69451 Weinheim, Germany - Wiley-VCH · 2008. 9. 30. · 2 1. Preparation of [(COD)Ir(L2)] (K1)...
Transcript of 69451 Weinheim, Germany - Wiley-VCH · 2008. 9. 30. · 2 1. Preparation of [(COD)Ir(L2)] (K1)...
Supporting Information
© Wiley-VCH 2008
69451 Weinheim, Germany
Ir-Catalyzed Asymmetric Allylic Substitutions - Very High Regio-selectivity and Air Stability with a Catalyst Derived from
Dibenzo[a,e]cyclooctatetraene and a Phosphoramidite
Stephanie Spiess, Carolin Welter, Géraldine Franck, Jean-Philippe Taquet and Günter Helmchen*
Organisch-Chemisches Institut, Ruprecht-Karls-Universität Heidelberg, D-69120 Heidelberg, Im Neuenheimer
Feld 270
Contents
1. Preparation of [(COD)Ir(L2)] (K1) 2. Crystallographic Data for K1 3. Preparation of [(COD)Ir(P,C-L2)] (K2) 4. Spectral Data for [(COD)Ir(P,C-L2)] (K2) 5. Preparation of [(DBCOT)Ir(L2)] (K3) 6. Spectral Data for [(DBCOT)Ir(L2)] (K3) 7. Preparation of [(DBCOT)Ir(P,C-L2)] (K4) 8. Spectral Data for [(DBCOT)Ir(P,C-L2)] (K4) 9. Determination of Enantiomeric Excess of 2a – 2e by HPLC 10. Reversal of C,H Activation by Addition of Acetic Acid.
2
1. Preparation of [(COD)Ir(L2)] (K1)
[Ir(COD)Cl]2 (6.7 mg, 10.0 µmol) and L2 (12.0 mg, 20.0 µmol) were dissolved in dry d8-
THF (0.5 mL) under an atmosphere of argon. The orange solution was transferred into a
dry NMR tube under argon.
-19 8 7 6 5 4 3 2 1 0 ppm
-16.7 -16.8 -16.9 ppm
Fig. 1 1H NMR spectrum of K1 (d8-THF, 250 MHz).
IrCl
L2
K1
(COD)Ar = o-(MeO)C6H4
K1H
P
N
OO
H2C
ArAr
IrCl
H*
(COD)
3
105110115120125130135140145150 ppm Fig. 2 31P NMR spectrum of K1 (d8-THF, 101 MHz). This is an enlarged version of Fig. 1 (I) in the article.
2. Crystallographic Data for K1 Under an atmosphere of argon, a saturated solution of [(COD)IrCl(L2)] (K1) in THF
deposited crystals suitable for X-ray diffraction. These were isolated by filtration.
The reflections were collected with a Bruker SMART 1K-diffractometer (Mo Ka-radiation,
graphite monochromator). Data collection and reduction were performed with Bruker
SMART and SAINT software. The structure was solved by direct methods and refined against
F2 with a Full-matrix least-squares algorithm using the SHELXTL (6.10)1 software package.
1 (software package SHELXTL V6.10 for structure solution and refinement), G. M. Sheldrick, Bruker
Analytical X-ray-Division, Wisconsin 2001.
K1H
IrCl
L2
K1
(COD)
Ar = o-(MeO)C6H4
P
N
OO
H2C
ArAr
IrCl
H*
(COD)
4
Fig. 3 Drawing of [(COD)IrCl(L2)] (K1) determined from an X-ray structural analysis. Crystal data and structure refinement for K1
Empirical formula C46H46ClIrNO4P Formula weight 935.46 Temperature 200(2) K Wavelength 0.71073 Å Crystal system monoclinic Space group P21 Z 2 Unit cell dimensions a = 11.0551(14) Å a = 90 deg. b = 11.3552(15) Å ß =93.647(2) deg. c = 15.410(2) Å ? = 90 deg. Volume 1930.5(4) Å3 Density (calculated) 1.61 g/cm3 Absorption coefficient 3.62 mm-1 Crystal shape polyhedron Crystal size 0.13 x 0.07 x 0.04 mm3 Crystal colour red Theta range for data collection 1.9 to 28.3 deg. Index ranges -14≤h≤14, -15≤k≤15, -20≤l≤20 Reflections collected 19688 Independent reflections 9408 (R(int) = 0.0410) Observed reflections 8586 (I >2s (I)) Absorption correction Semi-empirical from equivalents Max. and min. transmission 0.87 and 0.65
5
Refinement method Full-matrix least-squares on F2 Data/restraints/parameters 9408 / 171 / 487 Goodness-of-fit on F2 1.19 Final R indices (I>2 s (I)) R1 = 0.052, wR2 = 0.100 Absolute structure parameter 0.005(8) Largest diff. peak and hole 2.40 and -3.29 eÅ-3 CCDC 688502 contains the supplementary crystallographic data for this paper. These data
can be obtained free of charge from The Cambridge Crystallographic Data Centre via
www.ccdc.cam.ac.uk/data_request/cif.
3. Preparation of [(COD)Ir(P,C-L2)] (K2)
[Ir(COD)Cl]2 (6.7 mg, 10.0 µmol), L2 (12.0 mg, 20.0 µmol) and n-propylamine (30.0 µL,
364.9 µmol) were dissolved in dry d8-THF (0.5 mL) under an atmosphere of argon. The
orange solution was heated at 50°C for 1 h. The resultant yellow solution (solution A) was
transferred into a dry NMR tube under argon.
4. Spectral Data for [(COD)Ir(P,C-L2)] (K2)
105110115120125130135140145150155160165 ppm
(1)
K2
IrL2
P
N
OO
H2C
ArAr
*
(COD)Ar = o-(MeO)C6H4
6
105110115120125130135140145150155160165 ppm Fig. 4 31P NMR spectrum of K2 (solution A) at rt (1) and at -60°C (2) (d8-THF, 202 MHz). Spectrum (2) is
an enlarged version of Fig. 1 (II) in the article.
5. Preparation of [(DBCOT)Ir(L2)] (K3)
[Ir(DBCOT)Cl]2 (8.6 mg, 10.0 µmol) and L2 (11.9 mg, 19.8 µmol) were dissolved in dry
d8-THF (0.5 mL) under an atmosphere of argon. The orange solution was transferred into
a dry NMR tube under argon.
(2) K2
IrL2
P
N
OO
H2C
ArAr
*
(COD)
Ar = o-(MeO)C6H4
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6. Spectral Data for [(DBCOT)Ir(L2)] (K3)
1H NMR, (d8-THF, 600 MHz)
P
O
O
Ir
NMeO
OMe
K3
D12
D1
D5
D3 D2
D4
D6
D10
D11
D7
D8
1
6
3
45
2
8
B3
B4 B4a
B5
B6
B7
B8B8a
B8a'B8'
B7'
B6'
B5'B4a'B4'
B3'
D9
7
Cl
δ = 1.61 (d, J = 6.9 Hz, 6 H, 8-H), 3.21 (t, J = 6.9 Hz, 1 H, D3-H), 3.59 (s, 6 H, OCH3), 3.89
(mc, 1 H, D4-H), 5.38-5.43 (mc, 2 H, 7-H), 5.51 (d, J = 7.5 Hz, 1 H, D8-H), 6.06-6.08 (m, 1 H,
D1-H or D2-H), 6.14-6.16 (m, 1 H, D1-H or D2-H), 6.31 (dd, J = 7.4 Hz, J = 7.4 Hz, 1 H,
D7-H), 6.64 (dd, J = 7.5 Hz, J = 7.5 Hz, 2 H, 4-H), 6.69-6.71 (m, 3 H, 6-H, D6-H), 6.76-6.83
(m, 4 H, D5-H, D10-H, D11-H, D12-H), 6.94 (d, J = 7.5 Hz, 1 H, D9-H), 7.00-7.03 (mc, 2 H,
5-H), 7.16 (d, J = 8.8 Hz, 1 H, B3’-H), 7.21-7.26 (m, 3 H, BINOL-H), 7.30-7.34 (m, 2 H,
BINOL-H), 7.43-7.46 (mc, 1 H, BINOL-H), 7.56 (d, J = 8.7 Hz, 2 H, BINOL-H), 7.79 (d, J =
7.6 Hz, 2 H, 3-H), 7.99 (d, J = 8.2 Hz, 1 H, BINOL-H), 8.03 (d, J = 8.9 Hz, 1 H, BINOL-H),
8.14 (d, J = 8.9 Hz, 1 H, BINOL-H).
13C NMR, (d8-THF, 145 Hz)
δ = 22.94 (2 q, C-8), 53.70 (d, C-D4), 53.51, 54.55 (2 d, C-7), 54.76, 54.78 (2 q, OCH3),
59.21 (d, C-D3), 96.44 (dd, JC,P = 19.3 Hz, C-D1 or C-D2), 98.50 (dd, JC,P = 19.8 Hz, C-D1
or C-D2),109.97 (d, C-6 or C-D6), 120.11 (2 d, C-4), 122.46 (s, Aryl-C), 122.62 (d, JC,P = 2.8
Hz, Aryl-C), 123.32 (d, JC,P = 3.9 Hz, Aryl-C), 125.03 (d, C-6 or C-D6), 125.12 (d, C-D),
125.24 (d, C-D8), 125.40, 125.46, 125.52 (3 d, C-BINOL), 125.71 (d, C-D9), 126.11 (d, C-
D7), 126.25, 126.43 (2 d, C-D), 126.74, 126.81, 126.87 (3 d, C-BINOL), 127.47 (d, C-
BINOL), 128.49 (d, C-6 or C-D6), 128.67, 129.58, 130.22, 130.28 (4 d, C-BINOL), 130.77 (d,
JC,P = 4.4 Hz, Aryl-C), 131.0 (d, C-3), 131.78, 132.57, 132.68, 133.43 (s, Aryl-C), 141.53 (d,
JC,P = 3.9 Hz, Aryl-C), 142.73 (d, JC,P = 3.3 Hz, Aryl-C), 147.65 (d, JC,P = 2.2 Hz, Aryl-C),
8
148.52 (d, JC,P = 2.8 Hz, Aryl-C), 149.64 (d, JC,P = 3.9 Hz, Aryl-C), 150.40, 150.50, 157.71 (3
s, Aryl-C).
31P NMR, (d8-THF, 243 MHz)
δ = 106.20.
MS (HR-FAB+)
C54H46NO4P35Cl191Ir Calcd. 1029.2459
[M]+ Found 1029.2373 diff.: -8.6 mmu.
C54H46NO4P37Cl191Ir Calcd. 1031.2429
[M]+ Found 1031.2451 diff.: +2.2 mmu.
C54H46NO4P35Cl193Ir Calcd. 1031.2482
[M]+ Found 1031.2451 diff.: -3.1 mmu.
C54H46NO4P37Cl193Ir Calcd. 1033.2453
[M]+ Found 1033.2456 diff.: +0.3 mmu.
8.0 7.5 7.0 6.5 6.0 5.5 5.0 4.5 4.0 3.5 3.0 2.5 2.0 1.5 1.0 0.5 0.0 ppm Fig. 5 1H NMR spectrum of K3 (d8-THF, 600 MHz).
IrCl
L2
K3
(DBCOT)
9
2030405060708090100110120130140150160 ppm Fig. 6 13C NMR spectrum of K3 (d8-THF, 145 MHz).
190 180 170 160 150 140 130 120 110 100 90 80 70 60 50 40 30 20 10 ppm Fig. 7 31P NMR spectrum of K3 (d8-THF, 243 MHz). This is an enlarged version of Fig. 1 (III) in the
article.
IrCl
L2
K3
(DBCOT)
IrCl
L2
K3
(DBCOT)
10
7. Preparation of [(DBCOT)Ir(P,C-L2)] (K4)
Procedure 1 [Ir(DBCOT)Cl]2 / L2 (1:2)
[Ir(DBCOT)Cl]2 (25.9 mg, 30.0 µmol), L2 (36.4 mg, 60.7 µmol) and n-propylamine (74.0
µL, 900.0 µmol) were dissolved in dry d8-THF (1 mL) under an atmosphere of argon. The
orange solution was heated at 50°C for 1 h. Upon removal of volatiles in vacuo and
dissolution of a residual yellow powder in dry d8-THF (1 mL) a yellow solution was
obtained (solution B). The yellow solution was transferred into an dry NMR tube.
Procedure 2 [Ir(DBCOT)Cl]2 / L2 (1:4)
[Ir(DBCOT)Cl]2 (17.2 mg, 19.9 µmol), L2 (48.0 mg, 80.0 µmol) and n-propylamine (49.3
µL, 600.0 µmol) were dissolved in dry d8-THF (0.5 mL) under an atmosphere of argon.
The orange solution was heated at 50°C for 1 h. Upon removal of volatiles in vacuo and
dissolution of a residual yellow powder in dry d8-THF (1 mL) a yellow solution was
obtained (solution C). The yellow solution was transferred into an dry NMR tube.
8. Spectral Data for [(DBCOT)Ir(P,C-L2)] (K4)
8 7 6 5 4 3 2 1 0 ppm Fig. 8 1H NMR spectrum of K4 (solution C) (d8-THF, 500 MHz).
K4
IrL2
P
N
OO
H2C
ArAr
*
(DBCOT)
Ar = o-(MeO)C6H4
11
160 150 140 130 120 110 100 90 80 70 60 50 40 30 20 10 0 ppm Fig. 9 13C NMR spectrum of K4 (solution C) (d8-THF, 126 MHz).
115120125130135140145150155 ppm Fig. 10 31P NMR spectrum of K4 (solution C) (d8-THF, 202 MHz). This is an enlarged version of Fig. 1
(IV) in the article.
K4
IrL2
P
N
OO
H2C
ArAr
*
(DBCOT)
K4
IrL2
P
N
OO
H2C
ArAr
*
(DBCOT)
Ar = o-(MeO)C6H4
Ar = o-(MeO)C6H4
12
9. Determination of Enantiomeric Excess of 2a – 2e by HPLC
According to Table 1 in the article the enantiomeric excess of 2a – 2e was determined by
HPLC on chiral columns.
R OCO2CH3 [Ir] (2 mol%)L* (4 mol%), baseTHF
1
O
OP N
H3C
Ar
H3C
Ar
S
S
aS
L1 Ar = Ph
L2 Ar = o-(MeO)C6H4
L3 Ar = Naphthyl
NuM
R
Nu
2
a R = Ph, b R = CH2CH2Ph,
c R = CH2OSiPh2t-Bu, d R = CH2OCPh3,
e R = CH2CH2OCPh3
COD DBCOT
[Ir] = [Ir(COD)Cl]2
or [Ir(DBCOT)Cl]2
R+
Nu
3
Scheme 1 Ir-catalyzed allylic substitutions.
In most cases published procedures were applied: 2a, Nu = BnNH,[2] Nu = PhNH,[2] Nu =
HC(CO2Me)2;[3] 2b, Nu = BnNH;[4] 2c, Nu = BnNH,[5] Nu = HC(CO2Me)2;[5] 2d, Nu = o-
NsNH,[5] Nu = HC(CO2Me)2;[3] 2e, Nu = HC(CO2Me)2: Daicel Chirapak AD-H, 250×4.6
mm, 5 µm with guard cartridge AD-H, 10×4 mm, 5 µm, 0.5 mLmin-1, n-
hexane/isopropanol 98:2, 20°C, 210 nm, tR[(-)-R] = 14.5 min, tR[(+)-S] = 15.5 min.
10. Reversal of C,H Activation by Addition of Acetic Acid
Addition of acetic acid to a solution of K2 effected reversal of C-H activation to give K1.
Thus, solution A was prepared as described, but n-PrNH3Cl was removed by precipitation
with toluene/diethyl ether 1:1 and centrifugation. Then acetic acid (30 equiv.) was added.
The 31P NMR then surprisingly showed the spectrum of K1. The chloride ion required for
the formation of K1 must have come from residual [Ir(COD)Cl]2 (Scheme 3 (cf. article)).
[2] C. A. Kiener, C. Shu, C. Incarvito, J. F. Hartwig, J. Am. Chem. Soc., 2003, 125, 14272-14273.
[3] C. Gnamm, S. Förster, N. Miller, K. Brödner, G. Helmchen, Synlett, 2007, 5, 790-794.
[4] C. Welter, A. Dahnz, B. Brunner, S. Streiff, P. Dübon, G. Helmchen, Org. Lett., 2005, 7, 1239-1242.
[5] C. Gnamm, G. Franck, N. Miller, T. Stork, K. Brödner, G. Helmchen, Synthesis, 2008, accepted.
13
IrCl
L2L
L
L2 (2 equiv.)THF
K1K3
IrL
L L2
P
NH2C
ArAr
K2K4
CODDBCOT
+ n-PrNH2
- n-PrNH3Cl
+ 1/2
O
O
2
IrCl
L
L
2
IrCl
L
L
2
LL
LL
==
Scheme 3 Base induced C-H activation (Ar = o-(MeO)C6H4).
Quantification of the reaction K2→K1 was not possible upon use of n-PrNH2 because
side products were also formed. A very clean reaction was found upon C-H activation
with DBN as follows. DBN (40 µmol) was added to a solution of K1 (20 µmol) in d8-THF
(0.5 mL); after stirring for 1h at rt, the resultant solution contained K2 (10 µmol),
[Ir(COD)Cl]2 (5 µmol), DBN·HCl (10 µmol) and residual DBN (30 µmol). Then acetic
acid was added portionwise and the ratio of K1 and K2 was determined by 31P NMR (Fig.
11). After complete reaction an excess of DBN (160 µmol) was added, which effected
clean reformation of complex K2.
In another experiment, solution B (cf. above) was prepared by reacting K3 with 15
equiv. of n-PrNH2 for 1 h at 50°C. Subsequent removal of the excess of n-PrNH2 did not
effect reversal of C-H activation.
However, the addition of acetic acid (Fig. 11) led to a complete back-formation of the
chlorocomplex K3. These experiments demonstrated that C-H activation is cleanly
reversible for K1/K2 as well as K3/K4 upon addition of acetic acid.
14
0 10 20 30 40 500
20
40
60
80
100
K1 K2 K3 K4
[%]
Equiv. of acetic acid relative to activated complex
Fig. 11 Addition of acetic acid to the activated complexes K2 (containing 1 equiv. of DBN·HCl and 3 equiv. of
DBN) and K4 (containing 1 equiv. of n-PrNH3Cl) yielding K1 and K3, respectively.
In order to prove the assumption that [Ir(COD)Cl]2 could act as the chloride source
during the reformation of K1, C-H activation was carried out with [Ir(COD)Cl]2/L2 = 1:4,
in order to avoid an excess of [Ir(COD)Cl]2 in the system. In this experiment DBN (40
µmol) was added to a solution of [Ir(COD)Cl]2 (10 µmol) and L2 (40 µmol) in d8-THF
(0.5 mL); after stirring for 1h at rt, the resultant solution contained K2 (20 µmol),
DBN·HCl (20 µmol) and residual DBN (20 µmol). When the DBN·HCl was removed by
precipitation with diethyl ether and centrifugation, back-formation to K1 did not occur
even upon addition of acetic acid.
15
Fig. 12 Black spectrum: C-H activation carried out with [Ir(COD)Cl]2/L2 = 1:4 ; Red spectrum: Addition of acetic acid to the activated complex K2; Blue spectrum: Subsequent addition of 1 equiv. of [Ir(COD)Cl]2.
The reformation of K1 could then be induced by adding 1 equiv. of [Ir(COD)Cl]2 to the
system confirming the hypothesis that [Ir(COD)Cl]2 could deliver the required chloride
ion (Fig. 12).
IrCl
L2L
L4 equiv. L2
K1
IrL
L L2
P
NH2C
ArAr
K2
[Ir(COD)Cl]2
+ base- base⋅HCl O
O
L
L=
2
COD
+ 2 equiv. L2+ CH3COOH
2
Ar = o-(MeO)C6H4