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Organohalides-Catalyzed Dehydrative O-Alkylation between Alcohols: A Facile Etherification Method for Aliphatic Ether Synthesis

March 2015
Green Chemistry 17(5)

March 2015
17(5)

DOI:10.1039/C5GC00284B

Authors:

Lei Yu

Yangzhou University

Show all 6 authorsHide

Organohalides are found to be effective catalysts for dehydrative O-alkylation reactions between the alcohols, providing selective, practical, green, and easily scalable homo- and cross-etherification methods for preparation of the useful symmetrical and unsymmetrical aliphatic ethers from the readily available alcohols. Mechanistic studies revealed that organohalides are regenerated as reactive intermediates and recycled to catalyze the reactions.

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S1

Electronic Supplementary Information

Organohalides-Catalyzed Dehydrative O-Alkylation between

Alcohols: A Facile Etherification Method for Aliphatic Ether

Synthesis

Qing Xu,*a,b Huamei Xie,‡a Pingliang Chen,‡a Lei Yu,a,b Jianhui Chen,a and Xingen Hu*a

a College of Chemistry and Materials Engineering, Wenzhou University, Wenzhou, Zhejiang 325035

(China)

b Jiangsu Co-Innovation Center for Prevention and Control of Important Animal Infectious Diseases

and Zoonoses, Yangzhou University, Yangzhou, Jiangsu 225009 (China)

‡ These authors contributed equally to this work.

Email: qing-xu@wzu.edu.cn; hxgwzu@126.com

Table of Contents

Detailed Condition Screening Tables and Detailed Summary Tables of the

Etherification Reactions.............................................................................................S2

Experimental………...………………………………………………………………S8

Characterization of the Products….……………………………………………….S8

Mechanistic Studies…................................................………………………….….S24

1H and 13C NMR of the products……………………………………………….....S32

Electronic Supplementary Material (ESI) for Green Chemistry.

This journal is © The Royal Society of Chemistry 2015

S2

Detailed Condition Screening Tables and Detailed Summary Tables of the

Etherification Reactions

Table S1. Detailed Condition Screening and Optimization for Benzyl Halide-Catalyzed

O-Alkylative Homo-Etherification Reaction of Benzyl Alcohol.a

Ph OH cat. PhCH

under air, T, t Ph OPh

- H

1a 2a

run cat. (mol%), additive (mol%) T (oC) t (h) yield%b

1 - 120 24 0

2 PhCH2Br (1) 120 24 41

3 PhCH2Br (10) 30 8 0

4 PhCH2Br (10) 60 8 3

5 PhCH2Br (10) 100 8 20

6 PhCH2Br (10) 120 8 38

7 PhCH2Br (10) 120 24 >99 (97)

8 PhCH2Br (5) 120 24 71

9 PhCH2Br (8) 120 24 81

10 PhCH2Cl (10) 120 24 18

11c,d PhCH2Br (10), DBU (10), toluene 120 24 0

12c,d PhCH2Br (10), NaHCO3 (10), toluene 120 24 <5

13d PhCH2Br (10) 120 24 (93)

14c,d PhCH2Br (10), toluene 120 24 (51)

15c,e HBr (10), toluene 120 24

(57)

16e HBr 120 24

(60)

17 NaBr (10 mol%), H2SO4 (10-15 mol%) 120 24 (9)

18 NaBr (10 mol%), H3PO4 (10-15 mol%) 120 24 (17)

a Unless otherwise noted, the neat mixture of PhCH2OH 1a (10 mmol) and different loadings of

catalyst PhCH2X was directly sealed under air in a Schlenk tube (20 mL). The reaction was then

heated and monitored by GC-MS and TLC analysis. b GC yields (isolated yields in parenthesis)

based on 1a. c The reactions used 4 mmol 1a and 0.5 mL dry toluene (dried over CaH2 by heating,

redistilled under vacuum, and then collected and stored in a sealed Schlenk flask under nitrogen). d

Using 10 mol% dry PhCH2Br (dried over CaCl2 by heating, redistilled under vacuum, and then

collected and stored in a sealed Schlenk flask under nitrogen). e HBr (33 wt% in acetic acid) was

used.

DBU：1,8-Diazabicyclo[5,4,0]-undec-7-ene

S3

Table S2. Organohalide-Catalyzed O-Alkylative Homo-Etherification of Alcohols for Symmetrical

Dialkyl Ether Synthesis.a

R-X (10 mol%)

under air, T, t

- H

ROH ROR

run ROH (1) organohalide RX T, t 2: yield%b

1 PhCH2OH (1a) PhCH2Br 120

oC, 24 h 2a: >99 (97)

2 4-MeC6H4CH2OH (1b) 4-MeC6H4CH2Br 120

oC, 24 h 2b: >99 (96)

3 4-FC6H4CH2OH (1c) 4-FC6H4CH2Br 120

oC, 24 h 2c: >99 (88)

4 n-C5H11OH (1d) n-C5H11I 150

oC, 48 h 2d: 80 (65)

5 n-C6H13OH (1e) n-C6H13I 150

oC, 48 h 2e: 85 (60)

6 n-C7H15Br 150 oC, 30 h 2f: 45

7 n-C7H15OH (1f) n-C7H15I 150 oC, 30 h 2f: 85 (63)

8 n-C8H17Br 150 oC, 30 h 2g: 20

9 n-C8H17OH (1g) n-C8H17I 150 oC, 30 h 2g: 73 (64)

10c

Ph OH

(1h)

Ph Br

60 oC, 16 h 2h: 75 (58)

16d 30 oC, 13 h 2i: 6

17d 60 oC, 13 h 2i: 69

Ph Ph

(1i)

Ph Ph

80 oC, 13 h 2i: >99 (98)

(1i)

Ph Ph

80 oC, 13 h 2i: >99 (94)

11 30

oC, 24 h 2j: 8

12 90

oC, 24 h 2j: 56

(1j)

90 oC, 24 h 2j: >99 (89)

(1j)

90 oC, 24 h 2j: 80 (71)

n-C

(1k)

n-C

150 oC, 40 h 2k: 26 (20)

(1l)

150 oC, 40 h NRe

(1m)

150 oC, 40 h NRe

a See Table S1 for similar conditions. b GC yields (isolated yields in parenthesis) based on 1. c

Unidentified byproducts were observed. d Dioxane (0.5 mL) was added to dissolve the solid alcohol.

e No reaction.

S4

Table S3. Diphenylmethyl Bromide-Catalyzed O-Alkylative Cross-Etherification of Alcohols with

Diphenylmethanol for Unsymmetrical Dialkyl Ether Synthesis.a

under air, 80

C, 22 h

- H

Ph Ph

+ROPh

ROH Ph

CHBr (5 mol%)

(1.1 equiv.) 1i 3

1Ph OPh

PhPh

OR R

2i 2

run ROH conditionsa 3 : 2i : 2b 3: yield% c

1 80

oC, 22 h 96:4:0 3a: 96 (90)

2 100

oC, 22 h 94:6:0 3a: 94 (86)

3 Ph2CHCl (5 mol%)

80 oC, 22 h 81:5:0d 3a: 81 (75)

PhCH2OH

PhCH2Br (5 mol%)

80 oC, 22 h 93:6:1 3a: 93 (84)

5 4-MeC6H4CH2OH 80

oC, 22 h 95:5:0 3b: 95 (90)

6 4-FC6H4CH2OH 80

oC, 22 h 94:6:0 3c: 94 (90)

7 4-ClC6H4CH2OH 80

oC, 22 h 95:5:0 3d: 95 (92)

8 4-BrC6H4CH2OH 80

oC, 22 h 95:5:0 3e: 95 (91)

9 4-NO2C6H4CH2OH 80

oC, 22 h 96:4:0 3f: 96 (94)

10 CH3CH2OH 73

oC, 22 h 95:5:0 3g: 95 (94)

11 n-C4H9OH 80

oC, 22 h 96:4:0 3h: 96 (93)

12 n-C5H11OH 80

oC, 22 h 97:3:0 3i: 97 (92)

13 n-C6H13OH 80

oC, 22 h 96:4:0 3j: 96 (94)

14 n-C7H15OH 80

oC, 22 h 93:7:0 3k: 93 (92)

15 n-C8H17OH 80

oC, 22 h 93:7:0 3l: 93 (91)

16 Ph(CH2)2OH 80

oC, 22 h 97:3:0 3m: 97 (96)

17 Ph(CH2)3OH 80

oC, 22 h 96:4:0 3n: 96 (94)

(3 equiv.) 80 oC, 22 h 90:10:0 3o: 90 (80)

19 80 oC, 22 h

(1 equiv. 1k) 81:19:0 3p: 81

21 80 oC, 22 h

(3 equiv. 1k) 95:5:0 3p: 95 (92)

n-C

80 oC, 22 h

(5 equiv. 1k) 97:3:0 3p: 97

(3 equiv.) 80 oC, 22 h 97:3:0 3q: 97 (91)

Ph OH

80 oC, 22 h 75:25:0 3r: 75 (64)

a Unless otherwise noted, the neat mixture of ROH (5.5 mmol, 1.1 equiv.), Ph2CHOH 1i (5 mmol),

and Ph2CHBr (5 mol%) was directly sealed under air in a Schlenk tube (20 mL). The reaction was

then heated and monitored by GC-MS and TLC analysis. b Product ratios determined by GC-MS

analysis. c GC yields (isolated yields in parenthesis) based on the less-usesd alcohols. d Unidentified

byproducts were observed.

S5

Table S4. 1-Phenylethyl Bromide-Catalyzed O-Alkylative Cross-Etherification of Alcohols with

1-Phenylethanol for Unsymmetrical Dialkyl Ether Synthesis.a

Ph OPh

MeMe

OR R

2j 2

- H

ROH

(1.1 equiv.)

under air, 120

C, 24 h

Ph Me

ROMe

PhCH(CH

)Br (5 mol%)

11j 4

run ROH conditionsa 4 : 2j : 2b 4: yield%c

1 60

oC, 24 h 66:34:0 4a: 66 (50)

2 90

oC, 24 h 71:29:0 4a: 71 (64)

PhCH2OH

120 oC, 24 h 94:6:0 4a: 94 (81)

4 4-MeC6H4CH2OH 120

oC, 24 h 70:19:11 4b: 70 (66)

5 4-FC6H4CH2OH 120

oC, 24 h 82:18:0 4c: 82 (66)

6 4-ClC6H4CH2OH 120

oC, 24 h 82:18:0 4d: 82 (66)

7 4-BrC6H4CH2OH 120

oC, 24 h 87:13:0 4e: 87 (66)

120 oC, 24 h 81:19:0 4f: 81 (67)

9 C2H5OH 120

oC, 24 h 87:0:0d 4g: 87 (76)

10 n-C5H11OH 120

oC, 24 h 85:15:0 4h: 85 (83)

11 n-C6H13OH 120

oC, 24 h 92:8:0 4i: 92 (86)

12 n-C7H15OH 120

oC, 24 h >99:0:0 4j: >99 (82)

13 Ph(CH2)2OH 120

oC, 24 h >99:0:0 4k: >99 (80)

14 Ph(CH2)3OH 120

oC, 24 h 95:5:0 4l: 95 (75)

n-C

(3 equiv.)

120 oC, 38 h 82:0:0d 4m: 82 (66)

(3 equiv.) 120 oC, 38 h 71:8:0d 4n: 71 (52)

a Unless otherwise noted, the neat mixture of ROH (5.5 mmol, 1.1 equiv.), PhCH(CH3)OH 2j (5

mmol), and PhCH(CH3)Br (5 mol%) was directly sealed under air in a Schlenk tube (20 mL). The

reaction was then heated and monitored by GC-MS and TLC analysis. b Product ratios determined

by GC-MS analysis. c GC yields (isolated yields in parenthesis) based on the less alcohols. d

Unidentified byproducts were observed.

S6

Table S5. Cinnamyl Bromide-Catalyzed O-Alkylative Cross-Etherification of Alcohols with

Cinnamyl Alcohol for Unsymmetrical Dialkyl Ether Synthesis.a

ROH

(1.1 equiv.)

under air, 60

C, t

- H

Ph RO

OH PhCH=CHCH

Br (5 mol%) Ph

11h 5+

ROR

O2h PhPh

run ROH T, t 5 : 2h : 2b ether: yield% c

1 60

oC, 24 h 69:14:0d 5a: 69

2 PhCH2OH 60 oC, 46 h 82:18:0 5a: 82 (75)

3 60

oC, 24 h 65:8:0d,e 5b: 65

4 n-C5H11OH 60 oC, 46 h 72:10:0e 5b: 72 (56)

a The neat mixture of ROH 1 (5.5 mmol, 1.1 equiv.), PhCH=CHCH2OH 1h (5 mmol), and

PhCH=CHCH2Br (5 mol%) was directly sealed under air in a Schlenk tube (20 mL). The reaction

was then heated and monitored by GC-MS and TLC analysis. b Product ratios determined by GC-MS

analysis. c GC yields (isolated yields in parenthesis) based on 1h. d Reactions incomplete. e

Unidentified byproducts were observed.

Table S6. Benzyl Bromide-Catalyzed O-Alkylative Cross-Etherification of Alcohols with Benzyl

Alcohol for Unsymmetrical Dialkyl Ether Synthesis.a

under air, T, t

- H

PhCH

Br (5 mol%)

+ROPh

Ph OH

ROH

ROR

Ph OPh

run ROH T, t 6 : 2a : 2b ether: yield% c

1 4-MeOC6H4CH2OH

(1.2 equiv.) 120 oC, 32 h 59:12:29 6a: 59 (50)

2 n-C7H15OH (3 equiv.) 140 oC, 24 h 76:13:11 6b: 47 (35)d

a The neat mixture of ROH 1, PhCH2OH 1a (5 mmol), and PhCH2Br (5 mol%) was directly sealed

under air in a Schlenk tube (20 mL). The reaction was then heated and monitored by GC-MS and

TLC analysis. b Product ratios determined by GC-MS analysis. c GC yields (isolated yields in

parenthesis) based on 1a. d The reaction was incomplete.

S7

Table S7. t-Butyl Bromide-Catalyzed O-Alkylative Cross-Etherification of Alcohols with t-Butyl

Alcohol for Unsymmetrical Dialkyl Ether Synthesis.a

1l - H

+RO

t-BuBr (15 mol%)

ROH

(1.1 equiv.)

under air, 60

C, 57 h

ROR

run ROH T, t 7 : 2b 7: yield% c

1 60

oC, 32 h 100:0 7a: 55d

2 PhCH2OH 60 oC, 57 h 100:0 7a: 64 (57)d

3 60

oC, 32 h 100:0 7b: 77d

4 n-C7H15OH 60 oC, 57 h 100:0 7b: 82 (63)d

a The neat mixture of ROH 1 (5 mmol), t-BuOH (5.5 mmol, 1.1 equiv.), and t-BuBr (15 mol%) was

directly sealed under air in a Schlenk tube (20 mL). The reaction was then heated and monitored by

GC-MS and TLC analysis. b Product ratios determined by GC-MS analysis. c GC yields (isolated

yields in parenthesis) based on 1. d Reactions incomplete.

S8

Experimental

General. Unless otherwise noted, alcohols, organohalides, and other reagents used in the work

including (S)-PhCH(CH3)OH ((S)-1j, 98% ee) were all purchased and used without further

purification. Except the large scale reaction, all the reactions were directly sealed under air in a 20

mL Schlenk tube and then heated and monitored by TLC and/or GC-MS. Dry PhCH2Br was

obtained by a standard procedure: firstly dried over CaCl2 by heating, and then redistilled under

vacuum and collected and stored in a sealed Schlenk flask under nitrogen. Dry toluene was obtained

similarly: firstly dried over CaH2 by heating, and then redistilled under vacuum and collected and

stored in a sealed Schlenk flask under nitrogen. The products were purified by column

chromatography on silica gel using petroleum ether and ethyl acetate as the eluent. 1H and 13C NMR

spectra were recorded on a Bruker Avance III AV500 instrument (500 MHz for 1H and 125 MHz for

13C NMR spectroscopy) or a Bruker Avance-1B 300 instrument (300 MHz for 1H NMR

spectroscopy) by using CDCl3 as the solvent. Chemical shift values for 1H and 13C NMR were

referred to internal Me4Si (0 ppm). Mass spectra were measured on a Shimadzu GCMS-QP2010

Plus or a Shimadzu GCMS-QP2010 Ultra spectrometer (EI). HRMS (ESI) analysis was measured on

a Bruker microOTOF-Q II instrument. The optical rotatory power of diasteoromers of product 2j

was recorded with an Optical Activity LTD polAAr 3005 automatic Polarimeter.

Typical Procedure for Organohalides-Catalyzed O-Alkylative Homo-Etherification Reaction of

Alcohols for the Synthesis of Symmetrical Aliphatic Ethers. The mixture of benzyl alcohol 1a

(1.04 mL, 10 mmol) and benzyl bromide (0.12 mL, 1.0 mmol, 10 mol%) was sealed under air in a 20

mL Schlenk tube, stirred at 120 oC for 24 h, and then monitored by TLC and/or GC-MS. After

completion of the reaction, the mixture was directly purified, without any workup, through a silica

gel column using ethyl acetate and petroleum ether as the eluent, giving dibenzyl ether 2a in 97%

isolated yield.

Dibenzyl ether (2a). Colorless liquid. 1H NMR (500 MHz, CDCl3): δ 7.39-7.35 (m, 8H), 7.32-7.28

(m, 2H), 4.57 (s, 4H). 13C NMR (125.4 MHz, CDCl3): δ 138.3, 128.4, 127.8, 127.6, 72.1. MS (EI):

m/z (%) 198 (0.02, M+), 107 (14), 92 (100), 91 (81), 79 (15), 77 (13), 65 (17). This compound was

known: Jereb, M.; Vražič, D.; Zupan, M. Tetrahedron Lett. 2009, 50, 2347.

CH3

H3C

S9

Bis(p-methylphenylmethyl) ether (2b). Colorless liquid. 1H NMR (500 MHz, CDCl3): δ 7.25 (d, J

= 8.0 Hz, 4H), 7.16 (d, J = 8.0 Hz, 4H), 4.50 (s, 4H), 2.35 (s, 6H). 13C NMR (125.4 MHz, CDCl3): δ

137.2, 135.3, 129.0, 127.9, 71.8, 21.1. MS (EI): m/z (%) 226 (0.22, M+), 121 (11), 106 (100), 105

(59), 91 (49), 79 (13), 77 (18). This compound was known: Zhu, Z. L.; Espenson, J. H. J. Org.

Chem. 1996, 61, 324.

Bis(p-fluorophenylmethyl) ether (2c). Colorless liquid. 1H NMR (500 MHz, CDCl3): δ 7.34-7.31

(m, 4H), 7.06-7.03 (m, 4H), 4.51 (s, 4H). 13C NMR (125.4 MHz, CDCl3): δ 162.4 (d, JC-F = 245.0

Hz), 133.8 (d, JC-F = 3.1 Hz), 129.5 (d, JC-F = 8.2 Hz), 115.3 (d, JC-F = 21.3 Hz), 71.4. MS (EI): m/z

(%) 234 (0.37, M+), 138 (7), 125 (19), 110 (76), 109 (100), 97 (15), 83 (16). This compound was

known: Bach, P.; Albright, A.; Laali, K. K. Eur. J. Org. Chem. 2009, 1961.

Dipentyl ether (2d). Colorless liquid. 1

H NMR (500 MHz, CDCl3): δ 3.39 (t, J = 6.8 Hz, 4H),

1.60-1.55 (m, 4H), 1.33-1.31 (m, 8H), 0.90 (t, J = 7.0 Hz, 6H). 13C NMR (125.4 MHz, CDCl3): δ

71.0, 29.5, 28.4, 22.6, 14.1. MS (EI): m/z (%) 158 (1.52, M+), 129 (3), 115 (1), 101 (6), 71 (100), 70

(46), 69 (22), 55 (12). This compound was known: Zhang, Y.-J.; Dayoub, W.; Chen, G.-R. Lemaire,

M. Tetrahedron, 2012, 68, 7400.

Dihexyl ether (2e). Colorless liquid. 1

H NMR (500 MHz, CDCl3): δ 3.39 (t, J = 6.8 Hz, 4H),

1.59-1.54 (m, 4H), 1.34-1.29 (m, 12H), 0.89 (t, J = 7.0 Hz, 6H). 13C NMR (125.4 MHz, CDCl3): δ

71.0, 31.7, 29.8, 25.9, 22.6, 14.1. MS (EI): m/z (%) 186 (0.13, M+), 115 (2), 103 (5), 85 (100), 69

(16), 57 (23), 56 (41). This compound was known: Makowski, P.; Rothe, R.; Thomas, A.;

Niederberger, M.; Goettmann, F. Green Chem. 2009, 11, 34.

Diheptyl ether (2f). Colorless liquid. 1

H NMR (500 MHz, CDCl3): δ 3.39 (t, J = 6.8 Hz, 4H),

1.59-1.54 (m, 4H), 1.30-1.28 (m, 16H), 0.88 (t, J = 7.0 Hz, 6H). 13C NMR (125.4 MHz, CDCl3): δ

71.0, 31.8, 29.8, 29.2, 26.2, 22.6, 14.1. MS (EI): m/z (%) 214 (0.07, M+), 99 (13), 98 (13), 97 (15),

70 (29), 57 (100), 56 (15), 55 (14). This compound was known: Zolfigol, M. A.;

Mohammadpoor-Baltork, I.; Mirjalili, B. F.; Bamoniri, A. Synlett, 2003, (12), 1877.

Dioctyl ether (2g). Colorless liquid. 1

H NMR (500 MHz, CDCl3): δ 3.39 (t, J = 6.8 Hz, 4H),

1.58-1.54 (m, 4H), 1.30-1.26 (m, 20H), 0.88 (t, J = 7.0 Hz, 6H). 13C NMR (125.4 MHz, CDCl3): δ

S10

71.0, 31.8, 29.8, 29.5, 29.3, 26.2, 22.7, 14.1. MS (EI): m/z (%) 242 (0.05, M+), 112 (17), 84 (34), 71

(100), 69 (36), 57 (94). This compound was known: Zolfigol, M. A.; Mohammadpoor-Baltork, I.;

Habibi, D.; Mirjalili, B. F.; Bamoniri, A. Tetrahedron Lett. 2003, 44, 8165.

Dicinnamyl ether (2h). Colorless liquid. 1H NMR (500 MHz, CDCl3): δ 7.39 (d, J = 7.5 Hz, 4H),

7.33-7.29 (m, 4H), 7.25-7.22 (m, 2H), 6.63 (d, J = 16.0 Hz, 2H), 6.32 (dt, J = 6.0 Hz, J = 16.0 Hz,

2H), 4.20 (dd, J = 1.5 Hz, J = 6.0 Hz, 4H). 13C NMR (125.4 MHz, CDCl3): δ 136.7, 132.5, 128.5,

127.6, 126.5, 126.0, 70.7. MS (EI): m/z (%) 250 (0.01, M+), 155 (13), 154 (100), 153 (39), 152 (27),

76 (10). This compound was known: Kayaki, Y.; Koda, T.; Ikariya, T. J. Org.

Chem. 2004, 69, 2595.

Bis(diphenylmethyl) ether (2i). White solid. 1H NMR (500 MHz, CDCl3): δ 7.36 (d, J = 7.5 Hz 8H),

7.31 (t, J = 7.5 Hz, 8H), 7.25 (t, J = 7.0 Hz, 4H), 5.40 (s, 2H). 13C NMR (125.4 MHz, CDCl3): δ

142.2, 128.4, 127.4, 127.2, 80.0. MS (EI): m/z (%) 350 (0.38, M+), 207 (15), 183 (64), 168 (69), 165

(42), 152 (22), 106 (36), 105 (76), 91 (25), 77 (22). This compound was known: Le Bras, J.; Muzart,

J. Tetrahedron, 2007, 63, 7942.

(RR/SS/RS/SR ~1/1/1/1 mixtures)

Bis(1-phenylethyl) ether (2j). Colorless liquid. The NMR spectra are of a 50/50 mixture of dl and

meso isomers. 1H NMR (500 MHz, CDCl3): δ 7.39-7.29 (m, 10+10H), 4.55 (q, J = 6.5 Hz, 1+1H),

4.26 (q, J = 6.5 Hz, 1+1H), 1.48 (d, J = 6.5 Hz, 3+3H), 1.40 (d, J = 6.5 Hz, 3+3H). 13C NMR (125.4

MHz, CDCl3): δ 144.2 (or 144.1), 128.4 (or 128.2), 127.4 (or 127.1), 126.3 (or 126.2), 74.6 (or 74.4),

24.7 (or 23.0). MS (EI): m/z (%) 226 (0.01, M+), 121 (23), 106 (28), 105 (100), 91 (7), 79 (10), 77

(12). The above characterizations of 2j are in agreement with the literature data: (a) Yu, J.-J.; Wang,

L.-M.; Guo, F.-L.; Liu, J.-Q.; Liu, Y.; Jiao, N. Synth. Commun. 2011, 41, 1609. (b) Noji, M.; Ohno,

T.; Fuji , K.; Futaba, N.; Tajima, H.; Ishii, K. J. Org. Chem. 2003, 68, 9340.

O(RR/SS/RS/SR ~1/1/1/1 mixtures)

S11

Bis(2-heptyl) ether (2k). Colorless liquid. The NMR spectra are of a 50/50 mixture of dl and meso

isomers. 1H NMR (500 MHz, CDCl3): δ 3.44-3.37 (m, 2+2H), 1.50-1.46 (m, 2+2H), 1.39-1.28 (m,

14+14H), 1.12-1.09 (m, 6+6H), 0.90-0.87 (m, 6+6H). 13C NMR (125.4 MHz, CDCl3): δ 73.4 (or

73.0), 37.5 (or 37.2), 32.1 (or 32.0), 25.5 (or 25.4), 22.7, 21.1 (or 20.5), 14.09 (or 14.07). MS (EI):

m/z (%) 214 (0.11, M+), 143 (31), 125 (11), 99 (58), 57 (100), 55 (12). This compound was known:

Adams, J. M.; Ballantine, J. A.; Graham, S. H.; Laub, R. J.; Purnell, J. H.; Reid, Paul, I.; Shaman, W.

Y. M.; Thomas, J. M. Angew. Chem. 1978, 90, 290.

Typical Procedure for Ph2CHBr-Catalyzed O-Alkylative Cross-Etherification Reaction of

Benzhydrol with Alcohols for Synthesis of Unsymmetrical Aliphatic Ethers. The mixture of

benzhydrol 1i (0.921 g, 5 mmol), benzyl alcohol 1a (0.57 mL, 5.5 mmol, 1.1 equiv.) and

diphenylmethyl bromide (0.0618 g, 0.25 mmol, 5 mol%) was sealed under air in a 20 mL Schlenk

tube, stirred at 80 oC for 22 h, and then monitored by TLC and/or GC-MS. After completion of the

reaction, the mixture was directly purified, without any workup, through a silica gel column using

ethyl acetate and petroleum ether as the eluent, giving benzyl diphenylmethyl ether 3a in 90%

isolated yield.

Benzyl diphenylmethyl ether (3a). Colorless liquid. 1H NMR (500 MHz, CDCl3): δ 7.36-7.17 (m,

15H), 5.43 (s, 1H), 4.53 (s, 2H). 13C NMR (125.4 MHz, CDCl3): δ 142.2, 138.5, 128.5, 128.4, 127.8,

127.6, 127.5, 127.2, 82.6, 70.6. MS (EI): m/z (%) 274 (0.02, M+), 183 (100), 168 (49), 167 (83), 165

(38), 152 (24), 105 (64), 92 (31), 91 (95), 77 (27). This compound was known: Stanescu, M. A.;

Varma, R. S. Tetrahedron Lett. 2002, 43, 7307.

H3C

(p-Methylphenyl)methyl diphenylmethyl ether (3b). White solid. 1H NMR (500 MHz, CDCl3): δ

7.38-7.36 (m, 4H), 7.33-7.30 (m, 4H), 7.26-7.21 (m, 4H), 7.15 (d, J = 7.5 Hz, 2H), 5.43 (s, 1H), 4.50

(s, 2H), 2.34 (s, 3H). 13C NMR (125.4 MHz, CDCl3): δ 142.2, 137.2, 135.3, 129.0, 128.3, 127.8,

127.4, 127.1, 82.2, 70.3, 21.2. MS (EI): m/z (%) 288 (0.20, M+), 183 (63), 168 (68), 167 (100), 165

S12

(42), 152 (22), 106 (37), 105 (76), 91 (25). HRMS Calcd for C21H20NaO (M+Na): 311.1406; found:

311.1414.

(p-Fluorophenyl)methyl diphenylmethyl ether (3c). Colorless liquid. 1H NMR (500 MHz, CDCl3):

δ 7.39-7.33 (m, 10H), 7.29-7.26 (m, 2H), 7.06-7.02 (m, 2H), 5.44 (s, 1H), 4.51 (s, 2H). 13C NMR

(125.4 MHz, CDCl3): δ 162.3 (d, JC-F = 244.8 Hz), 142.0, 134.1 (d, JC-F = 3.0 Hz), 129.4 (d, JC-F =

8.0 Hz), 128.4, 127.5, 127.1, 115.2 (d, JC-F = 21.3 Hz), 82.5, 69.8. MS (EI): m/z (%) 292 (0.15, M+),

183 (54), 168 (93), 167 (100), 165 (44), 152 (24), 109 (69), 105 (49), 77 (20). This compound was

known: Stanescu, M. A.; Varma, R. S. Tetrahedron Lett. 2002, 43, 7307.

(p-Chlorophenyl)methyl diphenylmethyl ether (3d). White solid. 1H NMR (500 MHz, CDCl3): δ

7.37-7.23 (m, 14H), 5.41 (s, 1H), 4.48 (s, 2H). 13C NMR (125.4 MHz, CDCl3): δ 141.9, 136.9, 133.2,

129.0, 128.5, 128.4, 127.5, 127.0, 82.6, 69.7. MS (EI): m/z (%) 309 (M+1), 308 (0.03, M+), 183 (62),

168 (86), 167 (100), 165 (40), 152 (21), 125 (40), 105 (42), 89 (10), 77 (19). This compound was

known: Stanescu, M. A.; Varma, R. S. Tetrahedron Lett. 2002, 43, 7307.

(p-Bromophenyl)methyl diphenylmethyl ether (3e). White solid. 1H NMR (500 MHz, CDCl3): δ

7.48 (d, J = 8.5 Hz, 2H), 7.38-7.33 (m, 8H), 7.29-7.24 (m, 4H), 5.43 (s, 1H), 4.50 (s, 2H). 13C NMR

(125.4 MHz, CDCl3): δ 141.9, 137.4, 131.5, 129.3, 128.4, 127.6, 127.0, 121.4, 82.7, 69.8. MS (EI):

m/z (%) 353 (M+1), 352 (0.05, M+), 184 (40), 183 (15), 165 (11), 105 (100), 79 (26), 78 (34), 77

(50), 51 (15). This compound was known: Gharib, A.; Pesyan, N. N.; Jahangir, M.; Roshani, M.;

Scheeren, J. W. Bulg. Chem. Commun. 2012, 44, 11.

S13

(p-Nitrophenyl)methyl diphenylmethyl ether (3f). White solid. 1H NMR (500 MHz, CDCl3): δ

8.19 (d, J = 9.0 Hz, 2H), 7.52 (d, J = 8.5 Hz, 2H), 7.40-7.33 (m, 8H), 7.29-7.23 (m, 2H), 5.47 (s, 1H),

4.62 (s, 2H). 13C NMR (125.4 MHz, CDCl3): δ 147.3, 146.0, 141.5, 128.5, 127.73, 127.67, 126.9,

123.6, 83.4, 69.4. MS (EI): m/z (%) 319 (0.46, M+), 206 (12), 183 (71), 168 (61), 167 (100), 165 (47),

152 (26), 136 (19), 106 (37), 104 (74). This compound was known: Cast, J.; Stevens, T. S.; Holmes,

J. J. Chem. Soc. 1960, 3521.

Ethyl diphenylmethyl ether (3g). Colorless liquid. 1H NMR (500 MHz, CDCl3): δ 7.36-7.30 (m,

8H), 7.24-7.22 (m, 2H), 5.36 (s, 1H), 3.52 (q, J = 7.0 Hz, 2H), 1.27 (t, J = 7.0 Hz, 3H). 13C NMR

(125.4 MHz, CDCl3): δ 142.5, 128.3, 127.3, 126.9, 83.5, 64.5, 15.3. MS (EI): m/z (%) 212 (36.26,

M+), 183 (13), 168 (54), 167 (100), 165 (46), 152 (20), 135 (41), 105 (43), 77 (26). This compound

was known: Bikard, Y.; Weibel, J.-M.; Sirlin, C.; Dupuis, L.; Loeffler, J.-P.; Pale, P. Tetrahedron

Lett. 2007, 48, 8895.

n-Butyl diphenylmethyl ether (3h). Colorless liquid. 1H NMR (500 MHz, CDCl3) δ 7.37-7.30 (m,

8H), 7.26-7.23 (m, 2H), 5.34 (s, 1H), 3.46 (t, J = 6.5 Hz, 2H), 1.67-1.61 (m, 2H), 1.47-1.40 (m, 2H),

0.92 (t, J = 7.3 Hz, 3H). 13C NMR (125.4 MHz, CDCl3): δ 142.7, 128.3, 127.3, 126.9, 83.6, 68.9,

32.0, 19.5, 13.9. MS (EI): m/z (%) 240 (10.53, M+), 168 (51), 167 (100), 165 (36), 163 (15), 152 (19),

107 (35), 105 (27), 77 (14). This compound was known: Onishi, Y.; Nishimoto, Y.; Yasuda, M.;

Baba, A. Chem. Lett. 2011, 40, 1223.

S14

n-Pentyl diphenylmethyl ether (3i). Colorless liquid. 1H NMR (500 MHz, CDCl3): δ 7.37-7.30 (m,

8H), 7.26-7.22 (m, 2H), 5.34 (s, 1H), 3.45 (t, J = 6.5 Hz, 2H), 1.69-1.63 (m, 2H), 1.41-1.27 (m, 4H),

0.90 (t, J = 7.3 Hz, 3H). 13C NMR (125.4 MHz, CDCl3): δ 142.7, 128.3, 127.3, 126.9, 83.6, 69.3,

29.6, 28.4, 22.5, 14.0. MS (EI): m/z (%) 254 (5.62, M+), 177 (11), 168 (50), 167 (100), 165 (32), 152

(18), 107 (34), 105 (26), 77 (11). This compound was known: Stanescu, M. A.; Varma, R. S.

Tetrahedron. Lett. 2002, 43, 7307.

n-Hexyl diphenylmethyl ether (3j). Colorless liquid. 1H NMR (500 MHz, CDCl3): δ 7.37-7.30 (m,

8H), 7.26-7.22 (m, 2H), 5.34 (s, 1H), 3.45 (t, J = 6.5 Hz, 2H), 1.68-1.62 (m, 2H), 1.42-1.36 (m, 2H),

1.34-1.27 (m, 4H), 0.89 (t, J = 7.0 Hz, 3H). 13C NMR (125.4 MHz, CDCl3): δ 142.7, 128.3, 127.3,

127.0, 83.6, 69.3, 31.7, 29.8, 25.9, 22.6, 14.0. MS (EI): m/z (%) 268 (4.42, M+), 191 (10), 168 (45),

167 (100), 165 (26), 152 (15), 107 (39), 105 (29), 77 (10). This compound was known: Dzhemilev,

U. M.; Kutepov, B. I.; Grigor'eva, N. G.; Talipova, R. R.; Bubennov, S. V.; Yamali, E.

I. RU2404957 (in Russ.) C2, 2010, 20101127.

n-Heptyl diphenylmethyl ether (3k). Colorless liquid. 1H NMR (500 MHz, CDCl3): δ 7.36-7.30 (m,

8H), 7.26-7.22 (m, 2H), 5.34 (s, 1H), 3.45 (t, J = 6.5 Hz, 2H), 1.68-1.62 (m, 2H), 1.40-1.35 (m, 2H),

1.32-1.25 (m, 6H), 0.88 (t, J = 7.0 Hz, 3H). 13C NMR (125.4 MHz, CDCl3): δ 142.7, 128.3, 127.3,

127.0, 83.6, 69.3, 31.8, 29.9, 29.1, 26.2, 22.6, 14.1. MS (EI): m/z (%) 282 (2.39, M+), 168 (45), 167

(100), 165 (25), 152 (16), 115 (12), 107 (30), 105 (22), 57 (7). This compound was known:

Thiemann, T. Lett. Org. Chem. 2009, 6, 515.

S15

n-Octyl diphenylmethyl ether (3l). Colorless liquid. 1H NMR (500 MHz, CDCl3): δ 7.36-7.30 (m,

8H), 7.26-7.22 (m, 2H), 5.33 (s, 1H), 3.44 (t, J = 6.5 Hz, 2H), 1.67-1.61 (m, 2H), 1.37-1.25 (m, 10H),

0.88 (t, J = 6.8 Hz, 3H). 13C NMR (125.4 MHz, CDCl3): δ 142.7, 128.3, 127.3, 126.9, 83.6, 69.2,

31.8, 29.9, 29.4, 29.3, 26.2, 22.6, 14.1. MS (EI): m/z (%) 296 (1.77, M+), 219 (6), 183 (5), 168 (45),

167 (100), 165 (22), 152 (12), 107 (21), 105 (16). This compound was known: Paredes, R.; Perez, R.

L. Tetrahedron Lett. 1998, 39, 2037.

2-Phenylethyl diphenylmethyl ether (3m). White solid. 1H NMR (500 MHz, CDCl3): δ 7.30-7.22

(m, 15H), 5.36 (s, 1H), 3.67 (t, J = 7.0 Hz, 2H), 2.98 (t, J = 7.3 Hz, 2H). 13C NMR (125.4 MHz,

CDCl3): δ 142.3, 139.1, 129.0, 128.3, 128.2, 127.3, 126.9, 126.1, 83.7, 70.0, 36.5. MS (EI): m/z (%)

288 (10.34, M+), 183 (18), 168 (16), 167 (100), 165 (22), 105 (12), 77 (7). This compound was

known: Gharib, A.; Pesyan, N. N.; Jahangir, M.; Roshani, M.; Scheeren, J. W. Bulg. Chem. Commun.

2012, 44, 11.

3-Phenylpropyl diphenylmethyl ether (3n). White solid. 1H NMR (500 MHz, CDCl3): δ 7.37-7.31

(m, 8H), 7.27-7.25 (m, 4H), 7.19-7.17 (m, 3H), 5.34 (s, 1H), 3.49 (t, J = 6.3 Hz, 2H), 2.76 (t, J = 7.8

Hz, 2H), 2.00-1.96 (m, 2H). 13C NMR (125.4 MHz, CDCl3): δ 142.5, 142.0, 128.5, 128.33, 128.27,

127.3, 127.0, 125.7, 83.6, 68.3, 32.5, 31.5. MS (EI): m/z (%) 302 (2.07, M+), 183 (14), 168 (21), 167

(100), 165 (16), 105 (11), 91 (23). This compound was known: Gharib, A.; Pesyan, N. N.; Jahangir,

M.; Roshani, M.; Scheeren, J. W. Bulg. Chem. Commun. 2012, 44, 11.

S16

Isopropyl diphenylmethyl ether (3o). Colourless liquid. 1H NMR (500 MHz, CDCl3): δ 7.37-7.29

(m, 10H), 5.50 (s, 1H), 3.70-3.63 (m, 1H), 1.22 (d, J = 6.5 Hz, 6H). 13C NMR (125.4 MHz, CDCl3):

δ 142.5, 127.8, 126.7, 126.6, 80.0, 68.6, 21.8. MS (EI): m/z (%) 226 (8.14, M+), 183 (10), 168 (86),

167 (100), 152 (18), 107 (61), 79 (15), 77 (19). This compound was known: Venkateswara Rao, K.

T.; Rao, P. S. N.; Sai Prasad, P. S.; Lingaiah, N. Catalysis Commun. 2009, 10, 1394-1397.

2-Heptyl diphenylmethyl ether (3p). Colorless liquid. 1H NMR (300 MHz, CDCl3): δ 7.30-7.13 (m,

10H), 5.41 (s, 1H), 3.47-3.37 (m, 1H), 1.62-1.53 (m, 1H), 1.42-1.14 (m, 7H), 1.10 (d, J = 6.0 Hz,

3H), 0.79 (t, J = 7.1 Hz, 3H). 13C NMR (125.4 MHz, CDCl3): δ 138.3, 127.8, 127.1, 126.9, 72.3,

70.1, 31.3, 29.3, 28.6, 25.7, 22.1, 13.5. MS (EI): m/z (%) 282 (0.30, M+), 168 (29), 107 (11), 105 (9).

HRMS Calcd for C20H26NaO (M+Na): 305.1876; found: 305.1869.

3-Pentyl diphenylmethyl ether (3q). Colourless liquid. 1H NMR (500 MHz, CDCl3): δ 7.36-7.22

(m, 10H), 5.47 (s, 1H), 3.31-3.27 (m, 1H), 1.59-1.53 (m, 4H), 0.86 (t, J = 7.5 Hz, 6H). 13C NMR

(125.4 MHz, CDCl3): δ 143.3, 128.2, 127.3, 127.1, 80.5, 78.7, 25.6, 9.4. MS (EI): m/z (%) 254 (0.43,

M+), 168 (25), 167 (100), 152 (9), 107 (6), 77 (3). This compound was known: Stanescu, M. A.;

Var ma , R . S . Tetrahedron Lett. 2002, 43, 7307-7309.

Cinnamyl diphenylmethyl ether (3r). Colorless liquid. 1H NMR (500 MHz, CDCl3): δ 7.40-7.20

(m, 15H), 6.60 (d, J = 16.0 Hz, 1H), 6.35 (dt, J = 6.0 Hz, J = 16.0 Hz, 1H), 5.48 (s, 1H), 4.18 (dd, J

= 1.5 Hz, J = 6.0 Hz, 2H). 13C NMR (125.4 MHz, CDCl3): δ 142.1, 136.7, 132.3, 128.5, 128.4, 127.6,

S17

127.4, 127.0, 126.4, 126.1, 82.6, 69.3. MS (EI): m/z (%) 300 (0.06, M+), 168 (18), 167 (100), 165

(24), 152 (16), 118 (36), 117 (15), 115 (12), 77 (10). This compound was known: Wagh, Y. S.;

Sawant, D. N.; Tambade, P. J.; Dhake, K. P.; Bhanage, B. M. Tetrahedron, 2011, 67, 2414.

Typical Procedure for 1-Phenylethyl Bromide-Catalyzed O-Alkylative Cross-Etherification

Reaction of 1-Phenyl ethanol with Alcohols for Synthesis of Unsymmetrical Aliphatic Ethers.

The mixture of 1-phenyl ethanol 1j (0.60 mL, 5 mmol), benzyl alcohol 1a (0.57 mL, 5.5 mmol, 1.1

equiv.), and 1-phenylethyl bromide (0.034 mL, 0.25 mmol, 5 mol%) was sealed under air in a 20 mL

Schlenk tube, stirred at 120 oC for 24 h, and then monitored by TLC and/or GC-MS. After

completion of the reaction, the mixture was directly purified, without any workup, through a silica

gel column using ethyl acetate and petroleum ether as the eluent, giving benzyl 1-phenylethyl ether

4a in 81% isolated yield.

Benzyl 1-phenylethyl ether (4a). Colorless liquid. 1H NMR (500 MHz, CDCl3): δ 7.38-7.27 (m,

10H), 4.51 (q, J = 6.5 Hz, 1H), 4.46 (d, J = 11.5 Hz, 1H), 4.31 (d, J = 12.0 Hz, 1H), 1.49 (d, J = 6.5

Hz, 3H). 13C NMR (125.4 MHz, CDCl3): δ 143.7, 138.6, 128.5, 128.3, 127.7, 127.48, 127.45, 126.3,

77.2, 70.3, 24.2. MS (EI): m/z (%) 212 (0.01, M+), 121 (14), 106 (51), 105 (35), 92 (19), 91 (100), 77

(12), 65 (7). This compound was known: Rahaim, R. J.; Maleczka, R. E. Org. Lett. 2011, 13, 584.

(p-Methylphenyl)methyl 1-phenylethyl ether (4b). Colorless liquid. 1H NMR (500 MHz, CDCl3):

δ 7.40-7.36 (m, 4H), 7.32-7.28 (m, 1H), 7.21 (d, J = 8.0 Hz, 2H), 7.15 (d, J = 8.0 Hz, 2H), 4.49 (q, J

= 6.5 Hz, 1H), 4.42 (d, J = 11.5 Hz, 1H), 4.25 (d, J = 12.0 Hz, 1H), 2.35 (s, 3H), 1.47 (d, J = 6.5 Hz,

3H). 13C NMR (125.4 MHz, CDCl3): δ 143.8, 137.1, 135.6, 129.0, 128.4, 127.8, 127.4, 126.3, 76.9,

70.1, 24.2, 21.1. MS (EI): m/z (%) 226 (0.08, M+), 121 (36), 106 (53), 105 (100), 91 (28), 79 (12), 77

(16). HRMS Calcd for C16H18NaO (M+Na): 249.1250; found: 249.1266.

(p-Fluorophenyl)methyl 1-phenylethyl ether (4c). Colorless liquid. 1H NMR (500 MHz, CDCl3): δ

7.40-7.35 (m, 4H), 7.32-7.26 (m, 3H), 7.04-7.00 (m, 2H), 4.49 (q, J = 6.5 Hz, 1H), 4.40 (d, J = 11.5

Hz, 1H), 4.27 (d, J = 11.5 Hz, 1H), 1.49 (d, J = 6.5 Hz, 3H). 13C NMR (125.4 MHz, CDCl3): δ 162.3

S18

(d, JC-F = 244.5 Hz), 143.6, 134.4 (d, JC-F = 3.1 Hz), 129.4 (d, JC-F = 8.0 Hz), 128.5, 127.6, 126.3,

115.2 (d, JC-F = 21.3 Hz), 77.3, 69.6, 24.1. MS (EI): m/z (%) 230 (0.03, M+), 110 (12), 109 (100),

106 (63), 105 (35), 91 (16), 77 (12). HRMS Calcd for C15H15FNaO (M+Na): 253.0999; found:

253.1003 .

(p-Chlorophenyl)methyl 1-phenylethyl ether (4d). Colorless liquid. 1H NMR (500 MHz, CDCl3):

δ 7.39-7.34 (m, 4H), 7.32-7.29 (m, 3H), 7.26-7.24 (m, 2H), 4.48 (q, J = 6.5 Hz, 1H), 4.40 (d, J =

12.0 Hz, 1H), 4.27 (d, J = 12.0 Hz, 1H), 1.49 (d, J = 6.5 Hz, 3H). 13C NMR (125.4 MHz, CDCl3): δ

143.4, 137.1, 133.2, 129.0, 128.53, 128.48, 127.6, 126.3, 77.4, 69.5, 24.1. MS (EI): m/z (%) 247

(M+1), 246 (0.07, M+), 127 (33), 126 (11), 125 (97), 106 (100), 105 (59), 91 (32), 89 (13), 79 (10),

77 (20). HRMS Calcd for C15H15ClNaO (M+Na): 269.0704; found: 269.0693.

(p-Bromophenyl)methyl 1-phenylethyl ether (4e). Colorless liquid. 1H NMR (500 MHz, CDCl3): δ

7.47-7.45 (m, 2H), 7.39-7.34 (m, 4H), 7.32-7.29 (m, 1H), 7.19 (d, J = 8.5 Hz, 2H), 4.48 (q, J = 6.5

Hz, 1H), 4.38 (d, J = 12.0 Hz, 1H), 4.25 (d, J = 12.5 Hz, 1H), 1.49 (d, J = 6.5 Hz, 3H). 13C NMR

(125.4 MHz, CDCl3): δ 143.4, 137.6, 131.4, 129.3, 128.5, 127.6, 126.3, 121.3, 77.4, 69.5, 24.1. MS

(EI): m/z (%) 291 (M+1), 290 (0.03, M+), 171 (53), 169 (54), 106 (100), 105 (53), 91 (31), 90 (18),

89 (12), 77 (18). HRMS Calcd for C15H15BrNaO (M+Na): 313.0198; found: 313.0183.

(1-Naphthyl)methyl 1-phenylethyl ether (4f). Colorless liquid. 1

H NMR (500 MHz,CDCl3): δ

8.07-8.05 (m, 1H), 7.88-7.86 (m, 1H), 7.81 (d, J = 8.0 Hz, 1H), 7.53-7.49 (m, 2H), 7.46-7.41 (m,

5H), 7.37-7.30 (m, 2H), 4.92 (d, J = 12.0 Hz, 1H), 4.74 (d, J = 12.0 Hz, 1H), 4.60 (q, J = 6.5 Hz, 1H),

1.51 (d, J = 6.5 Hz, 3H). 13C NMR (125.4 MHz, CDCl3): δ 143.6, 134.0, 133.7, 131.7, 128.51,

128.47, 128.4, 127.6, 126.4, 126.3, 126.0, 125.7, 125.2, 124.0, 77.4, 68.8, 24.2. MS (EI): m/z (%)

262 (6.94, M+), 142 (100), 141 (66), 129 (29), 115 (30), 106 (24), 105 (50), 91 (21), 77 (30).

HRMS Calcd for C19H18NaO (M+Na): 285.1250; found: 285.1255.

S19

Ethyl 1-phenylethyl ether (4g). Colorless liquid. 1H NMR (500 MHz, CDCl3): δ 7.36-7.29 (m, 5H),

4.40 (q, J = 6.5 Hz, 1H), 3.35 (q, J = 7.0 Hz, 2H), 1.44 (d, J = 6.5 Hz, 3H), 1.19 (t, J = 7.0 Hz, 3H).

13C NMR (125.4 MHz, CDCl3): δ 144.2, 128.4, 127.3, 126.1, 77.7, 63.9, 24.2, 15.4. MS (EI): m/z (%)

150 (1.97, M+), 135 (100), 106 (66), 105 (49), 79 (51), 77 (26). This compound was known: Podder,

S.; Choudhury, J.; Roy, S. J. Org. Chem. 2007, 72, 3129.

n-Pentyl 1-phenylethyl ether (4h). Colorless liquid. 1H NMR (500 MHz, CDCl3): δ 7.36-7.30 (m,

4H), 7.28-7.26 (m, 1H), 4.40 (q, J = 6.5 Hz, 1H), 3.28 (t, J = 6.8 Hz, 2H), 1.59-1.55 (m, 2H), 1.43 (d,

J = 6.5 Hz, 3H), 1.34-1.26 (m, 4H), 0.89-0.86 (m, 3H). 13C NMR (125.4 MHz, CDCl3): δ 144.3,

128.3, 127.2, 126.1, 77.9, 68.8, 29.6, 28.4, 24.2, 22.5, 14.0. MS (EI): m/z (%) 192 (0.16, M+), 177

(37), 107 (100), 106 (21), 105 (77), 79 (21), 77 (12). This compound was known: Ke, F.; Li, Z.-K.;

Xiang, H.-F.; Zhou, X.-G. Tetrahedron Lett. 2011, 52, 318.

n-Hexyl 1-phenylethyl ether (4i). Colorless liquid. 1H NMR (500 MHz, CDCl3): δ 7.35-7.30 (m,

4H), 7.27-7.24 (m, 1H), 4.38 (q, J = 6.5 Hz, 1H), 3.28 (t, J = 6.8 Hz, 2H), 1.57-1.53 (m, 2H), 1.43 (d,

J = 6.5 Hz, 3H), 1.33-1.23 (m, 6H), 0.87 (t, J = 7.0 Hz, 3H). 13C NMR (125.4 MHz, CDCl3): δ 144.3,

128.3, 127.2, 126.1, 77.9, 68.8, 31.7, 29.9, 25.9, 24.2, 22.6, 14.0. MS (EI): m/z (%) 206 (0.14, M+),

191 (31), 107 (100), 106 (21), 105 (73), 79 (16), 77 (9). This compound was known: Dzhemilev, U.

M.; Kutepov, B. I.; Grigor'eva, N. G.; Talipova, R. R.; Bubennov, S. V.; Yamali, E. I. RU2404957

(in Russ.) C2, 2010, 20101127.

n-Heptyl 1-phenylethyl ether (4j). Colorless liquid. 1H NMR (500 MHz, CDCl3): δ 7.36-7.25 (m,

5H), 4.38 (q, J = 6.5 Hz, 1H), 3.29 (t, J = 6.8 Hz, 2H), 1.59-1.54 (m, 2H), 1.44 (d, J = 6.5 Hz, 3H),

1.33-1.26 (m, 8H), 0.87 (t, J = 6.8 Hz, 3H). 13C NMR (125.4 MHz, CDCl3): δ 144.3, 128.3, 127.2,

126.1, 77.9, 68.8, 31.8, 30.0, 29.1, 26.1, 24.2, 22.6, 14.1. MS (EI): m/z (%) 220 (0.18, M+), 205 (41),

107 (100), 106 (21), 105 (75), 79 (18), 77 (11), 57 (19). Dzhemilev, U. M.; Kutepov, B. I.;

S20

Grigor'eva, N. G.; Talipova, R. R.; Bubennov, S. V. RU2384560 (in Russ.) C1, 2010, 20100320.

2-Phenylethyl 1-phenylethyl ether (4k). Colorless liquid. 1H NMR (500 MHz, CDCl3): δ 7.32-7.29

(m, 2H), 7.26-7.22 (m, 5H), 7.20-7.17 (m, 3H), 4.40 (q, J = 6.5 Hz, 1H), 3.51 (t, J = 7.5 Hz, 2H),

2.93-2.83 (m, 2H), 1.43 (d, J = 6.5 Hz, 3H). 13C NMR (125.4 MHz, CDCl3): δ 143.9, 139.0, 128.9,

128.3, 128.2, 127.3, 126.09, 126.06, 78.1, 69.6, 36.5, 24.1. MS (EI): m/z (%) 226 (5.63, M+), 106

(11), 105 (100), 104 (14), 79 (10). This compound was known: Rosenfeld, D. C.; Shekhar, S.;

Takemiya, A.; Utsunomiya, M.; Hartwig, J. F. Org. Lett. 2006, 8, 4179.

3-Phenylpropyl 1-phenylethyl ether (4l). Colorless liquid. 1

H NMR (500 MHz, CDCl3): δ

7.37-7.32 (m, 4H), 7.29-7.25 (m, 3H), 7.19-7.15 (m, 3H), 4.39 (q, J = 6.5 Hz, 1H), 3.34-3.32 (m,

2H), 2.75-2.61 (m, 2H), 1.92-1.86 (m, 2H), 1.46 (d, J = 6.5 Hz, 3H). 13C NMR (125.4 MHz, CDCl3):

δ 144.1, 142.1, 128.43, 128.36, 128.2, 127.3, 126.1, 125.7, 78.0, 67.8, 32.4, 31.5, 24.1. MS (EI): m/z

(%) 240 (0.56, M+), 135 (21), 134 (25), 105 (100), 104 (17), 91 (72), 77 (11). This compound was

known: Iwanami, K.; Yano, K.; Oriyama, T. Chem. Lett. 2007, 36, 38.

(RR/SS/RS/SR ~1/1/1/1 mixtures)

1-Phenylethyl 2-heptyl ether (4m). Colourless liquid. 1H NMR (500 MHz, CDCl3): δ 7.27-7.17

(m, 5H+5H), 4.47-4.42 (m, 1H+1H), 3.34-3.27 (m, 1H) or 3.23-3.17 (m, 1H), 1.49-1.11 (m,

11H+11H), 1.05 (d, J = 6.0 Hz, 3H) or 0.96 (d, J = 6.5 Hz, 3H), 0.83 (t, J = 7.0 Hz, 3H) or 0.76 (t, J

= 7.3 Hz, 3H). 13C NMR (125.4 MHz, CDCl3): δ 145.1 (144.6), 128.3 (128.2), 127.2 (127.1), 126.5

(126.2), 75.4 (74.5), 73.2 (71.9), 37.5 (36.0), 32.1 (31.8), 25.3 (25.0), 24.7 (24.4), 22.7 (22.6), 20.8

(19.3), 14.05 (14.00). MS (EI): m/z (%) 220 (0.01, M+), 205 (9), 107 (31), 105 (100), 77 (6).

HRMS Calcd for C15H24NaO (M+Na): 243.1719; found: 243.1711.

1-Phenylethyl 3-pentyl ether (4n). Colorless liquid. 1H NMR (500 MHz, CDCl3): δ 7.34-7.26 (m,

5H), 4.50 (q, J = 6.3 Hz, 1H), 3.12 (t, J = 5.8 Hz, 1H), 1.57-1.36 (m, 7H), 0.90 (t, J = 7.5 Hz, 3H),

S21

0.77 (t, J = 7.5 Hz, 3H). 13C NMR (125.4 MHz, CDCl3): δ 144.3, 127.7, 126.7, 126.0, 78.2, 74.6,

26.1, 24.7, 23.8, 9.4, 8.5. MS (EI): m/z (%) 178 (0.87, M+), 177 (7), 163 (10), 107 (14), 105 (100),

79 (8). HRMS Calcd for C13H20NaO (M+Na): 215.1406; found: 215.1397.

Typical Procedure for Cinnamyl Bromide-Catalyzed O-Alkylative Cross-Etherifiaction

Reaction of Cinnamyl Alcohol with Alcohols for Synthesis of Unsymmetrical Aliphatic Ethers.

The mixture of cinnamyl alcohol 1h (0.671 g, 5 mmol), benzyl alcohol 1a (0.57 mL, 5.5 mmol, 1.1

equiv) and cinnamyl bromide (0.0493 g, 0.25 mmol, 5 mol%) was sealed under air in a 20 mL

Schlenk tube, stirred at 60 oC for 46 h, and then monitored by TLC and/or GC-MS. After completion

of the reaction, the mixture was directly purified, without any workup, through a silica gel column

using ethyl acetate and petroleum ether as the eluent, giving benzyl cinnamyl ether 5a in 75%

isolated yield.

Benzyl cinnamyl ether (5a). Colorless liquid. 1H NMR (500 MHz, CDCl3): δ 7.42-7.27 (m, 10H),

6.65 (d, J = 15.5 Hz, 1H), 6.35 (dt, J = 6.0 Hz, J = 16 Hz, 1H), 4.60 (s, 2H), 4.22 (dd, J = 1.5 Hz, J =

6.0 Hz, 2H). 13C NMR (125.4 MHz, CDCl3): δ 138.2, 136.7, 132.5, 128.5, 128.4, 127.8, 127.65,

127.62, 126.5, 126.1, 72.1, 70.7. MS (EI): m/z (%) 224 (12.82, M+), 223 (80), 195 (22), 152 (26),

119 (14). This compound was known: Billard, F.; Robiette, R.; Pospisil, J. J. Org.

Chem. 2012, 77, 6358.

n-Pentyl cinnamyl ether (5b). Colorless liquid. 1H NMR (500 MHz, CDCl3): δ 7.40-7.38 (m, 2H),

7.34-7.30 (m, 2H), 7.25-7.22 (m, 1H), 6.61 (d, J = 16.0 Hz, 1H), 6.31 (dt, J = 6.0 Hz, J = 16.0 Hz,

1H), 4.14 (dd, J =1.5 Hz, J = 6.0 Hz, 2H), 3.48 (t, J = 7.0 Hz, 2H), 1.64-1.60 (m, 2H), 1.37-1.34 (m,

4H), 0.91 (t, J = 6.8 Hz, 3H). 13C NMR (125.4 MHz, CDCl3): δ 136.8, 132.1, 128.5, 127.6, 126.8,

126.4, 71.4, 70.6, 29.5, 28.4, 22.6, 14.0. MS (EI): m/z (%) 206 (M+2), 204 (1.28, M+), 190 (31), 133

(26), 117 (62), 115 (62), 92 (100), 91 (43), 78 (28).

Typical Procedure for Benzyl Bromide-Catalyzed O-Alkylative Cross-Etherifiaction Reaction

of Benzyl Alcohol with Alcohols for Synthesis of Unsymmetrical Aliphatic Ethers. The mixture

of benzyl alcohol 1a (0.52 mL, 5.0 mmol), (4-methoxyphenyl)methanol (0.74 mL, 6.0 mmol, 1.2

equiv) and benzyl bromide (0.03 mL, 0.25 mmol, 5 mol%) was sealed under air in a 20 mL Schlenk

S22

tube, stirred at 120 oC for 32 h, and then monitored by TLC and/or GC-MS. After completion of the

reaction, the mixture was directly purified, without any workup, through a silica gel column using

ethyl acetate and petroleum ether as the eluent, giving benzyl (p-methoxylphenyl)methyl ether 6a in

50% isolated yield.

H3CO

Benzyl (p-methoxylphenyl)methyl ether (6a). Colourless liquid. 1H NMR (500 MHz, CDCl3): δ

7.39-7.28 (m, 7H), 6.92-6.86 (m, 2H), 4.56 (S, 2H), 4.52 (S, 2H), 3.84 (s, 3H). 13C NMR (125.4

MHz, CDCl3): 159.3, 138.4, 130.4, 129.4, 128.4, 127.8, 127. 6, 113.8, 71.84, 71.79, 55.3. MS (EI):

m/z (%) 228 (13.32, M+), 137 (98), 121 (100), 109 (19), 91 (50), 77(19). This compound was known:

Zeng, C. -C.; Zhang, N. -T.; Lam, C. M.; Little, R. D. Org. Lett. 2012, 14, 1314-1317.

Benzyl 1-heptyl ether (6b). Colourless liquid. 1H NMR (500 MHz, CDCl3): δ 7.37-7.27 (m, 5H),

4.51 (s, 2H), 3.46 (t, J = 6.8 Hz, 2H), 1.64-1.59 (m, 2H), 1.37-1.26 (m, 8H), 0.

88 (t, J = 6.8 Hz, 3H). 13C NMR (125.4 MHz, CDCl3): δ 138.7, 128.3, 127.6, 127.5, 72.9, 70.5, 31.8,

29.8, 29.2, 26.2, 22.6, 14.1. MS (EI): m/z (%) 206 (12.82, M+), 97 (16), 92 (79), 91 (100), 55 (18).

This compound was known: Zhou, J. R. Fu, G. C. J. Am. Chem. Soc. 2003, 125, 12527-12530.

Typical Procedure for t-Butyl Bromide-Catalyzed O-Alkylative Cross-Etherifiaction Reaction

of t-Butyl Alcohol with Alcohols for Synthesis of Unsymmetrical Aliphatic Ethers. The mixture

of t-butyl alcohol 1l (0.46 mL, 5 mmol), benzyl alcohol 1a (0.57 mL, 5.5 mmol, 1.1 equiv) and

t-butyl bromide (0.028 mL, 0.25 mmol, 5 mol%) was sealed under air in a 20 mL Schlenk tube,

stirred at 60 oC for 57 h, and then monitored by TLC and/or GC-MS. After completion of the

reaction, the mixture was directly purified, without any workup, through a silica gel column using

ethyl acetate and petroleum ether as the eluent, giving Benzyl t-butyl ether 7a in 57% isolated yield.

Benzyl t-butyl ether (7a). Colorless liquid. 1H NMR (500 MHz, CDCl3): δ 7.37-7.32 (m, 5H), 4.45

(s, 2H), 1.30 (s, 9H). 13C NMR (125.4 MHz, CDCl3): δ 139.9, 128.3, 127.4, 127.1, 73.4, 64.1, 27.7.

MS (EI): m/z (%) 164 (2.45, M+), 149 (25), 107 (6), 91 (100), 79 (9), 57 (19). This compound was

known: Cui, X. J.; Zhang, S. G.; Shi, F.; Zhang, Q. H.; Ma, X. Y.; Lu, L. J.; Deng, Y.

Q. ChemSusChem, 2010, 3, 1043.

S23

n-Heptyl t-butyl ether (7b). Colorless liquid. 1H NMR (500 MHz, CDCl3): δ 3.32 (t, J = 7.0 Hz,

2H), 1.54-1.49 (m, 2H), 1.30-1.28 (m, 8H), 1.19 (s, 9H), 0.88 (t, J = 7.0 Hz, 3H). 13C NMR (125.4

MHz, CDCl3): δ 72.4, 61.7, 31.9, 30.7, 29.2, 27.6, 26.2, 22.6, 14.1. MS (EI): m/z (%) 172 (0.08, M+),

157 (30), 97 (3), 87 (4), 59 (100), 58 (6), 57 (93). This compound was known: Hartz, N.; Prakash, G.

K. S.; Olah, G. A. Synlett, 1992, (7), 569.

Large Scale Reaction of Benzyl alcohol (1a) Catalyzed by Benzyl Bromide for Dibenzyl Ether

(2a) Preparation (eq. 5 in the text). As shown by the picture below, to a 100 mL round-bottomed

flask equipped with a water separator and a condenser open to air were added 50 mL benzyl alcohol

1a (484 mmol) and PhCH2Br (6 mL, 50.5 mmol, 10.4 mol%). The mixture was then directly heated

under air at 120 oC. During the heating byproduct water was obviously generated and easily

collected in the water separator. GC analysis showed 90% conversion of 1a after 34 h’s heating at

120 oC. The condenser and the water separator were then removed and the reaction subjected to

distillation under reduced pressure. A careful vacuum distillation of the reaction mixture afforded

83% isolated yield of pure benzyl ether 2a.

S24

Mechanistic Studies

1. GC detection of considerable amounts of PhCH2Br (initial catalyst loading: 10 mol%) in an

almost completed etherification reaction of benzyl alcohol (1a).

Ph OH PhCH

Br (10 mol%)

under air, 120

CPh OPh

1a 2a

~ 90% conversion

5.0 7.5 10.0 12.5 15.0 17.5 20.0 22.5 25.0

0.0

1.0

(x10,000,000)

TIC

5.750 5.717 5.792 TIC 3048941 9.78 1961459 12.26 1.55 MI

6.401 6.375 6.442 TIC 2666968 8.56 1949246 12.18 1.36 MI

14.288 14.233 14.350 TIC 25447195 81.66 12088244 75.56 2.10 MI

Time：5.75 min (PhCH2OH 1a, MW 108)

50 100 150 200 250 300 350 400 450 500

0.0

25.0

50.0

75.0

100.0

108

110 317155 276 396 487183 466227 246 356 426

Time：6.40 min (catalyst PhCH2Br, MW 170, 172)

50 100 150 200 250 300 350 400 450 500

0.0

25.0

50.0

75.0

100.0

17051 143119 331 416362207 450295 488230 259

Time：14.28 min (PhCH2OCH2Ph 2a)

50 100 150 200 250 300 350 400 450 500

0.0

25.0

50.0

75.0

100.0

51 119 165 205 220 253 452392355 422306 327 484

S25

2. NMR detection of Ph2CHBr in Ph2CHBr-catalyzed cross-etherification reaction of benzyl

alcohol (1a) and Ph2CHOH (1i).

2.1 Standard 1H NMR spectra of the involved compounds

Ph2CHBr:

Ph2CHOH:

PhCH2OH:

S26

2.2 Results for 1H NMR analysis on variation of the components in Ph2CHBr-catalyzed

cross-etherification reaction of 1a and 1i. These data were then converted to the following

figure using Microsoft Excel 2010.

under air, 20

C, t

- H

Ph Ph

+OPh

CHBr (20 mol% added)

6 mmol 1i 3a

1a Ph OPh

PhPh

Ph OH

5 mmol

run NMR spectra No. time 3a% 1i % (conversion) Ph2CHBr (mol%)

1 (1) 20 min 10 13 21

2 (2) 1 h 43 54 14

3 (3) 2 h 57 73 13

4 (4) 3 h 65 82 10

4 (5) 5 h 72 90 9

Figure. (Figure 1 in the text).

S27

(1) 1H NMR spectra of run 1: 20 oC, 20 min

3a%: 0.48/(4.13+0.48+0.14) = 10%

1i% (conversion): (0.48 +0.14)/(4.13+0.48+0.14) = 13%

Ph2CHBr (mol%): 1.00/(4.13+0.48+0.14) = 1/4.75 = 21 mol% (initial catalyst loading 20 mol%)

(2) 1H NMR spectra of run 2: 20 oC, 1 h

3a%: 3.20/(3.39+3.20+0.85) = 43%

1i% (conversion): (3.20 + 0.85)/(3.39+3.20+0.85) = 54%

Ph2CHBr (mol%): 1/(3.39+3.20+0.85) = 1/7.44 = 14 mol%

S28

(3) 1H NMR spectra of run 3: 20 oC, 2 h

3a% = 4.51/(2.15+4.51+1.29) = 57%

1i% (conversion): (4.51 + 1.29) = 73%

Ph2CHBr mol% = 1/(2.15+4.51+1.29)=1/7.95 = 13 mol%

(4) 1H NMR spectra of run 4: 20 oC, 3 h

3a% = 6.36/(1.72+6.36+1.70) = 65%

1i% (conversion): (6.36 + 1.60)/(1.72+6.36+1.70) = 82%

Ph2CHBr mol% = 1/(1.72+6.36+1.70) = 1/9.78 = 10 mol%

S29

(5) 1H NMR spectra of run 5: 20 oC, 5 h

3a% = 8.17/(1.12+8.17+2.06) = 72%

1i% (conversion): (8.17 + 2.06)/(1.12+8.17+2.06) = 90%

Ph2CHBr mol% = 1/(1.12+8.17+2.06) = 1/11.35 = 9 mol%

S30

3. Racemic PhCH(CH3)Br-catalyzed diastereo-selective homo-etherification reaction of

optically active (S)-1-phenyl ethanol (1j, 98%ee) (eq. 6 in the text)

PhCH(CH

)Br (3 mol%) Ph OPh

(S)-1j, 98% ee (SS/RR)- and (RS)-2j

C, 24 h

40%

, 15%

isolated

dr ((SS+RR)/RS): 59/41

[α]

D19.7

= - 176.5 (c = 0.00553, CH

)

(lit. data

: (S,S)-2j, [α]

D20

= - 234; (R,R)-2j, [α]

D20

= + 224)

enantiomer ratio (SS/RR): ca. 88/12~89/11; ca. 76~78% ee

Ph Me



15% isolated yield (0.136 g) of 2j was obtained in an 8 mmol reaction.

0.0938 g isolated 2j was dissolved in 10 mL CH2Cl2, c1 = 0.00938.

Optical rotatory power measured: α = -0.977 (L = 1 dm; T = 19.7 ℃; λ = 589 nm)

(Eur. J. Org. Chem. 2008, 4963: (S,S)-diasteoromer, [α]D20 = - 234; (R,R)-, [α]D20 = + 224).

Therefore, the mixture contains mainly the (S,S)-diasteoromer.

Then, c2 = 0.00938*0.59 = 0.00553 (if 41% are the mixture of RR and SS isomers, then [α] will

exceed the known value of 224 or 234).

Therefore, [α]D19.7 = - 176.5 (c = 0.00553, CH2Cl2).

Therefore, enantiomer ratio SS/RR: ca. 88/12~89/11 (by comparison with the literature data).

Enantiomeric excess is ca. 76~78%.

(1) GC spectra and data of the above reaction: 59/41 dr

4.0 5.0 6.0 7.0 8.0 9.0 10.0 11.0 12.0 13.0 14.0 15.0 16.0 17.0

0.0

2.5

(x10,0 00,000)

TIC

5.394 5.350 5.425 TIC 48739446 60.48 28584120 57.98 1.70 MI

10.322 10.292 10.350 TIC 13101811 16.26 8485827 17.21 1.54 MI

10.410 10.383 10.458 TIC 18739662 23.26 12232992 24.81 1.53 MI

(2) GC spectra and data of a normal reaction using racemic 1j as the substrate:

5.0 6.0 7.0 8.0 9.0 10.0 11.0 12.0 13.0

0.0

5.0

(x1,000,000)

TIC

6.015 5.933 6.133 TIC 33707499 80.48 16895549 77.36 1.99 MI

7.131 7.092 7.183 TIC 5161344 12.32 3083563 14.12 1.67 MI

10.977 10.942 11.025 TIC 1468361 3.51 926689 4.24 1.58 MI

11.078 11.042 11.150 TIC 1545411 3.69 934374 4.28 1.65 MI

S31

(3) MS spectra of the involved compounds:

Retention Time：~5.4 or 6.0 min (1j, MW 122)

50 100 150 200 250 300 350 400 450 500

0.0

25.0

50.0

75.0

100.0

107

122

155 211183 341281 304 428387 450252 470365 494

Retention Time：~6.5 or 7.1 min (catalyst, MW 184, 186)

50 100 150 200 250 300 350 400 450 500

0.0

25.0

50.0

75.0

100.0

105

51 184

122 143 341 429218 281 478406235 450384 498310

Retention Time: ~10.32 or 10.98 min (isomers of 2j, MW 226)

50 100 150 200 250 300 350 400 450 500

0.0

25.0

50.0

75.0

100.0

105

121

77 211

51 148 167 233 268 355329305288 418 440378 497460

Retention Time: ~10.41 or 11.08 min (isomers of 2j, MW 226)

50 100 150 200 250 300 350 400 450 500

0.0

25.0

50.0

75.0

100.0

105

121

51 211

148 165182 377268 324 415252 356 463 494

S32

1H and 13C NMR Spectra of the Products

(2a)

1H NMR

13C NMR

S33

CH3

H3C

(2b)

1H NMR

13C NMR

S34

(2c)

1H NMR

13C NMR

S35

O (2d)

1H NMR

13C NMR

S36

O (2e)

1H NMR

13C NMR

S37

O (2f)

1H NMR

13C NMR

S38

O (2g)

1H NMR

13C NMR

S39

(2h)

1H NMR

13C NMR

S40

(2i)

1H NMR

13C NMR

S41

(2j)

1H NMR

13C NMR

S42

O (2k)

1H NMR

13C NMR

S43

(3a)

1H NMR

13C NMR

S44

H3C (3b)

1H NMR

13C NMR

S45

(3c)

1H NMR

13C NMR

S46

(3d)

1H NMR

13C NMR

S47

(3e)

1H NMR

13C NMR

S48

(3f)

1H NMR

13C NMR

S49

(3g)

1H NMR

13C NMR

S50

(3h)

1H NMR

13C NMR

S51

(3i)

1H NMR

13C NMR

S52

(3j)

1H NMR

13C NMR

S53

(3k)

1H NMR

13C NMR

S54

(3l)

1H NMR

13C NMR

S55

(3m)

1H NMR

13C NMR

S56

(3n)

1H NMR

13C NMR

S57

(3o)

1H NMR

13C NMR

S58

(3p)

1H NMR

13C NMR

S59

(3q)

1H NMR

13C NMR

S60

(3r)

1H NMR

13C NMR

S61

(4a)

1H NMR

13C NMR

S62

(4b)

1H NMR

13C NMR

S63

(4c)

1H NMR

13C NMR

S64

(4d)

1H NMR

13C NMR

S65

(4e)

1H NMR

13C NMR

S66

(4f)

1H NMR

13C NMR

S67

(4g)

1H NMR

13C NMR

S68

(4h)

1H NMR

13C NMR

S69

(4i)

1H NMR

13C NMR

S70

(4j)

1H NMR

13C NMR

S71

(4k)

1H NMR

13C NMR

S72

(4l)

1H NMR

13C NMR

S73

(4m)

1H NMR

13C NMR

S74

(4n)

1H NMR

13C NMR

S75

(5a)

1H NMR

13C NMR

S76

O (5b)

1H NMR

13C NMR

S77

(6a)

1H NMR

13C NMR

S78

O (6b)

1H NMR

13C NMR

S79

(7a)

1H NMR

13C NMR

S80

O (7b)

1H NMR

13C NMR

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Jan 2024
CHINESE J ORG CHEM

Silver‐Catalyzed Synthesis of Benzyl Ethers via Alkoxylation of Benzylic C(sp)−H Bonds

Article

Full-text available

Jun 2023
CHEM-ASIAN J

Alkoxylation of benzylic C(sp³)−H bonds has become one of the most important tools for the construction of benzyl ethers from feedstock chemicals. Herein, we reported a silver catalyzed alkoxylation of benzylic C(sp³)−H bonds employing potassium persulfate as an oxidant at room temperature. This strategy showed good functional‐group tolerance, site selectivity, and chemoselectivity. The reaction proceeded smoothly in the presence of various primary, secondary, and tertiary alcohol nucleophiles, affording corresponding benzyl ethers. Combined experimental studies provided mechanistic insights into the possible radical pathways. Furthermore, a possible mechanism was proposed for this method.

Transition-Metal-Free Cross-Coupling of Acetals and Grignard Reagents To Form Diarylmethyl Alkyl Ethers and Triarylmethanes

Article

May 2023

We herein report a transition-metal-free cross-coupling reaction of acetals and Grignard reagents. The method provides a modular preparation of diarylmethyl alkyl ethers, triarylmethanes and 1,1-diarylalkanes that constitute the core structures of many bioactive molecules and synthetic motifs. A series of readily accessible acetals bearing aryl, alkenyl, and alkyl substituents efficiently coupled with commercially available aryl, alkyl, and allylic magnesium bromide to give products in high yields. In addition to acyclic and cyclic acetals, ketal and orthoester also serve as viable substrates to afford sterically hindered tertiary ether and ketal respectively. A sequential difunctionalization of acetals led to the rapid synthesis of triarylmethanes and diarylalkanes.

Harnessing Protonated 2,2'-Bipyridinium Salts as Powerful Brønsted Acid Catalysts in Organic Reactions

Article

Mar 2023
J ORG CHEM

It is the first time that the readily available protonated 2,2'-bipyridinium salts are used as Brønsted acid catalysts to accelerate a series of organic transformations that included the hydration of aromatic alkynes, etherification of alcohols, cyclotrimerization of aliphatic aldehydes, Ritter reaction, Mannich reaction, Biginelli reaction, preparation of substituted alkenes from alcohols, synthesis of spirooxindole, bisindolylmethane, and noncyclized tetraketone with good to excellent yields. These results strongly suggest that there exists enormous potentiality in the development of the protonated 2,2'-bipyridinium catalytic system.

Mild and Selective Etherification of Wheat Straw Lignin and Lignin Model Alcohols by Moisture-Tolerant Zirconium Catalysis

Article

Full-text available

Jan 2023

The direct etherification of wheat straw lignin and lignin model compounds using alcohols as reagents and zirconocene triflate as water-tolerant Lewis acidic catalyst is herein described. Visual kinetic analysis was...

Heteropolyacid catalyzed O -alkylation of oximes with alcohols via a carbocation in dimethyl carbonate and mechanism insight

Article

Jan 2022

We have established H 3 PW 12 O 40 · x H 2 O catalyzed O -alkylation of oximes with alcohols in DMC, and investigated the corresponding mechanism.

Pd(ii)-catalyzed alkoxylation of unactivated C(sp3)–H and C(sp2)–H bonds using a removable directing group: efficient synthesis of alkyl ethers

Article

Full-text available

Aug 2013
Chem Sci

The Pd(II)-catalyzed alkoxylation of unactivated C(sp3)–H and C(sp2)–H bonds using a new bidentate directing group has been developed. Alkoxylation occurs selectively at the β position with broad substrate scope and high tolerance of functional groups (chloro, cyano, ether, ester, olefin, amino, etc.). Besides alkoxylation of the β-C–H bonds, γ-alkoxylation of C(sp2)–H bonds could also be achieved, provided that no reactive β-C–H bonds were present. In addition, this DG is readily available and removable.

CsOH/DMSO Promoted Reactions of Aryl Halides with Phenols: A Convenient Method for the Synthesis of Diaryl Ethers

Article

Full-text available

Jan 2014
CHINESE J ORG CHEM

The reactions of aryl halides with phenols promoted by CsOH/dimethyl sulfoxide (CsOH/DMSO) led to diaryl ethers. This method was free of transition metal catalysts and ligands, and could be performed without inert gas protection. Therefore, it was a concise and green synthetic method. Based on the experimental results, a mechanism involving the benzyne intermediates is supposed.

ChemInform Abstract: General, Green, and Scalable Synthesis of Imines from Alcohols and Amines by a Mild and Efficient Copper-Catalyzed Aerobic Oxidative Reaction in Open Air at Room Temperature.

Article

Full-text available

Oct 2012
ADV SYNTH CATAL

A general, green, and scalable synthesis of the useful imines and α,β-unsaturated imines is successfully achieved by a low-loading and powerful, mild and efficient copper-catalyzed aerobic oxidative reaction of alcohols and amines in the open air at room temperature under base- and dehydrating reagent-free conditions. This practical reaction can use air as the economic and green oxidant, tolerates a wide range of substrates, can afford high yields of the target imines on a large scale, and produces water as the only by-product, and thus being the best imination method as yet using alcohols and amines directly.

Palladium-catalyzed N-alkylation of amides and amines with alcohols employing the aerobic relay race methodology

Article

Oct 2012

Possibly because homogeneous palladium catalysts are not typical borrowing hydrogen catalysts and ligands are thus ineffective in catalyst activation under conventional anaerobic conditions, they had not been used in the N-alkylation reactions of amines/amides with alcohols in the past. By employing the aerobic relay race methodology with Pd-catalyzed aerobic alcohol oxidation being a more effective protocol for alcohol activation, ligand-free homogeneous palladiums are successfully used as active catalysts in the dehydrative N-alkylation reactions, giving high yields and selectivities of the alkylated amides and amines. Mechanistic studies implied that the reaction most probably proceeds via the novel relay race mechanism we recently discovered and proposed. By employing the aerobic relay race methodology with Pd-catalyzed aerobic alcohol oxidation being a more effective protocol for alcohol activation, ligand-free homogeneous palladiums are successfully used as active catalysts in the dehydrative N-alkylation reactions of amines and amides with alcohols, giving high yields and selectivities of the alkylated amines and amides. Mechanistic studies implied that the reaction most probably proceeds via the novel relay race mechanism we recently discovered and proposed. Copyright © 2012 SIOC, CAS, Shanghai & WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Selective Catalytic Synthesis of Unsymmetrical Ethers from the Dehydrative Etherification of Two Different Alcohols

Article

Sep 2014

The cationic ruthenium–hydride complex [(C6H6)(PCy3)(CO)RuH]+BF4– catalyzes selective etherification of two different alcohols to form unsymmetrically substituted ethers. The catalytic method exhibits a broad substrate scope while tolerating a range of heteroatom functional groups in forming unsymmetrical ethers, and it is successfully used to directly synthesize a number of highly functionalized chiral nonracemic ethers.

Aromatic Nucleophilic Substitution Reactions.

Article

Oct 1951

Recent Advances of Transition Metal-Catalyzed Aerobic Dehydrative Reactions of Alcohols and Amines and Related Researches

Article

Jan 2013
CHINESE J ORG CHEM

In comparison with other methods, transition metal-catalyzed dehydrative N-alkylation of amines and amides with alcohols, commonly known as the borrowing hydrogen or hydrogen autotransfer reactions and the methodology, is a comparatively green and atom-economic method for the synthesis of the useful amine and amide derivatives. Recently, transition metal-catalyzed aerobic dehydrative N-alkylation method has also attracted much attention, for the reactions can be readily conducted under milder and simpler conditions by using the more stable metal catalysts under the air atmosphere. In this review, we summarize the recent advances of transition metal-catalyzed aerobic dehydrative C-N and C=N bond forming reactions of alcohols with amines and amides for the synthesis of the amine and amide derivatives and imines, as well as those of the related aerobic dehydrative C-alkylation reactions. Mechanisms of the above reactions are also discussed.

ChemInform Abstract: Microwave-Promoted TBAF-Catalyzed SNAr Reaction of Aryl Fluorides and ArSTMS: An Efficient Synthesis of Unsymmetrical Diaryl Thioethers.

Article

Sep 2011
ChemInform

Optimized conditions are elaborated for each type of substrates to afford a broad spectrum of title compounds including fluoro derivatives with biological significance.

ChemInform Abstract: Pd(II)-Catalyzed Alkoxylation of Unactivated C(sp3)—H and C(sp2)—H Bonds Using a Removable Directing Group: Efficient Synthesis of Alkyl Ethers.

Article

Mar 2014
ChemInform

The Pd(II)-catalyzed alkoxylation of unactivated C(sp(3))-H and C(sp(2))-H bonds using a new bidentate directing group has been developed. Alkoxylation occurs selectively at the beta position with broad substrate scope and high tolerance of functional groups (chloro, cyano, ether, ester, olefin, amino, etc.). Besides alkoxylation of the beta-C-H bonds, gamma-alkoxylation of C(sp(2))-H bonds could also be achieved, provided that no reactive beta-C-H bonds were present. In addition, this DG is readily available and removable.

ChemInform Abstract: Sulfur-Silicon Bond Activation Catalyzed by Cl/Br Ions: Waste-Free Synthesis of Unsymmetrical Thioethers by Replacing Fluoride Catalysis and Fluorinated Substrates in S N Ar Reactions.

Article

Jun 2014
GREEN CHEM

In contrast to conventional activation of Nu–SiR3 reagents by F ion attributed to the strong affinity of Si to F, S–Si activation can now be achieved using Cl/Br ions of TBAX as catalysts via formation of weaker X–Si bonds and Me3Si–X. This led to a waste-free synthesis of unsymmetrical thioethers via F-free SNAr reactions of activated (hetero)aryl halides and RS–SiMe3, with recovery of the useful Me3Si–X reagent in high yields.

Organohalides-Catalyzed Dehydrative O-Alkylation between Alcohols: A Facile Etherification Method for Aliphatic Ether Synthesis

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