Novel Route for the Construction of Chroman Ring System Using Cross-Coupling between Benzylic and Aliphatic Alcohols in the Presence of NaHSO4/SiO2

Article abstract of DOI:10.1055/s-0034-1380863

Novel route for the construction of chromans from benzylic and aliphatic alcohols in the presence of NaHSO₄/SiO₂ has been developed. In this reaction, substituted olefins are formed from benzylic and aliphatic alcohols and then conve

Full text of DOI:10.1055/s-0034-1380863

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© Georg Thieme Verlag Stuttgart · New York
2015, 26, 1875–1879
letter
1875
T. Aoyama et al.
Letter
Synlett
Novel Route for the Construction of Chroman Ring System Using
Cross-Coupling between Benzylic and Aliphatic Alcohols in the
Presence of NaHSO4/SiO2
Tadashi Aoyama*a,b
R3
OH OH
Takuya Furukawaa
Mamiko Hayakawaa
Toshio Takidoa
R3
R2
R2
R1
O
R7
R6
R5
R7
R4
NaHSO4/SiO2
OH
R6
R5
+
Mitsuo Kodomaric
R1
R4
up to 98% yield
20 novel chromans
a Department of Materials and Applied Chemistry, College of
Science and Technology, Nihon University, Kanda Surugadai,
Chiyoda-ku, Tokyo 101-8308, Japan
aoyama.tadashi@nihon-u.ac.jp
b The Center for Creative Materials Research, Research Institute
of Science and Technology, College of Science and Technology,
Nihon University, Tokyo 101-8308, Japan
c The Institute of Natural Sciences, College of Humanities and
Science, Nihon University, Tokyo 156-8550, Japan
Received: 30.03.2015
Accepted after revision: 24.04.2015
Published online: 09.07.2015
R
OH
Ph
Ph
R = H
OH
+
Ph
DOI: 10.1055/s-0034-1380863; Art ID: st-2015-u0226-l
1
2
Abstract Novel route for the construction of chromans from benzylic
and aliphatic alcohols in the presence of NaHSO4/SiO2 has been devel-
oped. In this reaction, substituted olefins are formed from benzylic and
aliphatic alcohols and then converted to chromans through intramolec-
ular cyclization. Twenty novel chromans were synthesized by this sim-
ple procedure.
O
Ph
R = OH
OH
Scheme 1 Formation of chroman from 1 and 2
Ph
Key words chroman, tandem reaction, heterogeneous reaction, cou-
pling reaction, solid acid
The chroman is formed by intramolecular cyclization of
substituted olefin which is formed from 1a and tert-butyl
alcohol (Scheme 1). This method may be applied to the con-
struction of chroman ring system using benzylic alcohols
and aliphatic alcohols. Multisubstituted chromans, which
could not be synthesized by previous procedure, may be
synthesized from easily available alcohols by this method.
Thus our effort was directed to the development of the nov-
el route for the synthesis of chromans. Herein, we wish to
report the novel and efficient method for the multisubsti-
tuted chromans from benzylic and aliphatic alcohols. At
first, the reaction of 1a with tert-butyl alcohol (2a) was
chosen as a model reaction to optimize the reaction condi-
tions. The results are shown in Table 1. When a mixture of
1a (2 mmol), 2a (6 mmol) and NaHSO4/SiO2 (1 g, 2.1 mmol)
in 1,2-dichroloethane (DCE) was stirred at 50 °C for two
hours, the expected 3aa was obtained in 24% yield (Table 1,
entry 1). The same reaction running at 80 °C and 110 °C
gave 3aa in 50% and 24% yields, respectively (Table 1, en-
tries 2 and 3).
Recently, much attention has been paid to the develop-
ment of new methods for the synthesis of heterocyclic com-
pounds, due to their potential importance in the fields of
pharmaceutical and agricultural drugs. Chroman ring sys-
tem constitutes the basic skeleton of a variety of biological-
ly active natural compound.1–3 Traditionally chroman ring
systems were constructed by intramolecular cyclization
which involved Williamson-type etherification,[4} the con-
densation of phenolic alcohol with aliphatic alcohols,5
Friedel–Crafts-type alkylation,6 and cross-coupling of aryl
halide and aliphatic alcohols.7,8 Recent trend for the synthe-
sis of chromans are tandem methods such as: (i) annulation
of phenols with 1,3-dienes;9,10 (ii) cyclocoupling of phenols
with allylic alcohols11–14 or allylic acetates;15 (iii) copper(II)-
catalyzed C–C coupling of benzylic alcohols with ketene
dithioacetals.16 Hetero-Diels–Alder reaction was also devel-
oped.17 We have recently reported the simple method for
the synthesis of substituted olefins by cross-coupling of al-
cohols in the presence of NaHSO4/SiO2.18 In the course of
this study, we found out that chroman ring was formed
when the reaction was carried out by using o-hydroxybenz-
hydrol (1a) instead of benzhydrol.
In these reactions, it is considered that 2-methylpro-
pene which was formed from 2a vaporizes from the reac-
tion mixture. Thus, the reaction was carried out using a
© Georg Thieme Verlag Stuttgart · New York — Synlett 2015, 26, 1875–1879

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T. Aoyama et al.
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Table 1 Optimization of Reaction Conditions for the Synthesis of 3aa
and 3ab
icity, NaHSO4/SiO2 was selected for subsequent reactions.
2,2-Diphenyl chromans were synthesized from the reac-
tions of 2b with various o-hydroxybenzyl alcohols 1b–j.
The results obtained are summarized in Scheme 2. The
reactions using substituted o-hydroxybenzhydrols (1b–g)
gave the corresponding 3bb–gb in excellent yields, except
3fb. In the case of the reaction of 1f, 3fb was produced in
43% yield along with 7-hydroxy-2,2,4-triphenyl chroman
which is formed by deporting the benzyl group in 3fb.
When the reaction of 1-(o-hydroxyphenyl)ethanol (1h) was
carried out under the same conditions, the yield of 3hb de-
creased and highly polarized compounds were formed. In
order to clarify how these polarized compounds were
formed, a mixture of 1h and NaHSO4/SiO2 was stirred in
DCE at 80 °C, leading to self-polymerization of 1h to form
the similar polarized compounds. When 1-(2-hydroxy-5-
methylphenyl)ethanol (1i) and 1-(5-bromo-2-hydroxyphe-
nyl)ethanol (1j) were used instead of 1h in order to avoid
the polymerization, the desired chromans 3ib and 3jb were
obtained in excellent yields.
OH OH
O
R3
R2
R1
R2
NaHSO4/SiO2
OH
R3
Ph
R1
+
DCE
80 °C, 2 h
R2
2a–g
1a
3aa–ag
Entry
1a/2
(mmol)
2
Temp
(°C)
Acid amounta
(mmol)
Yield
(%)
1
2
2/6
2/6
2/6
2/10
2/10
2/15
2/2
2/4
2/4
2/4
2/4
2/4
2/4
2/4
2/4
2a
50
80
110b
80
80
80
80
80
80
80
80
80
80
80
80
NaHSO4/SiO2 (2.1)
NaHSO4/SiO2 (2.1)
NaHSO4/SiO2 (2.1)
NaHSO4/SiO2 (2.1)
NaHSO4/SiO2 (3.2)
NaHSO4/SiO2 (4.2)
NaHSO4/SiO2 (2.1)
NaHSO4/SiO2 (2.1)
ZnCl2/SiO2 (2.1)
PPA/SiO2
24
2a
2a
2a
2a
2a
2b
2b
2b
2b
2b
2b
2b
2b
2b
50
24
38
56
67
68
92
96
91
79
81
79
76
ND
3
4
5
6
7
8
9
OH OH
O
Ph
Ph
10c
11
12
13
14
15d
NaHSO4/SiO2
OH
Ph
R2
+
SA/SiO2 (2.1)
DCE
80 °C, 2 h
Ph
R1
Amberlyst 15
R2
2b
(4 mmol)
R1
1b–j
(2 mmol)
NaHSO4·H2O (2.1)
H2SO4 (2.1)
3bb–jb
SiO2
O
Ph
Ph
O
Ph
Ph
O
Ph
Ph
a PPA = polyphosphoric acid; SA = sulfamic acid.
b Chlorobenzene was used as solvent.
MeO
Br
c The amount of PPA used as an acid was 0.1 g.
d The amount of SiO2 used was 1.0 g.
Ph
Ph
Ph
3bb 97%
3cb 96%
3db 96%
large excess of 2a (Table 1, entries 4–6). Accordingly, an in-
crease in the amount of 2a required a large amount of NaH-
SO4/SiO2 in order to obtain 3aa in high yield. Compound 3aa
was obtained in good yield when the reaction was carried
out using 2 mmol of 1a, 15 mmol of 2a and 4.2 mmol of
NaHSO4/SiO2 (Table 1, entry 6). The reaction with 2b which
has high boiling point did not need to use 2b in excess to
obtain the corresponding 3ab, because the intermediate
1,1-diphenylethylene which is formed through the dehy-
dration of 2b does not volatilize at 80 °C and readily reacts
with 1a to give 3ab (Table 1, entry 7). When the same reac-
tion was run with two equivalents of 2b, 92% yield of 3ab
was obtained (Table 1, entry 8). Various acids were tested
for the reaction of 1a with 2b (Table 1, entries 8–15). All ac-
ids tested were effective for this reaction except for silica
gel and 3ab was obtained in good to excellent yields. The
reaction using silica gel as an acid did not proceed under
the same conditions. Compounds 1a and 2b were recovered
quantitatively (Table 1, entry 15). This procedure is widely
applicable because both Brønsted and Lewis acids can be
used as a catalyst. In view of easy preparation and low tox-
Br
MeO
O
Ph BnO
Ph
O
Ph
Ph
O
Ph
Ph
Br
Ph
Ph
Ph
3eb 83%
3fb 43%
3gb 98%
O
Ph
Ph
O
Ph
Ph
O
Ph
Ph
Br
3hb 32%
3ib 89%
3jb 95%
Scheme 2 Reaction of 2b with various benzylic alcohols
Various aliphatic alcohols 2a–g were tested for this re-
action. The reaction using 2-phenyl-2-propanol (2c) gave
3ac in 75% yield (Table 2, entry 3). On the other hand, the
reaction with tert-amyl alcohol yielded chromans 3ad in
53% yield along with 20% yield of 2-isopropyl-2-methyl-3-
phenyldihydrobenzofuran (3′ad). A plausible reaction path-
© Georg Thieme Verlag Stuttgart · New York — Synlett 2015, 26, 1875–1879

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T. Aoyama et al.
Letter
Synlett
way for the reaction of 1a and 2d is shown in Scheme 3. The
first step is the protonation of the substituted olefin which
was formed from 1a and 2d to afford two types of tert-car-
bocation. The second step is the intramolecular cyclization
of each carbocation to form 3ad and 3′ad, respectively.
these results, it is considered that the reactivity of the ole-
fin 2′′, which is slightly formed by isomerization of 2′ in the
presence of acid, against the carbocation 1′d is higher than
that of the olefin 2′. Consequently, 3′de and 3′df are formed
as major products.
OH OH
Ph
Table 2 Reaction of 1a and Various Aliphatic Alcohols
R1 = H
OH
OH OH
+
R2
3ae or 3af
O
R3
R2
R1
R2
NaHSO4/SiO2
OH
R3
1a (R1 = H)
2e (R2 = Ph)
2f (R2 = Ac)
Ph
R1
+
R1
1d (R1 = Br)
R
1 = Br
DCE
80 °C, 2 h
R2
2a–g
1a
3aa–ag
O
O
R2
+
Entry 1a/2 (mmol)
2
R1
R2
Me
R3
Me
3
Yield (%)
Br
R2
Br
1a
2
3
4
5
6
7
2/15
2/4
2/4
2/4
2/4
2/4
2/4
2a
H
3aa
3ab
3ac
3ad
3ae
3af
67
92
75
53
ND
ND
ND
Ph
Ph
3de (R2 = Ph): 17%
3df (R2 = Ac): 7%
3'de (R2 = Ph): 57%
3'df (R2 = Ac): 24%
2b
2c
2d
2e
2f
H
Ph
Ph
Ph
Me
Me
Me
H
H
Me
Me
Me
Me
Ph
Me
Ph
Ac
H
R2
path A
3de or 3df
2'
2e
or
2f
1d
+
2g
3ag
a Amount of NaHSO4 used was 4.2 mmol.
R2
2''
path B
OH
3'de or 3'df
+
Ph
O
1a
+
2d
+
path B
1'd
Br
Scheme 4 Formation of 3 and 3′
OH Ph
Ph
3ad: 53%
H+
Various combinations of benzylic and aliphatic alcohols
were applicable for the synthesis of substituted chromans.
The results obtained are summarized in Table 3. In all reac-
tions, the corresponding chromans were obtained in mod-
erate to excellent yields. For instance, the reaction of (2-hy-
droxyphenyl)thienylmethanol (1k) with 2b afforded 2,2-di-
phenyl-4-(2-thienyl)chroman (3kb) in 50% yield.
O
OH Ph
+
Ph
3'ad: 20%
OH Ph
Scheme 3 Formation of 3ad and 3′ad
In the reactions using 2e, 2f and 2g, the corresponding
chromans were not yielded. The reactions using 2e and 2f
gave the substituted olefins (2′e and 2′f) and oligomer of
1a. In these reactions, the rate of addition of the carboca-
tion arising from 1a to the olefins was slower than that of
oligomerization of 1a. In order to inhibit an oligomerization
of 1a, 1d was used instead of 1a (see Scheme 4). The reac-
tion of 1d with 2e gave the desired product 3de in 17% yield
along with 2-benzyl-2-methyl-4-phenylchroman (3′de) in
57% yield. When the reaction of 1d with 2f was carried out
under the same conditions, only 7% yield of the desired
product 3df was obtained along with 24% yield of 3′df. Un-
expected products 3′de and 3′df were formed by the reac-
tion of benzhydrylic cation (1′d) with each olefins 2′ or 2′′.
The olefin 2′ is thermodynamically more stable than 2′′, but
both 3′de and 3′df were formed as major products. From
In conclusion, we developed a simple and efficient
method for the synthesis of multisubstituted chromans
from a combination of benzylic and aliphatic alcohols.19
This reaction proceeds via the formation of the substituted
olefin and an intramolecular cyclization of it. Both steps
easily proceeded in the presence of NaHSO4/SiO2. Twenty
novel multisubstituted chromans were synthesized in mod-
erate to excellent yields by this synthetic method. The syn-
thesis of further analogues is now in progress.
Acknowledgment
This work was financially supported by the Nihon University College
of Science and Technology Grants-in-Aid for Fundamental Science Re-
search.
© Georg Thieme Verlag Stuttgart · New York — Synlett 2015, 26, 1875–1879

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Table 3 Reaction of Various Combinations of Benzylic and Aliphatic alcohols
R2
OH OH
R2
NaHSO4/SiO2
(2.1 mmol)
O
R5
R4
R3
OH
+
R4
R5
DCE
80 °C, 2h
R1
R1
R1
1
2
3
R3
Entry
1/2 (mmol)
1
R2
R3
Ph
2
R4
Me
R5
Ph
3
Yield (%)
1
2a
3
2/4
1a
1b
1b
1c
1c
1d
1d
1g
1g
1k
H
H
2c
2a
2c
2a
2c
2a
2c
2a
2c
2b
3ac
3ba
3bc
3ca
3cc
3da
3dc
3ga
3gc
3kb
75
73
84
60
82
88
80
75
72
50
2/15
2/4
Me
Me
OMe
OMe
Br
H
H
H
H
H
H
Br
Br
H
Ph
Me
Me
Me
Me
Me
Me
Me
Me
Ph
Me
Ph
Ph
4a
5
2/15
2/4
Ph
Me
Ph
Ph
6a
7
2/15
2/4
Ph
Me
Ph
Br
Ph
8a
9
2/15
2/4
Br
Ph
Me
Ph
Br
Ph
10
2/4
H
2-thienyl
Ph
a Amount of NaHSO4 used was 4.2 mmol.
Supporting Information
(16) Liang, D.; Wang, M.; Bekturhum, B.; Xiong, B.; Liu, Q. Adv. Synth.
Catal. 2010, 352, 1593.
(17) Taylor, R. R. R.; Batey, R. A. J. Org. Chem. 2013, 78, 1404.
(18) Aoyama, T.; Koda, S.; Takeyoshi, Y.; Ito, T.; Takido, T.; Kodomari,
M. Chem. Commun. 2013, 49, 6605.
Supporting information for this article is available online at
http://dx.doi.org/10.1055/s-0034-1380863.
S
u
p
p
ortiInfogrmoaitn
S
u
p
p
ortioInfgrmoaitn
(19) Melting points were determined on Büchi Melting Point B-540
apparatus. NMR spectra were recorded on a JEOL ECX 400 spec-
trometer. Tetramethylsilane (δ = 0 ppm) was used as an internal
standard for 1H NMR and CDCl3 (δ = 77.0 ppm) for 13C NMR
measurements. Mass analyses were performed on an Agilent
G1969 LC/MDS TOF instrument. IR spectra were recorded on a
JASCO FT/IR-6100 equipment. Elemental analyses were per-
formed on a J Science Lab. microcorder JM-10 instrument.
Preparation of NaHSO4/SiO2: SiO2 [Wakogel C-200 (Wako
Pure Chemical Ind. Ltd.), 10 g] was added to a solution of
NaHSO4·H2O (30 mmol, 4.14 g) in distilled H2O, and the mixture
was stirred at r.t. for 0.5 h. The H2O was removed by rotary
evaporator under reduced pressure, and the resulting reagent
was dried in vacuo (10 mmHg) at 120 °C for 5 h.
References and Notes
(1) Sankaran, M. S.; Prasad, M. R. N. Contraception 1974, 9, 279.
(2) Deng, J.-Z.; Starck, S. R.; Li, S.; Hecht, S. M. J. Nat. Prod. 2005, 68,
1625.
(3) Maloney, D. J.; Deng, J.-Z.; Starck, S. R.; Gao, Z.; Hecht, S. M.
J. Am. Chem. Soc. 2005, 127, 4140.
(4) Inoue, S.; Ikeda, H.; Sato, S.; Horie, K.; Ota, T.; Miyamoto, O.;
Sato, K. J. Org. Chem. 1987, 52, 5495.
(5) Cohen, N.; Lopresti, R. J.; Neukom, C. J. Org. Chem. 1981, 46,
2445.
(6) Parham, W. E.; Jones, L. D.; Sayed, Y. A. J. Org. Chem. 1976, 41,
1184.
(7) Palucki, M.; Wolfe, J. P.; Buchwald, S. L. J. Am. Chem. Soc. 1996,
118, 10333.
(8) Suchand, B.; Krishna, J.; Mritunjoy, K.; Satyanarayana, G. RCS
Adv. 2014, 4, 13941.
(9) Adrio, L. A.; Hii, K. K. (M.). Chem. Commun. 2008, 2325.
(10) Youn, S. W.; Eom, J. I. J. Org. Chem. 2006, 71, 6705.
(11) Naik, M. M.; Kamat, D. P.; Tilve, S. G.; Kamat, V. P. Tetrahedron
2014, 70, 5221.
Typical Procedure: A mixture of 1 (2 mmol), 2 (4 or 15 mmol)
and NaHSO4/SiO2 (2.1 mmol/g, 1.0 or 2.0 g) in DCE (10 mL) was
stirred at 80 °C for 2 h, and then the used supported reagent
was removed by filtration. The filtrate was evaporated to leave
crude product, which was purified by column chromatography
(hexane–CHCl3) to obtain substituted chromans 3.
6-Methyl-2,2,4-triphenylchroman (3bb): yield: 0.7315
g
(97%); white solid; mp 173–175 °C (MeOH). 1H NMR (400 MHz,
CDCl3): δ = 2.08 (s, 3 H), 2.60 (dd, J = 13.9, 12.6 Hz, 1 H), 3.06
(dd, J = 13.9, 5.4 Hz, 1 H), 3.86 (dd, J = 12.6, 5.4 Hz, 1 H), 6.42 (s,
1 H), 6.95 (dd, J = 8.2, 2.3 Hz, 1 H), 7.03 (d, J = 8.2 Hz, 1 H), 7.18–
7.34 (m, 11 H), 7.47–7.52 (m, 4 H). 13C NMR (100 MHz, CDCl3):
δ = 20.5, 40.1, 42.2, 81.6, 117.0, 124.8, 125.6, 126.3, 126.7,
127.0, 127.3, 128.2, 128.5, 128.6 (overlap), 128.8, 129.5, 129.7,
143.5, 144.5, 145.8, 152.0. IR (neat): 3057, 2920, 1591, 1487,
1445, 1283, 1231, 1110, 1061, 1007, 920, 846, 805, 784, 748,
(12) Coutant, E.; Young, P. C.; Barker, G.; Lee, A. Beilstein J. Org. Chem.
2013, 9, 1797.
(13) Yamamoto, Y.; Itonaga, K. Org. Lett. 2009, 11, 717.
(14) Ishino, Y.; Mihara, M.; Hayakawa, N.; Miyata, T.; Kaneko, Y.;
Miyata, T. Synth. Commun. 2001, 31, 439.
(15) Vece, V.; Ricci, J.; Poulain-Martini, S.; Nava, P.; Craissan, Y.;
Humbel, S.; Duñach, E. Eur. J. Org. Chem. 2010, 6239.
© Georg Thieme Verlag Stuttgart · New York — Synlett 2015, 26, 1875–1879

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732, 695, 628, 585, 539 cm–1. HRMS (TOF–CI): m/z [M + H]+
calcd for C28H25O: 377.1905; found: 377.1896. Anal. Calcd for
7.16–7.35 (m, 11 H) 7.47–7.52 (m, 4 H). 13C NMR (100 MHz,
CDCl3): δ = 39.5, 42.2, 55.3, 82.1, 101.7, 107.4, 117.6, 125.7,
126.3, 126.7, 127.1, 127.3, 128.2, 128.6 (overlap), 128.7, 130.2,
143.4, 144.6, 145.6, 155.0, 159.3. IR (neat): 2969, 1611, 1580,
1495, 1444, 1410, 1318, 1258, 1195, 1158, 1101, 1058, 1033,
C28H24O: C, 89.33; H, 6.43. Found: C, 89.58; H, 6.15.
6-Methoxy-2,2,4-triphenylchroman (3cb): yield: 0.7534
g
(96%); white solid; mp 106–108 °C (MeOH). 1H NMR (400 MHz,
CDCl3): δ = 2.59 (dd, J = 13.9, 12.6 Hz, 1 H), 3.08 (dd, J = 13.9, 5.4
Hz, 1 H), 3.52 (s, 3 H), 3.87 (dd, J = 12.6, 5.4 Hz, 1 H), 6.15 (d, J =
3.0 Hz, 1 H), 6.73 (dd, J = 8.9, 3.0 Hz, 1 H), 7.07 (d, J = 8.9 Hz, 1
H), 7.17–7.33 (m, 11 H), 7.47–7.52 (m, 4 H). 13C NMR (100 MHz,
CDCl3): δ = 40.4, 42.0, 55.4, 81.5, 113.8, 114.1, 117.8, 125.6,
125.8, 126.3, 126.8, 127.0, 127.2, 128.2, 128.6, 128.6, 128.8,
143.4, 144.2, 145.8, 148.2, 153.2. IR (neat): 3055, 2827, 1604,
1489, 1451, 1417, 1252, 1211, 1155, 1100, 1036, 950, 912, 859,
809, 755, 698, 588, 512 cm–1. HRMS (TOF–CI): m/z [M+] calcd for
1018, 966, 910, 835, 772, 734, 696, 627, 594, 556, 518 cm–1
.
HRMS (TOF–CI): m/z [M + H]+ calcd for C28H25O2: 393.1854;
found: 393.1851. Anal. Calcd for C28H24O2: C, 85.68; H, 6.16.
Found: C, 85.88; H, 6.02.
6,8-Dibromo-2,2,4-triphenylchroman (3gb): yield: 1.0283 g
1
(98%); white solid; mp 166–167 °C (EtOH). H NMR (400 MHz,
CDCl3): δ = 2.55 (dd, J = 14.1, 12.6 Hz, 1 H), 3.21 (dd, J = 14.1, 5.5
Hz, 1 H), 3.93 (dd, J = 14.1, 12.6 Hz, 1 H), 6.69 (d, J = 2.4 Hz, 1 H),
7.13–7.35 (m, 11 H), 7.48–7.60 (m, 5 H). 13C NMR (100 MHz,
CDCl3): δ = 40.3, 41.2, 83.4, 112.5, 112.6, 125.0, 125.6, 127.3,
127.4, 127.5, 128.4, 128.6, 128.9, 129.0 (overlap), 131.4, 133.6,
142.7, 142.9, 144.9, 149.8. IR (neat): 3074, 3032, 1490, 1440,
C28H24O2: 392.1776; found: 392.1777. Anal. Calcd for C28H24O2:
C, 85.68; H, 6.16. Found: C, 85.77; H, 6.16.
6-Bromo-2,2,4-triphenylchroman (3db): yield: 0.8474
g
(96%); white solid; mp 158–160 °C (MeOH). 1H NMR (400 MHz,
CDCl3): δ = 2.59 (dd, J = 14.0, 12.7 Hz, 1 H), 3.08 (dd, J = 14.0, 5.5
Hz, 1 H), 3.85 (dd, J = 12.7, 5.5 Hz, 1 H), 6.74 (d, J = 2.3 Hz, 1 H),
7.02 (d, J = 8.7 Hz, 1 H), 7.15–7.35 (m, 12 H), 7.45–7.48 (m, 4 H).
13C NMR (100 MHz, CDCl3): δ = 40.1, 41.6, 82.2, 112.7, 119.1,
125.6, 126.1, 127.1, 127.3, 127.5, 127.6, 128.3, 128.7, 128.7,
128.8, 130.8, 132.1, 143.0, 143.4, 145.2, 153.3. IR (neat): 3056,
1592, 1469, 1396, 1240, 1203, 1110, 1062, 1007, 915, 877, 842,
811, 777, 754, 694, 585, 542 cm–1. HRMS (TOF–CI): m/z [M+]
calcd for C27H21BrO: 440.0775; found: 440.0776. Anal. Calcd for
1248, 1153, 1114, 1058, 1015, 941, 862, 771, 741, 695, 582 cm–1
.
HRMS (TOF–CI): m/z [M+] calcd for C27H20Br2O: 517.9880;
found: 517.9872. Anal. Calcd for C27H20Br2O: C, 62.33; H, 3.87.
Found: C, 62.45; H, 3.77.
6-Bromo-4-methyl-2,2-diphenylchroman (3jb): yield: 0.7257
g (95%); white solid; mp 146–147 °C. 1H NMR (400 MHz,
CDCl3): δ = 1.32 (d, J = 6.8 Hz, 3 H), 2.15 (dd, J = 13.7, 12.2 Hz, 1
H), 2.67–2.77 (m, 1 H), 2.87 (dd, J = 13.7, 5.3 Hz, 1 H), 6.93–6.96
(m, 1 H), 7.18–7.33 (m, 8 H), 7.39–7.45 (m, 4 H). 13C NMR (100
MHz, CDCl3): δ = 19.8, 26.7, 41.0, 82.0, 112.7, 119.0, 125.7,
126.3, 127.1, 127.4, 128.2, 128.5, 129.1, 129.8, 130.3, 143.2,
145.6, 152.7. IR (neat): 3058, 2871, 1572, 1473, 1397, 1321,
1218, 1180, 1122, 1094, 1056, 982, 899, 824, 761, 727, 696, 670,
603, 512 cm–1. HRMS (TOF–CI): m/z [M+] calcd for C22H19BrO:
378.0619; found: 378.0620. Anal. Calcd for C22H19BrO: C, 69.67;
H, 5.05. Found: C, 69.65; H, 5.07.
C27H21BrO: C, 73.48; H, 4.80. Found: C, 73.68; H, 4.71.
7-Methoxy-2,2,4-triphenylchroman (3eb): yield: 0.6579
g
(83%); white solid; mp 148–149 °C (MeOH). 1H NMR (400 MHz,
CDCl3): δ = 2.59 (dd, J = 13.8, 12.6 Hz, 1 H), 3.07 (dd, J = 13.8, 5.4
Hz, 1 H), 3.78 (s, 3 H), 3.88 (dd, J = 12.6, 5.4 Hz, 1 H), 6.33 (dd, J =
8.6, 2.6 Hz, 1 H), 6.51 (d, J = 8.6 Hz, 1 H), 6.70 (d, J = 2.6 Hz, 1 H),
© Georg Thieme Verlag Stuttgart · New York — Synlett 2015, 26, 1875–1879