Direct allylation of quinones with allylboronates

Article abstract of DOI:10.1021/acs.joc.5b00264

Allylboronates undergo C-H allylation of unsubstituted or monosubstituted benzoquinone and naphthoquinone substrates. In the case of 2,5-or 2,6-disubstituted quinones addition involving the substituted carbon takes place. Allylation with stereodefined allylboronates occurs with retention of the configuration.

Full text of DOI:10.1021/acs.joc.5b00264

Note
pubs.acs.org/joc
Direct Allylation of Quinones with Allylboronates
Hong-Ping Deng, Dong Wang, and Kalman J. Szabo*
́
́
́
Department of Organic Chemistry, Stockholm University, SE-106 91 Stockholm, Sweden
S
* Supporting Information
ABSTRACT: Allylboronates undergo C−H allylation of unsubstituted or
monosubstituted benzoquinone and naphthoquinone substrates. In the case
of 2,5- or 2,6-disubstituted quinones addition involving the substituted
carbon takes place. Allylation with stereodefined allylboronates occurs with
retention of the configuration.
llyl and isoprenoid quinones represent a very important
class of bioactive compounds. These species are very
decided to explore the synthetic potential of allyl-Bpin
compounds for synthesis of allyl and isoprenoid benzo- and
naphthoquinone derivatives.
We have found that the reaction of BQ derivatives 1 and
allylboronates 2 in a 2:1 ratio (method A) results in allyl-BQs 3
in high yield and in most cases with high selectivity (Scheme
1). In the case of 2,5-disubstituted quinones (R4 ≠ H), the
addition product (3′) was formed by mixing equimolar
amounts of the reaction components (Scheme 1).
A
important components of the cell membrane in living
organisms. The benzoquinone (BQ) derivatives participate in
the respiratory chain in eukaryotic mitochondria (such as
ubiquinones) and are important components in the photo-
synthetic electron transport chains in plants (such as
plastoquinones), while naphthoquinone based K-vitamins are
essential in cell respiration.1 The quinone core is very
important in medicinal applications as well.2 Quinone
derivatives with antibiotic (such as bhimamycin),3 anticancer
(for example embelin derivatives),4 and antimalarial5 activities
have received a lot of recent attention. In addition, quinone
derivatives are also useful cocatalysts, usually as oxidants, in
transition-metal-catalyzed reactions.6
a
Scheme 1. Allylation of Quinones with Allylboronates
Obviously, there is a considerable demand for development
of new synthetic procedures to obtain functionalized quinones
and related compounds. Recently, excellent procedures
appeared in the literature for the synthesis of aryl and alkyl
quinone derivatives.7 In some of these procedures organo-
boranes are used as the coupling component.7a,b,f,g However,
the synthesis of allyl and isoprenoid quinones is a somewhat
less developed area. In most applications, allyl-stannanes8 have
been used to introduce the allyl moiety, but in some
applications allyl-Ni,9 allyl trifluorosilyl10 and allyl-indium
species11 have also been applied. Surprisingly few applications
have been reported for allylation of quinones with allylboron
compounds.
As far as we know, the only example was published by Baran
and co-workers7b on using farnesyl-BF3K in the presence of Ag-
catalyst for the synthesis of farnesyl-BQ. Allylboronates,12 react
with high selectivity and offer a benign alternative to allyl-
stannanes and allyl-Ni derivatives. In addition, allyl-Bpin
compounds are easily accessible from allyl-alcohols,12c,13
alkenes,14 and other allylic precursors.12f,15 Therefore, we
a
For methods A and B see footnote “a” of Table 1.
Benzoquinone 1a (BQ) reacted readily with cinnamylboro-
nate 2a to give BQ-derivative 3a with high yield and excellent
regio- and stereoselectivity (Table 1). Exclusively the
monosubstituted linear allyl species was formed, in which the
double bond had an E geometry. A clean C−H functionaliza-
tion reaction (entry 1) required the use of 2 equiv of BQ,
otherwise a mixture of the hydroquinone and BQ products was
formed. This suggested that 1 equiv of BQ 1a was substituted
to form a hydroquinone derivative, and the other equivalent of
BQ was used as oxidant (see below).
Using alkyl-Bpin substrate 2b the reaction with BQ (1a) led
to 3b (entry 2), but the reaction was slower than with cinnamyl
boronate 2a. By addition of CF3COOH (50 mol %) the
reaction proceeded with acceptable rate and yield. The ratio of
Received: February 4, 2015
© XXXX American Chemical Society
A
DOI: 10.1021/acs.joc.5b00264
J. Org. Chem. XXXX, XXX, XXX−XXX

The Journal of Organic Chemistry
Note
that the allylation with allylstannes requires Lewis acid (e.g.,
BF3) catalysts, while the reaction with allylboronate proceeds
without catalysts. The regio- and stereochemistry16 of the Lewis
acid-catalyzed process of allyl-stannanes of carbonyls is
determined by a Type II (open) TS, while the allylation by
allylboronates is determined by a Type I (six-membered ring)
TS (see below the mechanistic rationalization of the reaction).
Farnesyl-Bpin 2c also reacted easily with 1a to give natural
product, farnesyl-BQ 3c. Interestingly, Baran and co-workers7b
reported a sluggish reactivity for the AgNO3-catalyzed process
using K2S2O8 as oxidant in CH2Cl2/water (1:1) mixture. Under
our conditions, using 1a as oxidant without any catalyst in
chloroform the reaction gives 3c smoothly. Baran and co-
workers employed farnesyl-BF3K instead of farnesyl-Bpin 2c
and obtained 3c with essentially the same E/Z selectivity as we
did (entry 3) but in somewhat lower yield. Naphthoquinone 1b
can be simply isoprenylated with 2d to obtain 3d.
Table 1. Allylation of Quinones with Allylboronates
Not only allyl and isoprenyl boronates but also cyclic
boronates, such as 2e and 2f, reacted with BQ 1a (entries 5 and
6). The reactivity of the cyclic boronates 2e,f was lower than for
cinnamyl boronate 2a. However, the addition of diphenylphos-
phonic acid accelerated the reaction, and 3e,f were formed in
acceptable yields. As 2f is a stereodefined allylboronate, the
reaction with 1a (entry 6) gave insight about the stereo-
chemistry of the allylation of quinones. The product 3f was
formed as a single diastereomer in which the COOMe and the
BQ groups are on the different sides of the cyclohexenyl ring.
Considering the fact that the COOMe and the Bpin groups had
the same stereochemistry in substrate 2f, the allylation process
takes place with retention of the configuration of the Bpin
leaving group. Although, several other allylating reagents have
been employed for allylation of quinones,8−11 as far as we know
this is the first case (entry 6) when the stereochemistry of the
allylation of BQ 1a is determined.
The C−H functionalization of monosubstituted BQ
derivative 1c proceeds with high stereoselectivity but with a
poor regioselectivity as the 5- and 6-cinnamyl derivatives were
formed in a 1:2.5 ratio (entry 7). Surprisingly the 2,6-dimethyl-
substituted derivative 1d with 2a gave a single addition product
3h (entry 8). This product was formed in high yield even using
about equimolar ratio of 1d and 2a (method B), indicating that
the reaction does not involve an oxidation step. The 1,4-
dimethyl-substituted quinone derivative 1e also gave an
addition product 3i with 2a (entry 9). The addition product
(3j) was readily formed even in the presence of bulky alkyl
t
substituents, such as Bu groups (entry 10). Dimethoxy
quinone 1g reacted more reluctantly (entry 11) than its
methyl-substituted counterpart 1d. However, using a slight
excess of 2a an acceptable yield of the addition product 3k
could be obtained. Substituted naphthoquinones 1h and 1i
reacted similarly to the corresponding BQ derivatives, affording
the corresponding addition products 3l−o (entries 12−14).
Interestingly, the stereoselectivity is equally high with both
cinnamyl (2a) and alkyl (2b) boronates (entries 12−13). The
electronic character of the substituent did not influence the
outcome of the reaction. Even in the case of a COOMe
substituent (1i), the corresponding addition product 3n was
formed in excellent selectivity (entry 14). In the case of mixed
OMe and Me substituents, such as in 1j, the addition takes
place at the Me substituent, such as in 3o (entry 15).
a
Method A: The reactions were carried out with 1 (0.2 mmol) and 2
(0.1 mmol) in CDCl3 (0.5 mL) at room temperature for 24 h. Method
B: The reactions were carried out with 1 (0.1 mmol) and 2 (0.12
mmol) in CDCl3 (0.5 mL) for 24 h. Isolated yield. CF3COOH (0.05
mmol) was used as an additive. Diphenylphosphinic acid (0.05
b
c
d
e
mmol) was used as an additive. The 5- and 6-Me-substituted
f
regioisomers were formed in a 1:2.5 ratio. 1 (0.15 mmol) was used.
g
CF3COOH (0.1 mmol) was used as an additive.
E/Z isomers in 3b was 6:1, indicating lower stereoselectivity
than with cinnamylboronic acid 2a (cf. entries 1 and 2).
Interestingly, the reaction of alkyl-allylstanne analog of 2b with
BQ gives the branched regioisomer.8d A possible explanation is
The mechanism of the reaction is presumed to involve three
major steps (Scheme 2) in the case of unsubstituted or
monosubstituted quinones and naphthoquinone (such as 1a−
B
DOI: 10.1021/acs.joc.5b00264
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The Journal of Organic Chemistry
Note
and naphthoquinone derivatives using allyl-Bpin reagents
usually without using any catalysts or additives. In some
reactions catalytic amounts of Brønsted acid was used to
accelerate the process. This reaction may find useful
applications in the synthesis of isoprenyl natural products and
terpenes with a BQ core. For example, hemitectol23 7 can be
synthesized in only three steps from naphthoquinone 1b and
allyl alcohol based isoprenyl-Bpin 2d followed by biomimetic
6π-electrocyclization8c in pyridine (Scheme 4). The reactions
Scheme 2. C−H Allylation of BQ 1a by Allyl-Bpin
Scheme 4. Synthesis of Hemitectol from 3d
c). The first step is probably addition of the allylboronate to the
carbonyl group via a six-membered ring TS structure,16
affording the branched isomer 4a.12a,b,17 It is surprising that
allyl-Bpin is added to a keto group under the present mild
conditions.12c,d,h,j,17b,18 However, the double bonds in the
quinoid structure probably activate the carbonyl group for the
addition reactions. We attempted to observe intermediate 4a
(and its methyl-substituted analogs) by monitoring the reaction
with 1H NMR spectroscopy. However, these attempts remained
fruitless. This indicates that the allylborated initial intermediates
(such as 4a) are highly reactive species, which are rapidly
consumed. The next reaction step is probably a fast Cope-type
[3,3′]-rearrangement to 5a. Similar rearrangements are known
for adducts formed from BQ and allyl-indium and allyl-Ni
species.9,11 After tautomerization hydroquinone derivative 6a is
formed, which can be oxidized by another BQ molecule to
quinone derivative 3. This was also verified by reaction of
isolated 6a (R = Ph) with 1a, which resulted in 3a in a clean
reaction. Thus, 1a serves as both substrate and as oxidant in the
C−H allylation of quinones. This is the reason for using
quinones 1a−c and allylboronates in a 2:1 ratio to obtain C−H
allylated product 3. The acid catalyst is supposed to accelerate
two steps in the reaction. The Hall16,19 and Miyaura20 groups
reported that allylboronates react faster with carbonyl
compounds in the presence of Lewis and Brønsted
acids.12g,h,13b,18,21 As a consequence, the allylation process (1a
→ 4a) is probably accelerated by proton catalysis. In addition,
the oxidation potential of BQ is pH dependent.22 Therefore,
the acid catalysis probably accelerates the oxidation step (6a →
3) as well.
are highly regio- and stereoselective. Using stereodefined
allylboronates, the reaction occurs with clean retention of the
stereochemistry (entry 6). In the case of 2,4- and 2,6-
substituted quinones the reaction gives addition products
(such as 3h−p) in high selectivity, which further extends the
synthetic scope of preparation of quinone-based isoprenoids,
which are important components of the cell membrane1 and
important motifs in drug intermediates.2−5
EXPERIMENTAL SECTION
■
General Information. 1i24 and 2a−f13d,e were prepared according
to literature procedures. All other chemicals were obtained from
commercial sources and used as received. All operations were carried
1
out under Ar. H NMR and 13C NMR spectra were recorded using
400 or 500 MHz spectrometers. Chemical shifts were reported using
the residual solvent peak as internal standard. ESI or APCI technique
and mass analyzer type TOF were used for the high-resolution mass
(HRMS) measurements. For column chromatography, silica gel (35−
70 μm) was used.
General Procedure for Allylation of Quinones. A solution of
allylboronates 2 (0.1 mmol), BQ 1a (21.6 mg, 0.2 mmol) in CDCl3
(0.5 mL) was stirred at room temperature for 24 h. The product was
purified by silica chromatography.
2-Cinnamyl-1,4-benzoquinone (3a). The product was prepared
according to the above general procedure from 2a (24.4 mg, 0.1
mmol) and BQ 1a (21.6 mg, 0.2 mmol). After chromatography
(pentane:Et2O = 20:1) the product 3a (20.2 mg, 90% yield) was
When 2,4- or 2,6-disubstituted quinones are employed
(Scheme 3), the same initial steps take place as above, i.e.,
1
obtained as a yellow oil. H NMR (500 MHz, CDCl3): δ 7.35−7.37
Scheme 3. Allylation of 2,4- (or 2,6-) Disubstituted Quinone
Derivatives by Allyl-Bpin
(m, 2H), 7.29−7.33 (m, 2H), 7.23−7.26 (m, 1H), 6.79 (d, J = 10.0
Hz, 1H), 6.73 (dd, J = 10.0, 2.5 Hz, 1H), 6.64 (dt, J = 2.5, 1.6 Hz, 1H),
6.52 (d, J = 15.6 1H), 6.18 (dt, J = 15.8, 7.1 Hz, 1H), 3.34 (dt, J = 7.2,
1.5 Hz, 2H). 13C{1H}NMR (125 MHz, CDCl3) δ 187.7, 187.2, 147.8,
136.7, 136.5, 134.2, 133.0, 128.6, 127.7, 126.2, 123.9, 32.3. The 13C
signals of C5 and C6 are probably overlapping. HRMS-APCI m/z:
Calcd for C15H13O2 [M + H]+ 225.0910. Found 225.0901.
2-(Oct-2-en-1-yl)-1,4-benzoquinone (3b). The product was
prepared according to above general procedure from 2b (23.8 mg,
0.1 mmol), BQ 1a (21.6 mg, 0.2 mmol), and CF3CO2H (0.05 mmol).
After chromatography (pentane:Et2O = 50:1) the product 3b (11 mg,
50% yield, E:Z = 5.8:1) was obtained as a yellow oil. E isomer (major),
1H NMR (400 MHz, CDCl3): δ 6.75 (d, J = 10.0 Hz, 1H), 6.71 (dd, J
= 2.4, 10.0 Hz, 1H), 6.56 (dt, J = 1.6, 2.4 Hz, 1H), 5.54−5.62 (m, 1H),
5.35−5.43 (m, 1H), 3.10−3.13 (m, 2H), 2.00−2.06 (m, 2H), 1.25−
1.38 (m, 6H), 0.88 (t, J = 6.8 Hz, 3H); 13C{1H}NMR (100 MHz,
CDCl3): δ 187.8, 187.3, 148.6, 136.7, 136.3, 135.7, 132.6, 123.6, 32.5,
31.8, 31.4, 28.9, 22.5, 14.0. HRMS-APCI m/z: Calcd for C14H19O2 [M
+ H]+ 219.1380. Found 219.1384.
addition to get 4b followed by a [3,3′]-rearrangement to 5b.
However, after tautomerization 3i is formed, which cannot be
oxidized to quinone derivative (as compound 6a) because of
the presence of the Me (or other non-H) group.
In summary, we presented a useful synthetic method for
allylation and isoprenylation of quinone derivatives. The
process is suitable for simple C−H functionalization of BQ
2-((6E)-3,7,11-Trimethyldodeca-2,6,10-trien-1-yl)-1,4-benzoqui-
none (3c). The product was prepared according to above general
C
DOI: 10.1021/acs.joc.5b00264
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Note
procedure from farnesyl-Bpin 2c (33.2 mg, 0.1 mmol) and BQ 1a
(21.6 mg, 0.2 mmol). After chromatography (pentane:Et2O = 20:1)
the product (26 mg, 83% yield, E:Z = 1.2:1) was obtained as a
colorless oil. The NMR shifts were determined from the spectra of the
isomer mixture. These shift values agree with the published spectral
data.7b Major isomer, 1H NMR (400 MHz, CDCl3): δ 6.75 (d, J = 10.0
Hz, 1H), 6.70 (dd, J = 2.4, 10.0 Hz, 1H), 6.54 (dd, J = 2.4, 4.0 Hz,
1H), 5.05−5.17 (m, 3H), 3.12−3.13 (m, 2H), 1.93−2.12 (m, 8H),
1.67 (s, 3H), 1.63 (d, J = 1.2 Hz, 1H), 1.59 (s, 6H); 13C{1H}NMR
(100 MHz, CDCl3): δ 187.9, 187.6, 148.5, 140.2, 136.7, 136.3, 135.4,
132.4, 131.3, 124.3, 123.7, 117.6, 39.6, 27.4, 26.7, 26.3, 25.7, 17.7, 16.1,
16.0. Minor isomer, 1H NMR (400 MHz, CDCl3): δ 6.75 (d, J = 10.0
Hz, 1H), 6.70 (dd, J = 2.4, 10.0 Hz, 1H), 6.52 (dd, J = 2.4, 4.0 Hz,
1H), 5.05−5.17 (m, 3H), 3.12−3.13 (m, 2H), 1.93−2.12 (m, 8H),
1.77 (d, J = 1.2 Hz, 1H), 1.67 (s, 3H), 1.59 (s, 6H); 13C{1H}NMR
(100 MHz, CDCl3): δ 187.9, 187.5, 148.8, 140.2, 136.7, 136.3, 135.4,
132.3, 131.3, 124.2, 123.5, 118.3, 39.7, 39.6, 31.9, 27.2, 26.6, 26.4, 25.7,
23.5, 16.0. HRMS-ESI m/z: Calcd for C21H28NaO2 [M + Na]+
335.1982. Found 335.1975.
2-(3-Methylbut-2-en-1-yl)-1,4-naphthoquinone (3d). The product
was prepared according to the above general procedure from
isoprenyl-Bpin 2d (19.6 mg, 0.1 mmol) and naphthoquinone 1b
(31.6 mg, 0.2 mmol). After chromatography (pentane:Et2O = 30:1)
the product (12 mg, 53% yield) was obtained as a light yellow oil. The
NMR data are in agreement with the literature values.3 1H NMR (400
MHz, CDCl3): δ 8.02−8.12 (m, 2H), 7.69−7.74 (m, 2H), 6.76 (t, J =
1.6 Hz, 1H), 5.19−5.24 (m, 1H), 3.27 (d, J = 7.3 Hz, 2H), 1.78 (s,
3H), 1.66 (s, 3H). 13C{1H}NMR (100 MHz, CDCl3) δ 185.4, 185.3,
150.8, 136.4, 134.7, 133.64, 133.59, 132.4, 132.2, 126.5, 126.1, 118.2,
28.0, 25.8, 17.8. HRMS-ESI m/z: Calcd for C15H15O2 [M + H]+
227.1067. Found 227.1057.
(29.3 mg, 0.12 mmol) and 2,6-dimethyl-BQ 1d (13.6 mg, 0.1 mmol).
After chromatography (pentane:ethyl acetate =12:1) the product 3h
(24 mg, 94% yield) was obtained as a light yellow oil. H NMR (400
1
MHz, CDCl3): δ 7.27−7.33 (m, 4H), 7.20−7.24 (m, 1H), 6.57 (d, J =
1.2 Hz, 1H), 6.38 (d, J = 15.6 Hz, 1H), 6.05 (ddd, J = 7.2, 8.0, 15.6 Hz,
1H), 2.91 (d, J = 16.4 Hz, 1H), 2.61−2.67 (m, 2H), 2.35 (ddd, J = 1.2,
8.0, 13.6 Hz, 1H), 2.01 (d, J = 1.2 Hz, 3H), 1.27 (s, 3H);
13C{1H}NMR (100 MHz, CDCl3): δ 202.6, 197.7, 149.1, 137.2, 136.8,
134.4, 128.5, 127.5, 126.2, 124.3, 49.3, 48.9, 42.5, 24.6, 16.7. HRMS-
ESI m/z: Calcd for C17H18NaO2 [M + Na]+ 277.1199. Found
277.1201.
5-Cinnamyl-2,5-dimethylcyclohex-2-ene-1,4-dione (3i). The
product was prepared according to the above general procedure
from 2a (29.3 mg, 0.12 mmol) and 2,5-dimethyl-BQ 1e (13.6 mg, 0.1
mmol) and without additives. After chromatography (pentane:ethyl
acetate =8:1−4:1) the product (20 mg, 79% yield) was obtained as a
1
light yellow oil. H NMR (400 MHz, CDCl3): δ 7.27−7.33 (m, 4H),
7.19−7.23 (m, 1H), 6.52 (q, J = 1.6 Hz, 1H), 6.38 (d, J = 15.6 Hz,
1H), 6.05 (ddd, J = 7.2, 8.0, 15.6 Hz, 1H), 2.93 (d, J = 16.0 Hz, 1H),
2.62−2.68 (m, 2H), 2.30 (ddd, J = 1.2, 8.0, 13.6 Hz, 1H), 1.98 (d, J =
1.6 Hz, 3H), 1.26 (s, 3H); 13C{1H}NMR (100 MHz, CDCl3): δ 202.4,
198.6, 150.2, 136.8, 136.5, 134.4, 128.5, 127.5, 126.2, 124.4, 49.4, 49.1,
42.4, 24.7, 15.9. HRMS-ESI m/z: Calcd for C17H18NaO2 [M + Na]+
277.1199. Found 277.1211.
2,6-Di-tert-butyl-6-cinnamylcyclohex-2-ene-1,4-dione (3j). The
product was prepared according to the above general procedure 2a
(29.3 mg, 0.12 mmol) and 2,6-di-tert-butyl-BQ 1f (22.0 mg, 0.1
mmol). After chromatography (pentane:ethyl acetate = 24:1) the
1
product 3j (23 mg, 68% yield) was obtained as a light yellow oil. H
NMR (400 MHz, CDCl3): δ 7.27−7.29 (m, 1H), 7.17−7.25 (m, 4H),
6.57 (s, 1H), 6.36 (d, J = 15.6 Hz, 1H), 5.94 (ddd, J = 6.0, 9.2, 15.6
Hz, 1H), 3.07 (ddd, J = 1.6, 6.0, 13.2 Hz, 1H), 2.82−2.92 (m, 2H),
2.04 (ddd, J = 0.8, 9.2, 13.2 Hz, 1H), 1.26 (s, 9H), 0.99(s, 9H);
13C{1H}NMR (100 MHz, CDCl3): δ 201.6, 200.0, 161.8, 137.0, 136.4,
134.7, 128.5, 127.4, 126.3, 126.1, 57.8, 43.6, 38.4, 38.1, 35.8, 29.2, 26.8.
HRMS-ESI m/z: Calcd for C23H30NaO2 [M + Na]+ 361.2138. Found
361.2152.
2-(Cyclohex-2-en-1-yl)-1,4-benzoquinone (3e). The product was
prepared according to the above general procedure from cyclohexenyl-
Bpin 2e (20.8 mg, 0.1 mmol), BQ 1a (21.6 mg, 0.2 mmol) and
diphenylphosphinic acid (12.5 mg, 0.05 mmol). After chromatography
(pentane:Et2O = 30:1) the product 3e (13 mg, 69% yield) was
1
obtained as a yellow oil. H NMR (400 MHz, CDCl3): δ 6.76 (d, J =
10.0 Hz, 1H), 6.71 (dd, J = 2.4, 10.0 Hz, 1H), 6.56 (dd, J = 1.2, 2.4 Hz,
1H), 5.96−6.00 (m, 1H), 5.45−5.49 (m, 1H), 3.55−3.61 (m, 1H),
1.93−2.07 (m, 3H), 1.53−1.67 (m, 2H), 1.36−1.44 (m, 1H); 13C-
{1H}NMR (100 MHz, CDCl3): δ 188.0, 187.0, 152.5, 136.9, 136.2,
132.8, 130.9, 126.2, 33.8, 28.7, 24.8, 19.8. HRMS-APCI m/z: Calcd for
C12H13O2 [M + H]+ 189.0910. Found 189.0910.
6-Cinnamyl-2,6-dimethoxycyclohex-2-ene-1,4-dione (3k). The
product was prepared according to the above general procedure
from 2a (36.6 mg, 0.15 mmol) and 2,6-dimethoxyl-BQ 1g (16.8 mg,
0.1 mmol). After chromatography (pentane:ethyl acetate = 4:1−2:1)
the product 3k (18 mg, 63% yield) was obtained as a light yellow oil.
1H NMR (400 MHz, CDCl3): δ 7.27−7.34 (m, 4H), 7.20−7.23 (m,
1H), 6.57 (d, J = 1.2 Hz, 1H), 6.46 (d, J = 15.6 Hz, 1H), 6.07 (dd, J =
7.2, 15.6 Hz, 1H), 5.96 (s, 1H), 3.79 (s, 3H), 3.26 (s, 3H), 3.05 (dd, J
= 1.2, 16.4 Hz, 1H), 2.88 (d, J = 16.4 Hz, 1H), 2.73 (dt, J = 1.2, 2.4
Hz, 2H); 13C{1H}NMR (100 MHz, CDCl3): δ 194.6, 191.8, 161.0,
136.7, 134.9, 128.5, 127.6, 126.2, 122.4, 112.1, 80.9, 56.5, 52.2, 46.8,
36.1. HRMS-ESI m/z: Calcd for C17H18NaO4 [M + Na]+ 309.1097.
Found 309.1109.
2-Cinnamyl-2-methyl-2,3-dihydronaphthalene-1,4-dione (3l).
The product was prepared according to the above general procedure
from 2a (29.3 mg, 0.12 mmol) and menadione 1h (17.2 mg, 0.1
mmol) and without additives. After chromatography (pentane:ethyl
acetate = 16:1−12:1) the product 3l (26 mg, 90% yield) was obtained
as a colorless oil. 1H NMR (400 MHz, CDCl3): δ 8.08−8.11 (m, 1H),
8.00−8.03 (m, 1H), 7.70−7.78 (m, 2H), 7.25−7.31 (m, 4H), 7.18−
7.22 (m, 1H), 6.38 (dt, J = 1.2, 15.6 Hz, 1H), 6.11 (ddd, J = 7.2, 8.4,
15.6 Hz, 1H), 3.11 (d, J = 16.0 Hz, 1H), 2.88 (d, J = 16.0 Hz, 1H),
2.74 (ddd, J = 1.2, 7.2, 14.0 Hz, 1H), 2.41 (ddd, J = 1.2, 8.0, 14.0 Hz,
1H), 1.34 (s, 3H); 13C{1H}NMR (100 MHz, CDCl3): δ 200.4, 196.3,
136.9, 134.9, 134.43, 134.38, 134.0, 133.8, 128.5, 127.5, 127.4, 126.2,
126.1, 124.3, 49.5, 49.3, 42.1, 24.1. HRMS-ESI m/z: Calcd for
C20H18NaO2 [M + Na]+ 313.1199. Found 313.1203.
(E)-2-Methyl-2-(oct-2-en-1-yl)-2,3-dihydronaphthalene-1,4-dione
(3m). The product was prepared according to the above general
procedure from 2b (28.6 mg, 0.12 mmol), menadione 1h (17.2 mg,
0.1 mmol), and CF3CO2H (14.4 mg, 0.1 mmol). After chromatog-
raphy (pentane:ethyl acetate =30:1) the product (18 mg, 63% yield)
was obtained as a colorless oil. 1H NMR (400 MHz, CDCl3): δ 8.05−
trans-2-(Methyl-cyclohex-3-ene-1-carboxylate)-1,4-benzoqui-
none (3f). The product was prepared according to the above general
procedure from 2f (trans:cis =12:1, 27.9 mg, 0.1 mmol), BQ 1a (21.6
mg, 0.2 mmol), and diphenylphosphinic acid (12.5 mg, 0.05 mmol).
After chromatography (pentane:Et2O = 16:1−8:1) the product 3f (11
1
mg, 45% yield) was obtained as a yellow oil. H NMR (400 MHz,
CDCl3): δ 6.79 (d, J = 10.0 Hz, 1H), 6.73 (dd, J = 2.4, 10.0 Hz, 1H),
6.52 (dd, J = 1.2, 2.4 Hz, 1H), 6.01−6.06 (m, 1H), 5.49−5.54 (m,
1H), 3.69−3.73 (m, 1H), 3.66 (s, 3H), 2.38−2.46 (m, 1H), 2.23−2.33
(m, 2H), 2.05 (ddd, J = 6.8, 11.6, 13.6 Hz, 1H), 1.84−1.89 (m, 1H);
13C{1H}NMR (100 MHz, CDCl3): δ 187.6, 186.6, 175.3, 150.6, 137.0,
136.3, 134.0, 129.5, 125.2, 51.8, 35.1, 32.6, 29.4, 27.3. HRMS-APCI m/
z: Calcd for C14H14NaO4 [M + Na]+ 269.0784. Found 269.0791.
2-Cinnamyl-5-methyl-1,4-benzoquinone (3g). The product was
prepared according to the above general procedure from 2a (24.4 mg,
0.1 mmol) and 2-methyl-BQ 1c (24.4 mg, 0.2 mmol). After
chromatography (pentane:Et2O = 50:1) the product 3g together
with the 6-Me isomer was obtained as a yellow oil (16.4 mg, 69%
1
yield). The NMR data of the major isomer. H NMR (400 MHz,
CDCl3): δ 7.29−7.37 (m, 4H), 7.22−7.25 (m, 1H), 6.57 (s, 2H), 6.51
(d, J = 15.8, 1H), 6.18 (dt, J = 15.8, 7.1 Hz, 1H), 3.33 (d, J = 7.1, 2H),
2.07 (d, J = 1.3 Hz, 2H). 13C{1H}NMR (100 MHz, CDCl3) δ 187.9,
187.7, 147.8, 146.0, 136.7, 134.0, 133.3, 132.9, 128.7, 127.7, 126.2,
124.2, 32.6, 16.2. HRMS-APCI m/z: Calcd for C16H15O2 [M + H]+
239.1067. Found 239.1070.
6-Cinnamyl-2,6-dimethylcyclohex-2-ene-1,4-dione (3h). The
product was prepared according to above general procedure from 2a
D
DOI: 10.1021/acs.joc.5b00264
J. Org. Chem. XXXX, XXX, XXX−XXX

The Journal of Organic Chemistry
Note
8.08 (m, 1H), 8.00−8.02 (m, 1H), 7.69−7.76 (m, 2H), 5.37−5.44 (m,
1H), 5.23−5.32 (m, 1H), 3.02 (d, J = 16.0 Hz, 1H), 2.82 (d, J = 16.0
Hz, 1H), 2.47 (ddd, J = 0.8, 6.8, 13.6 Hz, 1H), 2.16−2.22 (m, 1H),
1.93 (dd, J = 6.8, 13.6 Hz, 2H), 1.16−1.32 (m, 9H), 0.85 (d, J = 7.2
Hz, 3H); 13C{1H}NMR (100 MHz, CDCl3): δ 200.8, 196.6, 136.0,
135.0, 134.4, 134.0, 133.9, 127.5, 126.0, 123.7, 49.5, 49.1, 42.0, 32.5,
31.3, 28.9, 23.7, 22.5, 14.0. HRMS-ESI m/z: Calcd for C19H24NaO2
[M + Na]+ 307.1669. Found 307.1658.
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(19 mg, 57% yield) was obtained as a colorless oil. H NMR (400
MHz, CDCl3): δ 8.04−8.09 (m, 2H), 7.73−7.77 (m, 2H), 7.20−7.33
(m, 5H),, 6.48 (d, J = 15.6 Hz, 1H), 6.12 (dt, J = 8.0, 15.6 Hz, 1H),
3.65 (s, 3H), 3.46 (d, J = 16.4 Hz, 1H), 2.93−3.04 (m, 3H);
13C{1H}NMR (100 MHz, CDCl3): δ 193.4, 192.8, 170.3, 136.6, 135.3,
134.9, 134.6, 134.4, 134.2, 128.5, 127.7, 127.6, 126.6, 126.3, 123.2,
60.9, 53.2, 44.8, 37.7. HRMS-ESI m/z: Calcd for C21H18NaO4 [M +
Na]+ 357.1097. Found 357.1080.
5-Cinnamyl-2,3-dimethoxy-5-methylcyclohex-2-ene-1,4-dione
(3o). The product was prepared according to the above general
procedure from 2a (29.3 mg, 0.12 mmol) and 2,3-dimethoxyl-5-
methyl-BQ 1j (18.2 mg, 0.1 mmol) and without additives. After
chromatography (pentane:ethyl acetate = 8:1−4:1) the product (26
mg, 87% yield) was obtained as a light yellow oil. 1H NMR (400 MHz,
CDCl3): δ 7.26−7.32 (m, 4H), 7.19−7.23 (m, 1H), 6.39 (d, J = 16.0
Hz, 1H), 6.05 (ddd, J = 7.2, 16.0 Hz, 1H), 3.953 (s, 3H), 3.946 (s,
3H), 2.86 (d, J = 16.0 Hz, 1H), 2.66 (ddd, J = 1.2, 6.8, 13.6 Hz, 1H),
2.59 (d, J = 16.0 Hz, 1H), 2.336 (ddd, J = 1.2, 8.0, 13.6 Hz, 1H), 1.28
(s, 3H); 13C{1H}NMR (125 MHz, CDCl3): δ 198.0, 193.4, 149.2,
148.3, 136.7, 134.5, 128.5, 127.6, 126.2, 124.2, 60.62, 60.59, 48.0, 47.9,
42.8, 24.8. HRMS-ESI m/z: Calcd for C18H20NaO4 [M + Na]+
323.1254. Found 323.1268.
Hemitectol (7). A solution of 3d (23 mg, 0.1 mmol) in pyrridine
(0.5 mL) was refluxed for 24 h. The solution was then concentrated in
vacuo, and the residue was purified by chromatography (pentane:eth-
yl-acetate = 18:1−12:1) to give dark yellow oil 17 mg, yield 75%. The
spectral data agree with the corresponding literature values.23 1H NMR
(400 MHz, CDCl3): δ 8.15−8.17 (m, 1H), 8.04−8.06 (m, 1H), 7.43−
7.49 (m, 2H), 6.54 (s, 1H), 6.34 (d, J = 9.6 Hz, 1H), 5.65 (d, J = 9.6
Hz, 1H), 4.92 (s, 1H), 1.49 (s, 6H). Hemitectol easily undergoes
dimerization,23 and therefore the NMR spectra were recorded in
diluted solutions. Because of this, some of the quaternary carbon
atoms cannot be detected by 13C spectroscopy. 13C{1H}NMR (100
MHz, CDCl3): δ 130.3, 125.8, 125.5, 122.6, 122.0, 121.4, 76.3, 27.6.
HRMS-ESI m/z: Calcd for C15H15O2 [M + H]+ 227.1067. Found
227.1063.
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AUTHOR INFORMATION
Corresponding Author
■
́
́
*E-mail: kalman@organ.su.se; Web: http://www.organ.su.se/
ks/; Fax: +46-8-15 49 08
́
Notes
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The authors declare no competing financial interest.
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ACKNOWLEDGMENTS
■
The authors thank the financial support of the Swedish
Research Council (VR) and the Knut och Alice Wallenbergs
Foundation. H.-P.D. acknowledges a postoctoral position from
the Wenner-Gren Foundation.
E
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