www.sciencemag.org/content/full/342/6162/1076/suppl/DC1

Supplementary Material for

Cobalt Precursors for High-Throughput Discovery of Base Metal Asymmetric Alkene Hydrogenation Catalysts.

Max R. Friedfeld, Michael Shevlin, Jordan M. Hoyt, Shane W. Krska, Matthew T. Tudge, Paul J. Chirik

Published 29 November 2013, Science 342, 1076 (2013) DOI: 10.1126/science.1243550

This PDF file includes:

Materials and Methods

Figs. S1 to S27

Tables S1 to S6

Full Reference List

2

Table of Contents

Experimental Section. S3 I. General Considerations. S3 II. Synthesis of Cobalt Precatalysts. S5 III. Representative Procedures for Catalytic Hydrogenation. S7 IV. Preparation and Purification of Alkene Substrates. S9 V. Characterization of Alkane Products. S10 VI. NMR Spectra of Alkane Products. S15

VII. Crystallographic Data. S19 VIII. Phosphine Evaluation with Methyl 2-acetamidoacrylate (MAC) S20 IX. Phosphine Evaluation with Acetomidostyrene. S29 X. Phosphine Evaluation with trans-(α)-Methylstilbene S37 XI. Evaluation of Cobalt Sources for the Hydrogenation of MAC. S52 XII. GC and SFC Chromatograms of Enantiopure Alkanes. S53 XIII. References. S56

3

I. General Considerations. All air- and moisture-sensitive manipulations were carried

out using standard high vacuum line, Schlenk or cannula techniques or in an M. Braun

intert atmosphere drybox containing an atmosphere of purified nitrogen. The M. Braun

drybox was equipped with a cold well designed for freezing samples in liquid nitrogen.

Solvents for air- and moisture-sensitive manipulations were dried and deoxygenated

using literature procedures.(42) Deuterated solvents for NMR spectroscopy were distilled

from sodium metal under an atmosphere of argon and stored over 4 Å molecular sieves.

Anhydrous cobalt dichloride and anhydrous cobalt(II) benzoate were purchased from

Acros Organics, Alfa Aesar or Aldrich and used as received. Bidentante chiral

phosphines were obtained from commercial sources including Aldrich, Strem, Solvias,

Takasago, and Chiral Quest.

1H NMR spectra were recorded on a Varian Inova 400 Spectrometer operating at

399.860 MHz or a Bruker AVANCE-500 equipped with a TCI cryoprobe optimized for 1H

detection operating at 500.62 MHz. All chemical shifts are reported relative to SiMe4

using 1H (residual) chemical shifts of the solvent as a secondary standard. 13C NMR

spectra were recorded on a Bruker 500 spectrometer equipped with a DCH cryoprobe

optimized for 13C detection operating at 125.71 MHz. 13C chemical shifts are reported

relative to SiMe4 using chemical shifts of the solvent as a secondary standard where

applicable. Elemental analyses were performed at Robertson Microlit Laboratories, Inc.,

in Ledgewood, NJ. Solid-state magnetic moments were determined using a Johnson

Matthey Magnetic Susceptibility Balance, collected at room temperature, unless

otherwise noted. Solution magnetic moments were determined by the method of Evans

at 22 ºC using a ferrocene standard unless otherwise noted.(43) High-resolution mass

spectra were measured using an Agilent 6220 Accurate-Mass TOF LC/MS. The mass

spectrometer was calibrated externally before each use with purine and the Agilent ES-

4

TOF tuning mix (part number = G1969-85000). These compounds were assigned a

(M+H)+ m/z ratio of 121.050873 and 922.009798 respectively. Optical rotations were

recorded on a Perkin Elmer Model 341 polarimeter (1-mL cell, 1 dm path length);

concentration (c) is in g / 100 mL and [α]D values are in degrees. The optical rotations for

methyl 2-acetamido-3-phenylacrylate and 1,2-diphenylpropane were compared to

literature data.(34, 44 ) Racemic alkanes were independently synthesized using a

heterogeneous Pd/C catalyst to obtain chiral analysis and for comparison to

enantioselective catalytic experiments. Representative NMR spectra are included.

Gas chromatography for the alkane products was performed on a Shimadzu GC-

2010 gas chromatograph. GC analyses were performed using a Restek 15 m x 0.25 mm

RTX-5 5% diphenyl/95% dimethyl polysiloxane column with a film thickness of 0.25 μm.

The following temperature program was used: 60 ºC, 1 min ; 15 ºC/min to 250 ºC; hold 1

min. Chiral gas chromatography for the alkane products was performed on a Shimadzu

GC-2010 gas chromatogram using a Supelco 30 m x 0.25 mm BETA DEX 120 capillary

column as noted for each product. Supercritical fluid chromatography (SFC) was

performed on a Berger Minigram equipped with a diode array UV detector (λ = 214-300

nm) using a chiral column (25 cm) and guard column (5 cm) as noted for each

compound.

Single crystals suitable for X-ray diffraction were coated with polyisobutylene oil

in a drybox, transferred to a nylon loop and then quickly transferred to the goniometer

head of a Bruker X8 APEX2 DUO diffractometer equipped with a molybdenum X-ray

tube (λ = 0.71073). Preliminary data revealed the crystal system. The data collection

strategy was optimized for completeness and redundancy using the Bruker COSMO

software suite. The space group was identified, and the data were processed using the

Bruker SAINT+ program and corrected for absorption using SADABS. The structures

5

were solved using direct methods (SHELXS) completed by subsequent Fourier synthesis

and refined by full-matrix least-squares procedures.

II. Synthesis of Cobalt Precatalysts.

Preparation of (SL-A109-2)CoCl2. A 20 mL scintillation vial was

charged with 0.236 g (0.205 mmol) of SL-A109-2, 0.028 g (0.215

mmol) anhydrous cobalt dichloride and 4 mL of THF. The reaction

mixture was stirred for 30 minutes at room temperature. Excess

cobalt dichloride was removed by filtration through Celite and the

filtrate solvent was removed in vacuo. The resulting green solid was washed with 1 mL

of pentane and dried in vacuo to yield 0.221 g (0.205 mmol, 81%) of (SL-A109-2)CoCl2.

Analysis for C74H104Cl2P2O6Co: Calc. C, 69.36; H, 8.18. Found C, 68.84; H, 8.45. Solid-

state magnetic susceptibility μeff (293 K) = 3.8 μB.

Preparation of (R,R-iPr-Duphos)CoCl2. A 20 mL scintillation vial was

charged with 0.103 g (0.246 mmol) of R,R-iPr-Duphos and 0.034 g

(0.258 mmol) of anhydrous cobalt dichloride and 4 mL of THF. The

reaction mixture was stirred for 30 minutes at room temperature. Excess cobalt

dichloride was removed by filtration through Celite and the filtrate solvent was removed

in vacuo. The resulting red solid was washed with 1 mL of pentane and dried in vacuo

yielded 0.131 g (0.239 mmol, 97%) of (R,R-iPr-Duphos)CoCl2. Cooling a concentrated

diethyl ether/tetrahydrofuran (1:4) solution to -35 ºC furnished red crystals suitable for X-

ray diffraction. Analysis for C26H44Cl2P2Co: Calc. C, 56.94; H, 8.09. Found C, 56.72; H,

7.81. Solid-state magnetic susceptibility μeff (293 K) = 2.2 μB.

P

PCo

iPr iPr

iPr iPr

Cl

Cl

OO

PP

OMet-But-Bu

OMet-Bu t-Bu

Ar

ArCo

Cl

Cl

6

Preparation of (R,R-iPr-Duphos)Co(CH2SiMe3)2. A 20 mL

scintillation vial was charged with 0.029 g (0.069 mmol) of R,R-iPr-

Duphos and 2 mL of toluene. To this solution, 346 μL of a 0.2 M

solution (0.069 mmol) of (py)2Co(CH2SiMe3)2 in toluene were added and rapid formation

of an orange solution was observed. After 15 minutes of stirring at room temperature, the

volume of the orange solution was reduced in vacuo. The resulting orange film was

extracted into 5 mL of pentane and filtered through Celite. The orange filtrate was

evaporated to dryness and yielded 0.043 g (0.066 mmol, 95%) of an orange solid

identified as (R,R-iPr-Duphos)Co(CH2SiMe3)2. Cooling a concentrated pentane solution

of (R,R-iPr-Duphos)Co(CH2SiMe3)2 to -35 ºC furnished crystals suitable for X-ray

diffraction. Analysis for C34H66P2Si2Co: Calc. C, 62.64; H, 10.20. Found C, 62.58; H,

10.25. 1H NMR (C6D6, 400 MHz): -44.90 (614 Hz), -34.19 (689 Hz), -29.85 (627 Hz), -

17.12 (85 Hz), -14.80 (166 Hz), -13.84 (104 Hz), -6.68 (214 Hz), 1.27 (54 Hz), 2.22 (173

Hz), 6.32 (68 Hz), 7.50 (12 Hz), 16.08 (30 Hz), 25.80 (114 Hz). μeff (293 K, Evans,

benzene-d6) = 2.0 μB.

Preparation of (R,R-iPr-Duphos)Co(OBz)2. A 20 mL scintillation

vial was charged with 0.046 g (0.110 mmol) of R,R-iPr-Duphos and

0.035 g (0.115 mmol) of anhydrous cobalt (II) benzoate. The solids

were suspended in 5 mL of toluene. The reaction mixture was stirred for one hour at

room temperature. Excess cobalt (II) benzoate was removed by filtration through Celite

and the filtrate solvent was removed in vacuo. The resulting red solid was washed with

pentane and dried in vacuo to furnish 0.068 g (0.094 mmol, 86% yield) of a red solid

identified as (R,R-iPr-Duphos)Co(OBz)2. Cooling a concentrated toluene solution of

(R,R-iPr-Duphos)Co(OBz)2 at -35 ºC furnished crystals suitable for X-ray diffraction.

P

PCo

iPr iPr

iPr iPr

OC(O)Ph

OC(O)Ph

P

PCo

iPr iPr

iPr iPrSiMe3

SiMe3

7

Analysis for C40H54O4P2Co: Calc. C, 66.75; H, 7.56. Found C, 67.01; H, 7.43. Solid-state

magnetic susceptibility μeff (293 K) = 1.9 μB.

III. Representative Procedures for Catalytic Hydrogenation.

High Throughput Experiments: trans-Methylstilbene Screen. Each well of a 1 mL x

96 well plate array containing 4.1 x 10-4 mmol each of pre-dispensed phosphine ligands

was charged with 100 μL of a 4 mM toluene solution of (py)2Co(CH2SiMe3)2. After mixing

for 20 minutes, the volatile components were removed in vacuo using a Genevac

apparatus. Each well was then charged with 100 μL of a 40 mM toluene solution of

trans-methylstilbene. The 96 well plate was then placed in a high-pressure block and

purged with nitrogen gas and then was connected to a 1 L gas buret, followed by purging

with hydrogen gas. The block and buret were both pressurized to 500 psi. The apparatus

was agitated with mechanical shaking at room temperature for 24 hours, at which point

the block was purged with nitrogen gas and the 96 well plate was removed. The samples

were then analyzed by SFC.

High Throughput Experiments: Methyl 2-Acetamidoacrylate (MAC) Screen. Each

well of a 1 mL x 96 well plate array containing 4.1 x 10-4 mmol each of pre-dispensed

phosphine ligands was added 50 μL of an 8 mM THF solution of CoCl2. After mixing for

20 minutes, 50 μL of a 16 mM THF solution of LiCH2SiMe3 was added to each reaction

well. After 20 minutes of stirring, the volatile components were removed in vacuo using a

Genevac apparatus. Each reaction well was then charged with 100 μL of a 40 mM THF

solution of methyl 2-acetamidoacrylate. The 96 well plate was then placed in a high-

pressure block and purged with nitrogen gas and then was connected to a 1 L gas buret,

followed by purging with hydrogen gas. The block and buret were both pressurized to

8

500 psi. The apparatus was agitated via mechanical shaking at room temperature for 24

hours, at which point the block was purged with nitrogen gas and the 96 well plate was

removed. The samples were then analyzed by SFC.

Pre-formed Cobalt Precursor, Method A: A 45 mL glass well was charged with 0.047

g (0.328 mmol) of methyl 2-acetamidoacrylate, 0.011 g (0.016 mmol) of (R,R)-iPr-

DuphosCo(CH2SiMe3)2 and 8 mL of THF. Formation of an orange solution was observed.

In the glovebox, the glass well was charged into 45 mL Parr Reactor which was then

sealed, pressurized to 1000 psi H2, vented, re-pressurized to 1000 psi, and vented to the

desired pressure (500 psi). The reaction solution was mechanically stirred under the H2

pressure for the appropriate time, at which point the vessel was vented and the reaction

solution was retrieved from the vessel. The solvent was evaporated and the product was

purified by flash chromatography.

Pre-formed Cobalt Precursor, Method B: A 45 mL glass well was charged with 300 μL

of a 0.372 M solution (0.016 mmol) of (R,R)-iPr-DuphosCoCl2 and 3.7 mL of THF. A blue

solution was observed. A solution of LiCH2SiMe3 (88 μL of a 0.372 M solution, 0.033

mmol, 2 eq. relative to [Co], 10% relative to substrate) was added and a blue solution

was observed. Methyl 2-acetamidoacrylate (47 mg, 0.328 mmol) and 4 mL of THF was

added to the reaction solution. The glass well was then transferred to the Parr reactor,

which was sealed, pressurized to 1000 psi H2, vented, re-pressurized to 1000 psi, and

vented to the desired pressure (500 psi). The reaction solution was mechanically stirred

under the H2 pressure for the appropriate time, at which point the vessel was vented and

the reaction solution was retrieved from the vessel. The solvent was evaporated and the

product was purified by flash chromatography.

9

Method C: A 20 mL scintillation vial was charged with 0.007 g (0.016 mmol) of (R,R)-iPr-

Duphos, 1 mL of toluene and 82 μL of a 0.2 M solution (0.016 mmol) of

(py)2Co(CH2SiMe3)2. The reaction mixture was stirred for 10 minutes until the reaction an

orange solution was observed and the solvent was then removed under reduced

pressure. The orange residue was reconstituted in 5 mL of pentane, filtered through

celite and evaporated to afford (R,R)-iPr-DuphosCo(CH2SiMe3)2. This material was

transferred to a 45 mL glass well with 4 mL of THF. Methyl 2-aceamidoacrylate (47 mg,

0.328 mmol) was then added with an additional 4 mL of THF. The glass well was then

transferred to the Parr reactor, which was sealed, pressurized to 1000 psi H2, vented, re-

pressurized to 1000 psi, and vented to the desired pressure (500 psi). The reaction

solution was mechanically stirred under the H2 pressure for the appropriate time, at

which point the vessel was vented and the reaction solution was retrieved from the

vessel. The solvent was evaporated and the product was purified by flash

chromatography.

IV. Preparation and Purification of Alkene Substrates. Trans-methylstilbene was

purchased from Aldrich. The solid was dried in vacuo over night and brought into a glove

box. A homogenous toluene solution was passed through a plug of activated alumina

and trans-methylstilbene was recrystallized at -35 ºC from a concentrated toluene

solution. Methyl 2-acetamidoacrylate was purchased from Aldrich. The solid was dried in

vacuo over night and brought into a glove box. A homogenous tetrahydrofuran solution

was passed through a plug of activated alumina and methyl 2-acetamidoacrylate was

recrystallized at -35 ºC from the concentrated tetrahydrofuran solution. Methyl 2-

acetamido-3-phenylacrylate was prepared according the literature method(45) and the

10

solid was dried in vacuo over night and brought into a glove box. A homogenous

tetrahydrofuran solution was passed through a plug of activated alumina and methyl 2-

acetamido-3-phenylacrylate was recrystallized at -35 ºC from the concentrated

tetrahydrofuran solution. N-(1-phenylvinyl)acetamide,( 46 ) (Z)-ethyl 3-acetamido-3-

phenylacrylate(47) were prepared according to literature procedures and purified using

techniques described above.

V. Characterization of Alkane Products.

(rac)-1,2-diphenylpropane. To a thick-walled glass vessel was added 0.057

g (0.293 mmol) of α-trans-methylstilbene, 0.020 g of 5% Pd/C and

approximately 10 mL ethanol. The reaction mixture was stirred under 4 atm H2 at room

temperature for 24 hours. The Pd/C was removed through Celite filtration and the filtrate

solvent was removed in vacuo, affording 0.048 g (0.245 mmol, 83%) of a pale yellow oil

identified as 1,2-diphenylpropane. (48 mg, 0.245 mmol, 83% yield) as a pale yellow oil.

1H NMR (CDCl3, 500.15 MHz): δ 1.24 (d, 3JHH = 6.78 Hz, 3H, PhCHCH3), 2.77 (dd, 2JHH =

13.07 Hz, 3JHH = 8.17 Hz, 1H, PhCH2, one set of diastereotopic resonances), 2.95 (dd,

2JHH = 13.07 Hz, 3JHH = 6.40 Hz, 1H, PhCH2, one set of diastereotopic resonances), 3.00

(m, 1H, PhCHCH3, overlapping signal), 7.09 (m, 2H, Ph-CH), 7.22 (m, 8H, Ph-CH,

overlapping resonances with residual solvent resonance). 13C{1H} NMR (CDCl3, 125.88

MHz): δ 21.17 (PhCHCH3), 41.90 (PhCHCH3), 45.06 (PhCH2), 125.86 (Ph-CH), 126.04

(Ph-CH), 127.07 (Ph-CH), 128.12 (Ph-CH), 128.33 (Ph-CH), 129.19, (Ph-CH), 140.85

(ipso Ph-C), 147.07 (ipso Ph-C). GC-MS: Calcd for C8H9, [M-PhCH2], m/z 105.07.

Found, m/z 105.0. Chiral SFC analysis of 1,2-diphenylpropane: (OJ-H, 10% MeOH/CO2,

3.0 mL/min, 300 nm) enantiomer retention times: 3.16 min (R)-(–)-1,2-diphenylpropane;

3.85 min (S)-(+)-1,2-diphenylpropane; alkene retention time: 6.94 min. Absolute

PhPh

11

configuration measurement: multiple catalytic samples containing 1,2-diphenylpropane in

~89%ee were combined to afford 0.33 g of alkane that was used for the optical rotation

measurements. [α]22D = -56.92º (c = 16.7, CH2Cl2), corresponding to (R)-(–)-1,2-

diphenylpropane. The optical rotation measurent for (R)-(–)-1-methoxy-4-(1-

phenylpropan-2-yl)benzene was compared as a reference.44

(rac)-Methyl 2-acetamido-3-phenylpropanoate. To a thick-walled glass

vessel was added 0.091 g (0.415 mmol) of (Z)-methyl 2-acetamido-3-

phenylacrylate, 0.020 g of 5% Pd/C and approximately 10 mL of ethanol. The

reaction mixture was stirred under 4 atm H2 at room temperature for 12 hours. The Pd/C

was removed through Celite filtration and the filtrate solvent was removed in vacuo

affording 0.083 g (0.375 mmol, 90%) of a while solid identified as methyl 2-acetamido-3-

phenylpropanoate. 1H NMR (CDCl3, 500.15 MHz): δ 1.41 (d, 3JHH = 7.21 Hz, 3H,

CHCH3), 2.03 (s, 3H, HNC(O)CH3), 3.75 (s, 3H, CO2CH3), 4.60 (dq, 3JHH = 7.28 Hz, 3JHH

= 7.28 Hz, 1H, HNCHCH3), 6.11 (br s, 1H, NHCHCH3). 13C{1H} NMR (CDCl3, 125.89

MHz): δ 18.73 (HNCHCH3), 23.32 (HNC(O)CH3), 48.19 (HNCHCH3), 52.69 (CO2CH3),

169.81 (HNC(O)CH3), 173.75 (CO2CH3). HR-MS (+EI): Calcd for C6H11NO3Na, [M+Na]+,

m/z 168.063657. Found, m/z 168.06358. The product was analyzed on a Supelco 30 m

(S)(S)

(+)-(S)-1,2-diphenylpropane

(R)(R)

(–)-(R)-1,2-diphenylpropane

HN

O

O

O

12

x 0.25 mm BETA DEX 120 capillary column using the following temperature program: 90

ºC for 75 min, 20 ºC/min until 200 ºC, hold 200 ºC for 6 min.. Enantiomer retention times:

58.03 min (S)-methyl 2-aceamidopropanoate, 59.56 min (R)-methyl 2-

acetamidopropanoate. Alkene retention time: 44.38 min. Enantiopure samples of alkane

were purchased and analyzed using this separation method to determine the absolute

configuration.

Methyl 2-acetamido-3-phenylpropanoate. (Z)-methyl 2-acetamido-3-

phenylacrylate (91 mg, 0.415 mmol), 5% Pd/C (20 mg) in approximately

10 mL of ethanol was stirred at room temperature under 4 atm H2. After

12 hours, the mixture was filtered through celite and the solvent was removed under

reduced pressure affording methyl 2-acetamido-3-phenylpropanoate (83 mg, 0.375

mmol, 90% yield) as a colorless oil (Rf = 0.28, 50% EtOAc/hexanes) 1H NMR (CDCl3,

500.15 MHz): δ 1.99 (s, 3H, C(O)CH3), 3.09 (dd, 2JHH = 13.85 Hz, 3JHH = 5.74 Hz, 1H,

PhCH2 diastereotopic CH2 resonances are overlapping), 3.15 (dd, 2JHH = 13.85 Hz, 3JHH

HNO

O

O

(S)(S)

HNO

O

O

(R)(R)

HNO

O

O

13

= 5.74 Hz, 1H, PhCH2) 3.73 (s, 3H, CO2CH3), 4.88 (dt, 2JHH = 7.76 Hz, 3JHH = 5.76 Hz,

1H, PhCH2CH), 5.97 (br d, 3JHH = 6.26 Hz, 1H, NH), 7.09 (m, 2H o-Ph-CH), 7.27 (m, 3H,

m-Ph-CH and p-Ph-CH). 13C{1H} NMR (CDCl3, 125.89 MHz): δ 23.25 (NC(O)CH3),

37.95 (PhCH2), 52.49 (CO2CH3), 53.25 (PhCH2CH), 127.29 (Ph-CH), 128.73 (Ph-CH),

129.37 (Ph-CH), 135.91 (ipso Ph-C), 169.87 (NC(O)CH3), 172.22 (CO2CH3). HR-MS

(+EI): Calcd for C12H15NO3Na, [M+Na]+, m/z 221.10519. Found, m/z 221.10498. The

product was analyzed on a Supelco 30 m x 0.25 mm BETA DEX 120 capillary column

using the following temperature program: 130 ºC for 140 min, 20 ºC/min until 200 ºC,

hold 200ºC for 6 min. Enantiomer retention times: 129.49 min (R)-(–), 129.66 min (S)-(+).

Alkene retention time: 125.55 min. Absolute configuration measurement: a catalytic

experiment resulting in >99% conversion and 92.7% ee was purified using column

chromatography and used for an optical rotation measurement. [α]22D = +13.3º (c = 1.5,

methanol), corresponding to (S)-(+) methyl 2-acetamido-3-phenylacrylate.

(rac)-N-(phenylethyl)-acetamide. To a thick-walled glass vessel was

added 0.100 g (0.620 mmol) of N-(1-phenylvinyl)-acetamide (100 mg,

0.62 mmol), 0.020 g of 5% Pd/C and approximately 10 mL ethanol. was stirred at room

temperature under 4 atm H2. The reaction mixture was stirred under 4 atm H2 at room

temperature for 12 hours. The Pd/C was removed through Celite filtration and the filtrate

solvent was removed in vacuo, affording 0.089 g (0.545 mmol, 88% yield) of a clear oil

NH

O

HNO

O

O

14

identified as N-(phenylethyl)-acetamide.1H NMR (CDCl3, 500.15 MHz): δ 1.50 (d, 3JHH =

6.89 Hz, 3H, CHCH3), 1.99 (s, 3H, C(O)CH3), 5.14 (m, JHH = 7.36 Hz, 1H, CHCH3), 5.67

(br s, 1H, NH), 7.31 (m, 5H, C6H5 overlapping signals). 13C{1H} NMR (CDCl3, 125.89

MHz): δ 21.79 (CHCH3), 23.56 (C(O)CH3), 48.95 (CHCH3), 126.33 (Ph-CH), 127.54 (Ph-

CH), 128.82 (Ph-CH), 143.20 (ipso Ph-C), 169.34 (C(O)CH3). HR-MS (+EI): Calcd for

C10H13NO, [M]+, m/z 163.09971. Found, m/z 163.09968. The product was analyzed on a

Supelco 30 m x 0.25 mm BETA DEX 120 capillary column using the following

temperature program: 130 ºC for 140 min, 20 ºC/min until 200 ºC, hold 200ºC for 6 min.

Enantiomer retention times: 59.41 min (S), 62.33 min (R). Alkene retention time: 125.94

min. An authentic sample of (S)-N-(phenylethyl)-acetamide was independently prepared

and analyzed with this chiral GC method.

NH

O

15

VI. NMR Spectra of Alkane Products.

Figure S1. 1H NMR spectrum of 1,2-diphenylpropane in chloroform-d.

Figure S2. 13C NMR (APT) spectrum of 1,2-diphenylpropane in chloroform-d.

16

Figure S3. 1H NMR spectrum of methyl 2-acetamidopropanote in chloroform-d.

Figure S4. 13C NMR (APT) spectrum of methyl 2-acetamidopropanoate in chloroform-d.

NH O

OO

NH O

OO

17

Figure S5. 1H NMR spectrum of methyl 2-acetamido-3-phenylpropanoate in chloroform-d.

Figure S6. 13C NMR spectrum of methyl 2-acetamido-3-phenylpropanoate in chloroform-d.

HNO

O

O

HNO

O

O

18

Figure S7. 1H NMR spectrum of N-(1-phenylethyl)acetamide in chloroform-d.

NH

O

19

VII. Crystallographic Data

Figure S8. Solid state structures of (R,R)-(iPrDuPhos)Co(CH2SiMe3)2 (left), (R,R)-(iPrDuPhos)CoCl2 (middle) and (R,R)-(iPrDuPhos)Co(OBz)2 (right) at 30% probability ellipsoids. Hydrogen atoms and additional molecules present in the unit cell omitted for clarity.

Figure S9. Additional representations of the solid state structure of (R, R)-(iPrDuphos)CoCl2 at 30% probability ellipsoids. Hydrogen atoms and additional molecules in the unit cell omitted for clarity.

! !

!

!!

20

VIII. Phosphine Evaluation Screen with Methyl 2-acetamidoacrylate (MAC).

Figure S10. Evaluation of various enantiopure phosphine ligands in combination with (py)2Co(CH2SiMe3)2 for the asymmetric hydrogenation of methyl 2-acetamidoacrylate.

N CoN

SiMe3

SiMe3

chiral phosphine +

in situ generated catalyst

0.041 M substrate, 10% [Co] + ligand, 500 psi H2, 0.1 mL THF, 20 hr

O

NH O

OO

NH O

O

21

Figure S11. Evaluation of various enantiopure phosphine ligands in combination with (py)2Co(CH2SiMe3)2 for the asymmetric hydrogenation methyl 2-acetamidoacrylate.

22

Figure S12. Bubble plot representing results of high throughput evaluation of chiral phosphines in combination with (py)2Co(CH2SiMe3)2 for the asymmetric hydrogenation of methyl 2-acetamidoacrylate (MAC).

(R,R)-iPr-Duphos!

(S,S)-Et-DuPhos! (S,S)-Me-DuPhos!

(S)-Binapine!

(S,S)-1,2-(Me,PhP)Ph!

-20!

0!

20!

40!

60!

80!

100!

120!

>99% conversion >50% conversion 10% conversion

DuPhos

P

P

R R

RR

(S,S)-1,2-(Me,PhP)Ph

P

P

H3C Ph

Ph CH3

(S)-Binapine

PtBu

PtBu

H

H

N CoN

SiMe3

SiMe3

chiral phosphine +

in situ generated catalyst

0.041 M substrate, 10% [Co] + ligand, 500 psi H2, 0.1 mL THF, 20 hr

O

NH O

OO

NH O

O

23

Table S1. Percent conversion and enantioselectivity of various chiral phosphines in combination with (py)2Co(CH2SiMe3)2 for the asymmetric hydrogenation of methyl 2-acetamidoacrylate (MAC).

Ligand %ee product

conversion (%)

(R,R)-iPr-Duphos

94.0% (S) 92.3%

(S,S)-Et-Duphos

25.9% (S) 3.7%

(S,S)-Me-Duphos

23.5% (S) 20.9%

(S)-Binapine

14.6% (R) 5.6%

(S,S)-1,2-(Me,PhP)2Ph

6.7 (R) >99%

24

Figure S13. Evaluation of various enantiopure phosphine ligands in combination with CoCl2 and Me3SiCH2Li for the asymmetric hydrogenation of methyl 2-acetamidoacrylate.

chiral phosphine +

in situ generated catalyst

0.041 M substrate, 10% CoCl2 + ligand, 20% Me3SiCH2Li, 500 psi H2, 0.1 mL THF, 20 hr

CoCl2 + Me3SiCH2LiO

NH O

OO

NH O

O

!"!#

$!"!#

%!"!#

&!"!#

'!"!#

(!"!#

)!"!#

*!"!#

+!"!#

,!"!#

$!!"!#

-./.0123456789#

-./.01:;1<8:#

=>;?@43A#BCC-.0#

-./.0148D1E38F6G#

-./.01<H5I89#

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-./.01:;1E38F6G#

-@/@01<4G89#%L<M'#

@N18!(&1%#

-@/@01$/%1-B

H/8F808F#

-./.01BH1E38F6G#

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@N1P(!*1$#

-./.01BH1<8:#

@N1P%!&1%#

QHH#

Q#=65RHDG465#

25

Figure S14. Evaluation of various enantiopure phosphine ligands in combination with CoCl2 and Me3SiCH2Li for the asymmetric hydrogenation of methyl 2-acetamidoacrylate (MAC).

chiral phosphine +

in situ generated catalyst

0.041 M substrate, 10% CoCl2 + ligand, 20% Me3SiCH2Li, 500 psi H2, 0.1 mL THF, 20 hr

CoCl2 + Me3SiCH2LiO

NH O

OO

NH O

O

BPE:

(R,R)-Me-BPE: >99% (52.9% ee, R)(R,R)-Et-BPE: >99% (95.3% ee, R)

P

P

R R

R RN

N P

P

(R,R)-QuinoxP*: 93.2% (96.4% ee, R)

Duphos:

(R,R)-Me-Duphos: 9.0% (72.5% ee, R)(R,R)-Et-Duphos: 80.1% (90.3%ee, S)(R,R)-iPr-Duhpos: 92.3% (94.2% ee, S)

P

P

R R

R R

NN

P

P

O

O

catASium MNN(R):13.0% (94.7% ee, R)

P

P

(R,R)-BenzP*: >99% (93.4% ee, R)

P

P

tBu

tBu

HH

(SS!,RR!)-Tangphos: >99% (93.0% ee, R)

P

P

tBu

tBu

(S,S)-BisP* 2HBF4: >99% (86.5% ee, R)(ligand treated with 2 eq. KOtBu prior to use)

2 HBF4

FeP PPh2

SL-P053-2 (S,S,R)-Me-Kephos: 2.7% (78.0% ee, S)

P

P

H3C Ph

Ph CH3

(S,S)-1,2-(MePPh)2Ph: >99% (77.0% ee, S)

PtBu

PtBu

H

H

(S)-Binapine: 22.5% (70.9% ee, R)

Josiphos:

SL-J203-2: 3.8% (23.1% ee, R)SL-J507-1: 2.4% (63.4% ee, S)

Fe PR22R12P

26

Table S2. Percent conversion and enantioselectivity of various chiral phosphines in combination with CoCl2 and Me3SiCH2Li for the asymmetric hydrogenation of methyl 2-acetamidoacrylate.

Ligand %ee product

conversion (%)

(R,R)-QuinoxP*

96.4% (R) 93.2%

(R,R)-Et-BPE

95.3% (R) >99%

catASium MNN(R)

94.7% (R) 13.0%

(R,R)-iPr-Duphos

94.2% (S) 92.3%

(R,R)-BenzP*

93.4% (R) >99%

(S,S′,R,R′)-Tangphos

93.0 (R) >99%

N

N P

P

P

P

NN

P

P

O

O

P

P

iPr iPr

iPriPr

P

P

P

P

tBu

tBu

HH

27

(R,R)-Et-Duphos

90.3% (S) 80.1%

(S,S)-BisP* 2HBF4

86.5% (R) >99%

SL-P053-2

78.0% (S) 2.7%

(S,S)-1,2-(MePPh)2Ph:

77.0% (S) >99%

(R,R)-Me-Duphos

72.5% (R) 9.0%

(S)-Binapine

70.9% (R) 22.5%

SL-J507-1

63.4% (R) 2.4%

P

P

P

P

tBu

tBu

2 HBF4

FeP PPh2

P

P

H3C Ph

Ph CH3

P

P

PtBu

PtBu

H

H

FePP

28

(R,R)-Me-BPE

52.9% (R) >99% P

P

29

IX. Phosphine Evaluation Screen with Acetomidostyrene.

Figure 15. Evaluation of various enantiopure phosphine ligands in combination with (py)2Co(CH2SiMe3)2 for the asymmetric hydrogenation of N-(1-phenylvinyl)acetamide.

N CoN

SiMe3

SiMe3

chiral phosphine +

in situ generated catalyst

0.041 M substrate, 10% [Co] + ligand, 500 psi H2, 0.1 mL THF, 20 hr

NH

O

NH

O

!"!#

$!"!#

%!"!#

&!"!#

'!"!#

(!"!#

)!"!#

*!"!#

+!"!#

,!"!#

$!!"!#

-./01234#56#5789:;<#

1=>?)++>$#

:1@1<>$@%>:5

7@ABA<%AB#

:;@;<>57>C3ABD8#

:1<>E2F.G2F7#

:;<>E2F.GB.F7#

:;@;<>2AH>C3ABD8#

:;@;<>I32FDJAK#

:;<>EL6M=>A>M2AH#

:1@1@;@;<>N.FOABD8#

:;@;<>E7FPAK#

Q77#

Q#-DFR7H82DF#

30

Figure S16. Evaluation of various enantiopure phosphine ligands in combination with (py)2Co(CH2SiMe3)2 for the asymmetric hydrogenation of N-(1-phenylvinyl)acetamide.

N CoN

SiMe3

SiMe3

chiral phosphine +

in situ generated catalyst

0.041 M substrate, 10% [Co] + ligand, 500 psi H2, 0.1 mL THF, 20 hr

NH

O

NH

O

P

P

catASium MN MesF(R):36.8% (83.1% ee, S)

N

O

OF3C

F3C FePH PO

SL-J688-1:6.2%% (81.2% ee, R)

P

P

H3C Ph

Ph CH3

(S,S)-1,2-(MePPh)2Ph: 17.8% (54.1% ee, R)

Duphos:

(R,R)-Me-Duphos: 99% (54.1% ee, R)(R,R)-iPr-Duhpos: 9.8% (8.7% ee, S)

P

P

R R

R R

PtBu

PtBu

H

H

(S)-Binapine: 4.8% (26.4% ee, R)

P

P

(R)-Binaphane: 4.1% (10.3% ee, S)N

N P

P

(R,R)-QuinoxP*: 4.2% (5.1% ee, R)

O

OP O

(R)-BINOL-P-OiPr:3.3% (3.8% ee, R)

P

P

tBu

tBu

HH

(SS!,RR!)-Tangphos: 27.9% (2.7% ee, R)

P

P

(R,R)-BenzP*: 14.4% (2.6% ee, R)

31

Table S3. Percent conversion and enantioselectivity of various chiral phosphines in combination with (py)2Co(CH2SiMe3)2 for the asymmetric hydrogenation of N-(1-phenylvinyl)acetamide.

Ligand %ee product

conversion (%)

catASium MN MesF(R)

83.1% (S) 36.8%

SL-J688-1

81.2% (R) 6.2%

(S,S)-1,2-(Me,PhP)2Ph

54.1% (R) 17.8%

(R,R)-Me-Duphos

31.1% (R) 99.0%

(S)-Binapine

26.4% (S) 4.8%

(R)-Binaphane

10.3% (R) 4.1%

P

PN

O

OF3C

F3C

FePH PO

P

P

H3C Ph

Ph CH3

P

P

PtBu

PtBu

H

H

PP

32

(R,R)-iPr-Duphos

8.7% (S) 9.8%

(R,R)-QuinoxP*

5.1% (R) 4.2%

(R)-BINOL-P-OiPr

3.8% (R) 3.3%

(S,S′,R,R′)-Tangphos

2.7% (R) 27.9%

(R,R)-BenzP*

2.6% (R) 14.4%

P

P

iPr iPr

iPr iPr

N

N P

P

O

OP O

P

P

tBu

tBu

HH

P

P

33

Figure S17. Evaluation of various enantiopure phosphine ligands in combination with CoCl2 and Me3SiCH2Li for the asymmetric hydrogenation of N-(1-phenylvinyl)acetamide.

chiral phosphine +

in situ generated catalyst

0.041 M substrate, 10% [oCl2 + ligand, 20% NsLi, 500 psi H2, 0.1 mL THF, 20 hr

NH

O

NH

OCoCl2 + Me3SiCH2Li

!"

#!"

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%!"

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)!"

*!"

+!"

#!!"

,-.-/0120345678"

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,-/05>7J678"

,-/0<=A@J6@A;"

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34

Figure S18. Evaluation of various enantiopure phosphine ligands in combination with CoCl2 and Me3SiCH2Li for the asymmetric hydrogenation of N-(1-phenylvinyl)acetamide.

chiral phosphine +

in situ generated catalyst

0.041 M substrate, 10% [oCl2 + ligand, 20% NsLi, 500 psi H2, 0.1 mL THF, 20 hr

PtBu

PtBu

H

H

(S)-Binapine: 16.1% (26.9% ee, R)

NH

O

NH

OCoCl2 + Me3SiCH2Li

NN

P

P

Duphos:

(R,R)-Me-Duphos: 35.5% (9.2%, S)(R,R)-Et-Duphos: 98.1% (73.9% ee, R)(R,R)-iPr-Duphos: 7.3% (49.7% ee, S)

P

P

R R

R R

(R,R)-Et-BPE: 5.7% (52.5% ee, R)

P

P

H3C Ph

Ph CH3

(S,S)-1,2-(MePPh)2Ph: 64.9% (29.7% ee, R)

P

P

tBu

tBu

HH

(SS!,RR!)-Tangphos: 96.0% (41.4% ee, R)

P

P

tBu

tBu

(S,S)-BisP* 2HBF4: 2.1% (33.8% ee, S)(ligand treated with 2 eq. KOtBu prior to use)

2 HBF4

O

O

catASium MNN(R):20.7% (29.2% ee, S)

P

P

R R

R R

P

P

(R,R)-BenzP*: 10.7% (26.4% ee, S)

N

N P

P

(R,R)-QuinoxP*: 65.9% (15.8% ee, R)

PPO

OO

O

(S,S,S,S)-Me-ketalphos: 13.2% (15.0% ee, S)

FeHP PR2

R2

R1

O

JoSPOphos:

SL-J681-1: 4.0% (11.4% ee, R)SL-J688-1: >99% (8.2% ee, S)

FeP PPh2

SL-P051-1 (R,R,R)-Me-Kephos: 13.1% (-9.7% R)SL-P053-2 (S,S,R)-Me-Kephos: 11.8% (9.9% ee, S)

PPh2

NH2(1R,2R)-2-(diphenylphosphino)cyclohexanamine:3.8% (8.7% ee, S)

FeP P

SL-J302-1: 2.3% (8.2% ee, S)

PPh2

PPh2

(R)-Prophos: 11.9% (6.2% ee, R)

PP

(R)-Binaphane: 4.6% (5.3% ee, S)

Fe

PN

O

F3C

F3CSL-N007-2: 28.2% (3.9% ee, S)

35

Table S4. Percent conversion and enantioselectivity of various chiral phosphines in combination with CoCl2 and Me3SiCH2Li for the asymmetric hydrogenation of N-(1-phenylvinyl)acetamide.

Ligand %ee product

conversion (%)

(R,R)-Et-Duphos

73.9% (R) 98.1%

(S,S)-1,2-(Me,PhP)2Ph

64.9% (R) 29.7%

(R,R)-Et-BPE

52.5% (R) 5.7%

(R,R)-iPr-Duphos

49.7% (S) 7.3%

(S,S′,R,R′)-Tangphos

41.4% (R) 96.0%

(S,S)-BisP*-2HBF4 (treated with 2 eq. KOtBu prior to use)

33.8% (S) 2.1%

catASium MNN(R) 29.2% (S) 20.7%

P

P

P

H3C Ph

Ph CH3

P

P

P

iPr iPr

iPriPr

P

P

tBu

tBu

HH

P

P

tBu

tBu

2 HBF4

36

(S)-Binapine

26.9% (R) 16.1%

(R,R)-BenzP*

26.4% (S) 10.7%

(R,R)-QuinoxP*

15.8% (R) 65.9%

(S,S,S,S)-MeKetalPhos

15.0% (S) 13.2%

SL-J681-1

11.4% (R) 4.0%

SL-P053-2

9.9% (S) 11.8%

NN

P

P

O

O

PtBu

PtBu

H

H

P

P

N

N P

P

PPO

OO

O

FeHP PO

FeP PPh2

37

SL-P051-1

9.7% (R) 13.1%

(R,R)-MeDuphos

9.2% (S) 35.5%

(1R,2R)-2-(diphenylphosphino)cyclohexanamine

8.7% (S) 3.8%

SL-J302-1

8.2% (S) 2.3%

SL-J688-1

8.2% (S) >99%

(R)-Prophos

6.2% (R) 11.9%

(R)-Binaphane

5.3% (S) 4.6%

FeP PPh2

P

P

PPh2

NH2

FePP

FePH PO

PPh2

PPh2

PP

38

SL-N007-2

3.9% (S) 28.2%

Fe

PN

O

F3C

F3C

39

X. Phosphine Evaluation with trans-(α)-Methylstilbene.

Figure S19. Evaluation of various enantiopure phosphine ligands in combination with (py)2Co(CH2SiMe3)2 for the asymmetric hydrogenation of trans-(α)-methylstilbene.

chiral phosphine + (py)2Co(CH2SiMe3)2

0.041 M substrate, 10% [Co] + ligand, 500 psi H2, 0.1 mL toluene

in situ generated catalyst

PhPh

PhPh

0!

10!

20!

30!

40!

50!

60!

70!

80!

90!

100!

SL-A

109-

2!(R

,R)-B

ICP!

SL-J

417-

1!SL

-J03

4-1!

(R)-D

TBM

-Seg

Phos!

(R)-D

M-S

egPh

os!

SL-A

120-

2!SL

-J41

2-1!

SL-N

007-

2!SL

-A10

2-1!

SL-J

220-

1!SL

-J03

1-1!

(Rc,S

p)-D

uanP

hos!

SL-N

004-

2!SL

-J40

4-1!

(S,S

)-1,2

-(MeP

Ph)2

Ph!

SL-J

001-

1!SL

-J20

4-1!

SL-J

851-

2!Ca

rboP

hos!

(S)-B

inapin

e!SL

-J85

3-2!

(S,S

)-Me-

UCAP

-DTB

M!

SL-J

408-

1!SL

-J50

5-1!

SL-J

418-

1!SL

-N00

8-2!

SL-P

053-

2!SL

-M01

2-1!

SL-J

222-

1!(S

,S)-C

hiraP

hos!

SL-F

011-

2!SL

-J01

1-1!

SL-J

301-

1!(-)

-Mod

DIO

P!SL

-J00

5-1!

SL-J

852-

2!

Hydrogenation of trans-methylstilbene!

%ee!% conversion!

40

Figure S20. Evaluation of various enantiopure phosphine ligands in combination with (py)2Co(CH2SiMe3)2 for the asymmetric hydrogenation of trans-(α)-methylstilbene.

N CoN

SiMe3

SiMe3

chiral phosphine +

in situ generated catalyst

Ph Ph Ph Ph

0.041 M substrate, 10% [Co] + ligand, 500 psi H2, 0.1 mL toluene, 22 ºC, 20 hr

OO

PPAr

ArAr

Ar

PPAr

ArAr

ArO

O

O

O

MeO-Biphep:

SL-A102-1: 14.7% (49.2% ee, S) SL-A120-2: 23.9% (55.7% ee, R)SL-A109-2: 83.1% (93.8% ee, R)

Segphos:

(R)-DM-Segphos: 27.4% (58.4%, S)(R)-DTBM-Segphos: 23.8% (61.5%, S)

P

P

tBu

tBu

HH

(RR!,SS!)-Duanphos: 22.0% (43.1% ee, S)

Fe

PAr

Ar N

O

SL-N004-2: 24.1% (43.0% ee, S)SL-N007-2: 15.4% (49.2% ee, R)SL-N008-2: 24.6% (8.1% ee, S)

Fe PR22R12P

Josiphos:

SL-J001-1: 15.2% (30.7% ee, S)SL-J005-1: 13.6% (1.0% ee, S)SL-J011-1: 13.2% (2.0% ee, R)SL-J031-1: 13.0% (46.6% ee, S)SL-J034-1: 80.1% (62.2% ee, R)

SL-J204-1: 16.2% (29.0% ee, S)SL-J220-1: 17.0% (47.3% ee, S)SL-J222-1: 21.0% (3.7% ee, S)

SL-J301-1: 33.7% (1.3% ee, R)

SL-J404-1: 21.2% (33.2% ee, S)SL-J408-1: 67.5% (15.7% ee, S)SL-J412-1: 22.3% (50.7% ee, S)SL-J417-1: 22.3% (71.6% ee, S)SL-J418-1: 41.5% (14.7% ee, S)

SL-J505-1: 24.5% (15.7% ee, S)

SL-J851-2: 86.1% (28.6% ee, R)SL-J852-2: 22.5% (0.5% ee, S)SL-J853-2: 70.6% (18.6% ee, R)

PPh2HPPh2

H

(R,R)-BICP: 12.9% (74.9% ee, S)

P

P

H3C Ph

Ph CH3

(S,S)-1,2-(MePPh)2Ph: 13.9% (31.9% ee, R)O OOC(O)Ph

OC(O)Ph

O P

OP

CarboPhos: 64.4% (27.3% ee, S) PtBu

PtBu

H

H

(S)-Binapine: 34.1% (21.2% ee, R)

P

P

tBu

tBu tBu O

tBu

O

(S,S)-Me-UCAP-DTBM: 23.8% (16.7%, R)

FeP PPh2

SL-P053-2: 29.4% (5.0% ee, S)

FePPh

NMe2

P

Me2N Ph

SL-F011-2: 43.8% (2.5% ee, R)

PPh2

PPh2

(S,S)-Chiraphos: 20.3% (2.8% ee, S)

FePh2PNPh2P

PPh2

N PPh2

OO

PP

O

OO

O

(–)-Mod-DIOP: 43.6% (1.1% ee, S)

SL-M012-1: 44.7% (4.0% ee, R)

41

Table S5. Percent conversion and enantioselectivity of various chiral phosphines in combination with (py)2Co(CH2SiMe3)2 for the asymmetric hydrogenation of trans-(α)-methylstilbene.

Ligand %ee product conversion (%)

SL-A109-2

93.8 (R) 83.1

(R,R)-BICP

74.9 (S) 12.9

SL-J417-1

71.6 (S) 22.3

SL-J034-1

62.2 (R) 80.1

(R)-DTBM-SegPhos

61.5 (S) 23.8

OO

PP

OMetButBu

OMetBu tBu

Ar

Ar

PPh2HPPh2H

FePP

Fe PPh2P

Me3Si

PP

OMetButBu

OMetBu tBu

Ar

ArO

O

O

O

42

(R)-DM-SegPhos

58.4 (S) 27.4

SL-A120-2

55.7 (R) 23.9

SL-J412-1

50.7 (S) 22.3

SL-N007-2

49.2 (R) 15.4

SL-A102-1

49.2 (S) 14.7

PP

Ar

ArO

O

O

O

OO

PP

Ar

Ar

FePP

CF3

CF3

CF3F3C

Fe

PF3C

CF3

F3C CF3

N

O

OO

PP

Ar

Ar

43

SL-J220-1

47.3 (S) 17.0

SL-J031-1

46.6 (S) 13.0

(Rc,Sp)-DuanPhos

43.1 (S) 22.0

SL-N004-2

43.0 (S) 24.1

SL-J404-1

33.2 (S) 21.2

(S,S)-1,2-(MePPh)2Ph

31.9 (R) 13.9

FeP P

O

O

FePP

P

P

tBu

tBu

HH

Fe

PN

O

Fe PP

P

P

H3C Ph

Ph CH3

44

SL-J001-1

30.7 (S) 15.2

SL-J204-1

29.0 (S) 16.2

SL-J851-2

28.6 (R) 86.1

CarboPhos

27.3 (S) 64.4

(S)-Binapine

21.2 (R) 34.1

Fe PPh2P

FePP

F3C

F3C

FePh2P

PCy2

PPh2

PCy2

O OOC(O)Ph

OC(O)Ph

O P

OP

PtBu

PtBu

H

H

45

SL-J853-2

18.6 (R) 70.6

(S,S)-Me-UCAP-DTBM

16.7 (R) 23.8

SL-J408-1

15.7 (S) 67.5

SL-J505-1

15.7 (S) 24.5

SL-J418-1

14.7 (S) 41.5

FeP

PtBu2

P

PtBu2

O

O

O

O

P

P

tBu

tBu tBu O

tBu

O

FePP

FePPtBu

tBu

FeP P

O

O

46

SL-N008-2

8.1 (S) 24.6

SL-P053-2

5.2 (S) 29.4

SL-M012-1

4.0 (R) 44.7

SL-J222-1

3.7 (S) 21.0

(S,S)-ChiraPhos

2.8 (S) 20.3

SL-F011-2

2.5 (R) 43.8

SL-J011-1

2.0 (R) 13.2

Fe

PN

O

O

O

FeP PPh2

FeP

PhNMe2

P

Me2N Ph

FeP P

O

O

tBu

tBu

PPh2

PPh2

FePh2PN

Ph2P

PPh2

N PPh2

FePP

F3C

F3C

tBu

tBu

47

SL-J301-1

1.3 (R) 33.7

(-)-Mod DIOP

1.1 (S) 43.6

SL-J005-1

1.1 (S) 13.6

SL-J852-2

0.5 (S) 22.5

FePP tBu

tBu

O

O

P

P

O O

OO

FePP

Fe

PPh2

PPh2

P P

48

Figure S21. Evaluation of various enantiopure phosphine ligands in combination with CoCl2 and two equivalents of LiCH2SiMe3 for the asymmetric hydrogenation of trans-(α)-methylstilbene.

chiral phosphine +

in situ generated catalyst

0.041 M substrate, 10% CoCl2 + ligand, 20% LiCH2SiMe3, 500 psi H2, 0.1 mL THF, 24 hr

CoCl2 + LiCH2SiMe3

!"

#!"

$!"

%!"

&!"

'!"

(!"

)!"

*!"

+!"

#!!"

SL-A104-1!

SL-J222-1!

(R,R)-BenzP*!

SL-J605-1!

(S,S,R,R)-TangPhos!

SL-J004-1!

(R,R)-iPr-DuPhos!

(S)-DTBM-Garphos!

(R,R)-iPr-BPE!

SL-J001-1!

(S)-Binapine!

SL-J203-2!

(R,R)-Me-Ferrolane!

SL-J688-1!

SL-J408-1!

SL-J220-1!

(S)-C5-TunePhos!

SL-P051-1!

SL-J005-1!

SL-P053-2!

,--"

,"./01-234/0"

49

Figure S22. Evaluation of various enantiopure phosphine ligands in combination with CoCl2 and two equivalents of LiCH2SiMe3 for the asymmetric hydrogenation of trans-(α)-methylstilbene.

chiral phosphine +

in situ generated catalyst

0.041 M substrate, 10% CoCl2 + ligand, 20% LiCH2SiMe3, 500 psi H2, 0.1 mL THF, 24 hr

CoCl2 + LiCH2SiMe3

OO P

MeOOMe

OMeOMe

OMe

OMeP

MeOOMe

OMeOMe

OMe

OMe

SL-A104-1: 17.4% (-70.3% ee)

Josiphos:

SL-J001-1: 6.9% (32.5% ee)SL-J004-1: 7.1% (-49.7% ee)SL-J203-2: 6.2% (17.0% ee)SL-J220-1: 11.4% (-9.0% ee)SL-J222-1: 7.3% (69.8% ee)SL-J408-1: 7.0% (-10.4% ee)

Fe PR22R12P

P

P

(R,R)-BenzP*: 11.1% (-60.0% ee)

FeP PCy2

Ph

SL-J605-1: 38.4% (-57.8% ee)

P

P

tBu

tBu

HH

(SS!,RR!)-Tangphos: 6.2% (-51.8% ee)

P

P

iPr iPr

iPriPr

(R,R)-iPrDuphos:7.6% (37.1% ee)

OO P

t-BuOMe

t-But-Bu

OMe

t-BuP

t-Bu OMet-But-Bu

OMe

t-Bu

MeO

MeO

(S)-DTBM-Garphos:7.7% (34.6% ee)

P

P

iPr iPr

iPriPr

(R,R)-iPrBPE:7.5% (33.5% ee)

PtBu

PtBu

H

H

(S)-Binapine: 11.5% (18.1% ee)

FeP

P

(R,R)-Me-Ferrolane:8.6% (-14.7% ee )

FePH P

Ph

O

SL-J688-1: 13.8% (-13.2% ee)

OO P

P (S)-C5-TunePhos: 6.0% (7.4% ee)

FeP PPh2

SL-P051-1 (R,R,R)-Me-Kephos: 7.4% (4.2% ee)SL-P053-2 (S,S,R)-Me-Kephos: 7.0% (2.9% ee)

50

Table S6. Percent conversion and enantioselectivity of various chiral phosphines in combination with CoCl2 and two equivalents of LiCH2SiMe3 for the asymmetric hydrogenation of trans-(α)-methylstilbene.

Ligand %ee product conversion (%)

SL-A104-1

-70.3% 17.4%

SL-J222-1

69.8% 7.3%

(R,R)-BenzP*

-60.0% 11.1%

SL-J605-1

-57.8% 38.4%

(SS′,RR′)-TangPhos

-51.8% 6.2%

SL-J004-1

-49.7% 7.1%

OO P

MeOOMe

OMeOMe

OMe

OMeP

MeOOMe

OMeOMe

OMe

OMe

FeP P

MeO

MeO

P

P

FePPCy2

Ph

P

P

tBu

tBu

HH

FePPPh

Ph

51

(R,R)-iPrDuphos

37.1% 7.6%

(S)-DTBM-Garphos

34.6% 7.7%

(R,R)-iPrBPE

33.5% 7.5%

SL-J001-1

32.5% 6.9%

(S)-Binapine

18.1% 11.5%

SL-J204-1

17.0% 6.2%

P

P

iPr iPr

iPriPr

OO P

t-BuOMe

t-But-Bu

OMe

t-BuP

t-Bu OMet-But-Bu

OMe

t-Bu

MeO

MeO

P

P

iPr iPr

iPriPr

FePPPh

Ph

PtBu

PtBu

H

H

FePP

F3C

F3C

52

(R,R)-Me-Ferrolane

-14.7% 8.6%

SL-J688-1

-13.2% 13.8%

SL-J408-1

-10.4% 7.0%

SL-J220-1

-9.0% 11.4%

(S)-C5-TunePhos

7.1% 6.0%

SL-P051-1

4.2% 7.4%

FeP

P

FePH P

Ph

O

FePP

FeP P

MeO

MeO

OO P

P

FeP PPh2

53

SL-J005-1

4.0% 5.3%

SL-P053-2

2.9% 7.0%

FePP

FeP PPh2

54

XI. Evaluation of Cobalt Sources for the Hydrogenation of MAC.

Figure S23. Evaluation of various cobalt sources and additives for the asymmetric hydrogenation of MAC.

0.0 (--)!

0.0!(--)!

0.0!(--)!

>99 (38.4)!

0.0 (--)!

0.0!(--)!

0.0 (--)!

64.8 (85.9)!

0.0!(--)!

>99 (90.7)!

>99 (84.7)!

>99 (78.1)!

>99 (40.4)!

>99 (76.6)!

>99 (84.9)!

>99 (86.1)!

>99 (80.6)!

0.0!(--)!

>99 (80.2)!

96.5 (83.7)!

92.3 (67.8)!

46.8 (81.5)!

29.5 (70.0)!

>99 (87.9)!

>99 (83.6)!

>99 (84.9)!

0.0!(--)!

96.8 (75.8)!

49.4 (87.7)!

81.4 (86.4)!

>99 (70.3)!

33.0 (89.0)!

>99 (89.5)!

>99 (84.7)!

>99 (95.6)!

0.0 !(--)!

0.0 (--)!

0.0!(--)!

>99 (67.1)!

92.6 (81.7)!

>99 (77.4)!

0.0!(--)!

>99 (77.2)!

0.0!(--)!

>99 (-5.3)!

93.0 (93.5)!

>99 (43.5)!

95.2 (68.3)!

>99 (80.4)!

17.2 (88.0)!

>99 (51.5)!

98.3 (90.4)!

>99 (65.4)!

51.4 (6.4)!

97.0 (95.6)!

>99 (24.3)!

>99 (66.5)!

97.7 (68.5)!

>99 (83.3)!

>99 (61.0)!

>99 (93.0)!

>99 (41.6)!

0.0!(--)!

91.4 (57.5)!

92.4 (72.9)!

85.4 (39.4)!

94.9 (73.7)!

94.5 (52.8)!

93.3 (48.5)!

96.1 (86.2)!

>99 (96.4)!

94.4 (87.8)!

94.5 (86.8)!

>99 (47.2)!

>99 (46.8)!

>99 (67.6)!

54.5 (85.4)!

>99 (-28.6)!

>99 (84.0)!

>99 (55.3)!

>99 (88.4)!

>99 (85.5)!

0.0!(--)!

0.0!(--)!

>99 (81.3)!

0.0 (--)!

>99 (84.1)!

0.0 (--)!

>99 (91.6)!

>99 (91.3)!

>99 (38.4)!

>99 (90.0)!

>99 (82.8)!

>99 (23.9)!

>99 (77.4)!

>99 (72.5)!

>99 (83.6)!

>99 (79.4)!

>99 (88.2)!

>99 (91.9)!

>99 (92.4)!

>99 (93.5)!

>99 (89.0)!

>99 (87.3)!

>99 (92.1)!

>99 (89.4)!

>99 (91.4)!

>99 (83.6)!

Me 3SiCH 2L

i!Me 3S

iCH 2MgC

l!MeM

gCl!

Me 3Al!

PhMgB

r!

Et 2Zn!

i PrMgC

l!2-F

-BnZnC

l!PhZ

nCl!

No add

itive!

CoF2!

CoCl2!

CoBr2!

CoI2!

Co(acac)3!

Co(OAc)2!

Co(OBz)2!

(py)2Co(CH2SiMe3)2!

Co(OAc)2*4H2O!

Co(BF4)2*6H2O!

CoCl2*6H2O!

Co(ClO4)2*6H2O!

>90% ee!

80-90% ee!

70-80% ee!

<70% ee!

55

XII. GC and SFC Chromatograms of Enantiopure Alkanes.

Figure S24. Hydrogenation of MAC with (R,R)-QuinoxP*Co(CH2SiMe3)2.

Figure S25. Hydrogenation of (Z)-methyl 2-acetamido-3-phenylacrylate with (R,R)-iPrDuPhosCo(CH2SiMe3)2.

N

N P

PCo

CH2SiMe3

CH2SiMe3

4 atm H2

0.041 M substrate, 1% [Co], 8 mL THF, 18 hr, 25 ºC

NH

OO

ONH

OO

O>99% conversion, 99.0% ee

P

P

iPr iPr

iPriPr

CoCH2SiMe3

CH2SiMe3

500 psi H20.041 M substrate, 5% [Co], 8 mL THF, 12 hr, 25 ºC

HNO

O

O

HNO

O

O

>99% conversion, 92.7% ee

56

Figure S26. Hydrogenation of α-acetamidostyrene with (R,R)-EtDuPhosCo(CH2SiMe3)2.

P

P

Et Et

EtEt

CoCH2SiMe3

CH2SiMe3

500 psi H20.041 M substrate, 5% [Co], 8 mL THF, 6 hr, 25 ºC

NH

O

NH

O

>99% conversion, 82.0% ee

57

Figure S27. Hydrogenation of α-trans-methylstilbene with SL-A109-2 and (py)2Co(CH2SiMe3)2.

OO P

tBuOMe

tButBu

OMe

tBuP

tBuOMe

tButBu

OMe

tBu N CoN

SiMe3

SiMe3

0.041 M substrate, 5% [Co], 8 mL PhMe, 1 hr, 25 ºC

500 psi H2

>98% conversion, 89.4% ee

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