Samarium diiodide mediated barbier-type reaction of 2-chloromethylbenzoxazole and 2-chloromethylbenzothiazole with carbonyl compounds: A convenient synthesis of 1-(β-hydroxyalkyl)benzoxazoles and 1-(β-hydroxyalkyl)benzothiazoles

Article abstract of DOI:10.1081/SCC-120024742

1-(β-Hydroxyalkyl)benzoxazoles and 1-(β -hydroxyalkyl)benzothiazoles were prepared via reductive addition reactions of 2-chloromethylbenzoxazole and 2-chloromethylbenzothiazole with carbonyl compounds under mild conditions mediated by SmI₂.

Full text of DOI:10.1081/SCC-120024742

This article was downloaded by: [University of California, San Diego]
On: 08 June 2015, At: 01:34
Publisher: Taylor & Francis
Informa Ltd Registered in England and Wales Registered Number: 1072954 Registered office: Mortimer House,
37-41 Mortimer Street, London W1T 3JH, UK
Synthetic Communications: An International Journal
for Rapid Communication of Synthetic Organic
Chemistry
Publication details, including instructions for authors and subscription information:
http://www.tandfonline.com/loi/lsyc20
Samarium Diiodide Mediated Barbier-Type
Reaction of 2-Chloromethylbenzoxazole and
2-Chloromethylbenzothiazole with Carbonyl
Compounds: A Convenient Synthesis of 1-
(β-Hydroxyalkyl)benzoxazoles and 1-(β-
Hydroxyalkyl)benzothiazoles
Professor Xiaoliang Xu a & Yongmin Zhang a b
a Department of Chemistry , Zhejiang University (Campus Xixi) , Hangzhou, P.R. China
b State Key Laboratory of Organometallic Chemistry , Shanghai Institute of Organic
Chemistry , Chinese Academy of Sciences , Shanghai, P.R. China
Published online: 15 Aug 2006.
To cite this article: Professor Xiaoliang Xu & Yongmin Zhang (2003) Samarium Diiodide Mediated Barbier-Type Reaction of
2-Chloromethylbenzoxazole and 2-Chloromethylbenzothiazole with Carbonyl Compounds: A Convenient Synthesis of 1-(β-
Hydroxyalkyl)benzoxazoles and 1-(β-Hydroxyalkyl)benzothiazoles, Synthetic Communications: An International Journal for
Rapid Communication of Synthetic Organic Chemistry, 33:20, 3551-3559, DOI: 10.1081/SCC-120024742
To link to this article: http://dx.doi.org/10.1081/SCC-120024742
PLEASE SCROLL DOWN FOR ARTICLE
Taylor & Francis makes every effort to ensure the accuracy of all the information (the “Content”) contained
in the publications on our platform. However, Taylor & Francis, our agents, and our licensors make no
representations or warranties whatsoever as to the accuracy, completeness, or suitability for any purpose of the
Content. Any opinions and views expressed in this publication are the opinions and views of the authors, and
are not the views of or endorsed by Taylor & Francis. The accuracy of the Content should not be relied upon and
should be independently verified with primary sources of information. Taylor and Francis shall not be liable for
any losses, actions, claims, proceedings, demands, costs, expenses, damages, and other liabilities whatsoever
or howsoever caused arising directly or indirectly in connection with, in relation to or arising out of the use of
the Content.
This article may be used for research, teaching, and private study purposes. Any substantial or systematic
reproduction, redistribution, reselling, loan, sub-licensing, systematic supply, or distribution in any
form to anyone is expressly forbidden. Terms & Conditions of access and use can be found at http://
www.tandfonline.com/page/terms-and-conditions

MARCEL DEKKER, INC. • 270 MADISON AVENUE • NEW YORK, NY 10016
©2003 Marcel Dekker, Inc. All rights reserved. This material may not be used or reproduced in any form without the express written permission of Marcel Dekker, Inc.
SYNTHETIC COMMUNICATIONSÕ
Vol. 33, No. 20, pp. 3551–3559, 2003
Samarium Diiodide Mediated Barbier-Type
Reaction of 2-Chloromethylbenzoxazole and
2-Chloromethylbenzothiazole with Carbonyl
Compounds: A Convenient Synthesis of
1-(b-Hydroxyalkyl)benzoxazoles and
1-(b-Hydroxyalkyl)benzothiazoles
Xiaoliang Xu1 and Yongmin Zhang1,2,
*
1Department of Chemistry,
Zhejiang University (Campus Xixi),
Hangzhou, P.R. China
2State Key Laboratory of Organometallic Chemistry,
Shanghai Institute of Organic Chemistry,
Chinese Academy of Sciences, Shanghai, P.R. China
*Correspondence: Yongmin Zhang, Professor, Department of Chemistry,
Zhejiang University (Campus Xixi), Tianmu-Shan Road, Hangzhou, 310028,
P.R. China; State Key Laboratory of Organometallic Chemistry, Shanghai
Institute of Organic Chemistry, Chinese Academy of Sciences, Shanghai,
200032, P.R. China; Fax: 86-571-88807077; E-mail: yminzhang@mail.hz.zj.cn.
3551
DOI: 10.1081/SCC-120024742
Copyright & 2003 by Marcel Dekker, Inc.
0039-7911 (Print); 1532-2432 (Online)
www.dekker.com

MARCEL DEKKER, INC. • 270 MADISON AVENUE • NEW YORK, NY 10016
©2003 Marcel Dekker, Inc. All rights reserved. This material may not be used or reproduced in any form without the express written permission of Marcel Dekker, Inc.
3552
Xu and Zhang
ABSTRACT
1-(b-Hydroxyalkyl)benzoxazoles and 1-(b-hydroxyalkyl)benzothia-
zoles were prepared via reductive addition reactions of
2-chloromethylbenzoxazole and 2-chloromethylbenzothiazole with
carbonyl compounds under mild conditions mediated by SmI2.
Key Words: 2-Chloromethylbenzoxazole; 2-Chloromethylbenzo-
thiazole; Carbonyl compounds; 1-(b-Hydroxyalkyl)benzoxazole; 1-
(b-Hydroxyalkyl)benzothiazole; Samarium diiodide.
The metal mediated carbon–carbon bond formation between
alkyl halides and carbonyl compounds, the Barbier-type reaction, is a
fundamental reaction in organic chemistry.[1] Such a reaction has
played the key role in synthesizing numerous important biological and
abiological compounds. Samarium diiodide, the Kagan’s reagent, has
found the widespread application to promote the inter- and intra-
molecular Barbier-type reactions.[2] A large variety of organic halides
such as, primary and secondary alkyl halides, allylic and benzylic halides,
1-iodoalkynes, a-heterosubstituted alkyl halides can be used as substrates
in this transformation.[2e] In contrast, the a-heterocyclic substituted alkyl
halides have remained unexplored. To the best of our knowledge, no
literature reported the synthesis of 1-(b-hydroxyalkyl)benzoxazole and
1-(b-hydroxyalkyl)benzothiazole by using SmI2 as a reagent. Herein,
we wish to describe a novel Barbier-type reaction of 2-chloromethylben-
zoxazole and 2-chloromethylbenzothiazole[3] with carbonyl compounds
mediated by SmI2 (Sch. 1).
When substrates 1 and carbonyl compounds 2 were added to a
solution of 2.2 equiv. of SmI2 in THF at room temperature under a
nitrogen atmosphere, the deep blue color of SmI2 changed to a yellow
color immediately. TLC showed that the reductive coupling reaction was
complete within a few minutes and afforded 1-(b-hydroxyalkyl)benzox-
azole and 1-(b-hydroxyalkyl)benzothiazole smoothly in good to excellent
yields upon subsequent protonation.
Scheme 1.

MARCEL DEKKER, INC. • 270 MADISON AVENUE • NEW YORK, NY 10016
©2003 Marcel Dekker, Inc. All rights reserved. This material may not be used or reproduced in any form without the express written permission of Marcel Dekker, Inc.
Barbier-Type Reaction
3553
Benzoxazole and benzothiazole derivatives constitute an important
class of heterocyclic compounds for their antibacterial and antifungal
activities.[4] Several methods have already been reported for the
preparation of 1-(b-hydroxyalkyl)benzoxazole and 1-(b-hydroxyalkyl)-
benzothiazole. The aldol-type method for the preparation of 1-(b-hydro-
xyalkyl)benzoxazole and 1-(b-hydroxyalkyl)benzothiazole requires the
use of n-BuLi at the temperature ꢀ70ꢁC ꢂꢀ100ꢁC[5] or the unavailable
9-BBN triflate.[6] In addition, these derivatives can also be obtained
from reductive coupling of 2-(bromodifluoromethyl)benzoxazole and
aldehydes with the aid of tetrakis(dimethylamino)ethylene.[7] Although
the existing methodology can afford the desired products, they often
involve in the expensive reagents, low temperature conditions, and
unsatisfactory yields.
To investigate the ability of SmI2 to promote these Barbier-type
reactions, different experiments were performed. Table 1 summarizes
our results. All the reactions were completed at room temperature within
5 min. The reactions proceeded in good to excellent yields for the aliphatic
aldehydes and ketones. However, when acetophenone or benzaldehyde
Table 1. Barbier-type reaction of 2-chloromethylbenzoxazole and 2-chloro-
methylbenzothiazole with carbonyl compounds promoted by SmI2.
Entry
X, Y
R1, R2
CH3, CH3
Product
Yield (%)a,b
1
H, O
H, O
H, O
H, O
H, O
H, O
H, O
H, O
Cl, O
Cl, O
Cl, O
H, S
H, S
H, S
H, S
3a
3b
3c
3d
3e
3f
92, 85c, 70d
2
CH3, CH3CH2
CH3, CH3(CH2)3
H, (CH3)2CH
H, (CH3)2CHCH2
Cyclopenxanone
Cyclopentanone
C6H5, C6H5
87
95
82
85
97
81
77
87
76
95
90
87
96
83
3
4
5
6
7
3g
3h
3i
8
9
CH3, CH3
10
11
12
13
14
15
H, (CH3)2CH
Cyclohexanone
CH3, CH3
3j
3k
3l
H, (CH3)2CH
Cyclohexanone
Cyclopentanone
3m
3n
3o
1
aAll compounds were fully characterized by H NMR, MS, EA, and IR.
bYields refer to % of isolated products based on substrate 1.
c0.5 mL HMPA was added.
d2 mmol MeOH was added.

MARCEL DEKKER, INC. • 270 MADISON AVENUE • NEW YORK, NY 10016
©2003 Marcel Dekker, Inc. All rights reserved. This material may not be used or reproduced in any form without the express written permission of Marcel Dekker, Inc.
3554
Xu and Zhang
used as substrates, which are more easily reduced to pinacol by samarium
diiodide than aliphatic aldehydes and ketones, they only gave complex
mixtures. As for the benzophenone, 77% yield of the product is obtained.
When 0.5 mL HMPA or 2 mmol MeOH were added to the reaction system,
the yields of the products were relatively lower.
Although the mechanism of the above reaction has not been studied,
the requirement of at least 2 M equiv. of samarium diiodide would
suggest for the initial formation of a radical species and its further
reduction to an organosamarium species by the second equivalent of
samarium diiodide.
In conclusion, the method outlined for the synthesis of 1-(b-hydro-
xyalkyl)benzoxazoles and 1-(b-hydroxyalkyl)benzothiazoles represents a
convenient approach with some advantages to known procedures: good
to excellent yields, mild and neutral conditions, easy work-up of the
reaction and recovery of the products. Thus, this procedure may provide
a practical method to synthesize the above compounds.
EXPERIMENTAL
Tetrahydrofuran was distilled from sodium-benzophenone
immediately prior to use. All reactions were conducted under a nitrogen
atomsphere. Melting points are uncorrected. 1H NMR spectra were
recorded on a Bruker 400 MHz instrument as CDCl3 solutions using
TMS as internal standard. Infrared spectra were recorded using KBr
disks or thin films with a Bruker Vector-22 infrared spectrometer.
Elemental analyses were performed on a EA-1110 instrument. Metallic
samarium and all solvents were purchased from commercial sources, and
used without further purification.
General procedure for the synthesis of 1-(b-hydroxyalkyl)benzoxazole
and 1-(b-hydroxyalkyl)benzothiazole. A solution of 2-chloromethylben-
zoxazole and 2-chloromethylbenzothiazole (1 mmol) with aldehydes or
ketones (1.2 mmol) in dry THF (3 mL) was added to the solution of
SmI2 (2.2 mmol) in THF (20 mL) at room temperature under a nitrogen
atmosphere. The deep blue color of the solution immediately changed to
yellow. After being stirred for 5 min (Table 1, the reaction was monitored
by TLC), the reaction mixture was quenched with 0.1 M hydrochloric
acid (5 mL) and extracted with ether (3 ꢃ l5 mL). The organic phase
was successively washed with brine (15 mL), water (15 mL), and dried
over anhydrous Na2SO4. The solvent was removed under reduced
pressure to give the crude products, which were purified by preparative
TLC using ethyl acetate and cyclohexane (1:5) as eluant.

MARCEL DEKKER, INC. • 270 MADISON AVENUE • NEW YORK, NY 10016
©2003 Marcel Dekker, Inc. All rights reserved. This material may not be used or reproduced in any form without the express written permission of Marcel Dekker, Inc.
Barbier-Type Reaction
3555
Compound 3a. M.p.: 74–75ꢁC. ꢀmax: 3316, 3054, 2973, 2932, 1614,
1570, 1462, 1247, 1227, 767, 748 cmꢀ1. ꢁH (CHCl3): 7.68–7.73 (1H, m),
7.56–7.62 (1H, m), 7.32–7.52 (2H, m), 3.68 (1H, brs), 3.13 (2H, s), 1.40
(6H, s). m/z (%): 192 (Mþ þ 1, 4.90), 176 (6.70), 134 (21.49), 133 (1.00),
104 (12.52), 59 (68.57). Anal. calcd. C11H13NO2: C, 69.09; H, 6.85; N,
7.32. Found: C, 69.12; H, 6.71; N, 7.23%.
Compound 3b. Viscous oil. ꢀmax: 3379, 2973, 2937, 1613, 1567, 1456,
909, 733 cmꢀ1. ꢁH (CDCl3): 7.66–7.71 (1H, m), 7.47–7.49 (lH, m),
7.28–7.30 (2H, m), 3.68 (1H, brs), 3.02–3.12 (2H, q), 1.62–1.64 (2H,
m), 1.29 (3H, s), 0.96–1.03 (3H, t). m/z (%): 206 (Mþ þ 1, 100), 188
(14.59), 133 (100), 73 (48.96), 43 (57.26). Anal. calcd. C12H15NO2: C,
70.22; H, 7.37; N, 6.82. Found: C, 70.13; H, 7.36; N, 6.89%.
Compound 3c. Viscous oil. ꢀmax: 3342, 2935, 2912, 1614, 1567, 1456,
1381, 902 cmꢀ1. ꢁH (CDCl3): 7.70–7.50 (2H, m), 7.31–7.33 (2H, m), 3.62
(IH, brs), 3.03–3.13 (2H, q), 1.30–1.62 (9H, m), 0.89–0.93 (3H, t). m/z
(%): 234 (Mþ þ 1, 4.26), 216 (4.21), 176 (10.07), 133 (100), 101 (18.00), 43
(39.98). Anal. calcd. C14H19NO2: C, 72.07; H, 8.21; N, 6.00. Found: C,
72.15; H, 8.33; N, 5.87%.
Compound 3d. M.p.: 52–54ꢁC. ꢀmax: 3365, 2964, 2865, 1614, 1569,
1456, 745 cmꢀ1. ꢁH (CDCl3): 7.43–7.63 (2H, m), 7.25–7.27 (2H, m),
3.99–4.05 (1H, m), 3.78 (1H, brs), 2.95–3.08 (2H, m), 1.80–1.83 (1H,
m), 0.99–1.02 (6H, d). m/z (%): 206 (Mþ þ l, 100), 188 (13.80),
162 (8.08), 133 (29.71), 119 (0.79), 105 (7.95), 43 (25.49). Anal. calcd.
C12H15NO2: C, 70.22; H, 7.37; N, 6.82. Found: C, 70.09; H, 7.33;
N, 6.75%.
Compound 3e. Viscous oil. ꢀmax: 3386, 2958, 2870, 1614, 1579, 1244,
734 cmꢀ1. ꢁH (CDCl3): 7.45–7.65 (2H, m), 7.27–7.29 (2H, m), 4.25–4.32
(1H, m), 3.81 (1H, brs), 2.96–3.09 (2H, m), 1.85–1.91 (1H, m), 1.57–1.61
(1H, m), 1.32–1.39 (1H, m), 0.95–0.97 (6H, d). m/z (%): 220 (Mþ þ 1,
1.22), 201 (3.35), 186 (1.24), 162 (10.77), 133 (100), 77 (7.06), 43 (22.19).
Anal. calcd. C13H17NO2: C, 71.21; H, 7.81; N, 6.39. Found: C, 71.34; H,
7.75; N, 6.42%.
Compound 3f. M.p.: 80–81ꢁC. ꢀmax: 3333, 2937, 2860, 1610, 1567,
1218, 1142, 870 cmꢀ1. ꢁH (CHCl3): 7.51–7.70 (2H, m), 7.27–7.35 (2H,
m), 3.44 (1H, brs), 3.11 (2H, s), 1.52–1.73 (10H, m). m/z (%): 232
(Mþ þ 1, 3.55), 214 (2.85), 188 (1.90), 133 (100), 77 (9.70), 41 (24.93).
Anal. calcd. C14H17NO2: C, 72.70; H, 7.41; N, 6.06. Found: C, 72.59; H,
7.37; N, 6.12%.
Compound 3g. M.p.: 70–72ꢁC. ꢀmax: 3372, 2952, 2867, 1610, 1568,
1457, 1241, 748 cmꢀ1. ꢁH (CHCl3): 7.52–7.70 (2H, m), 7.32–7.35 (2H, m),
3.67 (1H, brs), 3.21 (2H, s), 1.67–1.90 (8H, m). m/z (%): 218 (Mþ þ 1,
62.61), 200 (32.15), 188 (1.72), 175 (6.21), 133 (100), 104 (19.13), 41

MARCEL DEKKER, INC. • 270 MADISON AVENUE • NEW YORK, NY 10016
©2003 Marcel Dekker, Inc. All rights reserved. This material may not be used or reproduced in any form without the express written permission of Marcel Dekker, Inc.
3556
Xu and Zhang
(48.13). Anal. calcd. C13H15NO2: C, 71.87; H, 6.96; N, 6.45. Found: C,
71.95; H, 6.97; N, 6.32%.
Compound 3h. M.p.: 164–165ꢁC. ꢀmax: 3420, 3027, 1608, 1564, 1454,
697 cmꢀ1. ꢁH (CHCl3): 7.53–7.62 (6H, m), 7.21–7.33 (8H, m), 5.78 (1H,
brs), 3.89 (2H, s). m/z (%): 316 (Mþ þ 1, 1.04), 315 (Mþ, 4.10), 238 (0.92),
183 (38.85), 133 (91.40), 105 (100), 77 (74.94). Anal. calcd. C21H17NO2:
C, 79.98; H, 5.43; N, 4.44. Found: C, 79.86; H, 5.51; N, 4.45%.
Compound 3i. M.p.: 103–104ꢁC. ꢀmax: 3363, 2989, 2971, 2934, 1600,
1451, 752 cmꢀ1. ꢁH (CHCl3): 7.68 (1H, s), 7.30–7.45 (2H, m), 3.53 (1H,
brs), 3.11 (2H, s), 1.39 (6H, s). m/z (%): 226 (Mþ þ 1, 17.04), 228
(Mþ þ 3, 5.54), 208 (11.00), 167 (57.33), 132 (2.71), 59 (100), 43 (55.86).
Anal. calcd. C11HI2ClNO2: C, 58.54; H, 5.36; N, 6.21. Found: C, 58.57;
H, 5.31; N, 6.32%.
Compound 3j. M.p.: 99–101ꢁC. ꢀmax: 3299, 2961, 2876, 1615, 1559,
1464, 1447, 821 cmꢀ1. ꢁH (CDCl3): 7.66 (1H, s), 7.28–7.44 (2H, m),
3.99–4.03 (1H, m), 3.21 (1H, brs), 2.98–3.13 (2H, m), 1.83–1.88 (1H,
m), 1.02–1.06 (6H, m). m/z (%): 240 (Mþ þ 1, 7.69), 242 (Mþ þ 3, 2.55),
222 (2.28), 196 (27.57), 167 (100), 132 (4.23). Anal. calcd. C12H14ClNO2:
C, 60.13; H, 5.89; N, 5.84. Found: C, 60.11; H, 5.97; N, 5.76%.
Compound 3k. M.p.: 107–109ꢁC. ꢀmax: 3328, 2932, 2858, 1616, 1565,
1257, 802 cmꢀ1. ꢁH (CHCl3): 7.67 (1H, s), 7.28–7.44 (2H, m), 3.26 (1H,
brs), 3.08 (2H, s), 1.50–1.73 (10H, m). m/z (%): 266 (Mþ þ 1, 100), 268
(Mþ þ 3, 32.19), 248 (16.44), 222 (0.61), 167 (8.86), 41 (14.13). Anal.
calcd. C14H16ClNO2: C, 63.28; H, 6.07; N, 5.27. Found: C, 63.22; H,
6.11; N, 5.39%.
Compound 3l. M.p.: 55–57ꢁC. ꢀmax: 3278, 2966, 2927, 1619, 1557,
1502, 762 cmꢀ1. ꢁH (CHCl3): 7.82–7.99 (2H, m), 7.31–7.48 (2H, m),
4.12 (IH, brs), 3.23 (2H, s), 1.34 (6H, s). m/z (%): 208 (Mþ þ 1, 100),
190 (19.40), 149 (29.04), 108 (9.03), 43 (28.89). Anal. calcd. C11H13NOS:
C, 63.73; H, 6.32; N, 6.76. Found: C, 63.82; H, 6.41; N, 6.87%.
Compound 3m. Viscous oil. ꢀmax: 3367, 2975, 2898, 1611, 1557,
732 cmꢀ1. ꢁH (CDCl3): 7.83–7.96 (2H, m), 7.28–7.47 (2H, m), 3.97–4.02
(1H, m), 3.85 (1H, brs), 3.16–3.26 (2H, m), 1.88–1.93 (1H, m), 1.02–1.06
(6H, m). m/z (%): 222 (Mþ þ 1, 0.82), 206 (0.58), 178 (26.58), 149 (100),
108 (10.43), 43 (15.92). Anal. calcd. C12H15NOS: C, 65.12; H, 6.83; N,
6.33. Found: C, 65.23; H, 6.92; N, 6.34%.
Compound 3n. M.p.: 103–104ꢁC. ꢀmax: 3384, 3053, 2985, 2950, 1570,
1456, 1436, 1254, 757 cmꢀ1. ꢁH (CHCl3): 7.99–8.01 (1H, d), 7.86–7.87
(1H, d), 7.28–7.48 (2H, m), 3.86 (1H, brs), 3.25 (2H, s), 1.51–1.68
(10H, m). m/z (%): 248 (Mþ þ 1, 4.90), 230 (1.57), 204 (2.05), 149
(100), 108 (8.66), 81 (22.53). Anal. calcd. C14H17NOS: C, 67.98; H,
6.93; N, 5.66. Found: C, 67.87; H, 7.05; N, 5.61%.

MARCEL DEKKER, INC. • 270 MADISON AVENUE • NEW YORK, NY 10016
©2003 Marcel Dekker, Inc. All rights reserved. This material may not be used or reproduced in any form without the express written permission of Marcel Dekker, Inc.
Barbier-Type Reaction
3557
Compound 3o. M.p.: 58–60ꢁC. ꢀmax: 3372, 2945, 2853, 1615, 1447,
1227, 738 cmꢀ1. ꢁH (CHCl3): 7.84–7.99 (2H, m), 7.35–7.49 (2H, m), 4.12
(1H, brs), 3.34 (2H, s), 1.65–1.88 (8H, m). m/z (%): 233 (Mþ, 3.52), 216
(0.62), 204 (2.04), 149 (100), 108 (9.30). Anal. calcd. C13H15NOS: C,
66.92; H, 6.48; N, 6.00. Found: C, 66.93; H, 6.48; N, 6.12%.
ACKNOWLEDGMENT
We are grateful to the National Natural Science Foundation of
China (Project No. 20072033) and the Specialized Research Fund for
the Doctoral Program of Higher Education of China for financial
support.
REFERENCES
1. (a) Barbier, P. Compt. Rend. 1898, 128, 110; (b) Blomberg, C. The
Barbier Reaction and Related One-Step Processes; Springer-Verlag:
New York, 1993; 183 pp; (c) Zn-promoted coupling: Hong, F.;
Tang, X.Q.; Hu, C.M. Zinc-promoted Barbier-type reaction of 2-
bromo-3,3,3-trifluoropropene with aldehydes. Chem. Commun.
1994, 289; (d) Sm-mediated coupling: Kunishima, M.; Hioki, K.;
Kono, K.; Sakuma, T.; Tani, S. Barbier-type reactions of aryl halides
with ketones mediated by samarium diiodide. Chem. Pharm. Bull.
1994, 42, 2190; (d) Comparison with Ni(0) insertion chemistry for
intramolecular cyclization: Kihara, M.; Kashimoto, M.; Kabayashi,
Y. A convenient synthesis of 4-substituted 1,2,3,4-tetrahydroiso-
quinolin-4-ols by a novel intramolecular barbier reaction and by an
insertion reaction; reaction scope and limitations. Tetrahedron 1992,
48, 67.
2. For reviews see: (a) Steel, P.G. J. Chem. Soc. Perkin Trans. 1 2001,
2727; (b) Girard. P., Namy, J.L.; Kagan, H.B. Divalent lanthanide
derivatives in organic synthesis 1. Mile preparation of SmI2 and YbI2
and their use as reducing or coupling agents. J. Am. Chem. Soc. 1980,
102, 2693; (c) Krief, A.; Laval, A.M.; Coupling of organic halides
with carbonyl compounds promoted by SmI2, the kagan reagent.
Chem. Rev. 1999, 99, 745; (d) Molander, G.A. Acc. Chem. Res.,
Diverse methods for medium ring synthesis. 1998, 31, 603; (e)
Molander, G.A.; Harris, C.R.; Sequenced reactions with
samarium(II) iodide. Tetrahedron 1998, 54, 3321; (f ) Molander,
G.A.; Harris, Sequenced reactions with samarium(II) iodide. C.R.

MARCEL DEKKER, INC. • 270 MADISON AVENUE • NEW YORK, NY 10016
©2003 Marcel Dekker, Inc. All rights reserved. This material may not be used or reproduced in any form without the express written permission of Marcel Dekker, Inc.
3558
Xu and Zhang
Chem. Rev. 1996, 96, 307; (g) Imamoto, T. Lanthanides in Organic
Synthesis; Academic Press: London, 1994; Chapter 4; (h) Molander,
G.A.; Application of lanthanide reagents in organic synthesis. Chem.
Rev. 1992, 92, 29; (i) Curran, D.P.; Fevig, T.L.; Jasperse, C.P.;
Totleben, M.J.; New mechanistic insights into reductions of halides
and radicals with samarium(II) iodide. Synlett. 1992, 943.
3. 2-Chloromethylbenzoxazole and 2-chloroanethylbenzothiazole were
easily prepared by the literature: Kristinsson, H. Syntese von hetero-
cyclen; IV. Neuer synthese weg zur herstellung von heterocyclischen
nitrilen. Synthesis 1979, 102.
4. (a) Hisano, T.; Ichikawa, M.; Tsumoto, K.; Tasaki, M. Synthesis of
benzoaxoles, benzothiazoles and benzimidazoles and evaluation of
their antifungal, insecticidal and herbicidal activities. Chem. Pharm.
Bull. 1982, 30, 2996; (b) Prudhomme, M.; Guyot, J.; Jeminet, G.
Semi-synthesis of A23187 (calcimycin) analogs. IV. Cation carrier
properties in mitochondria of analogs with modified benzoxazole
rings, antimicrobial activity. J. Antibiotics 1986, 39, 934; (c) Ersan,
S.; Nacak, S.; Berkem, R.; Ozden, T. Synthesis and antimicrobial
activities of 2-[(a-methylbenzylidene)hydrazino] benzoxazoles.
Arzneim. Forsch. 1997, 47, 963; (d) Sener, E.; Yalcin, I.; Sungur, E.
Synthesis and antimicrobial activities of 5-amino-2-(p-substituted-
phenyl)benzoxazole derivatives. Quant. Struct. Act. Relat. 1991, 10,
223; (e) Gunawardana, G.P.; Kohmoto, S.; Gunasekara, S.P.;
McConnel, O.J.; Koehn, F.E. Dercitine, a new biologically active
acridine alkaloid from a deep water marine sponge, dercitus sp. J.
Am. Chem. Soc. 1988, 110, 4856; (f ) Gunawardana, G.P.; Kohmoto,
S.; Burres, N.S. New cytotoxic acridine alkaloids from two deep
water marine sponges of the family pachastrellidae. Tetrahedron
Lett. 1989, 30, 4359; (g) Gunawardana, G.P.; Koehn, F.E.; Lee,
A.Y.; Clardy, J.; He, H.Y.; Faulkner, J.D. Pyridoacridine alkaloids
from deep-water marine sponges of the family pachastrellidae: struc-
ture revision of dercitin and related compounds and correlation with
the kuanoniamines. J. Org. Chem. 1992, 57, 1523; (h) Carroll, A.R.;
Scheuer, P.J. Kuanoniamines A, B, C, and D: pentacyclic alkaloids
from a tunicate and its prosobranch mollusk predator chelynotus
semperi. J. Org. Chem. 1990, 55, 4426; (i) Kim, J.S.; Sun, Q.;
Gatto, B.; Yu, C.; Liu, A.; Liu, L.F.; LaVoie, E.J. Structure-activity
relationships of benzimidazoles and related heterocycles as
tepoisomerase I poisons. Bioorg. Med. Chem. 1996, 4, 621.
5. Hoffman, J.M.; Smith, A.M.; Rooney, C.S.; Fisher, T.E.; Wai, J.S.;
Thomas, C.M.; Bamberger, D.L.; Barnes, J.L.; Williams, T.M.;
Jones, J.H.; Olson, B.D.; O’Brien, J.A.; Goldman, M.E.; Nunberg,

MARCEL DEKKER, INC. • 270 MADISON AVENUE • NEW YORK, NY 10016
©2003 Marcel Dekker, Inc. All rights reserved. This material may not be used or reproduced in any form without the express written permission of Marcel Dekker, Inc.
Barbier-Type Reaction
3559
J.H.; Quintero, J.C.; Schleif, W.A.; Emini, E.A.; Anderson, P.S. J.
Med. Chem. 1992, 56, 953.
6. Hamana, H.; Sugasawa, T. An aldol-type reaction of active methyl
groups of nitrogen-containing heteroaromatic compounds. Chem.
Lett. 1983, 333.
7. Burkholder, C.; Dolbier, W.R., Jr. Reaction of the 2-(bromodifluoro-
methyl) benzoxazole with tetrakis(dimethylamino)ethylene (TDAE)
in the presense of aldehydes. A convenient synthesis of 2-(difluoro-
methyl) benzoxazole alcohols. Tetrahedron Lett. 1997, 38, 821.
Received in Japan March 1, 2003

MARCEL DEKKER, INC. • 270 MADISON AVENUE • NEW YORK, NY 10016
©2003 Marcel Dekker, Inc. All rights reserved. This material may not be used or reproduced in any form without the express written permission of Marcel Dekker, Inc.