. Am. Chem. Soc. 1981, 103, 417-430
Yates P.; Eaton P., J.Am. Chem. Soc. 1960, 82, 4436
O
CH3
CH3
+
tBu
SH O
CH3
CH3ArS
75 % ee
cinchonidine (1 mol %)
benzene, 23 oC
N
OH
N
cinchonidine
•Jacobsen reported asymmetric hydrocyanation of aliphatic and aromatic aldehydes
R H
N+
2. TFAA
1.a (2 mol %)
toluene, -70 oCHCNR CN
NF3COC
R = Ph: 91 % eeR = tBu: 85 % ee
N
OCH3tBu
HO
NH
NH
StBu
N
O
Bn
H
a
Sigman, M. S.; Jacobsen, E. N. J. Am. Chem. Soc. 1998, 120, 4901
Lewis acid catalysis• Highly tunable
• Can vary counter ion, chiral ligand
• Lewis base/acid interactions are stronger
• Interactions are more directional
H-bond catalysisModerately tunable
Active catalyst
Potentially recoverable
Strength can vary from 0.4 to 40 kcalmol-1.
What is a hydrogen bond?
“An XH···A interaction is called a ,hydrogen bond', if 1. it constitutes a local bond, and 2. XH acts as a proton donor to A.”
Steiner, Angew. Chem. Int. Ed. 2002, 41, 48
Most Hydrogen bonding in H-bond catalysis is of moderate strength
G.A. Jeffrey, An Introduction to Hydrogen Bonding, Oxford University Press, New York, 1997
Role of H-bonds:DNA base pairingLigand/receptor binding
Specific acid catalysis
General acid catalysis
Brønsted acids can accelerate organic reactions by either of two fundamental mechanisms:
•protonation of the electrophile in a prior to nucleophilic attack
•proton transfer to the transition state in the rate-determining step
Modes of bonding
Double H-bond donors• Increased strength and directionality
e.g. Ureas, thioureas, Guanidinium and Amidinium ions
N
R3tBu
HO
NH
NH
XtBu
N
O
R1
R2
X = O, S
NR R
NNH
RRN
RNH
R
R
Guanidine Amidine
• Less strength than double H-bond donors
• Less directionality
Single H-bond donors
•e.g. Diols, biphenols, chiral phosphoric acids
O
O
OH
OH
Ar Ar
Ar Ar ArAr
ArAr
OH
OH
Ar
O
O
Ar
PO
OH
Bifunctional catalysis
•a single or dual H-bond donor site flanked by sites for secondary interaction with substrates.
e.g. Proline and proline analogs, cinchona alkaloids and derivatives
NH
CO2H
L- proline N
R
OH
N
Ureas and Thioureas
•Originally developed as ligands for lewis acidic metals.
•Most applicable class of chiral H-bond donors
•Can promote addition of a range of nucleophiles
•Imine activation
Double H-bond donors
N
R3tBu
HO
NH
NH
XtBu
N
O
R1
R2 b R1 = Bn, R2 = H, R3 = OCH3, X= S
c R1 = Bn, R2 = H, R3 = OCOtBu, X = O
d R1 = R2 = CH3, R3 = OCOtBu, X =S
e R1 = Bn, R2 = CH3, R3 = tBu, X = S
NH
NH
XtBuHN
O NR''R''
R'
X
Nu
LUMO activation
•Diels Alder reaction
•Aza Baylis-Hillman reaction
Double H-bond donors
CF3
F3C NH
NH
S
CF3
CF3
f
CF3
O
+solvent, 20 oC
catalyst f (10-100 mol%)
O
N
R3tBu
HO
NH
NH
XtBu
N
O
R1
R2
e R1 = Bn, R2 = CH3, R3 = tBu, X = S
N
Ph
NsDABCO
e (10 mol %)
xylenes, 4 oC
Ph OCH3
ONHNs
95 % ee40 % yield
N
N
+ OCH3
O
Wittkopp A.; Schreiner P. R., Chem. Eur. J. 2003, 9,
Raheem, I. T.; Jacobsen, E. N. AdV. Synth. Catal. 2005, 347, 1701
•Asymmetric Strecker reaction
Double H-bond donors
•Scaleable catalytic synthesis•Imines derived from alky, aryl, heteroaryl aldehydes•Aqueous cyanide salts•Robust catalyst•Access to the (R)-enantiomer of tert-leucine
Zuend S.J.; Coughlin M. P.; Lalonde M. P.; Jacobsen E. N., Nature, 2009, 461, 968
CF3
CF3NH
NH
StBu
N
O
Ph
Ph
g
R
NCHPh2 catalyst g, (0.5 mol %)
KCN, AcoH, H2O, tol, 0 oC, 4-8 hR
HNCHPh2
CN
H2SO4, HCl, 44-68 hNaOH, NaHCO3Boc2O, dioxane, 16 h
recrystallizeR
BocHNCHPh2
CO2H
98-99 % ee
•Asymmetric Pictet Spengler reaction
NH
N i-Bu
NH
AcCl2,6-lutidine
h (10 mol %)
Et2O, -60 oC
NAc
i-Bu
93 % ee75 % yield
i-BuN
NH
O
S
NH
t-Bui-Bu
N Ph
h
Double H-bond donors
Taylor, M. S.; Jacobsen, E. N. J. Am. Chem. Soc. 2004, 126, 10558
Bifunctional Thiourea derivatives
Takemoto catalyst
•Aza-henry reaction-(addition of nitroalkanes to imines )
CF3
F3C NH
NH
S
N(CH3)2
y
PhNO2 H3CO2C CO2CH3+ Ph
NO2
CO2CH3H3CO2C
93 % ee86 % yield
y (10 mol%)
toluene, 23 oC
T. Okino, Y. Hoashi, Y. Takemoto, J. Am. Chem. Soc. 2003, 125, 12672 – 12673O O
SPh
PhSH+ 85 % ee97 % yield
y (10 mol%)
4 A M.S.
CH2Cl2, 0 oC
•1,4- additions
Ph
NP(O)Ph2
+ CH3NO2
Ph
NH
NO2
Ph2(O)Py (10 mol%)
toluene, 23 oC
67 % ee87 % yield
T. Okino, S. Nakamura, T. Furukawa, Y. Takemoto, Org. Lett. 2004, 6, 625
B.-J. Li, L. Jiang, M. Liu, Y.-C. Chen, L.-S. Ding, Y. Wu, Synlett 2005, 4, 603
•1,2-additions
S
N
CH3
O
H3C
CH3
TMSCNy (5 mol%)
CF3CH2OH
CH2CL2, -78 oC
S
N
CH3
HO
H3C
CH3
CN i-Pr
NH
NH
SHN
O
t-Bu
y
D. E. Fuerst, E. N. Jacobsen, J. Am. Chem. Soc. 2005, 127, 8964
F3C
F3C
CF3
CF3
HNNHHN
SNH
S
z
efficient catalyst for Baylis-Hillman reactions
•Other thiourea catalysts
•Capable of double H-bond interactions
•Are positively charged so result in increased H-bond donor abiltity.
Double H-bond donors
NR R
NNH
RRN
RNH
R
R
Guanidine Amidine
Guanidinium and Amidinium ions
Ph
NCH2Ph
HCN
i (10 mol %)
toluene, -40 oC
Ph CN
NHPhH2C
•Strecker reaction
NH
N
NPhPh
i
T. Steiner, Angew. Chem. 2002, 114, 50; Angew. Chem. Int. Ed. 2002, 41, 48 .
Double H-bond donors
•Diels Alder reaction
•Nitro-Mannich reaction
Schuster T.; Bauch M.; Durner G.; Gmbel M. W.; Org. Lett. 2000, 2, 179 – 181.
Cl
NBoc
+ H3C No2
j (10 mol%)
toluene, -20 oC
Cl
NHBoc
CH3
NO282 % ee17:1 d.r.59 % yield
H3CO+ O
O
Et k (25 mol%)
CH2Cl2, 4 oC
H3CO
H
Et
H
O
OH
-44 % ee
70 % combined yield3.1:1 regioisomer ratio
H3COO
OH
Et
H
H
40 % ee
+
N
HN HN
NH
OTf
j
kAr = 3,5-(CF3)2C6H3
Amidinium catalysed reactions
•Hetero Diels Alder reaction catalysed by chiral diols
Single H-bond donors
•Baylis-Hillman reaction -Binol derivatives
Diols and Biphenols
Huang Y.; Unni, A. K.; Thadani, A. N.; Rawal V.H., Nature, 2003, 424, 146
TBSO
N(CH3)2
+ O
O
H
1. 10 mol % l or m
toluene, -40 oC
2. AcCl
CH2Cl2/toluene, -78 oCO
OO
with l 92 & ee 67 % yieldwith m >99 % ee 96 %
O
O
OH
OH
Ar Ar
Ar Ar
Ar = 1-Np
ArAr
ArAr
OH
OH
Ar = 4-F-3,5-Et2C6H2
l m
Ph
NTs
H
O
+n (10 mol %)
toluene/c-C5H9OCH3
-15 oC
Ph
NH OTs
87 % ee93 % yield
OH
OH
NN
n
•Chiral phosphoric acids
Ar
O
O
Ar
PO
OH
p Ar = 3,5-dimesitylphenylq Ar = 4-NO2-C6H4
r Ar = 4-(2-Np)-C6H4
•Mannich reaction
OH3CO+
H
NBoc
Ph
OH3CO
HN
Ph
Boc
97 % ee95 % yield
p (2 mol%)
ClCH2CH2Cl
-35 oC
T. Akiyama, J. Itoh, K. Yokota, K. Fuchibe, Angew. Chem. 2004, 116, 1592 – 1594 Angew. Chem. Int. Ed. 2004, 43, 1566 –1568D. Uraguchi, M. Terada, J. Am. Chem. Soc. 2004, 126, 5356 – 5357
HO
N
Ph
+
OTMS
OEt
CH3
toluene, -78 oC
q (10 mol%)
HO
HN
PhCH3
CO2Et
90 % ee; 19:1 d.r.91 % yield
Single H-bond donors
•Reductive amination
R. I. Storer, D. E. Carrera, Y. Ni, D. W. C. Macmillan, J. Am. Chem. Soc. 2006, 128, 84
O NH2
OMe
+
t (10 mol %)
HEH,40-50 oC
5 A MS, 24-96 h benzene
X HNX
OMe
X = F, Cl, OMe, NO2
83 -96 % ee60 -82 % yield
TPS
O
OP
OH
O
TPS
t
HEH = ethyl Hantzsch ester
NH
CO2EtEtO2C
Bifunctional catalysis
NH
CO2H
L- proline
•enatioselective aldol cyclizations
Proline catalysed reactions
H3C
O
CH3
L-proline (30 mol%)
DMSO, 23 oC
O
i-Pr
OH
96 % ee97 % yield
Z. G. Hajos, D. R. Parrish, (Hoffman-La-Roche),German Patent DE 2102623, 1971 [Chem. Abstr. 1972, 76, 59072];
Proposed mechanism for proline catalysed transformations
A. G. Doyle, E. N. Jacobsen, Chem. Rev., 2007, 5713-5743
NH
NH
NO
HN
PhHO
Ph
H OTf
u v
NH
HN
O
SO
O i-Pr
i-Pri-Pr
w
NH HN N
NN
x
u higher yields and selectivity compared to proline
O+
H
O
NO2
OH
NO2
O
DMSO, 23 oC
L-Proline or w (10 mol%) L-proline: 73 % ee 42 % yield w: 97 % ee 96 % yield
O
+OH
H CF3
x (5 mol%)
CH3CN, 23 oC
O OH
CF3
94 % (syn), 92 % ee (anti) 97.5:2.5 syn/anti 65 % yield
Proline analogues
x increased solubilityTetrazole is a pharmacore for carboxylic acid
Cinchona alkaloidsBifunctional catalysis
•Enatioselective conjugate additions
•Baylis-Hillman reaction
Nakano A. et . al. 2006, 62, 381Iwabuchi Y. et. al. J. Am. Chem. Soc. 1999, 121, 10219Connon S.J., Chem. Comm., 2008, 2499
OSH
tBu
cinchonidine
benzene, 23 oC
O
S
tBu
75 % ee
Ph
NTsO
+CH3CN/DMF
-30 oC
-isocupreidine (10 mol %) ONH
Ph
Ts
97 % ee80 % yield
N
R
OH
N
R = OCH3: quinineR = H: cinchonidine
N
R
OH
N
R = OCH3: quinidineR = H: cinchonine
N
OH
O
N
CH2CH3
isocupreidine
Oligiopeptides
• Cyclo(l-phenylalanine-l-histidine) hydrocyanation of aldehydes
O
HH3CO
HCNcyclo-(L-Phe-L-His) (2 mol%)
toluene, -20 oC
H3CO
OH
CN
97 % ee83 % conv.
HN
NH
O
Ph
O
NHN
cyclo-(L-Phe-L-His)
S. Inoue, J.-I. Oku, J. Chem. Soc. Chem. Commun. 1981, 229 –230
Bifunctional catalysis
Uncertainty concerning mechanism
Summary
• A dynamic and large area of research which is continuing to be explored
• Applicable to a wide number of transformations
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