Pd-catalyzed synthesis of 1-(hetero)aryl-2,2,2-trichloroethanols using chloral hydrate and (hetero)arylboroxines

Article abstract of DOI:10.1039/d1ra02403e

1-(Hetero)aryl-2,2,2-trichloroethanols are useful key intermediates for the synthesis of various bioactive compounds. Herein, we describe N-heterocyclic carbene (NHC)-coordinated cyclometallated palladium complex (CYP)-catalyzed (hetero)aryl addition of chloral hydrate using (hetero)arylboroxines, providing a new approach to 1-(hetero)aryl-2,2,2-trichloroethanols. Notably, PhS-IPent-CYP which coordinated the bulky yet flexible 2,6-di(pentan-3-yl)aniline (IPent)-based NHC showed good catalytic activities and promoted the transformation in 24-97% yields.

Full text of DOI:10.1039/d1ra02403e

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Pd-catalyzed synthesis of 1-(hetero)aryl-2,2,2-
trichloroethanols using chloral hydrate and
(hetero)arylboroxines†
Cite this: RSC Adv., 2021, 11, 17734
Minori Shimizu,a Yuta Okuda,b Koki Toyoda,c Ryo Akiyama,b Hiraku Shinozakic
abc
*
and Tetsuya Yamamoto
1-(Hetero)aryl-2,2,2-trichloroethanols are useful key intermediates for the synthesis of various bioactive
compounds. Herein, we describe N-heterocyclic carbene (NHC)-coordinated cyclometallated palladium
complex (CYP)-catalyzed (hetero)aryl addition of chloral hydrate using (hetero)arylboroxines, providing
a new approach to 1-(hetero)aryl-2,2,2-trichloroethanols. Notably, PhS-IPent-CYP which coordinated
the bulky yet flexible 2,6-di(pentan-3-yl)aniline (IPent)-based NHC showed good catalytic activities and
promoted the transformation in 24–97% yields.
Received 26th March 2021
Accepted 11th May 2021
DOI: 10.1039/d1ra02403e
rsc.li/rsc-advances
anticancer drugs, OLEDs and catalysts.11 Recently, we have
developed the NHC coordinated cyclometallated palladium
Introduction
complexes (CYPs) that catalyzed the 1,2-addition of organo-
boron compounds to a wide range of carbonyl compounds
including hemiacetals such as aqueous formaldehyde and
glyoxylate hemiacetals (Scheme 2).12 Therefore, we envisaged
that the NHC-CYPs exhibit a good catalytic activity of the
addition of arylboron compounds to chloral hydrate without
a dehydration process. Here, we report the direct aryl addition
to chloral hydrate with triarylboroxines using NHC-CYPs as
a catalyst.
1-(Hetero)aryl-2,2,2-trichloroethanols are one of the most useful
building blocks for the synthesis of bioactive compounds,1
because the carbinol moiety is easily transformed to various a-
substituted carboxylic acid derivatives.2–6 So far, 1-(hetero)aryl-
2,2,2-trichloroethanols have two kinds of possible synthetic
routes as depicted in Scheme 1. One is an addition of the tri-
chloromethyl anion to carbonyl compounds such as aldehydes
or ketones (i).7 This way has generally needed the use of toxic
trichloromethyl anion sources such as chloroform and tri-
chloroacetic acid. The other is an addition of moisture-sensitive
organometallic
reagents
such
as
organomagnesium
Results and discussion
compounds to dehydrated chloral (ii).8
The transition metal-catalyzed 1,2-addition of organo-
boronic acids and their derivatives to carbonyl compounds is
a convenient method compared to the Grignard reaction,
because this could be conducted in the presence of water.9
Although several research groups have reported the Rh-
catalyzed 1,2-addition of arylboronic acids to triuoromethyl
ketones,10 the transition metal-catalyzed addition of arylboron
compounds to trichloromethyl carbonyl compounds such as
chloral have not been examined yet. It is well known that N-
heterocyclic carbenes (NHC) coordinated palladium
complexes are useful for various applications such as
At rst, we examined CYPs-catalyzed 1,2-addition of chloral
hydrate 1 and 2-naphthylboron compounds (Table 1). PhS-IPr-
CYP have catalyzed the addition of arylboronic acids to an
excess amount of aqueous formaldehyde to provide the cor-
responding benzylic alcohols in satisfactory yields,12a,d
although
PhS-IPr-CYP
catalyzed
reaction
of
2-
aDepartment of Materials and Life Sciences, Tokyo Denki University, 5 Senju-Asahicho,
Adachi Tokyo 120-8551, Japan. E-mail: t-yamamoto@mail.dendai.ac.jp
bDepartment of Materials Science and Engineering, Tokyo Denki University, 5 Senju-
Asahicho, Adachi-ku, Tokyo 120-8551, Japan
cDepartment of Applied Chemistry, Tokyo Denki University, 5 Senju-Asahicho, Adachi-
ku, Tokyo 120-8551, Japan
† Electronic supplementary information (ESI) available. See DOI:
10.1039/d1ra02403e
Scheme 1 Previous synthesis of trichloromethylcarbinols.
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corresponding alcohol 5b in moderate yield of 65%. Arylbor-
oxines bearing electron-donating groups like tert-butyl,
phenyl, methoxy and methylthio groups furnished the corre-
sponding products 5c–5h in satisfactory yields of 66–97%.
Interestingly, sterically bulky 2-methoxyphenylboroxine reac-
ted more smoothly than 3-methoxyphenyl and 4-methox-
yphenylboroxines.
4-Fluorophenyl
and
4-
bromophenylboroxines provided the corresponding products
5i and 5j in excellent yields, but the reaction using arylbor-
oxines having strong electron-withdrawing groups such as
nitrile, nitro or methoxycarbonyl group have not afforded the
products 5k–5m. Remarkably, the bromo group on the
aromatic ring remained intact, and the Suzuki–Miyaura cross-
coupling product did not observe under this reaction condi-
tion. This catalytic reaction was also applicable to hetero-
arylboroxines containing oxygen or sulfur atom and provided
the products 5n–5r in low to moderate yields, but was not
applicable to an aliphatic boroxine such as 2-phenyl-
ethylboroxine 4s.
Since arylboroxines are more suitable for this reaction than
arylboronic acids, we examined an experiment under the reaction
conditions with H2O (Scheme 3). Because arylboroxines is known
to rapidly absorb H2O and transform to boronic acids, and adding
water is expected to reduce the dehydration performance of bor-
oxine. Practically, the yield declined as the amount of H2O added
increased, indicating that arylboroxines may be involved in the
dehydration step of chloral hydrate. So, we proposed a plausible
catalytic cycle which is described in Scheme 4. Initially, dehydrated
chloral and arylboronic acids are generated from the hydrolysis of
arylboroxines by chloral hydrate. Then arylpalladium intermediate
6 is formed from a base-promoted transmetallation between an
arylboronic acid and PhS-IPent-CYP, alkoxypalladium 7 is gener-
ated from an insertion of the aryl group on 6 to chloral. Finally,
a transmetallation of complex 7 between an arylboronic acid
Scheme
2 NHC-CYPs-catalyzed 1,2-addition of arylboron
compounds and carbonyl compounds.
naphthaleneboronic acid 2a and 4 equivalent of chloral
hydrate afforded the desired product 5a in 39% yield (entry 1). In
this case, the yield of 5a was improved by the use of an excess of 2a
relative to chloral hydrate (entry 2). Then, using 2-naph-
thaleneboronate 3a instead of 2a increased slightly the yield of 3a
to 70% (entry 3). We have conrmed the efficacy of arylboroxines
in the arylation of triuoroacetaldehyde hemiacetal from
a preliminary investigation.12c When this reaction was performed
using tri(naphthalene-2-yl)boroxine 4a, the yield of 5a was
improved considerably to 82% (entry 4). Dehydrated chloral was
usable as well as chloral hydrate for this addition reaction (entry 5).
H-IPr-CYP has shown more catalytic activity than PhS-IPr-CYP in
the CYPs-catalyzed arylation of glyoxylate hemiacetals,12b but it was
not suitable for this reaction (entry 6). PhS-IPent-CYP having
sterically bulky alkyl group had more active towards the addition
than PhS-IPr-CYP (entry 7).
Under the optimized conditions, we synthesized various
functionalized trichloromethyl carbinols using PhS-IPent-CYP
catalyzed reaction (Table 2). Substrates bearing sterically
hindered 1-naphthyl group was also converted to the
Table 1 Optimization of reaction conditions of CYPs-catalyzed 1,2-addition of chloral hydrate 1 and 2-naphtalenelboron compounds
Entry
1 (mmol)
B (mmol)
K2CO3 (mmol)
CYPs
Yielda (%)
1
2
2.0
0.5
0.5
0.5
0.5
0.5
0.5
0.5
1.5
1.5
0.5
0.5
0.5
0.5
0.5
1.5
1.5
1.5
1.5
1.5
1.5
PhS-IPr-CYP
PhS-IPr-CYP
PhS-IPr-CYP
PhS-IPr-CYP
PhS-IPr-CYP
H-IPr-CYP
39
66
70
82
3b
4c
5c,d
6c
7c
81
73
PhS-IPent-CYP
95 (95)e
Yields were determined by 1H-NMR using triphenylmethane as an internal standard. 3a was used instead of 2a. 4a was used instead of 2a.
a
b
c
d
Dehydrated chloral was used instead of chloral hydrate. e Isolated yield.
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Table 2 PhS-IPent-CYP-catalyzed 1,2-addition of arylboroxines 4 to
chloral hydrate 1a
Scheme 4 Proposed reaction mechanism.
as an arylcarbanion source but also as a dehydrating agent for
chloral hydrate.
Experimental
General
1
All reactions were carried out under an argon atmosphere. H, 13C,
and 19F NMR spectra were recorded on an AVANCE III 400 spec-
trometer (400.15 MHz) at ambient temperature. Melting points were
recorded on Yanako MP-S3. HRMS were recorded on a Thermo Fisher
Scientic Exactive (Orbitrap) using ESI or APCI. Commercially avail-
able organic and inorganic compounds were used without purica-
tion. PhS-IPr-CYP,12a H-IPr-CYP,12a PhS-IPent-CYP12d and arylboroxines
413 were prepared according to the literature procedures.
a
Reaction conditions: 1 (1 equiv., 0.5 mmol), 4 (1.0 equiv., 0.5 mmol),
K2CO3 (3.0 equiv., 1.5 mmol), PhS-Ipent-CYP (0.005 mmol, 1 mol%)
Preparation and characterizations of compounds
and toluene (1 mL) at 100 ꢀC for 2 h in a sealed tube. Isolated yield.
2,2,2-Trichloro-1-(naphthalen-2-yl)ethan-1-ol7b 5a. Chloral
hydrate (83 mg, 0.50 mmol), 2-naphtyl boroxine (231 mg, 0.500
mmol), PhS-IPent-CYP (6.1 mg, 0.0050 mmol) and potassium
carbonate (207 mg, 1.50 mmol) were charged in 10 mL test tube
sealed with a rubber septum. The test tube was evacuated and
backlled with argon. This sequence was repeated three times.
Then dehydrated toluene (1 mL) was added via the rubber
septum with syringe. In an argon ow, the rubber septum was
replaced with a Teon liner screw cap. The sealed test tube was
Scheme 3 The effect of the used amount of H2O on the catalytic placed into an oil bath preheated 100 ꢀC. Aer the reaction was
addition reaction.
stirred for 2 h and cooled to room temperature, the obtained
crude was puried by passing it though a silica gel column with
a hexane/ethyl acetate to give 131 mg (0.475 mmol, 95%) of
product 5a as a pale yellow solid, mp 93–94 ꢀC (lit.7b 93–94 ꢀC).
1H NMR (400 MHz, CDCl3, ppm): d 8.09 (s, 1H, ArH), 7.85–7.90
(m, 3H, ArH), 7.88 (dd, J1 ¼ 7.3 Hz, J2 ¼ 9.8 Hz, 1H, ArH), 7.52 (t,
J ¼ 4.1 Hz, 2H, ArH), 5.40 (d, J ¼ 3.4 Hz, 1H, CH(OH)CCl3), 3.39
(d, J ¼ 3.4 Hz, 1H, OH); 13C NMR (100 MHz, CDCl3, ppm):
d 133.8 (Ar), 132.5 (Ar), 132.3 (Ar), 129.3 (Ar), 128.4 (Ar), 127.7
results in the formation of 1-(hetero)aryl-2,2,2-trichloroethanol and
the regeneration of complex 6.
Conclusions
We have achieved a nucleophilic arylation to chloral hydrate (Ar), 127.4 (Ar), 126.9 (Ar), 126.4 (Ar), 126.2 (Ar), 103.3 (CCl3),
using PhS-IPent-CYP as a catalyst. The use of arylboroxine is 84.7 (CH(OH)CCl3); HRMS (EI) m/z: [M + Cl]ꢁ calcd for
critical for this reaction, and arylboroxines have acted not only
C
12H9OCl4: 308.9413. Found: 308.9424.
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2,2,2-Trichloro-1-(naphthalen-1-yl)ethan-1-ol3d 5b. Product
RSC Advances
2,2,2-Trichloro-1-(2-methoxyphenyl)ethan-1-ol 5g. Product
5b was prepared by utilizing the general procedure using 1- 5g was prepared by utilizing the general procedure using 2-
naphtyl boroxine (231 mg, 0.500 mmol) and was isolated as methoxyphenyl boroxine (201 mg, 0.500 mmol) and was iso-
a pale yellow liquid (91 mg, 0.33 mmol, 66%). 1H NMR (400 lated as a colourless liquid (113 mg, 0.44 mmol, 88%). 1H NMR
MHz, CDCl3, ppm): d 8.28 (d, J ¼ 8.5 Hz, 1H, ArH), 8.09 (d, J ¼ (400 MHz, CDCl3, ppm): d 7.60 (dd, J1 ¼ 1.7 Hz, J2 ¼ 7.7 Hz, 1H,
8.5 Hz, 1H, ArH), 7.91–7.97 (m, 2H, ArH), 7.51–7.62 (m, 3H, ArH), 7.35 (m, 1H, ArH), 6.91–7.01 (m, 1H, ArH), 5.59 (d, J ¼
ArH), 6.23 (d, J ¼ 4.2 Hz, 1H, CH(OH)CCl3), 3.45 (d, J ¼ 4.2 Hz, 6.9 Hz, 1H, CH(OH)CCl3), 4.25 (d, J ¼ 6.9 Hz, 1H, OH), 3.84 (s,
1H, OH); 13C NMR (100 MHz, CDCl3, ppm): d 133.5 (Ar), 132.0 3H, OCH3); 13C NMR (100 MHz, CDCl3, ppm): d 157.7 (Ar), 130.6
(Ar), 131.4 (Ar), 130.3 (Ar), 129.0 (Ar), 127.2 (Ar), 126.4 (Ar), 125.6 (Ar), 130.4 (Ar), 123.5 (Ar), 120.5 (Ar), 111.2 (Ar), 103.5 (CCl3),
(Ar), 124.9 (Ar), 123.7 (Ar), 103.5 (CCl3), 79.0 (CH(OH)CCl3); 80.3 (CH(OH)CCl3), 55.6 (OCH3); HRMS (EI) m/z: [M + Cl]ꢁ calcd
HRMS (EI) m/z: [M + Cl]ꢁ calcd for C12H9OCl4: 308.9413. Found: for C9H9O2Cl4: 288.9362. Found: 288.9371.
308.9422.
2,2,2-Trichloro-1-(4-(methylthio)phenyl)ethan-1-ol
5h.
1-([1,10-Biphenyl]-4-yl)-2,2,2-trichloroethan-ol 5c. Product 5c Product 5h was prepared by utilizing the general procedure
was prepared by utilizing the general procedure using 4- using 4-(methylthio)phenyl boroxine (225 mg, 0.500 mmol) and
biphenyl boroxine (270 mg, 0.500 mmol) and was isolated as was isolated as a pale yellow solid (107 mg, 0.394 mmol, 78%),
a pale yellow solid (136 mg, 0.451 mmol, 90%), mp 119–120 ꢀC. mp 89.5–90.0 ꢀC. 1H NMR (400 MHz, CDCl3, ppm): d 7.50 (d, J ¼
1H NMR (400 MHz, CDCl3, ppm): d 7.70 (s, 1H, Ar), 7.67 (s, 1H, 8.4 Hz, 2H, ArH), 7.23 (d, J ¼ 8.4 Hz, 2H, ArH), 5.14 (d, J ¼ 3.0 Hz,
Ar), 7.59–7.62 (m, 4H, Ar), 7.45 (t, J ¼ 7.5 Hz, 2H, Ar), 7.36 (t, J ¼ 1H, CH(OH)CCl3), 3.46 (d, J ¼ 3.0 Hz, 1H, OH), 2.48 (s, 3H,
7.5 Hz, 1H, Ar), 5.26 (s, 1H, CH(OH)CCl3), 3.32 (s, 1H, OH); 13
C
SCH3); 13C NMR (100 MHz, CDCl3, ppm): d 140.4 (Ar), 131.4 (Ar),
NMR (100 MHz, CDCl3, ppm): d 142.4 (Ar), 140.4 (Ar), 133.8 (Ar), 129.6 (Ar), 125.3 (Ar), 103.1 (CCl3), 84.2 (CH(OH)CCl3), 15.2
129.7 (Ar), 128.9 (Ar), 127.7 (Ar), 127.2 (Ar), 126.6 (Ar), 103.2 (SCH3); HRMS (EI) m/z: [M + Cl]ꢁ calcd for C9H9OCl4S: 304.9134.
(CCl3), 84.4 (CH(OH)CCl3); HRMS (EI) m/z: [M + Cl]ꢁ calcd for Found: 304.9146.
C
14H11OCl4: 334.9569. Found: 334.9583.
1-(4-(tert-Buthyl)phenyl)-2,2,2-trichloroethan-1-ol7a
2,2,2-Trichloro-1-(4-uorophenyl)ethan-1-ol1c 5i. Product 5i
5d. was prepared by utilizing the general procedure using 4-uo-
Product 5d was prepared by utilizing the general procedure rophenyl boroxine (183 mg, 0.500 mmol) and was isolated as
using 4-tert-buthylpheny boroxine (240 mg, 0.500 mmol) and a pale yellow liquid (99 mg, 0.41 mmol, 81%). 1H NMR (400
was isolated as a pale yellow solid (95 mg, 0.34 mmol, 67%), mp MHz, CDCl3, ppm): d 7.58–7.61 (m, 2H, ArH), 7.07 (t, J ¼ 8.7 Hz,
77–78 ꢀC. 1H NMR (400 MHz, CDCl3, ppm): d 7.52 (d, J ¼ 8.4 Hz, 2H, ArH), 5.20 (d, J ¼ 3.1 Hz, 1H, CH(OH)CCl3), 3.40 (d, J ¼
2H, ArH), 7.39 (d, J ¼ 8.4 Hz, 2H, ArH), 5.16 (d, J ¼ 4.1 Hz, 1H, 3.1 Hz, 1H, OH); 13C NMR (100 MHz, CDCl3, ppm): d 163.4 (d,
CH(OH)CCl3), 3.33 (d, J ¼ 4.1 Hz, 1H, OH) 1.32 (s, 9H, C(CH3)3); 1JC–F ¼ 247 Hz, Ar), 131.1 (d, 2JC–F ¼ 8.6 Hz, Ar), 130.6 (d, 3JC–F
¼
13C NMR (100 MHz, CDCl3, ppm): d 152.6 (Ar), 132.0 (Ar), 128.9 3.0 Hz, Ar), 114.9 (d, 4JC–F ¼ 21.4 Hz, Ar), 103.1 (d, 5JC–F ¼ 2.4 Hz,
(Ar), 124.8 (Ar), 103.3 (CCl3), 84.4 (CH(OH)CCl3), 34.7 (C(CH3)3), CCl3), 83.8 (CH(OH)CCl3); 19F (377 MHz, CDCl3, ppm):
31.3 (C(CH3)3); HRMS (EI) m/z: [M + Cl]ꢁ calcd for C12H15OCl4: d ꢁ117.8(s, 1F, ArF); HRMS (EI) m/z: [M + Cl]ꢁ calcd for
314.9882. Found: 314.9894.
C8H6OCl4F: 276.9162. Found: 276.9170.
2,2,2-Trichloro-1-(4-methoxyphenyl)ethan-1-ol7b 5e. Product
1-(4-Bromophenyl)-2,2,2-trichloroethan-1-ol7c 5j. Product 5j
5e was prepared by utilizing the general procedure using 4- was prepared by utilizing the general procedure using 4-bro-
methoxyphenyl boroxine (201 mg, 0.500 mmol) and was iso- mophenyl boroxine (274 mg, 0.500 mmol) and was isolated as
1
lated as a pale yellow liquid (90 mg, 0.35 mmol, 70%). 1H NMR a pale yellow liquid (138 mg, 0.45 mmol, 90%). H NMR (400
(400 MHz, CDCl3, ppm): d 7.52 (d, J ¼ 8.7 Hz, 2H, ArH), 6.90 (d, J MHz, CDCl3, ppm): d 7.49–7.56 (m, 4H, ArH), 5.18 (s, 1H,
¼ 8.7 Hz, 2H, ArH), 5.15 (d, J ¼ 2.3 Hz, 1H, CH(OH)CCl3), 3.81 (s, CH(OH)CCl3), 3.59 (s, 1H, OH); 13C NMR (100 MHz, CDCl3,
3H, OCH3), 3.35 (d, J ¼ 2.3 Hz, 1H, OH); 13C NMR (100 MHz, ppm): d 133.8 (Ar), 131.1 (Ar), 130.9 (Ar), 123.9 (Ar), 102.7 (CCl3),
CDCl3, ppm): d 160.4 (Ar), 130.4 (Ar), 127.0 (Ar), 113.2 (Ar), 103.5 83.9 (CH(OH)CCl3); HRMS (EI) m/z: [M + Cl]ꢁ calcd for C8H6-
(CCl3), 84.2 (CH(OH)CCl3), 55.3 (OCH3); HRMS (EI) m/z: [M + OBrCl4: 336.8362. Found: 336.8374.
Cl]ꢁ calcd for C9H9O2Cl4: 288.9362. Found: 288.9374.
2,2,2-Trichloro-1-(thiophen-2-yl)ethan-1-ol7b 5n. Product 5n
2,2,2-Trichloro-1-(3-methoxyphenyl)ethan-1-ol 5f. Product 5f was prepared by utilizing the general procedure using 2-thio-
was prepared by utilizing the general procedure using 3- phene boroxine (165 mg, 0.500 mmol) and was isolated as a pale
methoxyphenyl boroxine (201 mg, 0.500 mmol) and was iso- yellow liquid (47 mg, 0.20 mmol, 41%). 1H NMR (400 MHz,
1
lated as a colourless liquid (85 mg, 0.33 mmol, 66%). H NMR CDCl3, ppm): d 7.40 (dd, J1 ¼ 1.2 Hz, J2 ¼ 5.1 Hz, 1H, ArH), 7.31
(400 MHz, CDCl3, ppm): d 7.28 (dd, J1 ¼ 8.0 Hz, J2 ¼ 8.0 Hz, 1H, (m, 1H, ArH), 7.04 (dd, J1 ¼ 3.6 Hz, J2 ¼ 5.1 Hz, 1H, ArH), 5.48 (d,
ArH), 7.16–7.17 (m, 2H, ArH), 6.94 (d, J ¼ 8.0 Hz, 1H, ArH), 5.16 J ¼ 4.4 Hz, 1H, CH(OH)CCl3), 3.40 (d, J ¼ 4.4 Hz, 1H, OH); 13C
(d, J ¼ 4 Hz, 1H, CH(OH)CCl3), 3.80 (s, 3H, OCH3), 3.43 (d, J ¼ NMR (100 MHz, CDCl3, ppm): d 137.3 (Ar), 129.2 (Ar), 127.1 (Ar),
12 Hz, 1H, OH); 13C NMR (100 MHz, CDCl3, ppm): d 159.0 (Ar), 126.3 (Ar), 102.5 (CCl3), 81.6 (CH(OH)CCl3); HRMS (EI) m/z: [M +
136.4 (Ar), 128.8 (Ar), 121.8 (Ar), 115.0 (Ar), 114.9 (Ar), 103.0 Cl]ꢁ calcd for C6H5OCl4S: 264.8821. Found: 264.8833.
(CCl3), 84.4 (CH(OH)CCl3), 55.3 (OCH3); HRMS (EI) m/z: [M +
2,2,2-Trichloro-1-(thiophen-3-yl)ethan-1-ol14 5o. Product 5o
was prepared by utilizing the general procedure using 3-thiophene
boroxine (165 mg, 0.500 mmol) and was isolated as a pale yellow
Cl]ꢁ calcd for C9H9O2Cl4: 288.9362. Found: 288.9372.
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liquid (68 mg, 0.29 mmol, 59%). 1H NMR (400 MHz, CDCl3, ppm):
d 7.55 (t, J ¼ 2.4 Hz, 1H, ArH), 7.32 (m, 2H, ArH), 5.32 (d, J ¼ 4.4 Hz,
1H, CH(OH)CCl3), 3.29 (d, J ¼ 4.4 Hz, 1H, CCl3); 13C NMR (100
MHz, CDCl3, ppm): d 136.0 (Ar), 127.6 (Ar), 126.2 (Ar), 125.2 (Ar),
102.8 (CCl3), 81.3 (CH(OH)CCl3); HRMS (EI) m/z: [M + Cl]ꢁ calcd for
C6H5OCl4S: 264.8821. Found: 264.8831.
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2,2,2-Trichloro-1-(furan-3-yl)ethan-1-ol 5p. Product 5p was
prepared by utilizing the general procedure using 3-furan bor-
oxine (141 mg, 0.500 mmol) and was isolated as a pale yellow
liquid (50 mg, 0.23 mmol, 46%). 1H NMR (400 MHz, CDCl3,
ppm): d 7.66 (t, J ¼ 0.7 Hz, 1H, ArH), 7.45 (t, J ¼ 1.7 Hz, 1H, ArH),
6.66 (dd, J1 ¼ 0.7 Hz, J2 ¼ 1.7 Hz, 1H, ArH), 5.21 (d, J ¼ 4.7 Hz,
1H, CH(OH)CCl3), 3.28 (d, J ¼ 4.7 Hz, 1H, OH); 13C NMR (100
MHz, CDCl3, ppm): d 142.8 (Ar), 142.6 (Ar), 120.8 (Ar), 110.0 (Ar),
102.8 (CCl3), 79.0 (CH(OH)CCl3); HRMS (EI) m/z: [M + Cl]ꢁ calcd
for C6H5O2Cl4: 248.9049. Found: 248.9056.
1-(Benzo[b]thiophene-2-yl)-2,2,2-trichloroethan-1-ol8a
5q.
Product 5q was prepared by utilizing the general procedure
using 2-benzo[b]thiophene boroxine (240 mg, 0.500 mmol) and
was isolated as a pale yellow solid (34 mg, 0.12 mmol, 24%), mp
109–110 ꢀC(lit.8a 109–110 ꢀC). 1H NMR (400 MHz, CDCl3, ppm):
d 7.82–7.89 (m, 2H, ArH), 7.59 (s, 1H, ArH), 7.39–7.41 (m, 2H,
ArH), 5.57 (d, J ¼ 4.4 Hz, 1H, CH(OH)CCl3), 3.48 (d, J ¼ 4.4 Hz,
1H, OH); 13C NMR (100 MHz, CDCl3, ppm): d 140.1 (Ar), 138.4
(Ar), 138.0 (Ar), 126.2 (Ar), 125.2 (Ar), 124.5 (Ar), 124.1 (Ar), 122.3
(Ar), 102.1 (CCl3), 82.0 (CH(OH)CCl3); HRMS (EI) m/z: [M + Cl]ꢁ
calcd for C10H7OCl4S: 314.8977. Found: 314.8992.
1-(Benzofuran-2-yl)-2,2,2-trichloroethan-1-ol 5r. Product 5r
was prepared by utilizing the general procedure using 2-
benzofuran boroxine (207 mg, 0.500 mmol) and was isolated as
a pale yellow solid (80 mg, 0.30 mmol, 60%), mp 71–72 C. H
NMR (400 MHz, CDCl3, ppm): d 7.60 (m, 1H, ArH), 7.51 (m, 1H,
ArH), 7.24–7.36 (m, 2H, ArH), 6.98 (s, 1H, ArH), 5.35 (d, J ¼
7.2 Hz, 1H, CH(OH)CCl3), 3.59 (d, J ¼ 7.2 Hz, 1H, OH); 13C NMR
(100 MHz, CDCl3, ppm): d 154.7 (Ar), 150.7 (Ar), 127.4 (Ar), 125.3
(Ar), 123.3 (Ar), 121.6 (Ar), 111.6 (Ar), 107.9 (Ar), 100.9 (CCl3),
79.7 (CH(OH)CCl3); HRMS (EI) m/z: [M + Cl]ꢁ calcd. for
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ꢀ
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C
10H7O2Cl4: 298.9206. Found: 298.9216.
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Conflicts of interest
There are no conicts to declare.
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Acknowledgements
We thank Prof. Mino, Chiba University, for the HRMS
measurements. This work was supported in part by the
Research Institute for Science and Technology, Tokyo Denki
University Grant Number Q19E-06 and Q18E-04.
Notes and references
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