Download Asymmetric Hydrogenation

Asymmetric
Aminohydroxylation of Alkenes
R
R1
R2
NHX
XNClNa (X=Ts, Ms, CBz, Boc, Teoc)
OR XNBrLi (X=Ac)
4 mol% K 2 OsO 2 (OH)4
5 mol% (DHQ)2 PHAL
1:1 ROH:H 2 O
OH
R2
R1
+
R2
R1
OH
NHX
• originally developed with chloramine T (Na+ClNTs -), as for a racemic protocol developed by Sharpless in the 1980s
1980s
• found that the reaction works better with smaller N-substituents, (eg MeSO2-), and even better still with salts of
N-halocarbamates (NC(O)OR; ease of deprotection!) or N-haloamides
• regiocontrol is a problem, particularly with electronically unbiased alkene substituents
• in most respects the reaction is similar to the AD, including the model
for asymmetric induction
(note that, for a given olefin, the HO/NHR are delivered
to the same face in both regioisomeric products)
(DHQD)2 PHAL
β-face
slightly
hindered
chloramine-T: Angew.
., 1996, 35, 451
chloramine-M: Angew. Chem., Int. Ed. Engl., 1996, 35, 2810
halocarbamates: Angew. Chem., Int. Ed. Engl., 1996, 35, 2813
haloamides: Org. Lett., 2000, 2, 2221
attractive area good for aromatic
and alkyl substituents
"HO/ NHR"
"HO/ NHR"
RS
RM
RL
H
"HO/ NHR"
"HO/ NHR"
α-face
(DHQ)2PHAL
very!!!!!
hindered
Scope of the asymmetric aminohydroxylation
(all reactions shown carried out with (DHQ) 2 -PHAL; figure shown is ee)
Symmetrical trans-alkenes:
Symmetrical cis-alkenes:
OH
Ph
Ph
NHR
OH
CO 2 Et
EtO 2 C
NHR
R
R
R
R
=
=
=
=
Ts
Ms
Cbz
Ac
62
75
91
94
R
R
R
R
=
=
=
=
Ts
Ms
Cbz
Ac
77
95
84
--
Styrenes:
RHN
Ts
Ms
Cbz
Ac
45
66
63
--
OH
Ph
=
=
=
=
OH
O
O
OH
NHR
Ts
Ms
Cbz
Ac
Ph
50
-93
88
OMe
OMe
NHR
NHR
OH
2:1
-1:1
1:6
regiochemistry
R
R
R
R
=
=
=
=
Ts
Ms
Cbz
Ac*
81
95
94
99
* - iPr ester
•
=
=
=
=
Cinnamates (electronically distinguished):
RNH
R
R
R
R
R
R
R
R
OH
5
9
10
20
:
:
:
:
1
1
1
1
Regiochemical control by adjustment of aromatic linking group
CBzNH
O
O
(DHQ)2 PHAL
OMe
OH
OMe
or (DHQ) 2 AQN
(94% ee)
>10 : 1
21 : 79
(95% ee)
OH
NHCbz
(DHQ) 2 PHAL
or (DHQ)2 AQN
Ph
(DHQ) 2PHAL
(DHQ )2 AQN
Et
OMe
NHCBz
(DHQ )2 AQN
Ph
+
OH
(DHQ) 2 PHAL
(93% ee)
OH
+
Ph
H
H
Me O
O
O
O
O
N
(DHQ) 2AQN
H
1 : 13
N
H
OM e
N
NHCbz
ca. 1 : 1
Et
N
O
Tetrahedron Lett., 1998, 39, 2507;
Angew. Chem., Int. Ed. Engl., 1997, 36, 1483
(88% ee)
Asymmetric Hydrogenation of Alkenes
•
H2 is cheap and reduction is atom efficient! Can generate two asymmetric
centres simultaneously
•
Homogeneous catalysts based on Rh (I) or Ru (II) with chiral phosphine
ligands
X
For Rh catalysts, general substrate structure:
e.g. Aminoacrylates (X=NH, E=CO2R)
Also (usually Ru catalysts):
• Enamides
• Acrylic acids
• Allylic alcohols
P
P
Rh
O
Ph
basic carbonyl group
E
electron
withdrawing
group
Asymmetric Homogeneous Hydrogenation with
Chiral Diphosphines: Monsanto synthesis of L-DOPA
CO2Me
NHAc
CO2Me
NHAc
0.1% [(R,R)-(dipamp)Rh(COD)]+BF4
3 atm H2, 50°C, H2O / iPrOH
MeO
OMe
94% ee
MeO
OMe
HBr
OMe
P
CO2P
Ph
NH3+
Ph
MeO
= (R,R)-dipamp
HO
OH
L-DOPA
(anti-Parkinson's)
• W.S. Knowles – share of 2001 Nobel Prize.
Review of Monsanto work on L-DOPA synthesis: J. Chem. Ed., 1986, 63, 222
• First large-scale application of asymmetric hydrogenation, but the ligand lacks generality.
Mechanism of hydrogenation with Rh(I)dipamp
H
N
P
P
Rh
fast
P
Rh
E
H2
H
H
slow
O
Ph
H
N
Rh
P
P
+
E
H
O
Ph
P
H
N
S
Rh
P
+
E
O
Ph
more stable
(major isomer)
+
P
+
H
minor
S
NHCOMe
CO2Me
Ph
S
major H
less stable
(minor isomer)
fast
E
H
N
O
Ph
Rh
+
P
H2
P
fast
E
+
H
N
H
O
Ph
Rh
P
E
+
H
N
S
H
P
O
Ph
Rh
P
NHCOMe
CO2Me
Ph
H
P
But…recent work suggests that this does not operate in all cases (e.g. electron-rich phosphines)…
See commentary in Angew. Chem. Int. Ed. 2001, 40, 4611.
Rh(I)-BINAP Complexes
• Axially chiral binaphthyl diphosphine ligands offer improved ee's and wider substrate tolerance
in aminoacrylate reduction.
Ph
Ph
P
P
Ph
Ph
axial
P
L
equatorial
Rh
P
L
(S)-BINAP
Simplified by removing backbone:
axial
P
equatorial
Chiral enviromnment has 4 quadrants,
two "blocked" and two "open":
L
Rh
equatorially disposed phenyl
groups block coordination
in that 'quadrant'
P
L
blocked
open
For alternative pictures, see Figure 8 in: Noyori, J. Am. Chem. Soc. 2002, 124, 6649
Rh(I)-BINAP-catalysed hydrogenation of aminoacrylates
Noyori, J. Am. Chem. Soc. 1980, 102, 7932.
Note that for a given ligand enantiomer, the sense of asymmetric induction is determined by acrylate geometry
(hence need geometrically pure starting materials):
CO2R
Ph
Ph
NHAc
CO2H
NHAc
[(S)-(BINAP)Rh(nbd)]+ClO4H2, MeOH
CO2R
Ph
[(S)-(BINAP)Rh(nbd)]+ClO4H2, MeOH
NHAc
CO2H
Ph
R=Me 98%, 93% ee
R=H 97%, 100% ee
93%, 87% ee
NHAc
PPh2
One drawback is that chirality transfer from chiral backbone to coordinating PPh2 groups
is not always efficient.
Also, no bis(diarylphosphine) ligand gives >99% ee for a range of acylaminoacrylates
PPh2
(S)-BINAP
Rhodium (I)-diphosphole complexes:
electron rich, sterically demanding ligand systems
Review: Burk, Acc. Chem. Res. 2000, 33, 363
R
R
R
(R,R)-BPE
P
P
P
R = Me, Et, Pr
R R
(R,R)-DuPHOS
P
R R
R
electron rich alkylphosphines allow increased back-bonding to alkene substrates - more tightly held
flexible backbone in BPE leads to two ligand environments, one less selective than the other:
R
R groups held away
from coordination sites
P Rh
R
R
P
R
R
P Rh
R
R
P
R groups held towards
coordination sites
R
...so rigid DuPHOS generally better (although BPE can still be useful with VERY hindered substrates)
M. J. Burk, J. Am. Chem. Soc., 1993, 115, 10125
DuPHOS and BPE are outstanding ligands
for Rh catalysed hydrogenation of aminoacrylates
unlike BINAP, the sense of enantioselectivity is independent of acrylamide geometry - mixtures can be used!
CO2Me
R1
0.05% [Rh(R,R-nPr-DuPHOS)(COD)]+ TfOMeOH, 2 atm. H2
NHAc
R2
CO2Me
R1 = R2 = H
R1 = H, R2 = Me
NHAc R1 = Me, R2 = H
99.8% ee
99.6% ee
99.4% ee
also works for N-Cbz aminoacrylates - direct access to usefully protected amino acids
very substrate tolerant - the following all give >99% ee with Et-DuPHOS
CO2Me
NHAc
R
R = H, Me, Et, i-Pr, Ph, 1-naph, 2-naph, 2-thiophenyl, ferrocenyl,
4-(X)-Ph, 3-(X)-Ph, 3,5-di(X)-Ph (X = F, Br, OMe, CF3)
even works for tetrasubstituted aminoacrylates - other ligands give <70% ee and are slow
Et
Et
Ph
CO2Me
NHAc
0.2% [Rh((S,S)-Me-DuPHOS)(COD)]+ TfOMeOH, 90 psi H2
Ph
CO2Me
NHAc
88% ee
M. J. Burk, J. Am. Chem. Soc., 1993, 115, 10125; J. Am. Chem. Soc., 1995, 117, 9375
Asymmetric reduction of enamides
ruthenium BINAP mediated reduction of cyclic enamides
MeO
MeO
[Ru(R-BINAP)(COD)]+ TfO -
NAc
MeO
OMe
4 atm. H2, EtOH/DCM
100%,
99.5% ee
NAc
MeO
OMe
(rhodium BINAP gives 70% ee)
OMe
OMe
N-acetyl-tetrahydropapaverine
Noyori, Takaya, J. Am. Chem. Soc., 1986, 108, 7117
rhodium DuPHOS mediated reduction of acyclic enamides
enamide
geometry
unimportant
+
0.2% [Rh((S,S)-Me-DuPHOS)(COD)] TfO
Ph
NHAc
60 psi H2, MeOH
-
96%ee
Ph
NHAc
Burk, J. Am. Chem. Soc., 1996, 118, 5142
Ru-diphosphine catalysed reduction of acrylic acids
R3
R2
CO2H
R1
(BINAP)Ru(OAc)2
H2
R3
R2
CO2H
*
*
83-97% ee
R1
e.g.
CO2H
MeO
1% (S-BINAP)Ru(OAc)2
CO2H
100 atm H2, MeOH
MeO
92%, 97% ee
(S)-naproxen
(anti-inflammatory)
Noyori, Takaya, Inorg. Chem., 1988, 27, 566; J. Org. Chem. 1987, 52, 3174.
• Corresponding methyl esters are inert to this catalyst
For use of Rh-DuPHOS catalysts in acrylate reduction, see: Burk. J. Org. Chem., 1999, 64, 3290.
Mechanism of hydrogenation with Ru BINAP complexes
is different from Rh
Like the rhodium counterpart, the hydrogenation is stereospecifically syn; but unlike the rhodium reaction,
the α-hydrogen is incorporated from the gas source, the β-hydrogen from protonolysis by solvent
H
CO2H (R-BINAP)Ru(OAc)
2
CO2H
D
D2, CD3OD
CO2H
D2, CH3OH
H2, CD3OD
CO2H
D
Me
Me
H 0.95
D 1.06
D 0.34
H 0.71
Ruthenium (II) prefers to form monohydrides, whereas rhodium (I) prefers to form dihydrides
(G. Wilkinson, Nature, 1965, 208, 1203)
H2
HO2C
P
P
P
P
O
Ru
O
O
O
P
P
O
Ru
O
O
O
H2
(-AcOH)
P
P
O
Ru
S
O
Ru
O
O
O
O
O
P
O
O
H
rearrangement
P
P
protonolysis
HO2C
P
Ru
S
O
Ru
S
insertion
H
H. Takaya, R. Noyori, Tetrahedron Lett., 1990, 31, 7189, J. Am. Chem. Soc. 2002, 124, 6649
S
Ru-BINAP catalysed reduction of allylic alcohols
•Sense of induction depends on alkene geometry:
0.2% (S-BINAP)Ru(OAc)2
OH
30 atm H2, MeOH
OH
96% ee
0.2% (S-BINAP)Ru(OAc)2
30 atm H2, MeOH
OH
Noyori, Takaya, J. Am. Chem. Soc.., 1987, 109, 1596; J. Org. Chem. 1988, 53, 708.
OH
98% ee