O bond Formation via Oxidation of Amines with Benzoyl Peroxide · Direct N−O bond Formation via Oxidation of Amines with Benzoyl Peroxide Amit Banerjee* and Hisashi Yamamoto* Molecular

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Supporting Information

Direct N−O bond Formation via Oxidation of Amines with Benzoyl Peroxide

Amit Banerjee* and Hisashi Yamamoto*

Molecular Catalyst Research Center, Chubu University

1200, Matsumoto-cho, Kasugai, Aichi 487-8501, Japan

Electronic Supplementary Material (ESI) for Chemical Science.This journal is © The Royal Society of Chemistry 2019

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Table of contents Page No.

1. General 3

2. Optimization 4

3. Synthesis of bis-(benzoyloxy)-1,2-diamine 3a-3v 7

4. One pot synthesis of bis-(benzoyloxy)hydroxamic acid 5a-5h 15

5. Oxidation of mono amine 7a-7o 18

6. Hydrolysis of N−OBz to N−OH 23

7. General Procedure for bis-hydroxamic acid (BHA) ligand 24

8. Preparation of 1,2-diamine 26

9. HPLC analysis of 7e 30

10. Reference 31

11. Copies of 1H and 13C NMR spectra 32

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1. General

Chemicals. Anhydrous CH2Cl2, THF, Et2O and toluene were dried with Glass Contour solvent purification

system. Anhydrous EtOH, MeOH, DMF, and DMSO were purchased from WAKO chemicals and used as

received. 75% Benzoyl peroxide were purchased from Sigma Aldrich (517909-500G), Cesium carbonate

were purchased from WAKO chemical (036-06541) and trans-1,2-Cyclohexanediamine were purchased

from TCI.

Diamine: 1b, 1c, 1g, 1m, 1o, 1r were purchased from TCI. 1d, 1e, 1f were purchased from Sigma Aldrich.

Amines 6a-6o were purchased from TCI. All the bases were purchased from WAKO. All the chemicals are

stored under nitrogen atmosphere. All other chemicals were purchased from their commercial sources and

used as it received.

NMR spectra were recorded at 25 °C on a JEOL ECS-400 spectrometer (400 MHz for 1H, 100 MHz for

13C, 376 MHz for 19 F). Chemical shifts are reported in δ ppm referenced to an internal tetramethylsilane

standard or an internal nondeuterated solvent peak for 1H NMR. Chemical shifts of 13C NMR are given

relative to the solvent peak as an internal standard. Multiplicities are indicated as br (broad), s (singlet), d

(doublet), t (triplet), q (quartet), or m (multiplet). Coupling constants (J) are reported in Hertz (Hz). Infrared

(IR) spectra were recorded on Bruker ALPHA-E using ZnSe ATR. ESI-MS analyses were carried out on a

JEOL JMS-T100CS. High performance liquid chromatography (HPLC) was performed on Agilent

Technologies 1220 Inifinity LC instruments using Daicel Chiralpak OJ-H 4.6 mm × 25 cm column. Optical

rotations were measured on an ATAGO AP-300 polarimeter with a path length 100 mm at 589 nm. Low

temperature reactions were performed on UC reactor from Techno Signa. Column chromatography was

conducted with silica gel 60N (KANTO CHEMICAL, spherical, neutral, 40-50 or 63-210 μm). For thin-

layer chromatography (TLC) analyses throughout this work, Merck precoated TLC plates (silica gel 60

F254 0.25 mm) were used. Visualization was accomplished by UV light (254 nm), phosphomolybdic acid,

and I2/SiO2.

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2. Optimization of oxidation of amine with benzoyl peroxide.

Table 1. Optimization of solvent using K2CO3 as a base

Entry BPO Solvent N-O vs C-N (3:4)

NMR Yield (%) (3+4)

1 Pure BPO CH2Cl2 1.0: 10.0 49

2 75% BPO Toluene 1.0: 3.5 75

3 75% BPO Ether 1.0: 8.0 78

4 75% BPO THF 1.0: 3.0 80

5 75% BPO DMF 1.0: 7.0 70

6 75% BPO CH2Cl2 1.0: 1.2 82

7 75% BPO EtOAc 1.0: 4.5 75

8 75% BPO MeOH - <5

9 75% BPO CH3CN - <5

10 75% BPO CHCl3 1.0: 1.2 88

Table 2. Optimization of base in CHCl3

Entry Base Solvent N-O vs C-N (3:4)

NMR Yield (%) (3+4)

1 BaCO3 CHCl3 - <10

2 CaCO3 CHCl3 - <5

3 NH4HCO3 CHCl3 - <10

4 Na2CO3 CHCl3 1.0: 4.0 55

5 NaHCO3 CHCl3 1.0: 3.0 50

6 Li2CO3 CHCl3 1.0: 3.0 30

7 LiOH CHCl3 1.0: 4.0 10

8 Cs2CO3 CHCl3 1.3: 1.0 70

Table 3. Optimization of solvent using Cs2CO3

Entry solvent N-O vs C-N (3:4)

NMR Yield (%) (3+4)

1 Toluene 1.0: 13.0 20

2 Ether 1.0: 1.0 60

3 THF 1.0: 1.6 20

4 DMF - <5

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5 CH2Cl2 2.0: 1.0 80

6 EtOAc 1.0: 3.5 45

7 t-BuOH 1.0:15.0 35

8 i-PrOH 1.0:30.0 30

9 CHCl3 1.3: 1.0 70

10 1,2-DCE 1.0: 4.0 65

11 1,1,2,2-TCE 1.0: 1.0 30

12 Cl2CHCH2Cl 1.0: 1.0 60

13 PhCF3 1.1: 1.0 45

14 DMF - <10

15 DMSO - <5

16 Acetone 1.0: 20.0 20

17 NMP - <5

18 CH3CN 1.0: 1.0 45

19 Dioxane 1.0: 2.0 20

20 DME 1.0: 3.0 20

21 CPME 1.4: 1.0 10

22 2-Me-THF 1.0: 1.0 40

23 CH2Br2 1.0: 3.0 35

24 Pentane - <5

25 PhCl - <5 26 CCl3CN - <5 27 DMA - <5 28 DMI - <5 29 DMPU - <5

Table 4: Optimization of equivalent of Cs2CO3

Entry Equiv of Cs2CO3 N-O vs C-N (3:4)

NMR Yield (%) (3+4)

1 1.0 1.0: 6.0 50

2 2.0 1.0: 4.0 65

3 3.0 1.0: 1.1 60

4 4.0 2.0: 1.0 80

5 5.0 2.6: 1.0 80

6 6.0 5.0: 1.0 85

7 7.0 2.8:1.0 75

8 8.0 2.0:1.0 65

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Table 5. Reaction with base in CH2Cl2

Entry Base N-O vs C-N (3:4)

NMR Yield (%) (3+4)

1 Li2CO3 1.0: 10.0 30

2 Na2CO3 1.0: 5.0 78

3 K2CO3 1.0: 1.2 88

4 Cs2CO3 10.0: 1.0 95

5 Rb2CO3 1.0: 2.0 70

6 CaCO3 1.0: 15.0 20

7 MgCO3 1.0: 6.0 30

8 BaCO3 1.0: 20.0 10

9 NH4HCO3 - <5

10 NH4OH 1.0: 4.0 10

Table 6. Reaction with cesium salts

Entry Cesium Salt N-O vs C-N (3:4)

NMR Yield (%) (3+4)

1 CsOAc 1.0: 3.0 25

2 CsI - <5

3 CsNTf2 1.0: 25.0 60

4 CsHCO3 - <5

5 CsF 1.0: 1.0 12

6 CsOH 1.0: 2.0 45

7 CsClO4 1.0: 10.0 35

8 Cs(COO)2 1.0: 8.0 45

Table 7. Reaction with phosphate salt

Entry Phosphate salt N-O vs C-N (3:4)

NMR Yield (%) (3+4)

1 Na2HPO4 2.0: 1.0 65

2 NaH2PO4 1.0: 1.0 75

3 K3PO4 1.0: 2.0 60

4 Mg3(PO4)2 3.0: 1.0 80

5 KPF6 4.0: 1.0 90

6 (NH4)2HPO4 2.0: 1.0 85

7 Phosphate buffer 1.0: 10.0 30

8 Na3PO4 1.0: 1.5 50

9 K2HPO4 1.0: 7.5 32

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Table 8: Effect of water

Entry Amount of water N-O vs C-N (3:4)

NMR Yield (%) (3+4)

1 No water 1.0: 10.0 30

2 50uL H2O 1.0: 2.5 45

3 75uL H2O 2.5: 1.0 60

4 100uL H2O 3.3: 1.0 70

5 125uL H2O 8.0: 1.0 85

6 150uL H2O 7.0: 1.0 83

7 175uL H2O 3.2: 1.0 80

8 200uL H2O 3.0: 1.0 75

9 250uL H2O 2.0: 1.0 65

3. General Procedure for the synthesis of bis-(benzoyloxy)-1,2-diamine

BPO (2 mmol, 4.0 equiv) and Cs2CO3 (3 mmol, 6.0 equiv) were taken in an oven dried test tube equipped

with a magnetic stir bar and a rubber septum. CH2Cl2 (5 mL) was added to it and the heterogeneous mixture

was stirred for 2 h at room temperature.1 After that a solution of 1,2-diamine (0.5 mmol, 1.0 equiv, in 2 mL

CH2Cl2) was then added and the mixture was further stirred for 14 h.2 Then water 5 mL was added to the

reaction mixture and stirred for 5 min and extracted with CH2Cl2. The organic layer were washed with brine,

dried over Na2SO4 and concentrated to get crude product. The ratio of 3:4 was determined by 1H NMR

spectroscopy of crude reaction mixture using 1,1’,2,2’-tetrachloroethane as an internal standard. The crude

product was purified by silica gel column chromatography using petroleum ether/ethyl acetate as eluent to

yield bis-(benzoyloxy)-1,2-diamine.

3b (146.8 mg, 83% yield); [𝛼]𝐷25

= −70.0 (c 1.0, CHCl3,); IR (neat): 2936, 2860, 1716, 1450, 1064, 703,

685; 1H NMR (400 MHz, CDCl3) δ 8.03-8.01 (m, 4 H), 7.59-7.55 (m, 2 H), 7.49-7.42 (m, 4 H), 3.14-3.12

(m, 2 H), 2.15-2.12 (m, 2 H), 1.8-1.77 (m, 2 H), 1.49-1.45 (m, 2 H), 1.33-1.28 (m, 2 H); 13C NMR (100

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MHz, CDCl3) δ 166.7, 133.3, 129.4, 128.6, 128.4, 61.8, 29.6, 24.3; HRMS (ESI+): calcd for C20H22N2O4Na

([M+Na]+): 377.1477, found: 377.1481.

4a, 1H NMR (400 MHz, CDCl3) δ 7.96-7.93 (m, 2 H), 7.82-7.79 (m, 2 H), 7.58-7.52 (m, 1 H), 7.45-7.28

(m, 4 H), 6.6 (d, 2 H, J= 7.8 Hz), 4.06-3.98 (m, 1 H), 3.01-2.94 (m, 1 H), 2.27-2.24 (m, 1 H), 2.15-2.13 (m,

1 H), 1.77-1.69 (m, 2 H), 1.55-1.42 (m, 1 H), 1.35-1.3 (m, 3 H), ; 13C NMR (100 MHz, CDCl3) δ 167.7,

167.2, 134.8, 133.4, 131.4, 129.4, 128.6, 128.5, 128.3, 127.1, 64.2, 51.2, 32.5, 30.4, 24.6, 24.4; HRMS

(ESI+): calcd for C20H22N2O3Na ([M+Na]+): 361.1258, found: 361.1518.

3c (115.6 mg, 65%); IR (neat): 3237, 3067, 2984, 1713, 1262, 1087, 1065, 1023, 701, 685; 1H NMR (400

MHz, CDCl3) δ 8.23 (s, 2 H), 8.07-8.04 (m, 4 H), 7.6-7.56 (m, 2 H), 7.48-7.45 (m, 4 H), 1.34(s, 12 H); 13C

NMR (100 MHz, CDCl3) δ 166.9, 133.4, 129.4, 128.7, 128.4, 63.5, 21.4; HRMS (ESI+): calcd for

C20H24N2O4Na ([M+Na]+): 379.1633, found: 379.1626.

3d (109 mg, 62%); IR (neat): 3231, 3032, 2920, 2849, 1715, 1258, 1087, 1062, 1023, 702, 666; 1H NMR

(400 MHz, CDCl3) δ 8.25 (s, 2 H), 8.02-7.99 (m, 4 H), 7.56-7.53 (m, 2 H), 7.44-7.4 (m, 4 H), 5.64 (m, 2

H), 3.5-3.49 (m, 2 H), 2.56-2.52 (m, 2 H), 2.34-2.27 (m, 2 H); 13C NMR (100 MHz, CDCl3) δ 166.7, 133.4,

129.4, 128.6, 128.2, 124.4, 58.2, 28.8; HRMS (ESI+): calcd for C20H20N2O4Na ([M+Na]+): 375.1320,

found: 375.1314.

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3e (128.8 mg, 54%); [𝛼]𝐷25

= +103.0 (c 1.0, CHCl3,); IR (neat): 3221, 3067, 2957, 1719, 1266, 1066, 705;

1H NMR (400 MHz, CDCl3) δ 8.13-8.12 (m, 2 H), 8.02-7.99 (m, 4 H), 7.62-7.57 (m, 3 H), 7.51-7.46 (m, 6

H), 7.4-7.37 (m, 3 H), 7.2-7.18 (m, 4 H), 4.5 (s, 2 H), 3.47-3.46 (m, 2 H); 13C NMR (100 MHz, CDCl3) δ

166.3, 140.5, 139.2, 133.8, 133.5, 130.3, 129.5, 128.6, 128.5, 128.5, 127.1, 126.4, 124.6, 64.9, 47.3; HRMS


3f (109.1 mg, 64%); [𝛼]𝐷25

= +168.0 (c 1.0, CHCl3,); IR (neat): 3286, 3065, 2953, 2869, 1718, 1630, 1528,

1262, 693; 1H NMR (400 MHz, CDCl3) δ 7.79-7.76 (m, 4 H), 7.44-7.35 (m, 5 H), 7.25 (s, 2 H), 4.31-4.25

(m, 1 H), 2.37-2.33 (m, 2 H), 1.87-1.83 (m, 2 H), 1.64-1.59 (m, 2 H); 13C NMR (100 MHz, CDCl3) δ 168.7,

134.1, 131.6, 128.6, 127.1, 57.7, 29.6, 19.9; HRMS (ESI+): calcd for C19H20N2O4Na ([M+Na]+): 363.1321,

found: 363.1373.

3g (162.4 mg, 85%); IR (neat): 2939, 2861, 1730, 1243, 705; 1H NMR (400 MHz, CDCl3) δ 7.99-7.97 (m,

4 H), 7.55-7.51 (m, 2 H), 7.46-7.39 (m, 4 H), 3.22-3.2 (m, 2 H), 3.01 (s, 6 H), 2.23-2.18 (m, 2 H), 1.78-

1.72 (m, 2 H), 2.64-2.56 (m, 2 H), 1.33-1.28 (m, 2 H); 13C NMR (100 MHz, CDCl3) δ 165.1, 133.1, 129.6,

128.5, 128.4, 65.7, 42.1, 25.1, 23.1; HRMS (ESI+): calcd for C22H26N2O4Na ([M+Na]+): 405.1790, found:

405.1785.

3h (132.8 mg, 65%); [𝛼]𝐷25

= −10.0 (c 1.0, CHCl3,); IR (neat): 2936, 2859, 1734, 1238, 1057, 705; 1H NMR

(400 MHz, CDCl3) δ 8.02-8.0 (m, 4 H), 7.57-7.53 (m, 2 H), 7.44-7.4 (m, 4 H), 3.43-3.34 (m, 2 H), 3.28-

3.23 (m, 2 H), 3.22-3.3.13 (m, 2 H), 2.25-2.22 (m, 2 H), 1.74-1.7 (m, 2 H), 1.54-1.7 (m, 2 H), 1.3-1.22 (m,

2 H), 1.49 (m, 6 H ) ; 13C NMR (100 MHz, CDCl3) δ 165.7, 133.1, 129.5, 128.5, 64.7, 48.1, 25.9, 23.6,

12.3; HRMS (ESI+): calcd for C24H30N2O4Na ([M+Na]+): 433.2103, found: 433.2095.

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3i (147 mg, 63%); [𝛼]𝐷25

= +14.0 (c 1.0, CHCl3,); IR (neat): 2933, 2866, 1737, 1242, 1062, 706; 1H NMR


3.07 (m, 2 H), 2.24-2.21(m, 2 H), 1.74-1.72 (m, 2 H),1.59-1.48 (m, 5 H), 1.4-1.35 (m, 3 H), 1.27-1.25 (m,

2 H), 0.88-84 (m, 6 H); 13C NMR (100 MHz, CDCl3) δ 166.5, 132.9, 129.7, 129.5, 128.5, 65.3, 53.0, 29.6,

25.9, 24.1, 20.4, 14.1; HRMS (ESI+): calcd for C28H38N2O4Na ([M+Na]+): 489.2729, found: 489.2725.

3j (170.1 mg, 65%); [𝛼]𝐷25



2.22 (m, 2 H), 1.75-1.72 (m, 2 H), 1.61-1.38 (m, 6 H), 1.29-1.22 (m, 2 H), 0.87 (s, 18 H); 13C NMR (100

MHz, CDCl3) δ 166.5, 132.9, 129.7, 129.6, 128.5, 65.2, 50.4, 40.6, 29.7, 29.6, 26.5, 24.1; HRMS (ESI+):

calcd for C32H46N2O4Na ([M+Na]+): 545.3355, found: 545.3368.

3k (112 mg, 41%); [𝛼]𝐷25

= −36.0 (c 1.0, CHCl3,); IR (neat): 2938, 2861, 1734, 1260, 1085, 699; 1H NMR


7.22 (m, 4 H), 7.2-7.16 (m, 2 H), 4.89 (d, J= 10.8 Hz, 2 H), 4.25 (d, J= 13.2 Hz, 2 H), 3.6 (s, 2 H), 2.37 (d,

J= 12.8 Hz, 2 H), 1.87-1.85 (m, 2 H), 1.64-1.62 (m, 2 H), 1.32-1.28 (m, 2 H); 13C NMR (100 MHz, CDCl3)

δ 165.2, 137.8, 132.7, 129.6, 129.4, 128.3, 128.1, 127.1, 65.7, 55.9, 25.8, 25.1; HRMS (ESI+): calcd for

C34H34N2O4Na ([M+Na]+): 557.2416, found: 557.2410.

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3l (164.4 mg, 60%); [𝛼]𝐷25


(400 MHz, CDCl3) δ 8.01-7.99 (m, 4 H), 7.57-7.52 (m, 2 H), 7.45-7.41 (m, 4 H), 3.28-3.16 (m, 4 H),2.97-

2.93 (m, 2 H), 2.24-2.09 (m, 4 H), 1.73-1.52 (m, 14 H), 1.3-0.95 (m, 13 H); 13C NMR (100 MHz, CDCl3)

δ 165.2, 132.8, 129.9, 129.5, 128.4, 65.7, 59.4, 36.2, 31.8, 31.5, 26.8, 26.2, 26.0; HRMS (ESI+): calcd for

C34H46N2O4Na ([M+Na]+): 569.3355, found: 569.3360.

3m (190 mg, 79%); [𝛼]𝐷25

= −10.0 (c 1.0, CHCl3,); IR (neat): 3062, 2885, 1731, 1243, 698; 1H NMR (400

MHz, CDCl3) δ 7.99-7.97 (m, 4 H), 7.57-7.55 (m, 2 H), 7.46-7.42 (m, 4 H), 7.12-7.08 (m, 6 H), 7.03-7.01

(m, 4 H), 4.79 (s, 2 H), 2.88 (s, 6 H) ; 13C NMR (100 MHz, CDCl3) δ 164.9, 135.2, 133.2, 130.5, 129.5,

128.5, 127.7, 127.6, 73.8, 44.4; HRMS (ESI+): calcd for C30H28N2O4Na ([M+Na]+): 503.1946, found:

503.1947.

3n (193.3 mg, 76%); [𝛼]𝐷25

= −8.0 (c 1.0, CHCl3,); IR (neat): 3060, 2889, 1736, 1240, 696; 1H NMR (400

MHz, CDCl3) δ 8.01-7.99 (m, 4 H), 7.6-7.56 (m, 2 H), 7.46-7.42 (m, 4 H), 7.09-7.06 (m, 10 H), 4.86 (s, 2

H), 3.38 (br, 2 H), 2.92-2.87 (m, 2 H), 1.08 (t, J= 6.8 Hz, 6 H); 13C NMR (100 MHz, CDCl3) δ 165.9, 135.7,

133.1, 130.5, 129.7, 129.5, 128.5, 127.5, 72.0, 49.9, 11.9; HRMS (ESI+): calcd for C32H32N2O4Na

([M+Na]+): 531.2259, found: 531.2249.

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3o (165 mg, 71%); IR (neat): 2935, 2856, 1740, 1238, 770, 709; 1H NMR (400 MHz, CDCl3) δ 8.01-7.98

(m, 4 H), 7.58-7.53 (m, 2 H), 7.44-7.4 (m, 4 H), 3.27 (s, 4 H), 2.82-2.81 (m, 2 H), 1.94-1.92 (m, 4 H), 1.74-

1.71 (m, 4 H), 1.57-1.54 (m, 2 H), 1.32-1.27 (m, 8 H), 1.08-1.02 (m, 2 H); 13C NMR (100 MHz, CDCl3) δ

166.8, 133.2, 129.7, 129.0, 128.5, 66.6, 53.4, 28.9, 25.8, 25.2; HRMS (ESI+): calcd for C28H36N2O4Na

([M+Na]+): 487.2572, found: 487.2564.

3p (152.5 mg, 70%); IR (neat): 2934, 2855, 1738, 1240, 771, 708; 1H NMR (400 MHz, CDCl3) δ 7.99-7.97

(m, 4 H), 7.56-7.52 (m, 2 H), 7.43-7.38 (m, 4 H), 3.4-3.37 (m, 2 H), 3.24 (s, 4 H), 1.77-1.73 (m, 4 H), 1.66-

1.58 (m, 7 H), 1.47-1.45 (m, 4 H); 13C NMR (100 MHz, CDCl3) δ 166.1, 133.2, 129.7, 129.0, 128.5, 69.8,

56.1, 29.7, 24.5; HRMS (ESI+): calcd for C26H32N2O4Na ([M+Na]+): 459.2259, found: 459.2253.

3q (160.1 mg, 65%); IR (neat): 2935, 2855, 1738, 1240, 775, 705; 1H NMR (400 MHz, CDCl3) δ 8.0-7.98

(m, 4 H), 7.57-7.52 (m, 2 H), 7.43-7.38 (m, 4 H), 3.23 (s, 4 H), 2.81-2.8 (m, 4 H), 1.85-1.82 (m, 4 H), 1.64-

1.58 (m, 6 H), 1.47-1.42 (m, 2 H), 1.14-1.07 (m, 6 H), 0.94-0.85 (m, 4 H) ; 13C NMR (100 MHz, CDCl3) δ

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165.4, 133.2, 129.6, 129.2, 128.5, 67.1, 57.5, 35.7, 31.6, 26.6, 25.9; HRMS (ESI+): calcd for C30H40N2O4Na

([M+Na]+): 515.2885, found: 515.2899.

3r (131.2 mg, 80% yield); IR (neat): 2935, 2856, 1739, 1240, 770, 709; 1H NMR (400 MHz, CDCl3) δ

7.98-7.96 (m, 4 H), 7.55-7.51 (m, 2 H), 7.42-7.37 (m, 4 H), 3.24 (s, 4 H), 2.8 (s, 6 H); 13C NMR (100 MHz,

CDCl3) δ 165.1, 133.2, 129.6, 129.2, 128.5, 58.4, 47.7; HRMS (ESI+): calcd for C18H20N2O4Na ([M+Na]+):

351.1320, found: 351.1326.

3s (180.3 mg, 75%); IR (neat): 2988, 2893, 2836, 1744, 1236, 1032, 706; 1H NMR (400 MHz, CDCl3) δ

7.89-7.86 (m, 4 H), 7.89-7.86 (m, 2 H), 7.4-7.34 (m, 8 H), 7.25-7.19 (m, 6 H), 4.18 (s, 4 H), 3.34 (s, 4 H);

13C NMR (100 MHz, CDCl3) δ 165.2, 135.3, 133.2, 129.7, 129.5, 129.1, 128.5, 128.4, 127.8, 64.1, 56.8;

HRMS (ESI+): calcd for C30H28N2O4Na ([M+Na]+): 503.1946, found: 503.1943.

3t (181 mg, 71%); IR (neat): 2978, 2888, 2830, 1738, 1232, 1032, 705; 1H NMR (400 MHz, CDCl3) δ 8.03-

8.0 (m, 4 H), 7.6-7.56 (m, 2 H), 7.46-7.43 (m, 4 H), 7.24-7.19 (m, 4 H), 7.17-7.11 (m, 6 H), 3.35 (s, 4 H),

3.3-3.26 (m, 4 H), 2.92-2.88 (m, 4 H); 13C NMR (100 MHz, CDCl3) δ 165.7, 139.1, 133.4, 129.7, 128.7,


531.2257.

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3u (145 mg, 70%); IR (neat): 2935, 2856, 1740, 1242, 775, 705; 1H NMR (400 MHz, CDCl3) δ 8.0-7.98

(m, 4 H), 7.57-7.52 (m, 2 H), 7.43-7.39 (m, 4 H), 3.25 (s, 4 H), 2.98-2.94 (m, 4 H), 1.54-1.46 (m, 4 H),

1.35-1.25 (m, 4 H), 0.83 (t, J= 7.2 Hz, 6 H); 13C NMR (100 MHz, CDCl3) δ 165.7, 133.2, 129.6, 128.9,

128.5, 60.2, 57.1, 28.3, 20.4, 13.9; HRMS (ESI+): calcd for C24H32N2O4Na ([M+Na]+): 435.2259, found:

435.2265.

3v (170.9 mg, 73%); IR (neat): 2932, 2855, 1742, 1240, 775, 705; 1H NMR (400 MHz, CDCl3) δ 8.01-7.98

(m, 4 H), 7.57-7.53 (m, 2 H), 7.44-7.39 (m, 4 H), 3.25 (s, 4 H), 2.98-2.94 (m, 4 H), 1.55-1.48 8.0-7.98 (m,

4 H), 7.57-7.52 (m, 2 H), 7.43-7.39 (m, 4 H), 3.25 (s, 4 H), 2.98-2.94 (m, 4 H), 1.29-1.18 8.0-7.98 (m, 4

H), 7.57-7.52 (m, 2 H), 7.43-7.39 (m, 4 H), 3.25 (s, 4 H), 2.98-2.94 (m, 13 H), 0.8 (t, J= 7.2 Hz, 6 H); 13C

NMR (100 MHz, CDCl3) δ 165.7, 133.2, 129.6, 129.0, 128.5, 60.5, 57.1, 31.6, 26.8, 26.7, 22.5, 14.0; HRMS


Reaction in gram scale (2.3 g, 20 mmol)

BPO (80 mmol, 4.0 equiv) and Cs2CO3 (120 mmol, 6.0 equiv) were taken in an oven dried round bottom

flask equipped with a magnetic stir bar and a rubber septum. CH2Cl2 (200 mL) was added to it and the

heterogeneous mixture was stirred for 2 h at room temperature.1 After that a solution of 1,2-diamine 1 in

50 mL CH2Cl2 (20 mmol, 1.0 equiv) was then added and the mixture was further stirred for 14 h.2 Then

water 150 mL was added to the reaction mixture and stirred for 15 min and extracted with CH2Cl2. The

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organic layer were washed with brine, dried over Na2SO4 and concentrated to get crude product. The crude


yield bis-(benzoyloxy)-1,2-diamine (5.53g, 78%).

4. General Procedure for the one pot synthesis of bis-(benzoyloxy)hydroxamic acid

BPO (2 mmol, 4.0 equiv) and Cs2CO3 (3 mmol, 6.0 equiv) were taken in an oven dried test tube equipped



CH2Cl2) was then added and the mixture was further stirred for 14 h.2 Then a solution of RCOCl (2.0 mmol,

4.0 equiv, in 5 mL CH2Cl2) was added to it and stirred continued for another 6 h. Then water (10 mL) was

added to the reaction mixture and stirred for 5 min and extracted with CH2Cl2. The organic layer were

washed with sat. NaHCO3 solution, brine, dried over Na2SO4 and concentrated to get crude product. The

crude product was purified by silica gel column chromatography using petroleum ether/ethyl acetate as

eluent to yield bis-(benzoyloxy)hydroxamic acid.

5a (177.6 mg, 81%); [𝛼]𝐷25

= −102.0 (c 1.0, CHCl3,); IR (neat): 2942, 2864, 1764, 1672, 1230, 1009, 906,

726, 705; 1H NMR (400 MHz, CDCl3) δ 8.23-8.21 (m, 4 H), 7.66-7.62 (m, 2 H), 7.53-7.49 (m, 4 H), 4.91

(br, 2 H), 2.07-2.05 (m, 2 H), 2.02 (s, 6 H), 1.67-1.66 (m, 2 H), 1.26-1.21 (m, 4 H); 13C NMR (100 MHz,

CDCl3) δ 171.1, 165.3, 134.7, 130.5, 129.1, 126.4, 56.1, 29.6, 24.5, 20.6; HRMS (ESI+): calcd for

C24H26N2O6Na ([M+Na]+): 461.1688, found: 461.1702.

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5b (179.6 mg, 77%); [𝛼]𝐷25

= −90.0 (c 1.0, CHCl3,); IR (neat): 2941, 2863, 1764, 1673, 1225, 1011, 807,


(br, 2 H), 2.34-2.15 (m, 4 H), 2.11-2.03 (m, 2 H), 1.68-1.66 (m, 2 H), 1.35-1.22 (m, 4 H), 1.08 (t, J= 7.32

Hz, 6 H); 13C NMR (100 MHz, CDCl3) δ 174.3, 165.5, 134.6, 130.5, 129.1, 126.5, 56.3, 29.7, 25.7, 24.6,

8.4; HRMS (ESI+): calcd for C26H30O6Na ([M+Na]+): 489.2001, found: 489.1990.

5c (188 mg, 76%); [𝛼]𝐷25

= −86.0 (c 1.0, CHCl3,); IR (neat): 2937, 2865, 1764, 1668, 1229, 1013, 905, 726,

706; 1H NMR (400 MHz, CDCl3) δ 8.25-8.23 (m, 4 H), 7.67-7.64 (m, 2 H), 7.56-7.52 (m, 4 H), 4.94 (br, 2

H), 2.28-2.13 (m, 4 H), 2.07-2.04 (m, 2 H), 1.71-1.59 (m, 6 H), 1.25-1.19 (m, 4 H), 0.87 (t, J=7.32 Hz, 6

H); 13C NMR (100 MHz, CDCl3) δ 173.3, 165.5, 134.5, 130.5, 129.1, 126.5, 56.1, 34.2, 29.8, 24.6, 17.6,

13.9; HRMS (ESI+): calcd for C28H34N2O6Na ([M+Na]+): 517.2314, found: 517.2306.

5d (214.8 mg, 78%); [𝛼]𝐷25

= −80.0 (c 1.0, CHCl3,); IR (neat):2932, 2863, 1765, 1668, 1232, 1015, 804,


(br, 2 H), 2.28-2.13 (m, 4 H), 2.06-2.03 (m, 2 H), 1.67-1.54 (m, 6 H), 1.35-1.16 (m, 12 H), 0.8 (t, J=7.2 Hz,

6 H); 13C NMR (100 MHz, CDCl3) δ 173.3, 165.5, 134.6, 130.5, 129.1, 126.5, 56.1, 32.4, 31.6, 29.8, 24.6,

23.9, 22.5, 13.9; HRMS (ESI+): calcd for C32H42N2O6Na ([M+Na]+): 573.2940, found: 573.2931.

5e (221 mg, 72%); [𝛼]𝐷25

= −236.0 (c 1.0, CHCl3,); IR (neat): 3061, 2939, 2862, 1766, 1659, 1621, 1234,

1009, 757, 699; 1H NMR (400 MHz, CDCl3) δ 8.35-8.31 (m, 4 H), 7.73-7.69 (m, 4 H), 7.61-7.54 (m, 4 H),

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7.24-7.11 (m, 10 H), 6.6 (d, J=15.6 Hz, 2 H), 5.13 (br, 2 H), 2.22-2.19 (m, 2 H), 1.78-1.75 (m, 2 H), 1.38-

1.31 (m, 4 H); 13C NMR (100 MHz, CDCl3) δ 167.0, 165.6, 144.7, 134.8, 130.7, 129.9, 129.2, 128.6, 128.1,


637.2249.

5f (204 mg, 71%); [𝛼]𝐷25

= −58.0 (c 1.0, CHCl3,); IR (neat): 2931, 2856, 1765, 1665, 1233, 1009, 907, 727,

704; 1H NMR (400 MHz, CDCl3) δ 8.2-8.19 (m, 4 H), 7.67-7.64 (m, 2 H), 7.55-7.51 (m, 4 H), 4.92 (br, 2

H), 2.3-2.25 (m, 3 H), 2.07-2.04 (m, 2 H), 1.83-1.46 (m, 17 H), 1.29-1.15 (m, 4 H), 1.06-1.05 (m, 4 H); 13C

NMR (100 MHz, CDCl3) δ 176.3, 165.8, 134.5, 130.4, 129.1, 126.4, 56.1, 40.6, 30.3, 29.4, 28.9, 25.6, 25.5,

25.4, 24.7; HRMS (ESI+): calcd for C34H42N2O6Na ([M+Na]+): 597.2940, found: 597.2932.

5g (230 mg, 78%); [𝛼]𝐷25

= −8.0 (c 1.0, CHCl3,); IR (neat): 3063, 2927, 2862, 1763, 1671, 1228, 1002,

701; 1H NMR (400 MHz, CDCl3) δ 8.21-8.15 (m, 4 H), 7.7-4.66 (m, 2 H), 7.54-7.5 (m, 4 H), 7.29-7.22 (m,

10 H), 4.98 (br, 2 H), 3.55-3.51 (m, 4 H), 2.14-2.11 (m, 2 H), 1.71-1.7 (m, 2 H), 1.42-1.23 (m, 4 H); 13C

NMR (100 MHz, CDCl3) δ 171.2, 165.5, 134.7, 134.0, 130.5, 129.7, 129.0, 128.4, 127.0, 126.4, 56.3, 39.4,

30.1, 24.6; HRMS (ESI+): calcd for C36H34N2O6Na ([M+Na]+): 590.2401, found: 590.2417.

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5h (162 mg, 70%); [𝛼]𝐷25

= −148.0 (c 1.0, CHCl3,); IR (neat): 3065, 2941, 2863, 1765, 1667, 1411, 1225,

1008, 704; 1H NMR (400 MHz, CDCl3) δ 8.24-8.22 (m, 2 H), 7.67-7.63 (m, 1 H), 7.53-7.5 (m, 2 H), 6.41-

6.28 (m, 4 H), 5.64 (d, J=10.7 Hz, 2 H), 5.01 (br, 2 H), 2.11-2.09 (m, 2 H), 1.72-1.71 (m, 2 H), 1.32-1.21

(m, 4 H); 13C NMR (100 MHz, CDCl3) δ 166.1, 165.4, 134.7, 130.5, 129.9, 129.1, 126.2, 126.0, 56.5, 29.6,

24.6; HRMS (ESI+): calcd for C26H26O6N2Na ([M+Na]+): 485.1688, found: 485.1673.

5. General Procedure for the synthesis of N-(benzoyloxy)amine

BPO (1 mmol, 2.0 equiv) and Cs2CO3 (1.5 mmol, 3.0 equiv) were taken in an oven dried test tube equipped



CH2Cl2) was then added and the mixture was further stirred for 14 h.2 Then water (5 mL) was added to the

reaction mixture and stirred for 5 min and extracted with CH2Cl2. The organic layer were washed with brine,

dried over Na2SO4 and concentrated to get crude product. The ratio of 7: 8 was determined by 1H NMR

spectroscopy of crude reaction mixture using 1,1’,2,2’-tetrachloroethane as an internal standard. The crude


yield N-(benzoyloxy)amine 7b. Analytical data were in good accordance with data reported in the literature

(Ref. 3b).

7a3a (97.4 mg, 95%); IR (neat): 2931, 2855, 1715, 1265, 1065, 704; 1H NMR (400 MHz, CDCl3) δ 8.03-

8.01 (m, 2 H), 7.73 (s, 1 H), 7.59-7.55 (m, 1 H), 7.47-7.43 (m, 2 H), 3.72-3.67 (m, 1 H), 1.87-1.72 (m, 4

H), 1.67-1.56 (m, 4 H); 13C NMR (100 MHz, CDCl3) δ 167.1, 133.3, 129.4, 128.7, 128.6, 62.3, 30.5, 24.5.

7b3b (104 mg, 95%); IR (neat): 2930, 2855, 1714, 1266, 1066, 704; 1H NMR (400 MHz, CDCl3) δ 8.03-8.0

(m, 2 H), 7.72 (s, 1 H), 7.58-7.53 (m, 1 H), 7.46-7.41 (m, 2 H), 3.07-3.01 (m, 1 H), 2.01-1.94 (m, 2 H),

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1.79-1.74 (m, 2 H), 1.64-1.61 (m, 1 H), 1.34-1.17 (m, 5 H); 13C NMR (100 MHz, CDCl3) δ 167.1, 133.3,

129.4, 128.5 (2), 59.9, 30.4, 25.9, 24.5.

7c (100.2 mg, 86%); IR (neat): 2929, 2854, 1716, 1265, 1064, 705; 1H NMR (400 MHz, CDCl3) δ 8.03-8.0

(m, 2 H), 7.66 (s, 1 H), 7.58-7.54 (m, 1 H), 7.46-7.41 (m, 2 H), 3.26-3.21 (m, 1 H), 1.98-1.92 (m, 2 H),



7d3c (110.9 mg, 90%); IR (neat): 2931, 2856, 1714, 1264, 1065, 704; 1H NMR (400 MHz, CDCl3) δ 8.03-

8.0 (m, 2 H), 7.63 (s, 1 H), 7.59-7.54 (m, 1 H), 7.46-7.41 (m, 2 H), 3.28-3.22 (m, 1 H), 1.9-1.83 (m, 2 H),


61.3, 29.9, 27.1, 25.9, 24.1.

7e (94.1 mg, 85%); [𝛼]𝐷25

= −30.0 (c 1.0, CHCl3,); IR (neat): 3342, 2953, 2870, 1719, 1266, 1066, 704; 1H

NMR (400 MHz, CDCl3) δ 8.0-7.97 (m, 2 H), 7.56-7.52 (m, 1 H), 7.44-7.39 (m, 2 H), 4.17-4.1 (m, 1 H),

3.88-3.83 (m, 1 H), 3.78-3.73 (m, 1 H), 3.28-3.24 (m, 1 H), 3.14-3.08 (m, 1 H), 2.08-1.99 (m, 1 H), 1.92-



HLPC analysis: Daicel Chiralpak OJ-H, hexane/i-PrOH = 97/3, flow rate = 1.0 mL/min, λ= 254 nm,

retention time; tR(minor) = 15.8 min, tR(major) = 16.7 min.

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7f3b,c (90.7 mg, 80%); IR (neat): 3235, 3061, 3030, 2930, 1715, 1264, 1065, 685; 1H NMR (400 MHz,

CDCl3) δ 8.0-7.97 (m, 2 H), 7.59-7.56 (m, 1 H), 7.46-7.41 (m, 4 H), 7.39-7.31 (m, 3 H), 4.28 (s, 2 H); 13C

NMR (100 MHz, CDCl3) δ 166.9, 135.9, 133.4, 129.4, 129.0, 128.7, 128.6, 128.3, 128.0, 56.8.

7g3b (110.8 mg, 92%); IR (neat): 3233, 3062, 3028, 2931, 1716, 1264, 1066, 686; 1H NMR (400 MHz,

CDCl3) δ 8.01-7.99 (m, 2 H), 7.83 (s, 1 H), 7.59-7.56 (m, 1 H), 7.47-7.43 (m, 2 H), 7.39-7.31 (m, 2 H),

7.26-7.23 (m, 3 H), 3.43 (t, J=7.2 Hz, 2 H), 2.98 (t, J= 7.2 Hz, 2 H); 13C NMR (100 MHz, CDCl3) δ 166.7,

138.8, 133.4, 129.4, 128.8, 128.7, 128.6, 128.4, 126.6, 53.7, 33.9.

7h3a,4 (86.9 mg, 90%); IR (neat): 2935, 2855, 1714, 1266, 1065, 705; 1H NMR (400 MHz, CDCl3) δ 8.04-

8.02 (m, 2 H), 7.60-7.55 (m, 2 H, NH), 7.48-7.43 (m, 2 H), 1.23 (s, 9 H); 13C NMR (100 MHz, CDCl3) δ

166.9, 133.3, 129.4, 128.6 (2), 56.2, 26.7.

7i3d (77.1 mg, 87%); IR (neat): 3232, 3071, 2984, 2918, 1716, 1262, 703; 1H NMR (400 MHz, CDCl3) δ

8.02-7.99 (m, 2 H), 7.86 (s, 1 H), 7.89-7.54 (m, 1 H), 7.46-7.42 (m, 2 H), 5.99-5.88 (m, 1 H), 5.32-5.27 (m,

1 H), 5.22-5.21 (m, 1 H), 3.75-3.73 (m, 2 H); 13C NMR (100 MHz, CDCl3) δ 166.9, 133.4, 132.7, 129.4,

128.6, 128.4, 119.3, 55.3.

7j3a (82.0 mg, 85%); IR (neat): 2930, 2854, 1714, 1265, 1065, 704; 1H NMR (400 MHz, CDCl3) δ 8.04-

8.01 (m, 2 H), 7.59-7.55 (m, 1 H), 7.47-7.43 (m, 2 H), 3.14 (d, J=7.2 Hz, 2 H), 1.64-1.57 (m, 2 H), 1.48-

1.38 (m, 2 H), 0.95 (d, J=7.2 Hz, 3 H); 13C NMR (100 MHz, CDCl3) δ 167.1, 133.4, 129.4, 128.6, 128.3,

52.4, 29.3, 20.3, 14.1.

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7k4 (86.8 mg, 85%); IR (neat): 2955, 2857, 1730, 1273, 751, 698; 1H NMR (400 MHz, CDCl3) δ 8.0-7.98

(m, 2 H), 7.55-7.51 (m, 1 H), 7.43-7.39 (m, 2 H), 3.52-3.48 (m, 2 H), 2.79-2.72 (m, 2 H), 1.84-1.78 (m, 4

H), 1.69-1.63 (m, 1 H), 1.32-1.22 (m, 1 H); 13C NMR (100 MHz, CDCl3) δ 164.8, 132.9, 129.7, 129.4,

128.4, 57.6, 25.0, 23.4.

7l4 (93.1 mg, 90%); IR (neat): 2930, 2855, 1728, 1601, 1462, 751, 698; 1H NMR (400 MHz, CDCl3) δ 8.1-

7.99 (m, 2 H), 7.57-7.52 (m, 1 H), 7.44-7.39 (m, 2 H), 3.96-3.94 (m, 1 H), 3.86-3.81 (m, 1 H), 3.43 (d, J=

9.6 Hz, 2 H), 3.04-2.99 (m, 2 H); 13C NMR (100 MHz, CDCl3) δ 164.6, 133.2, 129.4, 129.4, 128.5, 65.9,

57.0.

7m4 (87.9 mg, 91%); IR (neat): 2932, 2850, 1730, 1601, 1465, 751, 698; 1H NMR (400 MHz, CDCl3) δ

8.02-8.0 (m, 2 H), 7.56-7.51 (M, 1 H), 7.43-7.39 (m, 2 H), 3.02 (q, J= 7.2 Hz, 4 H), 1.15 (t, J=7.2 Hz, 6 H);

13C NMR (100 MHz, CDCl3) δ 165.9, 133.1, 129.5, 129.2, 128.5, 53.5, 11.9.

7n4 (99.8 mg, 92%) ; IR (neat): 3080, 2836, 1737, 1237, 1060, 705; 1H NMR (400 MHz, CDCl3) δ 7.97-

7.94 (m, 2 H), 7.55-7.5 (m, 1 H), 7.42-7.37 (m, 2 H), 6.05-5.95 (m, 2 H), 5.26 (dd, J= 2.8, 1.6 Hz, 1 H),

5.22 (dd, J= 2.8, 1.6 Hz, 1 H), 5.18 (dd, J= 2.8, 1.2 Hz, 1 H), 5.15 (dd, J= 2.8, 1.2 Hz, 1 H), 3.65 (t, J=1.2

Hz, 2 H), 3.63 (t, J=1.2 Hz, 2 H); 13C NMR (100 MHz, CDCl3) δ 165.4, 133.1, 132.6, 129.5, 129.3, 128.4,

119.6, 61.8.

7o4 (139.5 mg, 88%); IR (neat): 2955, 2925, 2848, 1730, 1455, 698; 1H NMR (400 MHz, CDCl3) δ 7.85-

7.83 (m, 2 H), 7.52-7.45 (m, 5 H), 7.38-7.24 (m, 8 H), 4.2 (s, 4 H); 13C NMR (100 MHz, CDCl3) δ 165.0,

136.0, 132.9, 129.5, 129.4, 129.3, 128.5, 128.4, 127.7, 62.2.

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7p10 (62.6 mg, 48%); 1H NMR (400 MHz, CDCl3) δ 8.09-8.06 (m, 2 H), 7.57-7.51 (m, 1 H), 7.47-7.44 (m,

2 H), 1.81-1.67 (m, 3 H), 1.61-1.57 (m, 2 H), 1.48-1.43 (m, 1 H), 1.27 (s, 6 H), 1.12 (s, 6 H); 13C NMR

(100 MHz, CDCl3) δ 166.5, 132.9, 129.8, 128.9, 128.6, 60.5, 39.2, 32.1, 20.9, 17.1.

Comparison of results of Ref. 10d and our method

The known oxidation methods for mono-amine (Ref. 10a, 10b, 10c, 10d) in which Ref. 10a, 10b and 10c

reported amide side product formation but Ref. 10d didn’t observed any side product. Interestingly, we

tested Ref. 10d, in our hand shows a significant amount of amide side product for primary amine which is

very challenging but secondary amine works quite well as similar it is reported. In contrast, we have tested

several primary amines and secondary amines using our method without amide side product in most cases.

The all the known methods (Ref. 10a, 10b, 10c, 10d) only applicable for mono-amines with very limited

substrate scope whereas our current method is applicable for diamine as well as mono-amine with a wide

substrate scope. To make it clear, we have tested Ref. 10d and compared with our method given below.

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6. General Procedure N-(benzoyloxy)amine (N−OBz) hydrolysis to N−OH

To a stirred solution of N-(benzoyloxy)amine derivative (0.25 mmol, 1.0 equiv) in MeOH (2 mL) was added

LiOH. H2O (1.0 equiv per N−OBz) under nitrogen. After 10 min, the reaction mixture was concentrated

under reduced pressure and then to this water was added and extracted with CH2Cl2, washed with brine,

dried over Na2SO4, and filtered. The filtrate was concentrated under reduced pressure and the residue was

purified by flash column chromatography on silica gel to provide the pure N−OH derivatives

9A (94.6 mg, 99% yield); [𝛼]𝐷25

= +9.0 (c 1.0, CHCl3,); IR (neat): 3312, 3162, 2936, 2860, 1620, 1597,

1416, 1165, 693; 1H NMR (400 MHz, CDCl3) δ 9.11 (s, 2 H), 7.31-7.20 (m, 10 H), 4.39-4.31 (m, 2 H), 3.81

(d, J=14.7 Hz, 2 H), 3.54 (d, J=14.7 Hz, 2 H), 1.86-1.72 (m, 6 H), 1.32-1.24 (m, 2 H); 13C NMR (100 MHz,

CDCl3) δ 174.2, 134.9, 129.5, 128.7, 126.9, 55.8, 39.2, 27.8, 24.5; HRMS (ESI+): calcd for C22H26N2O4Na

([M+Na]+): 405.1790, found: 405.1782.

9B (54.3 mg, 99% yield); 1H NMR (400 MHz, CDCl3) δ 8.48 (s, 1 H), 7.49-7.43 (m, 5 H), 3.77-3.71 (m, 1

H), 1.91-1.85 (m, 2 H), 1.79-1.74 (m, 4 H), 1.58-1.55 (m, 1 H), 1.15-1.08 (m, 3 H); 13C NMR (100 MHz,

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CDCl3) δ 166.4, 132.9, 130.8, 128.7, 127.6, 59.9, 30.0, 25.4, 25.0. Analytical data were in good accordance

with data reported in the literature (Ref. 5).

9C (83.7 mg, 99% yield); [𝛼]𝐷25

= −37.14 (c 1.0, CHCl3,); IR (neat):3310, 2921, 2851, 1654, 1601, 1447,

751, 693; 1H NMR (400 MHz, CDCl3) δ 6.91 (br, 2 H)2.92-2.91 (m, 2 H), 2.76 (dd, J=12.8 Hz, 4.6 Hz, 2

H), 2.33-2.27 (m, 2 H), 1.95-1.87 (m, 4 H), 1.72-1.64 (m, 13 H), 1.35-1.11 (m, 11 H), 0.93-0.82 (m, 4 H);

13C NMR (100 MHz, CDCl3) δ 67.1, 61.6, 35.4, 31.9, 31.8, 26.8, 26.2, 26.0, 25.1; HRMS (ESI+): calcd for

C20H38N2O2Na ([M+Na]+): 361.2831, found: 361.2844.

9D (27.4 mg, 95% yield); 1H NMR (400 MHz, CDCl3) δ 2.85-2.78 (m, 1 H), 1.93-1.88 (m, 2 H), 1.79-1.72


30.5, 26.2, 24.7. Analytical data were in good accordance with data reported in the literature (Ref. 6).

7. General procedure for preparation of bis-hydroxamic acid (BHA) ligand

To a stirred solution of 3a (177 mg, 0.5 mmol) DIEA (1.76 mL, 10.0 mmol) in 1,2-DCE (5 mL) was added

acid chloride solution (400mg, 1.25 mmol, dissolved in 5 mL 1,2-DCE) under nitrogen. After 24 h, the

reaction mixture was treated with sat. NaHCO3 solution. After stirring for 10 min the reaction mixture was

extracted with CH2Cl2, washed with brine, dried over Na2SO4, and filtered. The filtrate was concentrated

under reduced pressure and the residue was purified by flash column chromatography on silica gel to

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provide the pure compound. 9E (250 mg, 54% yield); [𝛼]𝐷25

= −102.0 (c 1.0, CHCl3,); IR (neat): 3059,

3019, 2938, 2861, 1762, 1683, 1226, 1010, 752, 699; 1H NMR (400 MHz, CDCl3) δ 8.05-8.03 (m, 4 H),

7.67-7.64 (m, 2 H), 7.46-7.42 (m, 4 H), 7.14-7.07 (m, 25 H), 7.03-7.0 (m, 5 H), 4.9 (br, 2 H), 3.8 (d, J=

18.3 Hz, 2 H), 3.56 (d, J= 18.1 Hz, 2 H), 2.01-1.96 (m, 2 H), 1.59-1.58 (m, 2 H), 1.13-1.06 (m, 4 H); 13C

NMR (100 MHz, CDCl3) δ 169.4, 166.3, 147.2, 134.7, 130.9, 129.4, 129.3, 129.2, 127.9, 127.7, 126.4,

126.0, 125.8, 55.5, 54.8, 43.5, 30.2, 24.6; HRMS (ESI+): calcd for C62H54N2O6Na ([M+Na]+): 945.3732,

found: 945.3741.

To a stirred solution of 9E (231 mg, 0.25 mmol) in MeOH (2 mL) was added LiOH. H2O (21 mg, 1.25

mmol) under nitrogen. After 10 min, the reaction mixture was concentrated under reduced pressure and to

this water was added and extracted with CH2Cl2, washed with brine, dried over Na2SO4, and filtered. The

filtrate was concentrated under reduced pressure and the residue was purified by flash column

chromatography on silica gel to provide the pure compound 9F (176.8 mg, 99% yield); [𝛼]𝐷25

= +20.0 (c

1.0, CHCl3,); IR (neat): 3087, 3056, 3030, 2861, 1615, 1492, 1445, 699; 1H NMR (400 MHz, CDCl3) δ

8.47 (s, 2 H), 7.25-7.17 (m, 30 H), 4.19 (d, J=16.0 Hz, 2 H), 3.91-3.86 (m, 2 H), 3.57-3.53 (d, J=16.0 Hz,

2 H), 1.63-1.61 (m, 2 H), 1.44-1.42 (m, 2 H), 1.31-1.28 (m, 2 H), 1.07-1.02 (m, 2 H); 13C NMR (100 MHz,

CDCl3) δ 173.4, 147.1, 129.6, 127.7, 126.2, 56.4, 55.2, 42.1, 27.3, 24.5; HRMS (ESI+): calcd for

C48H46N2O4Na ([M+Na]+): 737.3329, found: 737.3341. All analytical data were in good accordance with

data reported in the literature (Ref. 7).

Known method for preparation of BHA ligand

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8. Preparation of 1,2-diamines

A. Preparation of 1h-1l, 1n, 1p-1q, 1s-3v

1h-1l, 1n were prepared using known procedure.8 A solution of 4 M NaOH (40 mL) was added to a

suspension of (1R,2R)-trans-cyclohexane1,2-diammonium (S)-tartrate (1.0 equiv, 3.78 mmol) in CH2Cl2

(25 mL) and the mixture was stirred until all the solid material had dissolved. Then acid chloride/aldehyde

(4.0 equiv) was added and the reaction mixture was stirred for 4 h at room temperature. Water (50 mL) was

added and the reaction mixture was extracted with CH2Cl2. The combined organic layers were washed with

brine, dried over Na2SO4 and concentrated in vacuo to give as a colorless solid (quantitative yield). The

amide used directly to next step without further purification. A solution of lithium aluminium hydride (2 M

in THF, 4.0 equiv) was added to a solution of diamide in THF at 0 °C and the reaction mixture was refluxed

for overnight. After cooling to room temperature, the reaction was quenched with moist Na2SO4, then the

solid was filtered through a Celite pad, washed with CH2Cl2 and concentrated in vacuo. The crude product

was purified to give 1,2-diamine 1h-1l, 1n.

1h8 (96%); 1H NMR (400 MHz, CDCl3) δ 2.62-2.54 (m, 2 H), 2.32-2.24 (m, 2 H), 1.98-1.8 (m, 4 H), 1.58-

1.5 (m, 2 H), 1.44-1.38 (m, 2 H), 1.09-1. (m, 2 H), 0.94-0.86 (m, 6 H), 0.84-0.72 (m, 2 H); 13C NMR (100

MHz, CDCl3) δ 61.5, 41.1, 31.6, 25.1, 15.6.

1i8 (89%); 1H NMR (400 MHz, CDCl3) δ 3.62-3.56 (m, 1 H), 2.69-2.62 (m, 2 H), 2.37-2.31 (m, 2 H), 2.02-

1.98 (m, 4 H), 1.64-1.62 (m, 2 H), 1.41-1.22 (m, 8 H), 1.17-1.12 (m, 4 H), 0.86-0.82 (m, 6 H), 1.79-1.72

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46.7, 32.7, 31.7, 25.2, 20.5, 14.3.

1j8 (88%); 1H NMR (400 MHz, CDCl3) δ 2.86-2.85 (m, 1 H), 2.78-2.72 (m, 2 H), 2.46-2.39 (m, 2 H), 2.19-

2.16 (m, 2 H), 2.1-2.06 (m, 2 H), 1.71-1.69 (m, 2 H), 1.42-1.3 (m, 4 H), 1.23-1.17 (m, 2 H), 1.1-1.0 (m, 2

H), 0.87 (s, 18 H); 13C NMR (100 MHz, CDCl3) δ 61.5, 44.1, 42.9, 31.2, 29.9, 29.6, 25.1.

1k8 (82%); 1H NMR (400 MHz, CDCl3) δ 7.32-7.29 (m, 4 H), 7.25-7.23 (m, 6 H), 3.92 (d, J=13.2 Hz, 2 H),

3.68 (d, J=13.0 Hz, 2 H), 2.28-2.26 (m, 2 H), 2.18-2.15 (m, 2 H), 1.97 (s, 1 H), 1.74-1.72 (m, 2 H), 1.25-


31.6, 25.1.

1l8 (89%); 1H NMR (400 MHz, CDCl3) δ 2.56-2.51 (m, 2 H), 2.25-2.2 (m, 2 H), 2.04-2.02 (m, 4 H), 1.73-

1.62 (m, 11 H), 1.56-1.54 (m, 4 H), 1.37-1.34 (m, 2 H), 1.26-1.11 (m, 8 H), 0.95-0.84 (m, 6 H); 13C NMR

(100 MHz, CDCl3) δ 61.9, 53.8, 38.5, 31.7, 31.6, 31.5, 26.8, 26.2, 25.2.

B. Preparation of 3p-3q, 3s-3v

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A solution of (CO2Et)2 (1.0 equiv) in toluene was added to a suspension of R-NH2 (2.0 equiv) in toluene

and the mixture was reflux for 2 h. Then cool to room temperature and a precipitate formed, which filtered

to give white solid product. The product used for next step without further purification. A solution of lithium

aluminium hydride (2 M in THF, 4.0 equiv) was added to a solution of diamide in THF at 0 °C and the

reaction mixture was refluxed for overnight. After cooling to room temperature, the reaction was quenched

with moist Na2SO4, then the solid was filtered through a Celite pad, washed with CH2Cl2 and concentrated

in vacuo. The crude product was purified to give 1,2-diamine

1p9a (92%); 1H NMR (400 MHz, CDCl3) δ 3.1 (s, 1 H), 2.98-2.91 (m, 2 H), 2.6 (s, 4 H), 1.77-1.69 (m, 4

H), 1.61-1.52 (m, 4 H), 1.48-1.39 (m, 4 H), 1.25-1.19 (m, 4 H); 13C NMR (100 MHz, CDCl3) δ 59.9, 48.6,

33.2, 24.1.

1q9b (93%); 1H NMR (400 MHz, CDCl3) δ 2.72-2.7 (m, 4 H), 2.42-2.41 (m, 4 H), 1.72-1.62 (m, 10 H),

1.22-1.11 (m, 6 H), 0.91-0.82 (m, 4 H); 13C NMR (100 MHz, CDCl3) δ 56.5, 49.0, 37.7, 31.4, 26.7, 26.1.

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1s9c (90%); 1H NMR (400 MHz, CDCl3) δ 7.33-7.24 (m, 10 H), 3.77 (s, 4 H), 2.76 (s, 4 H), 1.80 (s, 2 H);

13C NMR (100 MHz, CDCl3) δ 140.6, 128.5, 128.2, 127.1, 54.1, 48.9.

1t9d (85%); 1H NMR (400 MHz, CDCl3) δ 7.31-7.27 (m, 4 H), 7.22-7.18 (m, 6 H), 2.87-2.83 (m, 4 H), 2.81-

2.75 (m, 4 H), 2.71 (s, 4 H), 1.68-1.65 (m, 2 H); 13C NMR (100 MHz, CDCl3) δ 140.2, 128.8, 128.5, 126.2,

51.2, 49.2, 36.5.

1u9e (90%); 1H NMR (400 MHz, CDCl3) δ 2.63-2.62 (m, 4 H), 2.53-2.49 (m, 4 H), 1.41-1.21 (m, 10 H),

0.84-0.8 (m, 6 H); 13C NMR (100 MHz, CDCl3) δ 49.7, 49.6, 32.3, 20.5, 14.1;

1v9f (91%); 1H NMR (400 MHz, CDCl3) δ 2.7-2.65 (m, 4 H), 2.58-2.51 (m, 4 H), 1.47-1.38 (m, 4 H), 1.31-

1.2 (m, 14 H), 0.87-0.79 (m, 6 H); 13C NMR (100 MHz, CDCl3) δ 50.2, 49.7, 31.8, 30.2, 27.1, 22.7, 14.1.

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9. HPLC data of 7e

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10. Reference

1. After few minutes some solid stick in the reaction tube wall and make sure that all the solid heterogeneous

mixture should be free flowing.

2. Before addition of amine make sure that all the solids are free flowing and nothing stick in the wall of

the tube.

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J. Mathews, N. C. O. Tomkinson, Synlett 2008, 18, 2769; d) L. Grierson, M. J. Perkins, Tetrahedron

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4. a) A. M. Berman, J. S. Johnson, J. Org. Chem. 2006, 71, 219; b) Y.-H. Chen, S. Graßl, P. Knochel,

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Z. Slawin, A. D. Smith, Tetrahedron: Asymmetry 2010, 21, 582; b) M. Milan, M. Bietti and M. Costas,

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https://pubs.acs.org/author/Milan%2C+Michela

https://pubs.acs.org/author/Bietti%2C+Massimo

https://pubs.acs.org/author/Costas%2C+Miquel

https://pubs.acs.org/author/Etxebarria%2C+J

https://pubs.acs.org/author/Degenbeck%2C+H

https://pubs.acs.org/author/Felten%2C+A-S

https://pubs.acs.org/author/Serres%2C+S

https://pubs.acs.org/author/Nieto%2C+N

https://www.tandfonline.com/author/Talotta%2C+Carmen

https://www.tandfonline.com/author/Rubino%2C+Luca

https://www.tandfonline.com/author/Gaeta%2C+Carmine

https://www.tandfonline.com/author/Capitelli%2C+Francesco

https://www.tandfonline.com/author/Saviano%2C+Michele

https://www.tandfonline.com/author/Brancatelli%2C+Giovanna

https://www.tandfonline.com/author/Brancatelli%2C+Giovanna

https://onlinelibrary.wiley.com/action/doSearch?ContribAuthorStored=Pelckmans%2C+Michiel

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https://pubs.acs.org/author/Shen%2C+Baojian

https://pubs.acs.org/author/Li%2C+Zhiping

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12. Copies of 1H and 13C NMR spectra, 3a

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4a

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3c

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3d

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3f

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3j

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3k

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3l

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3m

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3n

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3o

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3p

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3q

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3r

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3s

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3t

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Documents

O bond Formation via Oxidation of Amines with Benzoyl Peroxide · Direct N−O bond Formation via Oxidation of Amines with Benzoyl Peroxide Amit Banerjee* and Hisashi Yamamoto* Molecular