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

7

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