Oxidative arylation of isochroman

Article abstract of DOI:10.1021/jo2021373

We report the use of a previously intractable nucleophile, anisole, in an oxidative "cross-dehydrogenative coupling" (CDC) reaction with the cyclic ether isochroman, as well as derivatives of both components. Metal catalysis was required for the reaction

Full text of DOI:10.1021/jo2021373

Article
pubs.acs.org/joc
Oxidative Arylation of Isochroman
Soo J. Park,† Jason R. Price,‡ and Matthew H. Todd*,†
†School of Chemistry and ‡Crystal Structure Analysis Facility, School of Chemistry, The University of Sydney, NSW 2006, Australia
S
* Supporting Information
ABSTRACT: We report the use of a previously intractable nucleophile, anisole,
in an oxidative “cross-dehydrogenative coupling” (CDC) reaction with the cyclic
ether isochroman, as well as derivatives of both components. Metal catalysis was
required for the reaction to proceed efficiently, and the reaction is highly sensitive
to modification of either coupling partner but is able to produce a range of novel
compounds via what is a synthetic alternative to the traditional oxa-Pictet−Spengler
reaction.
Recent examples of aromatic rings acting as nucleophiles in a
CDC reaction adjacent to a nitrogen atom required either the
addition of a metal triflate8 or the use of π-excessive heteroarenes.9
Shi’s recently reported oxidative arylation reaction employed
diarylmethanes as the proelectrophile, activated to reaction
by a combination of DDQ and iron catalysis; anisole only gave
regiocontrol in the arylation with the use of an ortho blocking
group.10
INTRODUCTION
It has been long known that oxidation of a benzylic ether can
lead to cleavage of that ether (Scheme 1A); this is the basis for
■
Scheme 1. (A) Oxidative Cleavage of Benzylic Ethers, or
Trapping of the Intermediate Oxonium Ion with a
Nucleophile; (B) Method Reported Here
We undertook to find conditions for the still-unreported coupl-
ing between anisole and isochroman and to investigate the syn-
thesis of various substituted derivatives (Scheme 1B). There are
several reasons for investigating this chemistry. First, while
many CDC methods are now known, there are very few studies
of their mechanisms. We are interested in elucidating such
mechanisms and so have a particular interest in any challenging
or unsuccessful examples and what these tell us about the scope
of CDC processes; the apparent refusal of anisole to participate
was from this standpoint of some interest. Compared with our
recent report of a CDC between a benzylic amine and nitro-
methane, which proceeds quantitatively at room temperature in
a few minutes,11 one cannot but ask why coupling between anisole
and isochroman should be such a challenge.
1-Arylated isochromans are normally formed via the oxa-
Pictet−Spengler reaction,12 typically requiring electron-donating
groups attached to the phenethylalcohol moiety. A CDC process
would offer an attractive alternative disconnection for a one-step
synthesis of such compounds that does not require the de novo
synthesis of the oxygen-containing ring. Apart from the example
mentioned above,7 this is an approach that has only previously
been achieved using attack of reactive nucleophiles (e.g., Grignard
or organozinc reagents, enolates) on isochromans that were
previously oxidized at the 1-position.13 The resulting structures
(3), which are found in some natural foodstuffs such as olive
oil,14 have demonstrated anti-inflammatory activity via inhibition
of cyclooxygenase-215 and have commercial significance as anti-
oxidants (Scheme 1B inset).16
the use of the p-methoxybenzyl (PMP) protecting group (and
analogues).1 Treatment of such ether-based protecting groups
with the oxidant DDQ (2,3-dichloro-5,6-dicyanobenzoquinone)
in common solvents such as dichloromethane results in efficient
cleavage, usually in a few minutes at room temperature.
The chemistry can be controlled to give carbon−heteroatom2
and carbon−carbon3 bond formation in what Li has termed “cross-
dehydrogenative coupling” (CDC),4 often resulting in convenient
one-pot reaction protocols.
The majority of such CDCs involve oxidative couplings next
to nitrogen atoms, with few examples of coupling next to oxygen5
or sulfur.6 An attempt to perform a CDC reaction between the
cyclic ether isochroman and anisole catalyzed by iron salts and
using a hydroperoxide oxidant failed to give any product, and
instead highly electron-rich aromatic groups were required.7
Received: October 15, 2011
Published: December 5, 2011
© 2011 American Chemical Society
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Article
temperatures gave reduced yields (entries 25 and 26). The
product yield was decreased using a decreased reaction time
(entries 27 and 28) but not increased with an extended reaction
time (entry 29). Collectively the optimum conditions were
found to be a reagent ratio of 1:6:1.1:0.1 (isochroman/anisole/
DDQ/catalyst) without solvent in a sealed tube at 100 °C for
36 h, giving the product 3a in 76% yield.
RESULTS AND DISCUSSION
■
A DDQ-mediated C−C bond formation between isochroman
and anisole was successful without solvent, yielding the desired
product 3a in a low yield (Table 1, entry 1). Addition of catalytic
Table 1. Optimization of the Arylation
We next explored variation in anisole substitution (Table 2).
The coupling reaction was insensitive to single methyl substitution
Table 2. Coupling between Isochroman and Anisole
Derivatives
a
entry
catalyst
FeCl2
equiv 1a/2a/DDQ/cat.
yield 3a [%]
1
1/6/1/0
27
50
33
56
49
0
2
1/6/1/0.1
1/6/1/0.1
1/6/1/0.1
1/6/1/0.1
1/6/1/0.1
1/6/1/0.1
1/6/1/0.1
1/6/1/0.1
1/6/1/0.05
1/6/1/0.02
1/6/1/0.2
1/6/1/0.4
1/3/1/0.1
1/2/1/0.1
1/1/1/0.1
1/6/1.1/0.1
3
Fe(OAc)2
PdCl2
ZnCl2
NiCl2
4
5
6
7
Cu(OTf)2
CuBr2
CuCl2
CuCl2
CuCl2
CuCl2
CuCl2
CuCl2
CuCl2
CuCl2
CuCl2
CuCl2
CuCl2
CuCl2
CuCl2
CuCl2
CuCl2
CuCl2
CuCl2
CuCl2
CuCl2
CuCl2
18
71
71
63
55
64
60
70
59
43
75
72
76
71
75
65
59
0
8
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
b
1/6/1/0.1
b
1/6/1.1/0.1
1/6/1.3/0.1
b
1/6/1.3/0.1
1/6/1.5/0.1
1/6/2/0.1
c
1/6/0/0.1
d
1/6/1.1/0.1
0
e
1/6/1.1/0.1
12
17
65
f
1/6/1.1/0.1
g
1/6/1.1/0.1
h
CuCl2
1/6/1.1/0.1
73
a
b
c
d
e
f
Isolated yield. Sealed tube. Open to the air. At rt. At 50 °C. 12 h
g
h
reaction time. 24 h reaction time. 48 h reaction time.
iron(II) chloride gave a 50% yield (entry 2); various metal salts
were screened, and some afforded the product in poor to fair
yields (entries 3−7), but copper halides were found to be the
best catalysts (entries 8 and 9). Interestingly, higher or lower
catalyst loadings did not improve the yield (entries 10−13).
Lowering the amount of anisole relative to other reagents
decreased the product yield; it was found that at least 3 equiv of
anisole was required to yield a reasonable amount of the prod-
uct (entries 14−6), but larger amounts (6 equiv) were found to
be preferable for the reaction to be well mixed and easier to
handle. A slight increase in the amount of DDQ from 1 to
1.1 equiv improved the yield (entry 17), and the use of a sealed
tube was found to be beneficial (entries 18 and 19). Further
increases in the amount of DDQ did not give improved yields
(entries 20−23). Use of atmospheric oxygen as oxidant did
not afford the desired product (entry 24). Lower reaction
of the anisole (entries 2 and 3). 2-Bromoanisole afforded the
desired product in greatly reduced yield (entry 4), which was
surprising given the similar electronic effect of bromine and
methyl on an aromatic ring. Several other products (<10%
isochroman and a mixture of ring-opened products) were
formed with the main byproduct being the overoxidized prod-
uct isochroman-1-one in 25% yield. Several naphthyl-based nucle-
ophiles gave good yields of novel ring systems 3e−g, with the
structures of two of them being proven by X-ray crystallography
(3e and 3g, Supporting Information). The successful formation
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of product 3g is in stark contrast to the failure of the reaction to
give product 3d, where the bromine atom is attached to the
same ring that participates in the bond-forming reaction. When
the more electron-rich 3-methoxyanisole is used as a nucleo-
phile, none of the expected product is formed. Isochroman is
consumed, but a mixture is generated that includes a nearly
quantitative yield of isochroman-1-one (ca. 50% by mass, but
production requires 2 equiv of DDQ).
substituent would be on opposite faces of the final molecule. A
strongly electron-withdrawing group in the 6-position (entry 4)
led to a high yield of product, while a strongly electron-donating
substituent (entry 5) gave no product. The latter reaction
yielded ring-opened side products. The marginally electron-
donating substituent (m-Br, entry 6) also gave a low yield of
product, indicating a high level of sensitivity to the electronics
of the isochroman ring, presumably because electron-donating
substituents reduce the reactivity of the presumed intermediate
oxonium ion. The effect of an extra substituent at the site of
reaction was examined using 1-methylisochroman, providing
only a small quantity of unidentified oxidation byproducts and
43% recovery of starting material (entry 7). This starting
material has been found to be unreactive in a related reaction.5c
To the best of our knowledge there are still no examples of the
formation of carbon−carbon bonds at the 1-position of 1-alkyl
substituted isochroman (with the exception of the use of stabilizing
groups in the 1-position employed in the generation of anions
through deprotonation, which then react with electrophiles).17
Experiments to elucidate the mechanism of this reaction are
ongoing. It is likely that the reaction involves the rapid initial
production of an oxonium ion; oxidative coupling between
isochroman and O-based nucleophiles have been reported to
proceed at room temperature.2b To test this, the parent reac-
tion described above was performed in the absence of copper at
room temperature and in the presence of 1 equiv of ethanol.
Product arising from attachment of ethanol (1-ethoxyisochro-
man) was isolated in 63% yield. Repeating the reaction of
entry 1 in Table 2 in the presence of 1 equiv of ethanol gave
1-ethoxyisochroman in 65% yield, with no formation of product
3a. These results (coupled with those in Table 1) suggest not
only that the formation of the oxonium ion is rapid under
ambient conditions but also that heating and copper catalysis
are required for the anisole to become an effective nucleophile.
It is tempting to suggest simple nucleophilic attack by the arene
on the oxonium ion. According to the Mayr nucleophilicity/
electrophilicity tables18 anisole and oxonium ions should
spontaneously react. That the reactive partners in the present
reaction do not react together unaided implies a more complex
mechanism. Indeed, if the mechanism were a straightforward
combination of nucleophile and electrophile, it would be
expected that the reaction would be easier with methoxyanisole
as nucleophile, yet when this reagent was used, no product was
obtained. These observations suggest the copper salt employed
is not merely engaged in counterion metathesis with the anion
associated with the oxonium ion, though at present this pos-
sibility cannot be excluded. The copper may be involved in a
redox process (as was recently suggested by Klussman in a
related reaction19), a possibility supported by the lack of any re-
action when Ni(II) was employed. Standard reduction potentials
can explain the lack of reactivity of Ni(II) (−0.23 V) yet do not
explain the formation of product in the case of Zn(II) (−0.76 V);
Zn(I) complexes are, however, known, while Ni(I) complexes are
not.20 If this redox process is not the oxidation of isochroman, the
copper may be participating in an unusual mechanistic cycle that
couples the anisole with the oxonium ion via Minisci chemistry
involving attachment of a radical to an activated heterocycle
(Scheme 2);21 this possibility was recently suggested by Shirakawa
and Hayashi for a related coupling.8 Such a mechanism would
require the conversion of an aryl C−H bond into a C−Cu bond
without adjacent directing groups; such transformations have been
proposed in Cu-catalyzed cross-coupling reactions,22 and related
structures have been crystallographically proven as intermediates
We next turned to structural variation in the isochroman
(Table 3). Reactions employing isochromans substituted with
Table 3. Coupling between Anisole and Various
Isochromans
methyl groups in the 4-, 5-, and 6- and 8-positions gave con-
siderable variation in product yields (entries 1−3). In the case
of the inseparable mixture of 6- and 8-methylisochroman (1:3
ratio, entry 2) the minor isomer did not generate product,
whereas the 8-methyl isomer did. The methyl group in the 6-
isomer is distant from the site of reaction but presumably exerts
a sufficiently strong electronic influence. Reaction of racemic
4-methylisochroman (entry 3) gave the product 3k as a 1:1
mixture of diastereomers; this implies either that the addition of
anisole to the intermediate oxonium ion is reversible or more
likely that there is no facial selectivity in the addition. The latter
possibility suggests there is no π−π interaction between anisole
and oxonium ion immediately prior to C−C bond formation,
since such an association would likely result in a majority of
anti product ((R,R) or (S,S)), where aromatic ring and methyl
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CDC protocol is operationally simple and requires no solvent,
merely an excess of one reagent that may be recovered. The
reaction exemplifies the advantage of CDC processes more
generally, in that no resources need to be consumed in the
generation of isolated nucleophiles and electrophiles.
Scheme 2. Tentative Mechanism for the Cu-Catalyzed
Oxidative Coupling of Isochroman with Anisole (X− =
Counterion Such as DDQH− or Cl−)
EXPERIMENTAL SECTION
■
General Information. 1H NMR chemical shifts are reported in
parts per million (δ) referenced to an internal TMS signal (peak at
0.00 ppm), whereas 13C NMR chemical shifts are reported with
reference to TMS using the carbon signals of the deuterated solvent
(CDCl3: 77.16 ppm). J coupling constant values are reported in Hertz.
Ionization of mass spectra samples was carried out using atmospheric
pressure chemical ionization (APCI). Flash column chromatography
was performed over silica gel 0.040−0.060 mm. Thin layer
chromatography (TLC) was performed using silica gel precoated
aluminum sheets (0.2 mm thickness) and visualized with ultraviolet
light at 254 nm. All reagents were purchased from commercial vendors
and used without further purification.
General Procedures for the Arylation of Isochromans. To a
sealed tube were added 1 (1.00 mmol unless otherwise stated,
1 equiv), DDQ (1.1 equiv), copper(II) chloride (0.1 equiv), and 2
(6 equiv). The reaction mixture was stirred at 100 °C for 36 h. The
mixture was allowed to cool to rt. Silica (0.80 g) was added to the
reaction mixture, and the resulting powder was directly applied to the
top of a flash column (typically eluting with hexane/ethyl acetate).
1-(4-Methoxyphenyl)isochroman (3a). Obtained on 1.0 mmol
scale and purified by flash column chromatography (hexane/ethyl
acetate = 20:1) and then recrystallized from hexane and ethyl acetate
to give 1-(4-methoxyphenyl)isochroman 3a as white needles (182 mg,
76% yield): mp 75−76 °C (lit.13a 75−77 °C); 1H NMR (CDCl3,
300 MHz) δ 2.80 (1 H, dt, J = 16.5, 3.7, H4), 3.13 (1 H, ddd, J = 16.2,
9.3, 5.7, H4), 3.80 (3 H, s, CH3), 3.92 (1 H, ddd, J = 11.3, 9.3, 4.0, H3),
4.17 (1 H, ddd, J = 11.4, 5.4, 4.1, H3), 5.70 (1 H, s, H1), 6.76 (1 H, d,
J = 7.7, Har), 6.87 (2 H, d, J = 8.7, Har), 7.05−7.10 (1 H, m, Har),
7.16−7.17 (2 H, m, Har), 7.22 (2 H, d, J = 8.6, Har); 13C NMR
(CDCl3, 75 MHz) δ 29.0, 55.4, 63.9, 79.3, 113.9, 126.0, 126.7, 127.1,
128.8, 130.3, 134.1, 134.7, 137.8, 159.6; IR νmax/cm−1 2839, 1611,
1512, 1456, 1247, 1175, 1090, 1034. 828, 747; LRMS m/z (%)
(APCI) 239.0 [M − H]+ (100). Anal. Calcd for C16H16O2: C, 79.97;
H, 6.71. Found: C, 79.82; H, 6.93.
in reactions involving aromatic rings contained within azamacro-
cycles.23 Collapse of such an intermediate to an aryl radical would
be the step facilitated by a redox-active metal ion. Coupling
with the oxonium ion (the equivalent of Minisci’s protonated
heterocycle) would give an intermediate radical cation that
would complete the catalytic cycle by oxidizing the copper
center. Proof of this mechanism is our current focus; it should
be noted that other copper oxidation states, including Cu(III),
could be valid intermediates in such a cycle. An alternative
possibility to this mechanism is initial electron transfer from
anisole to Cu(II) to generate Cu(I) followed by a Cu(I)
mediated coupling of the two cations, as suggested by a referee.
We cannot at this stage rule out this mechanism; it should
be noted that both mechanisms require redox cycling of the
metal ion. We have isolated a solid from the reaction between
isochroman and DDQ. It is likely that this solid contains the
intermediate oxonium ion or a derivative. While full character-
ization of this solid is ongoing, we have shown it is capable of
producing product 3a when the solid is mixed with anisole and
copper but no further oxidant, and this reaction fails to produce
product when 1 equiv of TEMPO is included, strongly suggest-
ing that the final carbon−carbon bond-forming event is radical-
mediated, as shown in the proposed mechanism. One observa-
tion that remains unexplained is why no product was ever observed
arising from ortho-attack of the anisole, nor any product from
anisole’s meta-position, which might be possible if the free
radical coupling in Scheme 2 is correct. The mechanism of the
reaction is in any case not straightforward because DDQ will
oxidize anisole before isochroman, meaning oxidized anisole is
probably the species responsible for the oxidation of isochro-
man. The outcome of this one-pot process probably arises from
a delicate balance of kinetics and thermodynamics.
1-(3-Methyl-4-methoxyphenyl)isochroman (3b). Obtained on
1.0 mmol scale and purified by flash column chromatography to give
191 mg of 1-(3-methyl-4-methoxyphenyl)isochroman as a colorless oil
1
(75% yield): H NMR (400 MHz, CDCl3) δ 2.18 (3 H, s, CCH3),
2.78 (1 H, dt, J = 16.3, 3.6, H4), 3.13 (1 H, ddd, J = 16.3, 9.2, 5.6, H4),
3.80 (3 H, s, OCH3), 3.90 (1 H, td, J = 11.3, 3.9, H3), 4.18 (1 H,
ddd, J = 11.3, 5.5, 3.9, H3), 5.66 (1 H, s, H1), 6.77 (2 H, d, J = 7.9,
Har), 7.05−7.09 (3 H, m, Har), 7.15−7.16 (2H, m, Har); 13C NMR
(CDCl3, 101 MHz) δ 16.4, 29.0, 55.4, 63.9, 79.5, 109.6, 126.0, 126.6,
126.8, 127.1, 127.6, 128.7, 131.2, 134.0, 134.1, 137.9, 157.7; IR
νmax/cm−1 2924, 1603, 1576, 1500, 1450, 1290, 1247, 812; LRMS m/z
(%) (APCI) 254.1 [M]+ (50), 223.1 [M − OCH3]+ (100); HRMS
+
calcd for C17H18O2 (M)+: 254.13069, found 254.13062.
1-(2-Methyl-4-methoxyphenyl)isochroman (3c). Obtained on
1.0 mmol scale and purified by flash column chromatography to
give 174 mg of 1-(2-methyl-4-methoxyphenyl)isochroman as a light
1
yellow oil (68% yield): H NMR (400 MHz, CDCl3) δ 2.32 (3 H, s,
CCH3), 2.81 (1 H, dt, J = 16.4, 3.8, H4), 3.12 (1 H, ddd, J =16.4, 9.3,
5.6, H4), 3.78 (3 H, s, OCH3), 3.91 (1 H, ddd, J = 11.3, 9.5, 4.0, H3),
4.18 (1 H, ddd, J = 11.3, 5.3, 4.1, H3), 5.87 (1 H, s, H1), 6.66 (1 H, dd,
J = 8.4, 2.7, Har), 6.71 (1 H, d, J = 7.7, Har), 6.74 (1 H, d, J = 2.6, Har),
7.00 (1 H, d, J = 8.4, Har), 7.03−7.09 (1 H, m, Har), 7.13−7.18 (2 H,
m, Har); 13C NMR (CDCl3, 101 MHz) δ 19.7, 28.9, 55.3, 64.0, 77.4,
110.7, 116.6, 126.1, 126.5, 126.5, 128.7, 131.3, 132.5, 134.1, 138.0,
139.0, 159.3; IR νmax/cm−1 2927, 1608, 1579, 1503, 1452, 1293, 1247,
812; LRMS m/z (%) (APCI) 254.8 [M]+ (100); HRMS calcd for
CONCLUSION
■
We have reported the first oxidative coupling between
isochroman and anisole. This represents an alternative to the
more traditional oxa-Pictet−Spengler reaction to such com-
pounds. The chemistry has several methodological advantages:
(i) copper(II) is an inexpensive metal ion exhibiting low
toxicity, (ii) DDQ is an oxidant that is simple to handle under
ambient conditions and may be recycled,24 and (iii) the one-pot
+
C17H18O2 (M)+: 254.13069, found 254.13066.
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1-(3-Bromo-4-methoxyphenyl)isochroman (3d). Obtained on
1.0 mmol scale and purified by flash column chromatography to give
19 mg of 1-(3-bromo-4-methoxyphenyl)isochroman as a light yellow
1-(4-Methoxyphenyl)-5-methylisochroman (3i). Obtained on
1.0 mmol scale and purified by flash column chromatography to
give a clear oil, which was crystallized from hexane and ethyl acetate to
give 190 mg of 1-(4-methoxyphenyl)-5-methylisochroman as white
needles (75% yield): mp 98.5−100 °C; 1H NMR (300 MHz, CDCl3)
δ 2.28 (3 H, s, CCH3), 2.70 (1 H, td, J = 16.6, 4.1, H4), 2.85−2.99 (1
H, m, H4), 3.80 (3 H, s, OCH3), 3.93 (1 H, ddd, J = 11.6, 9.0, 4.4, H3),
4.19 (1 H, ddd, J = 11.5, 5.7, 4.3, H3), 5.70 (1H, s, H1), 6.61 (1 H, d, J
= 7.5, Har), 6.86 (2 H, d, J = 8.6, Har), 6.94−7.08 (2 H, m, Har), 7.21 (2
H, d, J = 8.6, Har); 13C NMR (75 MHz, CDCl3) δ 19.2, 26.7, 55.4,
63.5, 79.4, 113.9, 124.8, 125.5, 128.0, 130.3, 132.7, 134.9, 136.2, 137.6,
159.5; IR νmax/cm−1 2834, 1606, 1589, 1507, 1458, 1241, 1171,
1102,1026, 999, 825, 797, 744; LRMS m/z (%) (APCI) 252.8 [M −
H]+ (100); HRMS calcd for C17H17O2+ (M − H)+: 253.12231, found
253.12238. Anal. Calcd for C17H18O2·0.2H2O: C, 79.16, H, 7.19,
found C, 79.35, H, 7.18.
1
liquid (6% yield): H NMR (300 MHz, CDCl3) δ 2.80 (1 H, dt, J =
16.4, 3.8, H4), 3.13 (1 H, m, H4), 3.89 (3 H, s, CH3), 3.87−3.95 (1 H,
m, H3, overlapping with CH3), 4.17 (1 H, ddd, J = 11.4, 5.5, 4.0, H3),
5.66 (1 H, s, H1), 6.75 (1 H, d, J = 7.6, Har), 6.86 (1 H, d, J = 8.4, Har),
7.09 (1 H, td, J = 8.3, 2.5, Har), 7.12−7.23 (3 H, m, Har), 7.49 (1 H, d,
J = 2.1, Har); 13C NMR (75 MHz, CDCl3) δ 28.9, 56.4, 64.0, 78.7,
111.7, 111.8, 126.2, 126.9, 127.0, 129.0, 129.2, 133.9, 134.0, 136.2,
137.1, 155.8; IR νmax/cm−1 2926, 1598, 1494, 1454, 1259, 1053, 746;
LRMS m/z (%) (APCI) 317.1 [M]+ (12), 239.1 (100); HRMS calcd
for C16H14BrO2+ (M − H)+: 317.01717 and 319.01512, found 317.01681
and 319.01465.
1-(4-Methoxynaphthalen-1-yl)isochroman (3e). Obtained on
1.0 mmol scale and purified by flash column chromatography to
give 213 mg of 1-(4-methoxynaphthalen-1-yl)isochroman as white
prisms (73% yield): mp 110 °C; 1H NMR (300 MHz, CDCl3) δ 2.94
(1 H, td, J = 16.3, 4.6, H4), 3.10−3.25 (1 H, m, H4), 3.93−4.07 (1 H,
m, overlapping with CH3, H3), 4.00 (3 H, s, CH3), 4.13−4.23 (1 H, m,
H3), 6.33 (1 H, s, H1), 6.71 (1 H, d, J = 7.9, Har), 6.77 (1 H, d, J = 7.8,
Har), 7.03 (1 H, t, J = 7.9, Har), 7.13−7.23 (3 H, m, Har), 7.40−7.50 (2
H, m, Har), 8.10−8.15 (1 H, m, Har), 8.26−8.32 (1 H, m, Har); 13C
NMR (75 MHz, CDCl3) δ 29.0, 55.7, 63.5, 77.4, 102.7, 122.5, 124.9,
125.2, 126.1, 126.5, 126.7, 126.8, 126.8, 128.7, 128.9, 129.5, 132.8,
134.1, 137.8, 156.0; IR νmax/cm−1 2962, 1584, 1459, 1391, 1241, 1087,
1056, 907, 724; LRMS m/z (%) (APCI) 132.6 (74), 272.8 (100),
290.6 [M − H]+ (71); HRMS calcd for C20H19O2+ (MH+): 291.13796,
found 291.13791. Anal. Calcd for C20H18O2: C, 82.73, H, 6.25. Found:
C, 82.60, H, 6.42.
1-(4-Methoxyphenyl)-8-methylisochroman (3j). Obtained single
product on 0.2 mmol scale of 3:1 mixture of 8-methyl isochroman and
6-methylisochroman respectively and purified by flash column
chromatography to give a clear oil, which was recrystallized from
hexane and ethyl acetate to give 26 mg of 1-(4-methoxyphenyl)-6-
1
methylisochroman as white needles (45% yield): mp 82−84 °C; H
NMR (400 MHz, CDCl3) δ 1.88 (3 H, s, CCH3), 2.76 (1 H, dt, J =
16.5, 3.6, H4), 3.00−3.09 (1 H, m, H4), 3.74−3.82 (2 H, m, overlapp-
ing with OCH3, H3), 3.79 (3 H, s, OCH3), 5.81 (1 H, s, H1), 6.83 (2 H,
d, J = 8.6, Har), 6.98 (1 H, d, J = 7.4, Har), 7.05 (1 H, d, J = 7.5, Har),
7.08 (1 H, d, J = 8.7, Har), 7.16 (1 H, t, J = 7.5, Har) ; 13C NMR (126
MHz, CDCl3) δ 19.2, 28.9, 55.3, 59.1, 75.4, 113.7, 126.8, 126.8, 128.2,
130.4, 133.2, 134.3, 134.5, 135.1, 159.3; IR νmax/cm−1 2924, 1601,
1507, 1462, 1247, 1168, 1096, 1029, 819, 773. LRMS m/z (%) (APCI)
+
252.8 [M − H]+ (100); HRMS calcd for C17H17O2 (M − H)+:
CCDC 834014 contains the supplementary crystallographic data for
this compound. These data can be obtained free of charge from The
Cambridge Crystallographic Data Centre via www.ccdc.cam.ac.uk/data_
request/cif.
253.12231, found 253.12247.
1-(4-Methoxyphenyl)-4-methylisochroman (3k). Obtained on
2.0 mmol scale and purified by flash column chromatography to
give 331 mg of 1-(4-methoxyphenyl)-4-methylisochroman as a light
1-(2-Methoxynaphthalen-1-yl)isochroman (3f). Obtained on a
1.0 mmol scale and purified by flash column chromatography to give
226 mg of 1-(2-methoxynaphthalen-1-yl)isochroman as white prisms
1
yellow oil (65% yield): found 1:1 ratio of diastereomers; H NMR
(400 MHz, CDCl3) δ 1.30 (3 H, d, J = 7.0, CCH3), 1.46 (3 H, d, J =
7.1, CCH3), 2.85−2.94 (1 H, m, H4), 3.14 (1 H, apparent sextet, J =
6.9, H4), 3.54 (1 H, dd, J = 11.3, 8.0 H3), 3.79 (3 H, s, OCH3), 3.79
(3 H, s, OCH3), 3.90 (1 H, dd, J = 11.2, 2.9, H3), 4.00 (1 H, dd, J =
11.3, 3.6, H3), 4.09 (1 H, dd, J = 11.3, 5.1, H3), 5.65 (1 H, s, H1), 5.73
(1 H, s, H1), 6.72 (1 H, d, J = 7.8, Har),6.75 (1 H, d, J = 7.8, Har),
6.82−6.89 (4 H, m, Har), 7.02−7.09 (2 H, m, Har), 7.16−7.33 (8 H, m,
Har); 13C NMR (101 MHz, CDCl3) δ 17.9, 21.7, 32.0, 32.9, 55.4, 55.4,
69.7, 70.0, 79.5, 79.8, 113.8, 113.9, 125.8, 126.0, 126.8, 126.9, 126.9,
126.9, 127.0, 128.3, 130.2, 130.3, 134.7, 134.8, 137.0, 137.2, 139.5,
139.6. 159.5, 159.6; IR νmax/cm−1 2959, 1609, 1511, 1452, 1243, 1174,
1107, 1030, 821, 753. LRMS m/z (%) (APCI) 252.8 [M − H]+ (100);
1
(78% yield): mp 131.5−132.5 °C; H NMR (300 MHz, CDCl3) δ
2.84 (1 H, dd, J = 16.4, 2.6, H4), 3.42−3.56 (1 H, m, H4), 3.96 (3 H, s,
CH3), 4.13 (1 H, td, J = 11.6, 3.2, H3), 4.45 (1 H, dd, J = 11.3, 5.9,
H3), 6.56 (1 H, d, J = 7.7, Har), 6.80 (1 H, s, H1), 6.91 (1 H, t, J = 7.5,
Har), 7.10 (1 H, t, J = 7.5, Har), 7.18−7.25 (3 H, m, Har), 7.32 (1 H, d,
J = 9.0, Har), 7.69−7.76 (1 H, m, Har), 7.84 (1 H, d, J = 9.1, Har),
7.87−7.91 (1 H, m, Har); 13C NMR (75 MHz, CDCl3) δ 29.1, 57.1,
66.6, 72.8, 113.4, 122.1, 123.5, 125.3, 126.0, 126.3, 126.3, 126.4, 128.4,
128.7, 130.2, 130.8, 132.4, 133.3, 139.2, 155.8; IR νmax/cm−1 2843,
1624, 1596, 1509, 1460, 1244, 1069, 994, 905, 727; LRMS m/z (%)
(APCI) 132.6 (100), 272.8 (96), 290.5 [M − H]+ (70); HRMS calcd
+
for C20H19O2 (MH+): 291.13796, found 291.13791. Anal. Calcd for
+
HRMS calcd for C17H17O2 (M − H)+: 253.12231, found 253.12248.
C20H18O2: C, 82.73, H, 6.25. Found: C, 82.85, H, 6.39.
6-Fluoro-1-(4-methoxyphenyl)isochroman (3l). Obtained on
1.0 mmol scale and purified by flash column chromatography to
give 178 mg of 6-fluoro-1-(4-methoxyphenyl)isochroman as white
prisms (69% yield): mp 89 °C; 1H NMR (400 MHz, CDCl3) δ 2.78 (1
H, dt, J = 16.5, 3.8, H4), 3.11 (1 H, ddd, J = 16.5, 5.7, 3.6, H4), 3.80 (3
H, s, CH3), 3.89 (1 H, ddd, J = 11.4, 9.4, 4.0, H3), 4.15 (1 H, ddd, J =
11.4, 5.4, 4.0, H3), 5.65 (1H, s, H1), 6.71 (1 H, dd, J = 8.6, JH−F = 5.8,
Har), 6.77 (1 H, td, J = 8.6, 2.6, Har), 6.84−6.89 (3 H, m, Har), 7.20
(2 H, d, J = 8.6, Har); 13C NMR (101 MHz, CDCl3) δ 29.1, 55.4, 63.5,
79.0, 113.3 (d, JC−F = 21.4), 114.0, 115.0 (d, JC−F = 20.8), 128.8 (d,
JC−F = 8.3) 130.2, 133.5 (d, JC−F = 3.0), 134.4, 136.3 (d, JC−F = 7.5),
159.6, 161.5 (d, JC−F =245.2); IR νmax/cm−1 2962, 1596, 1503, 1245,
1091, 1057, 827; LRMS m/z (%) (APCI) 257.0 [M − H]+ (70), 226.8
(100). Anal. Calcd for C16H15FO2; C, 74.40, H, 5.85. Found: C, 74.44,
H, 5.85.
1-(6-Bromo-2-methoxynaphthalen-1-yl)isochroman (3g). Ob-
tained on 1.0 mmol scale and purified by flash column chromatography
to give 291 mg of 1-(6-bromo-2-methoxynaphthalen-1-yl)isochroman as
white prisms (79% yield): mp 165−166 °C (no literature data available);
1H NMR (300 MHz, CDCl3) δ 2.85 (1 H, dd, J = 16.5, 2.6, H4), 3.40−
3.55 (1 H, m, H4), 3.97 (3 H, s, CH3), 4.12 (1 H, td, J = 11.7, 3.3, H3),
4.45 (1 H, dd, J = 11.3, 6.1, H3), 6.51 (1 H, d, J = 7.7, Har), 6.77 (1 H,
s, H1), 6.92 (1 H, t, J = 7.4, Har), 7.12 (1 H, t, J = 7.4, Har), 7.19 (1 H,
d, J = 7.5, Har), 7.23−7.30 (1 H, m, Har), 7.34 (1 H, d, J = 9.1, Har),
7.76 (2 H, t, J = 7.5, Har), 7.87 (1 H, d, J = 2.0, Har); 13C NMR (75
MHz, CDCl3) δ 29.0, 57.0, 66.7, 72.6, 114.2, 117.3, 122.5, 125.3,
126.3, 126.5, 127.9, 128.9, 129.5, 129.8, 130.2, 130.9, 131.3, 133.2,
138.8, 156.0; IR νmax/cm−1 2932, 1588, 1496, 1459, 1251, 1072, 742;
LRMS m/z (%) (APCI) 132.7 (100), 271.8 (46), 370.4 [M + H]+ (6).
Anal. Calcd for C20H17BrO2: C, 65.05, H, 4.64. Found: C, 65.12,
H, 4.62.
5-Bromo-1-(4-methoxyphenyl)isochroman (3n). Obtained on
1.0 mmol scale and purified by flash column chromatography to give
122 mg of 5-bromo-1-(4-methoxyphenyl)isochroman as white needles
(38% yield); (a sample was recrystallized from hexane and ethyl
acetate to remove traces of grease. The recrystallized sample was used
for characterization): mp 116 °C; 1H NMR (400 MHz, CDCl3) δ 2.86
CCDC 834015 contains the supplementary crystallographic data for
this compound. These data can be obtained free of charge from The
Cambridge Crystallographic Data Centre via www.ccdc.cam.ac.uk/
data_request/cif.
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The Journal of Organic Chemistry
Article
(1 H, dt, J = 17.2, 4.2, H4), 2.99 (1 H, ddd, J = 17.1, 9.0, 5.8, H4), 3.80
(3 H, s, CH3), 3.90 (1 H, ddd, J = 11.6, 9.0, 4.5, H3), 4.19 (1 H, ddd,
J = 11.6, 5.7, 4.1, H3), 5.66 (1 H, s, H1), 6.72 (1 H, d, J = 7.7, Har),
6.87 (2 H, d, J = 8.8, Har), 6.95 (1 H, t, J = 7.8, Har), 7.19 (2 H, d, J =
8.7, Har), 7.44 (1 H, d, J = 7.9, Har); 13C NMR (101 MHz, CDCl3) δ
29.8, 55.4, 63.5, 79.0, 114.0, 125.2, 126.2, 127.1, 130.3, 130.7, 133.9,
134.0, 140.5, 159.7; IR νmax/cm−1 2835, 1611, 1511, 1244, 1049, 1033,
825, 763; LRMS: m/z (%) (APCI) 319.1 [M]+ (42), 289.2 (74), 135.1
IR νmax/cm−1 2928, 1434, 1368, 1097, 1058, 1006, 956, 787. LRMS m/z
(%) (APCI) 152.9 [M + H]+ (100). Spectroscopic data match those in
the literature.13f
5-Bromo-3,4-dihydro-1H-isochromene (1n). Obtained on
1
7.5 mmol scale (0.83 g, 78%): H NMR (300 MHz, CDCl3) δ 2.86
(2 H, t, J = 5.6, H4), 3.99 (2 H, t, J = 5.7, H3), 4.78 (2 H, s, H1), 7.05−
7.25 (2 H, m, Har), 7.52 (1 H, d, J = 7.5, Har); IR νmax/cm−1 2941,
1445, 1387, 1099, 1064, 1008, 956, 780, 753. LRMS m/z (%) (APCI)
212.9 [M]+ (100). Spectroscopic data match those in the literature.25
3,4-Dihydro-6-methoxy-1H-isochromene (1m) and 1-methyl iso-
chroman (1o) were prepared according to the procedure reported
previously.28
+
(100); HRMS calcd for C16H14BrO2 (M − H)+: 317.01717 and
319.01512, found 317.01644 and 319.01478. Anal. Calcd for
C16H15BrO2·1/12(hexane) C, 60.72, H, 4.99. Found: C, 60.94, H, 4.63.
1-Ethoxyisochroman. Obtained on 1.0 mmol scale from the
competition experiment between anisole and ethanol and purified by
flash column chromatography (20:1 hexane/EtOAc) to give 116 mg of
3,4-Dihydro-6-methoxy-1H-isochromene (1m). Obtained on
1
26 mmol scale (1.02 g, 24% yield): H NMR (CDCl3, 300 MHz) δ
2.83 (2 H, t, J = 5.5, H4), 3.79 (3 H, s, CH3), 3.97 (2 H, t, J = 5.6,
H3), 4.72 (2 H, s, H1), 6.66 (1H, s, H5), 6.73 (1H, dd, J = 8.4, 2.4, H6),
6.89 (1H, d, J = 8.4, H7); 13C NMR (75 MHz, CDCl3) δ 28.6, 55.2,
65.2, 67.6, 112.3, 113.5, 125.4, 127.0, 134.4, 158.0; IR νmax/cm−1, 2934,
1610, 1503, 1464, 1382, 1312, 1272, 1243, 1096, 1034, 851; LRMS
m/z (%) (APCI) 162.9 [M − H]+ (100). Spectroscopic data match
those in the literature.13f
1
1-ethoxyisochroman as a colorless oil (65%): H NMR (300 MHz,
CDCl3), δ 1.28 (3H, t, J = 7.1, H2′), 2.60 (1H, ddd, J = 16.5, 3.2, 1.6,
H4), 3.00 (1H, ddd, J = 16.5, 11.9, 6.1, H4), 3.63−3.75 (1H, m, H3, or
H1′), 3.83−3.97 (2H, m, H3 or H1′), 4.14 (1H, td, J = 11.5, 3.6, H3),
5.54 (1H, s, H1), 7.08−7.23 (4H, m); 13C NMR (75 MHz, CDCl3)
15.5, 28.1, 57.9, 63.6, 96.7, 126.4, 127.5, 128.1, 128.6, 134.2, 124.5; IR,
νmax/cm−1 2973, 1158, 1119, 1092, 1072, 1047; MS m/z (APCI) 133
[M − OCH2CH3]+ 100%, 177 [M − H]+ 10%. This compound is
known. However, 1H and 13C NMR spectroscopic data are not
available in the literature.
Preparation of 1-Methyl Isochroman (1o). Obtained on 16 mmol
scale (0.61 g, 33% yield): 1H NMR (CDCl3, 300 MHz) δ 1.53 (3 H, d,
J = 6.5, CH3), 2.69 (1 H, td, J = 16.3, 3.3, H3), 3.03 (1 H, ddd, J = 16.2,
10.1, 5.7, H3), 3.80 (1 H, ddd, J = 11.3, 10.1, 3.7, H4), 4.15 (1 H, ddd,
J = 11.3, 5.6, 3.3), 4.86 (1 H, q, J = 6.5, H1), 7.06 − 7.19 (4 H, m,
General Procedure for the Preparation of Substituted
Isochromans. Substituted isochromans 1i−1l and 1n were prepared
according to the procedure reported previously.25
H
arm); 13C NMR (75 MHz, CDCl3) δ 21.8, 29.1, 63.6, 72.3, 124.7,
126.1, 126.2, 128.8, 133.4, 139.6.; IR νmax/cm−1 3031, 2927, 1451,
1372, 1292, 1264, 1170, 1114, 756; LRMS m/z (%) (APCI) 146.9
[M − H]+ (100). Spectroscopic data match those in the literature.29
General Procedure for the Preparation of Substituted
Anisoles. Substituted anisoles 2b−f were prepared according to the
procedure reported previously.30
3,4-Dihydro-5-methyl-1H-isochromene (1i). Obtained on
1
0.8 mmol scale (115 mg, 78% yield): H NMR (300 MHz, CDCl3)
δ 2.22 (3 H, s, CH3), 2.70 (2 H, t, J = 5.7, H4), 4.00 (2 H, t, J =
5.8, H3), 4.76 (2 H, s, H1), 6.82 (1 H, d, J = 7.1, Har), 7.00−7.10
(2 H, m, Har); 13C NMR (75 MHz, CDCl3) δ 18.9, 26.2, 65.6, 68.4,
122.1, 125.8, 127.8, 131.8, 134.9, 136.6; IR νmax/cm−1 2929, 1468,
1424, 1384, 1312, 1234, 1107, 1061, 997, 772. LRMS m/z (%) (APCI)
148.7 [M + H]+ (100). Spectroscopic data match those in the
literature.13f
2-Methylanisole (2b). Obtained on 20 mmol scale (1.41 g, 58%
yield): 1H NMR (CDCl3, 300 MHz) δ 2.22 (3 H, s, CCH3), 3.83 (3 H, s,
OCH3), 6.81 − 6.88 (2 H, m, Harm), 7.12 − 7.18 (2 H, m, Harm); 13
C
NMR (CDCl3, 75 MHz) δ 16.2, 55.2, 109.9, 126.6, 126.6, 130.6,
157.7; IR νmax/cm−1 2950, 2835, 1602, 1591, 1494, 1465, 1239; LRMS
m/z (%) (APCI) 122.9 [M + H]+ (35), 107.9 [M − CH3]+. (100).
Spectroscopic data match those in the literature.31
3,4-Dihydro-8-methyl-1H-isochromene and 3,4-dihydro-6-methyl-
1H-isochromene (1j). Obtained on 2.4 mmol scale (121 mg, 35%
yield): 1H NMR (300 MHz, CDCl3 3,4-dihydro-8-methyl-1H-isochromene
is designated by * and 3,4-dihydro-6-methyl-1H-isochromene by #)
#
δ 2.13 (3 H, s, CH3*), 2.30 (3 H, s, CH3 ), 2.80 (2 H, t, J = 5.7, H4#),
3-Methylanisole (2c). Obtained on 20 mmol scale (1.38 g, 56%
2.84 (2 H, t, J = 5.6, H4*), 3.93 (2 H, t, J = 5.7, H3*), 3.95 (2 H, t, J =
1
yield): H NMR (CDCl3, 300 MHz) δ 2.33 (3 H, s, CCH3), 3.79 (3
5.6, H3#), 4.70 (2 H, s, H1*), 4.73 (2 H, s, H1#), 6.87 (1 H, d, J = 7.7,
H, s, OCH3), 6.70 − 6.78 (3 H, m, Harm), 7.14 − 7.17 (1 H, t, J = 7.7,
arm); 13C NMR (CDCl3, 75 MHz) δ 21.5, 55.1, 110.8, 114.7, 121.1,
H
ar#), 6.94 (1 H, s, Har#), 6.95−7.03 (2 H, m, Har*, 1 H, m, Har#), 7.08
H
(1 H, t, J = 7.4, Har*); 13C NMR (75 MHz, CDCl3) δ 17.9, 21.2, 28.5,
28.9, 65.0, 65.5, 66.6, 68.0, 124.4, 126.2, 126.7, 126.9, 127.7, 129.5,
132.0, 133.2, 133.3, 133.3, 133.6, 136.0; IR νmax/cm−1 2938, 1469,
1383, 1103, 1058, 987, 778. The procedure used in this paper gave a
3:1 ratio of 8-methyl- to 6-methyl isochromans. A literature report
selectively gives the 8-methyl derivative, which matched the major product
from the above synthesis.26 Another literature report,13f using an alternative
procedure, gives a 1:2 product ratio (i.e., reversed product selectivity).
4-Methylisochroman (1k). Obtained on 4.5 mmol scale (566 mg,
129.1, 139.4, 159.6; IR νmax/cm−1 2952, 2920, 2835, 1602, 1585, 1489,
1463, 1289, 1151; LRMS m/z (%) (APCI) 122.9 [M + H]+ (43),
107.9 [M − CH3] (100). Spectroscopic data match those in the
literature.32
2-Bromoanisole (2d). Obtained on 5.0 mmol scale (0.87 g, 93%):
1H NMR (CDCl3, 300 MHz) δ 3.90 (3 H, s, CH3), 6.81 (1 H, dt, J =
7.6, 1.3, Harm), 6.90 (1 H, dd, J = 8.3, 1.3, Harm), 7.27 (1 H, m, Harm),
7.54 (1 H, dd, J = 7.8, 1.6, Harm); 13C NMR (CDCl3, 75 MHz) δ 56.1
111.7, 112.0, 121.8, 128.5, 133.3, 155.9; IR νmax/cm−1, 2838, 1586,
1479, 1247, 1053, 1021. Spectroscopic data match those in the
literature.33
1
86% yield): H NMR (400 MHz, CDCl3) δ 1.30 (3 H, d, J = 7.0,
CH3), 2.88−2.98 (1 H, m, H4), 3.67 (1 H, dd, J = 11.2, 5.4, H3), 3.97
(1 H, dd, J = 11.2, 4.4, H3), 4.78 (2 H, d, J = 5.7, H1), 7.14 (1 H, dd,
J = 7.0, 2.0, Har), 7.17−7.23 (2 H, m, Har), 7.31−7.35 (1 H, m, Har);
13C NMR (101 MHz, CDCl3) δ 19.4, 32,0, 68.5, 71.6, 124.3, 126.1,
126.7, 127.9, 134.4, 138.8; IR νmax/cm−1 2959, 2831, 1490, 1452, 1114,
1059, 756, 730; LRMS m/z (%) (APCI) 148.2 [M]+ (100).
Spectroscopic data match those in the literature.27
1-Methoxynaphthalene (2e). Obtained on 50 mmol scale (7.2 g,
1
91% yield): H NMR (300 MHz, CDCl3) δ 3.87 (3 H, s, CH3), 6.69
(1 H, d, J = 7.5, Har), 7.25−7.45 (4 H, m, Har), 7.72−7.75 (1 H, m,
Har), 8.23−8.27 (1 H, m, Har); 13C NMR (CDCl3, 75 MHz) δ 55.4,
103.9, 120.3, 122.1, 125.3, 125.8, 126.0, 126.5, 127.6, 134.6, 155.6; IR
νmax/cm−1 3053, 2955, 1580, 1462, 1393, 1266, 1237, 1101, 1068, 789,
765, 712. LRMS m/z (%) (APCI) 158.1 [M]+ (65). Spectroscopic
data match those in the literature.34
3,4-Dihydro-6-fluoro-1H-isochromene (1l). Obtained on
1
1.3 mmol scale (110 mg, 55% yield): H NMR (400 MHz, CDCl3)
δ 2.84 (2 H, t, J = 5.7, H4), 3.95 (2 H, t, J = 5.7, H3), 4.73 (2 H, s, H1),
6.82 (1 H, d, J =8.7, Har), 6.86 (1 H, dd, J = 8.6, 2.6, Har), 6.93 (1 H, t,
J = 8.4, Har); 13C NMR (101 MHz, CDCl3) δ 28.5, 65.1, 67.7, 113.3
(d, JC−F = 21.7), 115.4 (d, JC−F = 20.8), 126.0 (d, JC−F = 8.3), 130.6 (d,
JC−F =2.9), 135.4 (d, JC−F = 7.6), 161.4 (d, JC−F =244.2); (NB − peak
at 130.6 (smallest JC−F value) arises from carbon lacking attached H,
indicating this compound is indeed 6-fluoro- and not 8-fluoro derivative);
2-Methoxynaphthalene (2f). Obtained on 50 mmol scale (6.8 g,
86% yield): mp 72−74 °C (lit.35 73−74 °C); H NMR (300 MHz,
1
CDCl3) δ 3.90 (3 H, s, CH3), 7.11−7.17 (2 H, m, Har), 7.29−7.34 (1
H, m, Har), 7.39−7.45 (1H, m, Har), 7.70−7.77 (3 H, m, Har); 13C
NMR (CDCl3, 75 MHz) δ 55.4, 105.9, 118.8, 123.7, 126.5, 126.8,
127.8, 129.1, 129.5, 134.7, 157.7; IR νmax/cm−1 3056, 2960, 1630,
15997, 1470, 1263, 1220, 1172, 1029, 839, 816, 745. LRMS m/z (%)
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(APCI) 158.1 [M]+ (100). Spectroscopic data match those in the
literature.36
(16) (a) Lorenz, P.; Zeh, M.; Martens-Lobenhoffer, J.; Schmidt, H.;
Wolf, G.; Horn, T. F. W. Free Radical Res. 2005, 39, 535.
(b) Schoenfeld, P.; Kruska, N.; Reiser, G. Biochim. Biophys. Acta,
Gen. Subj. 2009, 1790, 1698.
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ASSOCIATED CONTENT
■
S
* Supporting Information
1H and 13C NMR spectra for all novel compounds and
crystallographic information in CIF format. This material is
available free of charge via the Internet at http://pubs.acs.org.
AUTHOR INFORMATION
Corresponding Author
*E-mail: matthew.todd@sydney.edu.au.
̀
(19) Boess, E.; Sureshkumar, D.; Sud, A.; Wirtz, C.; Fares, C.;
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Klussmann, M. J. Am. Chem. Soc. 2011, 133, 8106.
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(21) Minisci, F.; Citterio, A.; Vismara, E.; Giordano, C. Tetrahedron
1985, 41, 4157.
ACKNOWLEDGMENTS
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(22) Phipps, R. J.; Grimster, N. P.; Gaunt, M. J. J. Am. Chem. Soc.
2008, 130, 8172.
We thank The University of Sydney for an Australian
Postgraduate Award (to S.J.P.) and Dr. Chris McErlean (The
University of Sydney) for valuable advice.
(23) Ribas, X.; Xifra, R.; Parella, T.; Poater, A.; Sola,
Angew. Chem., Int. Ed. 2006, 45, 2941.
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M.; Llobet, A.
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(25) Favor, D. A.; Johnson, D. S.; Powers, J. J.; Li, T.; Madabattula,
R. Tetrahedron Lett. 2007, 48, 3039.
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