S1

Supporting Information

Regioselective deuteration of alcohols in D2O catalysed by homogeneous manganese and iron pincer complexes

Sayan Kar, Alain Goeppert, Raktim Sen, Jotheeswari Kothandaraman, and G. K. Surya Prakash*

Loker Hydrocarbon Research Institute and Department of Chemistry, University of Southern California, University Park, Los Angeles, California 90089-1661, United States.

Email: gprakash@usc.edu

Table of Contents

1. Materials and methods S2

2. Standard procedure for deuteration reactions S2

3. Selected spectral data for deuteration reactions S3

3.1. Deuteration of primary alcohols with manganese complex C-1 S3

3.2. Deuteration of primary alcohols with iron complex C-3 S8

3.3. Deuteration of secondary alcohols S11

4. Control experiments S12

5. EI-MS analysis of benzyl alcohol before and after deuteration S15

6. Recycling studies S17

7. References S18

Electronic Supplementary Material (ESI) for Green Chemistry.This journal is © The Royal Society of Chemistry 2018

S2

1. Materials and methods

All deuteration experiments were carried out under an inert atmosphere (with N2 or Ar).

Complexes MnBrPNPiPr(CO)2 (C-1) MnBrPNPCy(CO)2 (C-2), and FeHBrPNPiPr(CO) (C-3) were

prepared by previously reported methods.1,2 All catalysts were weighed inside an argon filled

glove box. Alcohols 1-21 and NaOH were bought from commercial vendors and used without

further purification. D2O (CIL, D-99.5%) was sparged with N2 for 1 h prior to use. 1H, 2H, 31P and 13C NMR spectra were recorded on 400 MHz or 500 MHz Varian NMR spectrometers. 1H and 13C

NMR chemical shifts were determined relative to the residual solvent signals (D2O, CDCl3). The 2H NMR chemical shift were determined based on external CDCl3 reference. Mass spectral data

were recorded on a Bruker 300-MS TQ Mass Spectrometer at 70 eV for EI.

MnP CO

N PH

CO

iPr iPr

iPr

iPr

Br

FeP CO

N PH

H

iPr iPr

iPr

iPr

Br

MnP CO

N PH

CO

CyCy

CyCy

Br

C-1 C-2 C-3

Figure S1. Catalytic complexes screened in this study

2. Standard procedure for deuteration reaction

In a J. Young NMR tube (total volume ~2.5 mL), catalyst C-1/C-2/C-3 was weighed inside an argon

globe box, followed by the addition of pre-dissolved NaOH (5-200 mol% with respect to alcohol)

in 0.4 mL D2O, and alcohol (0.25-0.5 mmol) under nitrogen atmosphere (10 µL 1,4-dioxane was

additionally added in case of ethanol (2), methanol (3), ethylene glycol (13), and isopropanol (20)

as an internal standard). The NMR tube was then sealed and a proton NMR spectrum was

recorded. Subsequently, the NMR tube was placed in a pre-heated oil bath (100 oC - 140 oC) for

a given amount of time (12-60 h). After the reaction, the NMR tube was cooled to room

temperature; after which the 1H and 13C NMR spectra were recorded. The amount of deuteration

was calculated from the 1H (and 2H, whenever necessary) NMR spectra based on integral ratios

of nondeuterable peaks (not α/β)/ internal standard peak with deuterated peaks. The deuterated

S3

alcohols were isolated through extraction with CDCl3. Maximum theoretical deuteration

achievable were calculated based on the numbers of exchangeable proton and deuterium atoms

present in the system. For example, for Table 1, entry 1, total exchangeable H atoms = [0.5x5

(from n-BuOH) + 1.0 (from NaOH)] mmol = 3.5 mmol. Total exchangeable D atom =

[400*1.11*2/20] (from D2O; d= 1.11; MW = 20) = 44.4 mmol. So, the theoretical maximum

deuteration = [44.4/(44.4+3.5)]*100% = 93%

3. Selected spectral data for deuteration reactions

3.1. Deuteration of primary alcohols with manganese complex C-1

0123456f1 (ppm)

CH3 OH

CH3

D D

D D

OD

93%

94%

α β

αβ

α β

A

B

C

no γ/ δdeuteration

Figure S2. 1H spectra of deuteration of 1 before (A) and after (B) reaction and 2H spectra of deuterated n-butanol (C). Reaction conditions: 1 (0.5 mmol), C-1 (1mol%), NaOH (5 mol%), D2O (0.4 mL), 120 oC, 12 h.

S4

020406080100120140160180200220f1 (ppm)

CH3

D D

D D

OD

Figure S3. 13C spectra of deuterated (α, β) n-butanol (1) in D2O. Reaction conditions: 1 (0.5 mmol), C-1 (1mol%), NaOH (5 mol%), D2O (0.4 mL), 120 oC, 12 h.

012345678910f1 (ppm)

CH3

OH

CH3OH

D D

D D

A

B

Figure S4. 1H spectra of 4 before (A) and after (B) reaction. Reaction conditions: 4 (0.5 mmol), C-1 (1 mol%), NaOH (5 mol%), D2O (0.4 mL), 120 oC, 12 h.

S5

0123456789f1 (ppm)

OHCH3

CH3

CH3

CH3

DD

DO

D

A

B

Figure S5. 1H spectra of deuteration of 5 before (A) and after (B) reaction. Reaction conditions: 5 (0.5 mmol), C-1 (0.5 mol%), NaOH (5 mol%), D2O (0.4 mL), 120 oC, 12 h.

-1012345678910f1 (ppm)

OH

DD

O

D

A

B

Figure S6. 1H spectra of deuteration of 6 before (A) and after (B) reaction. Reaction conditions: 6 (0.5 mmol), C-1 (0.5 mol%), NaOH (5 mol%), D2O (0.4 mL), 120 oC, 12 h.

S6

123456789f1 (ppm)

OH

OHD

D

D

A

B

Figure S7. 1H spectra of 7 before (A) and after (B) reaction. Reaction conditions: 7 (0.5 mmol), C-1 (1 mol%), NaOH (5 mol%), D2O (0.4 mL), 120 oC, 12 h.

012345678910f1 (ppm)

OH

DD

D

OH

DD

D

OH

A

B

C

Figure S8. 1H spectra of 9 before (A) and after (B) reaction and 2H spectra of deuterated 9 (C). Reaction conditions: 9 (0.5 mmol), C-1 (1 mol%), NaOH (5 mol%), D2O (0.4 mL), 120 oC, 12 h.

S7

12345678910f1 (ppm)

A

B

OH

O

DD

D

C

no H/D exchange inaromatic protons

Figure S9. 1H spectra of 10 before (A) and after (B) reaction and 2H spectra o deuterated 10 (C). Reaction conditions: 10 (0.5 mmol), C-1 (0.5 mol%), NaOH (5 mol%), D2O (0.4 mL), 120 oC, 12 h.

0123456789f1 (ppm)

OH

D D

D D

OH

A

B

Figure S10. 1H spectra of 12 before (A) and after (B) reaction. Reaction conditions: 12 (0.5 mmol), C-1 (0.5 mol%), NaOH (5 mol%), D2O (0.4 mL), 120 oC, 12 h.

S8

012345678910f1 (ppm)

OH

OH

DD

D D

OD

OD

A

B

Figure S11. 1H spectra of 15 before (A) and after (B) reaction. Reaction conditions: 15 (0.5 mmol), C-1 (1 mol%), NaOH (5 mol%), D2O (0.4 mL), 120 oC, 12 h.

3.2. Deuteration of primary alcohols with iron complex C-3

012345678f1 (ppm)

3.00

5.03

0.07

CH3 OH

D D

Figure S12. 1H spectra of α-deuterated 1. Reaction conditions: 1 (0.25 mmol), C-3 (2 mol%), NaOH (10 mol%), D2O (0.4 mL), 100 oC, 24 h.

S9

12345678f1 (ppm)

3.00

12.1

42.

011.

14

0.21

OH

D D

CH3

Figure S13. 1H spectra of α-deuterated 4. Reaction conditions: 4 (0.25 mmol), C-3 (2 mol%), NaOH (10 mol%), D2O (0.4 mL), 100 oC, 24 h.

0123456789f1 (ppm)

6.00

1.07

1.05

0.20

OHCH3

CH3

DD

Figure S14. 1H spectra of α-deuterated 5. Reaction conditions: 5 (0.25 mmol), C-3 (2 mol%), NaOH (10 mol%), D2O (0.4 mL), 100 oC, 24 h.

S10

0.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.08.59.09.5f1 (ppm)

Deuterium_03SK2-29-40

OHCH3

CH3

DD

Figure S15. 2H spectra of α-deuterated 5. Reaction conditions: 5 (0.25 mmol), C-3 (2 mol%), NaOH (10 mol%), D2O (0.4 mL), 100 oC, 24 h.

123456789f1 (ppm)

1.12

0.31

0.18

5.00

OH

D D

D D

Figure S16. 1H spectra of α, β-deuterated 12. Reaction conditions: 12 (0.25 mmol), C-3 (2 mol%), NaOH (10 mol%), D2O (0.4 mL), 100 oC, 24 h.

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3.2. Deuteration of secondary alcohol

123456789f1 (ppm)

OH

CH3

A

B

OH

D

DD D

Figure S17. 1H spectra of 17 before (A) and after (B) reaction. Reaction conditions: 17 (0.5 mmol), C-1 (2 mol%), NaOH (5 mol%), D2O (0.4 mL), 140 oC, 30 h.

0.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.08.59.09.510.0f1 (ppm)

Deuterium_01SK2-29-40

5.51

0.46

1.74

OD

DD

D

D92%87%

46%

87%

92%

46%

No H/D exchange inaromatic protons

Figure S18. 2H spectra of 17 after reaction. Reaction conditions: 17 (0.5 mmol), C-1 (2 mol%), NaOH (5 mol%), D2O (0.4 mL), 140 oC, 30 h.

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123456789f1 (ppm)

H2O

OH

O

D

H

A

B

Figure S19. 1H spectra of 19 before (A) and after (B) reaction. Reaction conditions: 19 (0.5 mmol), C-1 (2 mol%), NaOH (5 mol%), D2O (0.4 mL), 140 oC, 30 h.

4. Control experiments performed to understand the reaction mechanism

Observation of the active catalytic species in the reaction mixture

In a J Young NMR tube (total volume ~2.5 mL), catalyst C-1 was weighed inside an argon globe box,

followed by the addition of pre-dissolved NaOH (5 mol% with respect to alcohol) in 0.4 mL D2O, and n-

butanol (0.5 mmol) under nitrogen atmosphere. The NMR tube was then sealed and placed in a pre-

heated oil bath (120 oC). After 1 h, the NMR tube was cooled to room temperature and 0.2 mL THF was

added to the reaction mixture. The resultant homogeneous solution was then analyzed by 31P NMR

spectroscopy.

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0102030405060708090100110f1 (ppm)

C-1

LnMn-OnBu

Figure S20. Active species detected in the reaction mixture through 31P NMR after 1 h (0.2 mL THF was added to the reaction mixture to form a homogeneous solution)

Formation of manganese deuteroxide species (C-1B)

In a 50 mL Schlenk flask, C-1 (0.05mmol) was weighed inside an argon glove box and subsequently

dissolved in 5 mL of dry and degassed THF in a nitrogen atmosphere, followed by the addition of

1 mmol of t-BuOK (weighed inside an argon glove box). The formation of the manganese amido

complex (C-1A) was observed as a red solution. After stirring the resulting solution for 15

minutes, the red solution was filtered through Celite, and 5 mmol D2O was subsequently added

to the filtrate. The solution immediately turned yellow, signifying the formation of a deuteroxide

species. The solution was stirred for 30 minutes, after which the solvents were removed in vacuo.

Benzene-d6 was used as the deuterated solvent for the 31P NMR analysis of the resulting C-1B.

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0102030405060708090100110

f1 (ppm)

C-1

LnMn-OD

LnMn-OtBu

Figure S21. 31P spectra of manganese deuteroxide species [Mn(OD)PNDPiPr(CO)2] (C-1B).

α, β deuteration of n-butanol with C-1B

0123456789f1 (ppm)

3.00

2.18

0.93

0.95

0.59

CH3 OH

D D

D D

71%

53%

Figure S22. Deuteration of 1 by manganese deuteroxy complex (C-1B) without added base, Signifying the ability of C-1B to form C-1A in the solution at 120 oC. (THF peaks suppressed)

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5. EI-MS analysis of benzyl alcohol before and after deuteration

Figure S23. EI-MS spectra of benzyl alcohol

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Figure S24. EI-MS spectra of α deuterated benzyl alcohol. Reaction conditions: benzyl alcohol (0.5 mmol), C-1 (0.5 mol%), NaOH (5 mol%), D2O (0.4 mL), 120 oC, 12 h.

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6. Recycling studies

Standard procedure:

In a J. Young NMR tube (total volume ~2.5 mL), catalyst C-1 (2 mol%, 0.01 mmol) was weighed

inside an argon globe box, followed by the addition of pre-dissolved NaOH (5 mol% with respect

to alcohol) in 0.5 mL D2O, and alcohol (0.5 mmol) under nitrogen atmosphere. The NMR tube was

then sealed and a proton NMR spectrum was recorded. Subsequently, the NMR tube was placed

in a pre-heated oil bath (120 oC) for a given amount of time (12 h). After the reaction, the NMR

tube was cooled to room temperature; after which a 1H NMR spectra was recorded.

Subsequently, in a nitrogen atmosphere, 0.4 mL of degassed chloroform was added to the NMR

tube. From the resulting biphasic solution, the top D2O (with NaOH) layer was separated to afford

a yellow solution. The catalyst was then recovered by removing the deuterated n-BuOH and CHCl3

in vacuo. The recovered catalyst inside the J. Young NMR tube then recharged with fresh n-BuOH

(0.5 mmol), NaOH (5 mol%) and D2O (0.5 mL) for the next cycle.

94 969093 94 91

1 2 30

10

20

30

40

50

60

70

80

90

100

D(β)D(α)

Cycle

Deu

tera

tion

(%)

Figure S25. α and β deuteration observed in successive cycles. n-butanol (0.5 mmol), C-1 (2 mol%), NaOH (5 mol%), D2O (0.5 mL), 120 oC, 12 h.

S18

Figure S26. Image of the recovered catalyst inside the J.Young NMR tube

7. References

1. Elangovan, S.; Topf, C.; Fischer, S.; Jiao, H.; Spannenberg, A.; Baumann, W.; Ludwig, R.; Junge, K.; Beller, M. J. Am. Chem. Soc. 2016, 138, 8809–8814.

2. (a) Kothandaraman, J.; Goeppert, A.; Czaun, M.; Olah, G. A.; Prakash, G. K. S. Green Chem. 2016, 18 (21), 5831-5838. (b) S. Chakraborty, H. Dai, P. Bhattacharya, N. T. Fairweather, M. S. Gibson, J. A. Krause and H. Guan, J. Am. Chem. Soc. 2014, 136, 7869-7872.