Syntheses of 3,4-disubstituted pyrroles and furans via Lewis acid-promoted semipinacol rearrangement/alkyne-ketone metathesis reaction of (C)-2- N - Or O-((3-arylpropargyl)methyl)-tethered 3,5,5-trimethyl-2,3-epoxycyclohexan-1-ones

Article abstract of DOI:10.1021/jo402025z

The synthesis of 2,3-disubstituted pyrroles via TMSOTf-assisted cyclization reaction of 3,5,5-trimethyl-2,3-epoxycyclohexan-1-ones incorporating a (3-arylpropargyltosylamino)methyl tether at the C-2 position is described. The reaction starts with an acid-

Full text of DOI:10.1021/jo402025z

Article
pubs.acs.org/joc
Syntheses of 3,4-Disubstituted Pyrroles and Furans via Lewis Acid-
Promoted Semipinacol Rearrangement/Alkyne-Ketone Metathesis
Reaction of (C)-2‑N- or O‑((3-Arylpropargyl)methyl)-Tethered 3,5,5-
Trimethyl-2,3-epoxycyclohexan-1-ones
Ming-Chang P. Yeh,* Ming-Nan Lin, Ching-Hsien Hsu, and Chia-Jung Liang
Department of Chemistry, National Taiwan Normal University, 88 Ding-Jou Road, Section 4, Taipei 11677, Taiwan, Republic of
China
S
* Supporting Information
ABSTRACT: The synthesis of 2,3-disubstituted pyrroles via
TMSOTf-assisted cyclization reaction of 3,5,5-trimethyl-2,3-
epoxycyclohexan-1-ones incorporating
a (3-
arylpropargyltosylamino)methyl tether at the C-2 position is
described. The reaction starts with an acid-promoted semi-
pinacol rearrangement to give a ring contraction cyclo-
pentanone moiety bearing an arylpropargylaminoacetyl side
chain. A subsequent alkyne-ketone metathesis affords the
pyrrole derivatives in good yields. The 3,4-disubstituted furan
analogues can also be available from 3,5,5-trimethyl-2,3-
epoxycyclohexan-1-ones with a tethered arylpropargyl methyl
ether at the C-2 position and BF3·OEt2 under an atmosphere
of oxygen.
Scheme 1. Acid-Catalyzed Semipinacol Rearrangement/
Alkyne-Ketone Metathesis Reaction
INTRODUCTION
■
Furans1 and pyrroles2 are important heterocycles that are found
in many natural products and pharmaceuticals. Consequently,
many efforts have been devoted to the design of expedient and
efficient synthetic routes to these five-membered ring hetero-
cycles. Several general methods for the synthesis of pyrroles
and furans involve cyclization reactions of 1,4-dicarbonyl
derivatives,3 rhodium(III)-catalyzed additions of alkenes and
alkynes across C−N and C−O multiple bonds,4 metal-catalyzed
one-pot multicomponent coupling reactions of alkynes, carbon-
yl compounds and amines,5 gold(I)-catalyzed hydroamination
or hydration of 1,3-diynes,6 and the gold-catalyzed dehydrative
cyclization of 1-amino-3-alkyn-2-ols and 3-alkyne-1,2-diols.7
Moreover, a great number of attractive transition-metal-
catalyzed cyclization of various of organic substrates have
been developed for the construction of the furan and pyrrole
rings.8 Recently, we reported a method for the synthesis of
spiropiperidines via TfOH-catalyzed semipinacol rearrange-
ment/alkyne-aldehyde metathesis of (C)-3-((3-
arylpropargyltosylamino)methyl)-tethered 2,3-epoxycyclohex-
an-1-ols (Scheme 1, eq 1) and the corresponding epoxycyclo-
hexanone (Scheme 1, eq 2).9 To further explore this chemistry,
we envision that switching the tether to the C-2 position may
alter the reaction path and lead to other heterocyclic skeletons.
Herein, we report a sequential reaction that provides
cyclopentanone-substituted pyrroles and furans from cycliza-
tion of (C)-2-N- or O-((3-arylpropargyl)methyl)-tethered
3,5,5-trimethyl-2,3-epoxycyclohexan-1-ones with Lewis acids
(Scheme 1, eq 3). In this reaction, an acid-promoted
semipinacol rearrangement of the cyclic 2,3-epoxycyclohexa-1-
one occurred to give the ring contraction 2,4,4-trimethylcyclo-
pentanone moiety with an N- or O-3-arylpropargylmethyl side
Received: September 11, 2013
Published: December 2, 2013
© 2013 American Chemical Society
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chain at the C-2. A subsequent acid-promoted alkyne-ketone
metathesis furnished the five-membered ring heterocycles in
moderate to good yields under mild reaction conditions. To the
best of our knowledge, this is the first report on the use of the
semipinacol rearrangement/alkyne-carbonyl metathesis strategy
for the synthesis of pyrroles and furans.10
reaction. As revealed in Scheme 2, substrates with electron-
neutral and -donating aryl groups at the terminal position of the
acetylene gave the desired isoquinolinones 2a−f in satisfactory
yields (60−85%).15 Compound 1g, bearing an electron-
withdrawing ester group on the phenyl ring, gave a trace
amount of the corresponding isoquinolinone 2g, and a nitro
substituent on the phenyl ring, 1h, impeded the reaction.
A possible mechanistic explanation for the formation of
isoquinolinone 2 from 1 is stated in Scheme 3. The reaction
was initiated by the HNTf2-promoted semipinacol rearrange-
ment of 1a, which incorporated a hydride transfer to generate
the oxonium species 3a. A transfer of hydride in the
semipinacol rearrangement of 2,3-epoxy alcohols promoted
by TBSOTf was known in the literature.16 Intermediate 3a
underwent [2 + 2] cycloaddition and generated the oxete 3b.
The intermediate 3b proceeded [2 + 2] cycloreversion followed
by deprotonation and double bond migration to afford 2a.
Several Lewis- or Brønsted-acid-catalyzed transfers of the
oxygen atom from a carbonyl to an alkyne (a formal alkyne−
carbonyl metathesis) producing conjugated enones have been
reported in the literature.17
RESULTS AND DISCUSSION
■
The initial compound (C)-2-N-tosyl-N-((3-phenylpropargyl)-
methyl)-tethered 2,3-epoxycyclohexan-1-one 1a was prepared
starting from the reaction of cyclohex-2-en-1-one with
formaldehyde under the Baylis−Hillmann reaction condition.11
The resulting 2-hydroxymethylcyclohex-2-en-1-one was treated
with m-chloroperbenzoic acid followed by replacement of the
hydroxyl group with N-tosylpropargylamine using the Mitsu-
nobu reaction protocol.12 The resulting terminal alkyne was
transformed to 1a using the Sonogashira reaction condition.13
Since 2,3-epoxycyclohexan-1-one derivatives were known to
undergo semipinacol rearrangement generating cyclopentanone
derivatives under acidic conditions,14 compound 1a was
subjected to various acid catalysts for the initial study. However,
among the acids and the solvents tested, none of the desired
ring-contracted products were observed. Instead, isoquinoli-
none derivative 2a was isolated in 83% yield when 1a was
treated with 0.1 equiv of NHTf2 under the optimized reaction
conditions (CH2Cl2, 40 °C, 70 min, Scheme 2). Encouraged by
Surprisingly, when subjected to 2.0 equiv of FeCl3 at −15 °C
in CH2Cl2 for 1 h, compound 1a provided a major product,
identified as the heterotetracyclic compound 4a, as the only
stereoisomer isolated in 77% yield (Scheme 4). It is important
Scheme 4. FeCl3-Promoted Synthesis of Compounds 4a, 4c,
4f, and 4i
Scheme 2. Synthesis of Isoquinolinones 2a−h
to mention that three stereogenic centers of 4a are created;
however, only the single diastereomer shown was isolated. The
relative stereochemistry of 4a was accomplished by X-ray
diffraction analysis.15 The formation of 4a may start with
activation of both the carbonyl group and the oxirane by FeCl3
the success of NHTf2-catalyzed synthesis of the isoquinolinone
derivative 2a, we next examined the substrate scope of the
Scheme 3. Suggested Reaction Path for the Formation of 2a from 1a
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Scheme 5. Postulated Reaction Path for the Formation of 4a from 1a
followed by a regioselective SN2-type ring-opening of the
oxirane with a chloride ion and an anti-addition of the activated
carbonyl moiety and a chloride ion across the acetylene
resulting in the formation of the intermediate 5 (Scheme 5).
Detachment of the OFeCl2 anion from the quaternary carbon
center formed the postulated tertiary carbonium ion 6a, which
underwent a Friedel−Crafts type alkylation to give 6b.
Intermediate 6b led to heterotetracycle 4a after rearomatiza-
tion. Moreover, substrates 1c and 1f, bearing an electron-
neutral group and 1i, with an electron-donating methoxy
substituent at the meta position on the phenyl ring, also
delivered heterotetracycles 4c, 4f, and 4i in diastereoselective
fashion and in 46−76% yields (Scheme 4). Similarly, reaction of
1a with 2.0 equiv of FeBr3 at −15 °C in CH2Cl2 for 1 h
furnished the corresponding heterotetracyclic dibromide 7
(Figure 1) in 67% isolated yield.15
proven most efficacious for the semipinacol rearrangement.
Thus, subjection of 8 to 0.1 equiv of TMSOTf in CH3CN at 40
°C for 1 h gave the cyclopentanone derivative 9 with a
propargylaminomethyl tether in 79% isolated yield. Unfortu-
nately, compound 9 failed to undergo alkyne-ketone metathesis
reaction upon treatment with a variety of acids. Compound 9
was recovered quantitatively in most cases (Scheme 6).
Scheme 6. TMSOTf-Promoted Semipinacol Rearrangement
of 8 to 9
Next, substrate 8 with an additional methyl group at the C-3
position was investigated. When compound 8 was subjected to
a variety of acids (HNTf2, TBSOTf, Sn(OTf)2, and Fe(OTf)3
in DCM or DCE, reactions gave a complex mixture in each
case. However, the use of TMSOTf with 8 in CH3CN has
We further studied substrates 10 with an additional geminal
dimethyl group at the C-5 position of the six-membered ring.
As shown in Table 1, a series of reaction conditions was
screened using different acids and solvents. Treating of the
parent compound 10a with 0.5 equiv of BF3·OEt2 at 30 °C in
CH2Cl2 (DCM) for 24 h gave the semipinacol rearrangement
product 11a in 29% isolated yield, as well as the N-tosylpyrrole
derivative 12a and the pyrrole derivative 13a15 in 22 and 8%
yield, respectively (Table 1, entry 1). When 1a was subjected to
AgOTf (0.1 equiv) in dichloroethane (DCE) at 70 °C for 48 h,
11a (29%) and 12a (37%) were isolated (Table 1, entry 2). By
using In(OTf)3 (0.1 equiv) or Sn(OTf)3 in xylene as catalysts,
10a failed to increase the yield of the N-tosylpyrrole 12a, albeit
required an elevated temperature in each case (Table 1, entries
Figure 1. Structure of 7.
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Table 1. Optimizing of the Reaction Conditions in the Cycloisomerization of 10a with Lewis Acids
a
b
b
b
entry
acid (equiv)
conditions
11a (%)
12a (%)
13a (%)
1
BF3·OEt2 (0.5)
AgOTf (0.1)
DCM, 30 °C, 24 h
DCE, 70 °C, 48 h
xylene, 135 °C, 24 h
xylene, 135 °C, 24 h
DCM, 26 °C, 24 h
DCE, 70 °C, 24 h
DCE, 70 °C, 16 h
DCE, 70 °C, 24 h
CH3CN, 40 °C, 0.2 h
DCE, 75 °C, 26 h
xylene, 135 °C, 2 h
DCM, 29 °C, 24 h
DCM, 30 °C, 6 h
DCM, 30 °C, 4 h
DCM, 30 °C, 3 h
29
29
23
3
22
37
19
15
0
8
0
2
3
In(OTf)3 (0.1)
Sn(OTf)3 (0.1)
FeCl3 (1.2)
0
4
0
5
0
0
6
TMSCl (0.1)
TfOH (0.1)
25
0
0
0
7
36
34
0
0
8
Fe(OTf)3 (0.1)
TMSOTf (0.1)
TMSOTf (0.1)
TMSOTf (0.1)
TMSOTf (0.5)
TMSOTf (1.0)
TMSOTf (1.2)
TMSOTf (2.0)
0
0
9
92
3
0
10
11
12
13
14
15
42
45
22
18
18
18
0
4
0
29
0
28
32
36
38
0
0
a
b
All reactions were conducted using 0.1 M of 10a. Isolated yields by column chromatography.
Scheme 7. Synthesis of Pyrrole 13 from 10
3−4). While 1.2 equiv of FeCl3 in DCM at 26 °C failed to give
any cyclized product (Table 1, entry 5), a catalytic amount of
TMSCl (0.1 equiv) in DCE at 70 °C afforded only 11a in 25%
yield (Table 1, entry 6). Although 0.1 equiv of TfOH and
Fe(OTf)3 in DCE at 70 °C proved capable for the full
transformation of 10a to the N-tosylpyrrole 12a, low yields of
36 and 34% were obtained (Table 1, entries 7 and 8).
Employing TMSOTf (0.1 molar equiv) in CH3CN at 29 °C for
10 min produced 11a as the sole product in 92% yield (Table 1,
entry 9). The yield of the pyrrole 12a can be increased to 42
and 45%, respectively, when 10a was treated with 0.1 equiv of
TMSOTf in DCE at 75 °C or xylene at 135 °C (Table 1,
entries 10 and 11). Increasing the TMSOTf loading from 0.1 to
0.5 equiv in DCM at 28 °C for 24 h provided 11a (29%), 12a
(22%), and 13a (28%) (Table 1, entry 12). To our delight, the
treatment of 10a with 1.0 equiv of TMSOTf in DCM at 29 °C
for 6 h gave complete conversion to pyrrole derivatives 12a and
13a, which was isolated in 18 and 32% yield, respectively
(Table 1, entry 13). The use of 1.2 equiv of TMSOTf in DCM
at 29 °C for 4 h gave pyrrole derivatives 12a and 13a in 18 and
36% yield, respectively (Table 1, entry 14). Running the
reaction with 2.0 equiv of TMSOTf loading in DCM at 30 °C
for 3 h, however, did not significantly improve yields of pyrroles
12a and 13a (Table 1, entry 15). Since N-tosylpyrroles can be
easily transformed into pyrroles under basic conditions, it
would be practical to obtain pyrrole 13a from the starting
substrate 10a in a one-pot two-step process. Thus, 10a was
subjected to 1.2 equiv of TMSOTf in DCM at room
temperature for 4 h until the starting material 1a was not
detected by thin layer chromatography. A solution of 2.0 M
NaOH in methanol was then added to the reaction mixture at 0
°C, and the resultant mixture was stirred at this temperature for
2 h to provide the pyrrole derivative 13a as the major product
in 62% isolated yield. Thus, the use of 1.2 equiv of TMSOTf in
CH2Cl2 at ambient temperature followed by the basic
treatment (NaOH/MeOH) at 0 °C was employed as the
standard reaction conditions for the synthesis of pyrrole 13
from the starting substrate 10.
As can be seen in Scheme 7, substrates 10b−g, bearing
electron-neutral and -rich arenes at the alkyne terminus, gave
clean conversion to pyrroles 13b−g15 in 49−67% yields under
the standard reaction conditions. A bromine atom on the
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Scheme 8. Conversion of 10j,k to 11j,k
Scheme 9. Suggested Reaction Path for the Formation of 11a and 12a from 10a
Figure 2. Intermediates A, B, and C.
phenyl ring, for example, 10h, did not impede the cyclization
and afforded the desired pyrrole 13h in 48% yield. Interestingly,
a thiophenyl group at the alkyne terminus, 10i, also delivered
the corresponding pyrrole 13i15 in 52% yield. However, it must
be mentioned that substrates with the electron-withdrawing
nitro group, for example, compounds 10j and 10k, gave only
the semipinacol rearrangement products 11j and 11k in 66 and
89% isolated yield, respectively (Scheme 8). None of pyrrole
derivatives were observed.
A possible reaction path for the formation of N-tosylpyrrole
12a from the starting substrate 10a was that initial activation of
the oxirane by TMSOTf occurred to give the semipinacol
rearrangement product 11a (Scheme 9). A subsequent
TMSOTf-assisted intramolecular [2 + 2] cycloaddition
followed by [2 +2] cycloreversion (alkyne-ketone metathesis)
occurred to generate an N-tosyldihydropyrrole derivative.
Oxidation of the N-tosyldihydropyrrole during aqueous workup
and column chromatography furnished N-tosylpyrrole 12a.
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Moreover, in order to provide the evidence for the formation of
the pyrrole from the key alkyne−carbonyl metathesis of 11a,
compound 11a was subjected to the one-pot two-step process.
Thus, treatment of 11a with 1.2 equiv of TMSOTf in DCM at
30 °C for 4 h followed by basic treatments (1.0 M NaOH/
MeOH, 0 °C, 2 h) afforded pyrrole 13a in 67% isolated yield.
This result further suggested that pyrrole 13 is generated from
an acid-promoted alkyne-ketone metathesis of 11.
Scheme 11. Synthesis of Furan 16 from 14
It is important to mention that the alkyne−ketone metathesis
did not proceed with compound 8 lacking of a geminal
dimethyl group at the C-5 position of the ring. It is speculated
that the trimethylsilyl group may coordinate to both carbonyl
groups of 8 to form a bicyclic intermediate A (Figure 2). The
bulky trimethylsilyl and the adjacent methyl groups may inhibit
the alkyne from attacking the carbonyl carbon for further
cyclization. However, the presence of the geminal dimethyl and
the trimethylsilyl moieties causes a large amount of steric
congestion in B, and intermediate B would lead to C.
Intermediate C underwent an acid-promoted alkyne−ketone
metathesis to generate pyrrole derivatives.
(Figure 3), with TMSOTf or BF3·OEt2 resulted in decom-
position of the starting substrates, and none of the cyclized
products were obtained.
This method can be applied to the synthesis of 3,4-
disubstituted-dihydrofurans and -furans. The starting 2,3-
epoxycyclohexan-1-one with a tethered 3-arylpropargyl methyl
ether at the C-2 position of the ring, 14a, is prepared from
3,5,5-trimethylcyclohex-2-en-1-one in the similar fashion as that
of 1a. Among various acids and solvents screened, it was found
that BF3·OEt2 in DCE is most effective for the formation of
furan derivatives from 14a. Thus, reaction of 14a with 1.0 equiv
of BF3·OEt2 in DCE (0.025 M) at room temperature for 3 h
produced dihydrofuran 15a as the major products in 71%
isolated yields. Several examples for the synthesis of the
dihydrofuran derivatives are listed in Scheme 10. It must be
Figure 3. Structures of 17 and 18.
In conclusion, a simple transformation for the synthesis of
3,4-disubstituted pyrroles and furans has been developed. The
reaction is initiated by TMSOTf or BF3·OEt2-promoted
tandem semipinacol rearrangement/alkyne-ketone metathesis
of 2,3-epoxycyclohexa-1-ones with an N- or O-(3-
arylpropargyl)methyl tether at the C-2 position of the six-
membered ring followed by oxidation. The advantages of this
process are the mild and metal-free reaction conditions,
providing an alternative route to the 3,4-disubstituted pyrroles
and furans.
Scheme 10. BF3·OEt2-Mediated Synthesis of Dihydrofurans
15a−f
EXPERIMENTAL SECTION
■
General Considerations. All reactions were performed in oven-
dried glassware under nitrogen atmosphere unless otherwise indicated.
Anhydrous solvents or reaction mixtures were transferred via an oven-
dried syringe or cannula. Solvents were predried by molecular sieves
and then by passing through an Al2O3 column. Melting points were
determined in open capillaries with an electronic apparatus and are
uncorrected. Chromatographic purification was performed with flash
column chromatography on silica P60, 40−63 m (230−400 mesh). 1H
nuclear magnetic resonance (NMR) spectra were recorded with 400
and 500 MHz spectrometers. The chemical shifts are reported in parts
per million with either Me4Si (0.00 ppm) or CDCl3 (7.26 ppm) as
internal standard. 13C NMR spectra were recorded with 100 and 125
MHz spectrometers using CDCl3 (77.0 ppm) as internal standard.
Mass spectra were determined by using a spectrometer with 70-eV
ionizing voltage and were reported as mass/charge (m/e) with percent
relative abundance. High-resolution mass spectra were obtained with a
double-focusing mass spectrometer.
Representative Procedure for Synthesis of Starting Com-
pound 1. To a stirring solution of cyclohex-2-en-1-one (28.84 g, 0.30
mol) in MeOH (100 mL) and H2O (500 mL) at 0 °C under nitrogen
were added formaldehyde (37 wt % solution in water, 11.26 g, 0.38
mol), Ba(OH)2 (0.77 g, 4.5 mmol), and N-methyl-2-pyrrolidone
(NMP, 1.27 g, 15.00 mmol). The reaction mixture was stirred at 29 °C
for 4 h. The reaction was then quenched with 20 mL of HCl(aq) at 0
°C. After being stirred at 0 °C for 30 min, the reaction mixture was
neutralized with saturated NaHCO3(aq). The reaction mixture was
extracted with CH2Cl2 (300 mL × 3). The combined extracts were
washed with water (300 mL × 3), and brine (300 mL × 3), dried over
mentioned that a trace amount of furan 16, presumably arising
from oxidation of dihydrofuran 15 during aqueous workup and
purification process, was detected by thin layer chromatography
of the crude mixture in each case.
To our delight, furan 16a15 was isolated as the sole product
in 56% isolated yield when the BF3·OEt2-promoted cyclization
of 14a was carried out under an atmosphere of oxygen in DCE
at 70 °C for 4 h. Further investigations had revealed that
substrates lacking strongly electron-withdrawing substituents
on the phenyl ring reacted smoothly with BF3·OEt2 under the
reaction conditions. As seen in Scheme 11, substrates with an
electron-neutral or -rich aryl groups at the alkyne gave furans
16 in 45−65% isolated yields.
It must be mentioned that reaction of the corresponding
(C)-2-N- and O-3-((phenylpropargyl)methyl)-tethered 3,5,5-
trimethyl-2,3-epoxycyclohexan-1-ols, for example, 17 and 18
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anhydrous MgSO4 (20 g), and concentrated under reduced pressure to
give a crude oil. The crude mixture was purified by flash column
chromatography (silica gel, ethyl acetate/hexanes 1:3) to afford 2-
(hydroxymethyl)cyclohex-2-en-1-ol (22.35 g, 0.18 mol, 59%). To a 10
mL round-bottom flask equipped with a stirrer bar and capped with a
rubber septum were added 2-(hydroxymethyl)cyclohex-2-en-1-one
(22.35 g, 0.18 mol), 226 mL of MeOH and 8.9 mL of 2.0 M of NaOH
in MeOH. The reaction mixture was cooled to 0 °C, and to it was
added H2O2 (35% in H2O, 24.10 g, 0.71 mol). The reaction mixture
was stirred at 0 °C for 3 h. The mixture was treated with 20 mL of
saturated Na2S2O3(aq) solution. The resulting mixture was extracted
with methylene chloride (200 mL × 3), and the combined extracts
were washed with brine and dried over MgSO4. The filtrate was
concentrated under reduced pressure, and the residue was purified by
flash column chromatography on silica gel (ethyl acetate/hexanes 1:1)
to give 2,3-epoxy-2-(hydroxymethyl)cyclohex-2-en-1-one (17.23 g,
0.12 mol, 67%). To a solution of p-TsCl (6.29 g, 0.033 mol) in 100
mL of CH2Cl2 at 0 °C were added propargylamine (1.65 g, 0.030 mol)
and Et3N (3.6 g, 0.036 mol). The reaction was stirred at ambient
temperature for 12 h until no propargylamine was detected by TLC.
The reaction was quenched with 50 mL of saturated NH4Cl(aq), and
the resulting solution was extracted with CH2Cl2 (50 mL × 3), and the
combined extracts were washed with brine and dried (MgSO4). The
filtrate was concentrated under reduced to give the p-tosyl propargyl-
amine (5.58 g, 0.027 mol, 90%). To a solution of PPh3 (11.89 g, 0.045
mol) in 200 mL of THF under nitrogen at 0 °C was added diisopropyl
azodicarboxylate (DIAD, 9.17 g, 0.045 mol). The reaction was allowed
to stir at 0 °C for 20 min and to it was added p-tosyl propargylamine
(5.58 g, 0.027 mol). The mixture was allowed to stir at 0 °C for 20 min
and was treated with 2,3-epoxy-2-(hydroxymethyl)cyclohex-2-en-1-
one (5.58 g, 0.027 mol). The reaction was allowed to stir at 0 °C for
30 min and at ambient temperature for 4 h before being quenched
with 100 mL of saturated NH4Cl(aq). The resulting solution was
extracted with CH2Cl2 (40 mL × 3), and the combined extracts were
washed with brine and dried (MgSO4). The filtrate was concentrated
under reduced pressure to give a crude oil. The oil was purified by
flash column chromatography (silica gel, ethyl acetate/hexanes 1:4) to
produce 4-methyl-N-((2-oxo-7-oxabicyclo[4.1.0]heptan-1-yl)methyl)-
N-(prop-2-yn-1-yl)benzenesulfonamide (6.62 g, 0.020 mol, 74%). In a
50-mL round-bottom flask equipped with a stirring bar were added
Pd(PPh3)4 (0.065 g, 0.056 mmol), CuI (0.021 g, 0.11 mmol) and PhI
(0.69 g, 3.39 mmol). The system was purged with N2, and Et3N (2.8
mL) was added. The reaction was allowed to stir at ambient
temperature for 20 min followed by addition of 4-methyl-N-((2-oxo-7-
oxabicyclo[4.1.0]heptan-1-yl)methyl)-N-(prop-2-yn-1-yl)benz-enesul-
fonamide (0.94 g, 2.82 mmol). The reaction was left at ambient
temperature for 3 h. The reaction mixture was quenched with
saturated NH4Cl(aq). The mixture was extracted with CH2Cl2 (20 mL
× 3). The CH2Cl2 solution was washed with brine, dried with MgSO4
and concentrated under reduced pressure. The resulting oil was
purified by flash column chromatography on silica gel, eluting with
ethyl acetate/hexanes 1:4) to obtain 4-methyl-N-((2-oxo-7-oxabicyclo-
[4.1.0]heptan-1-yl)methyl)-N-(3-phenyl-prop-2-yn-1-yl)-
benzenesulfonamide (1a) as a white solid (0.90 g, 2.2 mmol, 78%):
mp 141−142 °C; 1H NMR (400 MHz, CDCl3) δ 7.76 (d, J = 8.2 Hz,
2H), 7.29−7.21 (m, 5H), 7.05 (d, J = 7.0 Hz, 2H), 4.52 (d, J = 18.6
Hz, 1H), 4.25 (d, J = 18.6 Hz, 1H), 4.02 (d, J = 15.8 Hz, 1H), 3.93 (s,
1H), 3.44 (d, J = 15.8 Hz, 1H), 2.56 (dt, J = 17.2 Hz, 4.8 Hz, 1H), 2.32
(s, 3H), 2.31−2.24 (m, 1H), 2.17−2.01 (m, 2H), 1.95−1.84 (m, 1H),
1.74−1.65 (m, 1H); 13C NMR (100 MHz, CDCl3) δ 205.8, 143.8,
135.5, 131.5 (2C), 129.6 (2C), 128.4, 128.0 (2C), 127.9 (2C), 122.1,
85.7, 82.0, 60.3, 60.2, 44.3, 40.3, 37.0, 23.0, 21.4, 17.3; IR (CH2Cl2)
2944, 1708, 1598, 1349, 1163, 1091 cm−1; MS (ESI) m/e (%) 432.1
([M + Na]+, 100), 286.1 (8), 243.1 (23), 143 (15), 122.54 (17) ;
HRMS (ESI) calcd for C23H23NO4NaS [M + Na]+ 432.1245, found
432.1250.
conditions. The resulting 3,5,5-trimethyl-2-(hydroxymethyl)cyclohex-
2-en-1-ol was oxidized with H2O2, amidation with N-tosylpropargy-
lamide and arylation with aryliodide as those described in the
experimental procedure previously.
Data for 4-Methyl-N-(3-phenylprop-2-yn-1-yl)-N-((4,4,6-trimeth-
y l - 2 - o x o - 7 - o x a b i c y c l o [ 4 . 1 . 0 ] h e p t a n - 1 - y l ) m e t h y l ) -
benzenesulfonamide (10a). (0.82 g, 1.81 mmol, 85%) A white solid:
mp 112−113 °C; 1H NMR (400 MHz, CDCl3) δ 7.79 (d, J = 8.0 Hz,
2H), 7.29−7.20 (m, 5H), 7.07 (dd, J = 8.0, 4.0 Hz, 2H), 4.46 (d, J =
17.6 Hz, 1H), 4.39 (d, J = 17.6 Hz, 1H), 3.77 (d, J = 16.0 Hz, 1H),
3.74 (d, J = 16.0 Hz, 1H), 2.65 (d, J = 17.6 Hz, 1H), 2.32 (s, 3H), 2.08
(d, J = 17.6 Hz, 1H), 1.99 (dd, J = 17.6, 4.0 Hz, 1H), 1.80 (dd, J =
17.6, 4.0 Hz, 1H), 1.62 (s, 3H), 1.01 (s, 3H), 0.95 (s, 3H); 13C NMR
(100 MHz, CDCl3) δ 206.5, 143.7, 135.3, 131.5, 129.5, 128.3, 128.1,
128.0, 122.3, 85.7, 82.3, 68.9, 63.9, 49.1, 43.9, 42.3, 39.9, 33.8, 30.4,
29.1, 21.5, 21.4; IR (CH2Cl2) 2959, 1714, 1642, 1351, 1163 cm−1; MS
(ESI) m/e 474.1 ([M + Na]+, 100), 452.2 (15), 339.1 (15), 323.1 (4),
259.0 (3), 238.0 (3), 171.0 (6); HRMS (ESI) calcd for
C26H29NO4NaS [M + Na] 474.1715, found 474.1711.
Data for 4-Methyl-N-(3-(p-tolyl)prop-2-yn-1-yl)-N-((4,4,6-tri-
methyl-2-oxo-7-oxabicyclo[4.1.0]heptan-1-yl)methyl)-
benzenesulfonamide (10b). (0.68 g, 1.47 mmol, 69%) A white solid:
mp 107−108 °C; 1H NMR (400 MHz, CDCl3) δ 7.78 (d, J = 8.2 Hz,
2H), 7.25 (d, J = 8.1 Hz, 2H), 7.03 (d, J = 8.0 Hz, 2H), 6.97 (d, J = 8.1
Hz, 2H), 4.44 (d, J = 18.6 Hz, 1H), 4.38 (d, J = 18.6 Hz, 1H), 3.79 (d,
J = 14.8 Hz, 1H), 3.73 (d, J = 14.8 Hz, 1H), 2.07 (d, J = 13.6 Hz, 1H),
2.31 (s, 3H), 2.29 (s, 3H), 2.07 (d, J = 13.6 Hz, 1H), 1.98 (dd, J =
13.6, 1.2 Hz, 1H), 1.82 (d, J = 15.1 Hz, 1H), 1.61 (s, 3H), 1.01 (s,
3H), 0.94 (s, 3H); 13C NMR (100 MHz, CDCl3) δ 206.4, 143.6,
138.4, 135.4, 131.4 (2C), 129.5 (2C), 127.8 (2C), 128.1 (2C), 119.2,
85.8, 81.6, 68.9, 63.9, 49.2, 43.9, 42.4, 40.0, 33.8, 30.4, 29.1, 21.4 (3C);
IR (CH2Cl2) 2957, 1713, 1599, 1510, 1451, 1351, 1164 cm−1; MS
(ESI) m/e 488.2 ([M + Na]+, 100), 477.3 (7), 467.2 (21), 466.2 (85);
HRMS (ESI) calcd for C27H31NO4NaS [M + Na]+ 488.1872, found
488.1868.
Data for 4-Methyl-N-(3-(m-tolyl)prop-2-yn-1-yl)-N-((4,4,6-tri-
methyl-2-oxo-7-oxabicyclo[4.1.0]heptan-1-yl)methyl)-
benzenesulfonamide (10c). (0.91 g, 1.95 mmol, 92%) A white solid:
mp 105−106 °C; 1H NMR (400 MHz, CDCl3) δ 7.79 (d, J = 8.2 Hz,
2H), 7.26 (d, J = 8.2 Hz, 2H), 7.13−7.06 (m, 2H), 6.89 (m, 2H), 4.45
(d, J = 18.6 Hz, 1H), 4.38 (d, J = 18.6 Hz, 1H), 3.79 (d, J = 14.8 Hz,
1H), 3.73 (d, J = 14.8 Hz, 1H), 2.65 (d, J = 13.6 Hz, 1H), 2.34 (s, 3H),
2.29 (s, 3H), 2.08 (d, J = 15.2 Hz, 1H), 1.98 (dd, J = 13.6, 1.2 Hz, 1H),
1.82 (dd, J = 15.1, 1.0 Hz, 1H), 1.62 (s, 3H), 0.94 (s, 3H), 0.88 (s,
3H); 13C NMR (100 MHz, CDCl3) δ 206.2, 143.5, 137.5, 135.2,
131.9, 129.4 (2C), 129.0, 128.5, 127.9 (2C), 127.8, 121.9, 85.8, 81.8,
68.7, 63.8, 49.0, 43.7, 42.2, 39.8, 33.6, 30.3, 28.9, 21.3 (2C), 21.0; IR
(CH2Cl2) 2958, 2929, 2228, 1714, 1600, 1351 cm−1; MS (ESI) m/e
466.2 ([M + H]+, 100), 429.2 (8), 440.2 (3), 353.1 (4); HRMS (ESI)
calcd for C27H32NO4S [M + H]+ 466.2052, found 466.2048.
Data for N-(3-([1,1′-Biphenyl]-4-yl)prop-2-yn-1-yl)-4-methyl-N-
((4,4,6-trimethyl-2-oxo-7-oxabicyclo[4.1.0]heptan-1-yl)methyl)-
benzenesulfonamide (10d). (0.79 g, 1.07 mmol, 50%) A white solid:
mp 102−103 °C; 1H NMR (400 MHz, CDCl3) δ 7.80 (d, J = 8.2 Hz,
2H), 7.55 (d, J = 7.5 Hz, 2H), 7.47−7.42 (m, 4H), 7.37 (d, J = 7.4 Hz,
1H), 7.27 (d, J = 8.4 Hz, 2H), 7.15 (d, J = 8.4 Hz, 2H), 4.48 (d, J =
18.6 Hz, 1H), 4.47 (d, J = 18.6 Hz, 1H), 3.81 (d, J = 14.8 Hz, 1H),
3.76 (d, J = 14.8 Hz, 1H), 2.66 (d, J = 13.6 Hz, 1H), 2.33 (s, 3H), 2.09
(d, J = 15.1 Hz, 1H), 1.99 (d, J = 13.6 Hz, 1H), 1.83 (d, J = 15.1 Hz,
1H), 1.63 (s, 3H), 1.02 (s, 3H), 0.95 (s, 3H); 13C NMR (100 MHz,
CDCl3) δ 206.5, 143.6, 141.0, 140.1, 135.3, 131.9 (2C), 129.5 (2C),
128.8 (2C), 128.0 (2C), 127.6, 126.9 (2C), 126.7 (2C), 121.1, 85.6,
83.0, 68.9, 63.9, 49.1, 43.9, 42.3, 39.9, 33.8, 30.4, 29.0, 21.4 (2C); IR
(CH2Cl2) 2960, 1714, 1599, 1487, 1350, 1261, 1163 cm−1; MS (ESI)
m/e 550.2 ([M + Na]+, 100), 545.2 (9), 528.2 (3), 200.1 (4); HRMS
(ESI) calcd for C32H33NO4SNa [M + Na]+ 550.2028, found 550.2017.
Data for 4-Methyl-N-(3-(naphthalen-1-yl)pro-2-yn-1-yl)-N-
((4,4,6-trimethyl-2-oxo-7-oxabicyclo[4.1.0]heptan-1-yl)methyl)-
benzenesulfonamide (10e). (0.77 g, 1.66 mmol, 78%) A white solid:
mp 130−131 °C; 1H NMR (400 MHz, CDCl3) δ 7.89−7.92 (m, 1H),
7.75−7.81 (m, 4H), 7.35−7.49 (m, 2H), 7.12−7.35 (m, 2H), 7.11 (d, J
General Experimental Procedure for Synthesis of Substrate
10. Compounds 10a−i were prepared in the similar fashion as those
of substrates 1a−h starting from treatment of 3,5,5-trimethylcyclohex-
2-en-1-one with formaldehyde under Baylis−Hillman reaction
12387
dx.doi.org/10.1021/jo402025z | J. Org. Chem. 2013, 78, 12381−12396

The Journal of Organic Chemistry
Article
= 8.0 Hz, 2H), 4.62 (d, J = 18.6 Hz, 1H), 4.55 (d, J = 18.6 Hz, 1H),
3.87 (s, 2H), 2.66 (d, J = 13.6 Hz, 1H), 2.14 (s, 1H), 2.07 (s, 3H), 1.98
(d, J = 13.6 Hz, 1H), 1.80 (d, J = 14.8 Hz, 1H), 1.63 (s, 3H), 0.99 (s,
3H), 0.93 (s, 3H); 13C NMR (100 MHz, CDCl3) δ 206.6, 143.8,
135.3, 133.0 (2C), 130.6 (2C), 129.5, 128.8, 128.1, 128.0 (2C), 126.7,
126.3, 126.1, 124.9, 120.0, 87.2, 84.0, 69.0, 64.0, 49.1, 44.0, 42.4, 40.1,
33.9, 30.4, 29.0, 21.5, 21.2; IR (CH2Cl2) 2956, 1712, 1598, 1350, 1164
cm−1; MS (ESI) m/e 524.2 ([M + Na]+, 100), 503.2 (12), 502.2 (39),
389.1 (5); HRMS (ESI) calcd for C30H31NO4SNa [M + Na]+
524.1872, found 524.1863.
Data for 4-Methyl-N-(3-(phenanthren-9-yl)prop-2-yn-1-yl)-N-
((4,4,6-trimethyl-2-oxo-7-oxabicyclo[4.1.0]heptan-1-yl)methyl)-
benzenesulfonamide (10f). (1.04 g, 1.89 mmol, 63%) A white solid:
mp 137−138 °C; 1H NMR (400 MHz, CDCl3) δ 8.62 (d, J = 7.3 Hz,
2H), 8.02 (d, J = 8.0 Hz, 1H), 7.83 (d, J = 8.2 Hz, 2H), 7.78 (d, J = 7.8
Hz, 1H), 7.68−7.56 (m, 5H), 7.14 (d, J = 8.2 Hz, 2H), 4.65 (d, J =
18.6 Hz, 1H), 4.59 (d, J = 18.6 Hz, 1H), 3.90 (s, 2H), 2.68 (d, J = 13.6
Hz, 1H), 2.09 (d, J = 15.2 Hz, 1H), 2.06 (s, 3H), 2.00 (d, J = 13.6 Hz,
1H), 1.83 (d, J = 15.2 Hz, 1H), 1.65 (s, 3H), 1.01 (s, 3H), 0.95 (s,
3H); 13C NMR (100 MHz, CDCl3) δ 206.7, 143.8, 135.4, 132.1,
130.9, 130.8, 130.2, 129.9, 129.5 (2C), 128.3, 128.0 (2C), 127.5, 127.0,
126.9, 126.8, 122.6, 118.8, 86.9, 84.1, 69.1, 64.1, 49.1, 44.0, 42.5, 40.1,
33.9, 30.5, 29.0, 21.5, 21.3; IR (CH2Cl2) 2957, 1712, 1600, 1598, 1451,
1350, 1163 cm−1; MS (ESI) m/e 574.2 ([M + Na]+, 100), 553.2 (4),
425.2 (2), 352.6 (3); HRMS (ESI) calcd for C34H33NO4SNa [M +
Na]+ 574.2028, found 574.2034.
Data for 4-Methyl-N-(3-(4-nitrophenyl)prop-2-yn-1-yl)-N-((4,4,6-
trimethyl-2-oxo-7-oxabicyclo[4.1.0]heptan-1-yl)methyl)-
benzenesulfonamide (10j). (0.93 g, 1.88 mmol, 88%) A white solid:
mp 126−127 °C; 1H NMR (400 MHz, CDCl3) δ 8.09 (d, J = 8.7 Hz,
2H), 7.77 (d, J = 8.2 Hz, 2H), 7.25 (d, J = 8.2 Hz, 2H), 7.22 (d, J = 8.7
Hz, 2H), 4.47 (d, J = 18.8 Hz, 1H), 4.40 (d, J = 18.8 Hz, 1H), 3.82 (d,
J = 14.7 Hz, 1H), 3.75 (d, J = 14.7 Hz, 1H), 2.65 (d, J = 13.6 Hz, 1H),
2.32 (s, 3H), 2.09 (d, J = 15.2 Hz, 1H), 1.93 (d, J = 13.6 Hz, 1H), 1.80
(d, J = 15.2 Hz, 1H) 1.52 (s, 3H), 1.00 (s, 3H), 0.92 (s, 3H); 13C
NMR (100 MHz, CDCl3) δ 206.9, 147.1, 143.8, 135.5, 132.3 (2C),
129.6 (2C), 129.2, 128.1 (2C), 123.3 (2C), 88.3, 83.9, 69.3, 63.9, 48.9,
44.0, 42.2, 39.6, 34.2, 30.6, 28.8, 21.5 (2C); IR (CH2Cl2) 2954, 2359,
1710, 1592, 1516, 1345, 1162 cm−1; MS (ESI) m/e 519.2 ([M + Na]+,
100), 514.2 (3); HRMS (ESI) calcd for C26H28N2O6SNa [M + Na]+
519.1566, found 519.1556.
Data for 4-Methyl-N-(3-(3-nitrophenyl)prop-2-yn-1-yl)-N-((4,4,6-
trimethyl-2-oxo-7-oxabicyclo[4.1.0]heptan-1-yl)methyl)-
benzenesulfonamide (10k). (0.94 g, 1.89 mmol, 89%) A white solid:
mp 131−132 °C; 1H NMR (400 MHz, CDCl3) δ 8.10 (dt, J = 6.9, 2.2
Hz, 1H), 7.82−7.83 (m, 1H), 7.78 (d, J = 8.2 Hz, 2H), 7.45−7.39 (m,
2H), 7.29 (d, J = 8.2 Hz, 2H), 4.47 (d, J = 18.8 Hz, 1H), 4.40 (d, J =
18.8 Hz, 1H), 3.80 (d, J = 14.8 Hz, 1H), 3.74 (d, J = 14.8 Hz, 1H),
2.65 (d, J = 13.6 Hz, 1H), 2.32 (s, 3H), 2.09 (d, J = 15.2 Hz, 1H), 1.94
(dd, J = 13.6, 1.4 Hz, 1H), 1.81 (dd, J = 15.2, 1.4 Hz, 1H) 1.62 (s,
3H), 1.00 (s, 3H), 0.93 (s, 3H); 13C NMR (100 MHz, CDCl3) δ
206.9, 147.9, 144.1, 137.2, 135.4, 129.5 (2C), 129.2, 128.1 (2C), 126.2,
124.0, 123.0, 85.4, 83.2, 69.2, 63.9, 48.9, 44.0, 42.1, 39.5, 34.1, 30.5,
28.8, 21.4 (2C); IR (CH2Cl2) 3086, 2958, 2873, 1714, 1532, 1351
cm−1; MS (ESI) m/e 519.2 ([M + Na]+, 100), 497.2 (43), 402.1 (5),
351.2 (5) 290.1 (5), 263.1 (8); HRMS (ESI) calcd for
C26H28N2O6SNa [M + Na]+ 519.1566, found 519.1555.
Representative Experimental Procedure for Synthesis of
Compound 14. To a solution of 1-(hydroxymethyl)-4,4,6-trimethyl-
7-oxabicyclo[4.1.0]heptan-2-one (1.84 g, 10.0 mmol) in 20.0 mL of
DCM at 0 °C under nitrogen was added 4-dimethylaminopyridine
(0.12 g, 1.0 mmol), NEt3 (1.39 g, 13.0 mmol) and 4-toluenesulfonyl
chloride (2.29 g, 12.0 mmol). The reaction mixture was stirred at
room temperature for 5 h before quenching with 50 mL of saturated
aqueous sodium hydrogen carbonate. The resulting solution was
extracted with CH2Cl2 (50 mL × 3). The combined organic solution
was washed with water (100 mL × 3) and brine 100 mL × 3) and
dried over MgSO4 (15 g) and concentrated to give a crude solid. The
crude mixture was purified by flash column chromatography (silica gel,
ethyl acetate/hexanes 1:3) to afford (4,4,6-trimethyl-2-oxo-7-
oxabicyclo[4.1.0]heptan-1-yl)methyl 4-methylbenzenesulfonate (7.45
g, 2.24 mmol, 75%). To the solution of (4,4,6-trimethyl-2-oxo-7-
oxabicyclo[4.1.0]heptan-1-yl)methyl 4-methylbenzenesulfonate (1.02
g, 3.0 mmol) in 6.0 mL of THF at 0 °C under nitrogen was added
sodium hydride (0.10 g, 4.5 mmol) and 3-phenylprop-2-yn-1-ol (0.60
g, 4.5 mmol). The reaction mixture was stirred at 55 °C for 5 h before
quenching with 50 mL of saturated aqueous sodium hydrogen
carbonate. The resulting solution was extracted with CH2Cl2 (50 mL
× 3). The combined organic solution was washed with water (100 mL
× 3) and brine (100 mL × 3), dried over MgSO4 (15 g), and
concentrated to give a crude liquid.
Data for N-(3-(3-Methoxyphenyl)prop-2-yn-1-yl)-4-methyl-N-
((4,4,6-trimethyl-2-oxo-7-oxabicyclo[4.1.0]heptan-1-yl)methyl)-
benzenesulfonamide (10g). (0.46 g, 0.96 mmol, 45%) A yellow oil:
1H NMR (400 MHz, CDCl3) δ 7.78 (d, J = 7.8 Hz, 2H), 7.26 (d, J =
7.8 Hz, 2H), 7.14 (t, J = 8.2 Hz, 1H), 6.82 (dd, J = 8.2, 1.8 Hz, 1H),
6.67 (d, J = 7.6 Hz, 1H), 6.62 (s, 1H), 4.45 (d, J = 18.6 Hz, 1H), 4.39
(d, J = 18.6 Hz, 1H), 3.80−3.72 (m, 5H), 2.65 (d, J = 13.6 Hz, 1H),
2.33 (s, 3H), 2.08 (d, J = 15.1 Hz, 1H), 1.98 (d, J = 13.6 Hz, 1H), 1.82
(d, J = 15.1 Hz, 1H), 1.62 (s, 3H), 1.01 (s, 3H), 0.94 (s, 3H); 13C
NMR (100 MHz, CDCl3) δ 206.3, 159.0, 143.6, 135.2, 129.4 (2C),
129.0, 127.9 (2C), 123.9, 123.1, 116.8, 114.3, 85.5, 82.1, 68.8, 63.8,
55.1, 49.0, 43.7, 42.2, 39.7, 33.7, 30.3, 28.9, 21.3, 21.2; IR (CH2Cl2)
3277, 2959, 2868, 1728, 1628, 1580 cm−1; MS (ESI) m/e 504.2 ([M +
Na]+, 100), 483.2 (5), 482.2 (20), 380.2 (8); HRMS (ESI) calcd for
C27H31NO5SNa [M + Na]+ 504.1821, found 504.1816.
Data for N-(3-(4-Bromophenyl)prop-2-yn-1-yl)-4-methyl-N-
((4,4,6-trimethyl-2-oxo-7-oxabicyclo[4.1.0]heptan-1-yl)methyl)-
benzenesulfonamide (10h). (0.60 g, 1.12 mmol, 53%) A white
powder: mp 105−106 °C; 1H NMR (400 MHz, CDCl3) δ 7.77 (d, J =
8.2 Hz, 2H), 7.36 (d, J = 8.4 Hz, 2H), 7.24 (d, J = 8.2 Hz, 2H), 6.93
(d, J = 8.4 Hz, 2H), 4.43 (d, J = 18.6 Hz, 1H), 4.36 (d, J = 18.6 Hz,
1H), 3.77 (br s, 2H), 2.65 (d, J = 13.6 Hz, 1H), 2.32 (s, 3H), 2.08 (d, J
= 15.2 Hz, 1H), 1.96 (d, J = 13.6 Hz, 1H), 1.81 (d, J = 15.2 Hz, 1H),
1.62 (s, 3H), 1.00 (s, 3H), 0.93 (s, 3H); 13C NMR (100 MHz, CDCl3)
δ 206.5, 143.6, 135.2, 132.8 (2C), 131.2 (2C), 129.4 (2C), 127.9 (2C),
122.4, 121.1, 84.5, 83.6, 68.9, 63.8, 48.9, 43.8, 42.1, 39.6, 33.9, 30.4,
28.8, 21.3 (2C); IR (CH2Cl2) 2957, 2930, 2871, 2246, 1915, 1713,
1598, cm−1; MS (ESI) m/e 552.1 ([M + Na]+, 100), 547.2 (1),530.1
(1), 440.2 (2); HRMS (ESI) calcd for C26H28NO4NaSBr [M + Na]+
552.0820, found 552.0815.
Data for 4-Methyl-N-(3-(thiophen-2-yl)prop-2-yn-1-yl)-N-((4,4,6-
trimethyl-2-oxo-7oxabicyclo[4.1.0]heptan-1-yl)methyl)-
benzenesulfonamide (10i). (1.12 g, 2.45 mmol, 82%) A yellow solid:
Data for 4,4,6-Trimethyl-1-(((3-phenylprop-2-yn-1-yl)oxy)-
methyl)-7-oxabicyclo-[4.1.0]heptan-2-one (14a). The crude mixture
was purified by flash column chromatography (silica gel, ethyl acetate/
hexanes 1:3) to afford 14a (0.54 g, 1.79 mmol, 60%) as a yellow oil:
1H NMR (400 MHz, CDCl3) δ 7.43 (dd, J = 5.9, 2.2 Hz, 2H), 7.32−
7.26 (m, 3H), 4.49 (d, J = 15.9 Hz, 1H), 4.39 (d, J = 15.9 Hz, 1H),
4.27 (d, J = 10.1 Hz, 1H), 3.68 (d, J = 10.1 Hz, 1H), 2.65 (d, J = 13.8
Hz, 1H), 2.11 (d, J = 15.9 Hz, 1H), 1.95 (dd, J = 13.8, 2.0 Hz, 1H),
1.75 (dd, J = 15.0, 2.0 Hz, 1H), 0.99 (s, 3H), 0.94 (s, 3H); 13C NMR
(100 MHz, CDCl3) δ 206.5, 131.7 (2C), 128.4, 128.3 (2C), 122.6,
86.5, 84.9, 67.5, 65.1, 63.7, 59.6, 48.6, 44.2, 34.4, 30.7, 27.7, 21.4; IR
(CH2Cl2) 2959, 1712, 1088 cm−1; MS (ESI) m/e (%) 321.1 [M +
Na]+, 66), 298.2 (3), 223.1 (100), 202.2 (1); HRMS (ESI) calcd for
C19H22O3Na [M + Na]+ 321.1467, found 321.1474.
1
mp 96−97 °C; H NMR (400 MHz, CDCl3) δ 7.77 (d, J = 8.2 Hz,
2H), 7.28 (d, J = 8.0 Hz, 2H), 7.18 (d, J = 4.9 Hz, 1H), 6.93 (d, J = 2.5
Hz, 1H), 6.87−6.90 (m, 1H), 4.47 (d, J = 18.7 Hz, 1H), 4.41 (d, J =
18.8 Hz, 1H), 3.73 (s, 2H), 2.65 (d, J = 13.6 Hz, 1H), 2.35 (s, 3H),
2.07 (d, J = 15.1 Hz, 1H), 1.97 (d, J = 13.6 Hz, 1H), 1.86 (d, J = 15.1
Hz, 1H), 1.60 (s, 3H), 1.00 (s, 3H), 0.94 (s, 3H); 13C NMR (100
MHz, CDCl3) δ 206.4, 143.7, 135.0, 132.2, 129.5 (2C), 127.8 (2C),
127.1, 126.6, 122.0, 86.3, 78.8, 68.8, 63.8, 49.0, 43.8, 42.3, 40.0, 33.7,
30.3, 28.9, 21.4, 21.3; IR (CH2Cl2) 3107, 3070, 2958, 1714, 1598,
1428, 1348, 1163 cm−1; MS (ESI) m/e 458.1 ([M + H]+, 100), 435.2
(10), 424.1 (10), 398.1 (6); HRMS (ESI) calcd for C24H28NO4S2 [M
+ H]+ 458.1460, found 458.1453.
12388
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Article
Data for 4,4,6-Trimethyl-1-(((3-(p-tolyl)prop-2-yn-1-yl)oxy)-
7.23−7.19 (m, 1H), 7.03 (d, J = 7.6 Hz, 1H), 6.97−6.96 (m, 1H), 6.87
(dd, J = 8.4, 2.6 Hz, 1H), 4.48 (d, J = 16.0 Hz, 1H), 4.39 (d, J = 16.0
Hz, 1H), 4.27 (d, J = 10.0 Hz, 1H), 3.79 (s, 3H), 3.68 (d, J = 10.0 Hz,
1H), 2.65 (d, J = 13.8 Hz, 1H), 2.11 (d, J = 14.8 Hz, 1H), 1.93 (dd, J =
13.8, 2.0 Hz, 1H), 1.74 (dd, J = 14.8, 2.0 Hz, 1H), 1.54 (s, 3H), 1.00
(s, 3H), 0.94 (s, 3H); 13C NMR (100 MHz, CDCl3) δ 206.2, 159.1,
129.2, 124.1, 123.4, 116.5, 114.8, 86.3, 84.6, 67.4, 65.0, 63.5, 59.4, 55.1,
48.4, 44.1, 34.3, 30.5, 27.6, 21.3; IR (CH2Cl2) 2957, 2366, 1717, 1604,
methyl)-7-oxa-bicyclo[4.1.0]heptan-2-one (14b). (0.65 g, 2.09
1
mmol, 70%) A yellow oil: H NMR (400 MHz, CDCl3) δ 7.32 (d, J
= 8.0 Hz, 2H), 7.10 (d, J = 8.0 Hz, 2H), 4.47 (d, J = 14.6 Hz, 1H), 4.38
(d, J = 14.6 Hz, 1H), 4.26 (d, J = 10.0 Hz, 1H), 3.68 (d, J = 10.0 Hz,
1H), 2.64 (d, J = 14.0 Hz, 1H), 2.34 (s, 3H), 2.10 (d, J = 14.8 Hz, 1H),
1.93 (dd, J = 14.0, 1.6 Hz, 1H), 1.74 (dd, J = 14.8, 1.6 Hz, 1H), 1.53
(s, 3H), 0.99 (s, 3H), 0.94 (s, 3H); 13C NMR (100 MHz, CDCl3) δ
206.4, 138.5, 131.6 (2C), 129.0 (2C), 119.5, 86.6, 84.1, 67.5, 64.9,
63.7, 59.6, 48.6, 44.3, 34.4, 30.6, 27.7, 21.5, 21.4; IR (CH2Cl2) 2957,
1716, 1509, 1465, 1447, 1357, 1089 cm−1; MS (ESI) m/e 335.2 [M +
Na]+, 100), 199.0 (7), 143.1 (4); HRMS (ESI) calcd for C20H24O3Na
[M + Na]+ 335.1623, found 335.1631.
+
1468, 1290 cm−1; MS (ESI) m/e 351.2 [M Na]+, 100), 346.2 (11),
291.1 (14), 268.1 (5); HRMS (ESI) calcd for C20H24O4Na [M + Na]+
351.1572, found 351.1574.
Data for 1-(((3-([1,1′-Biphenyl]-4-yl)prop-2-yn-1-yl)oxy)methyl)-
4,4,6-trimethyl-7-oxabicyclo[4.1.0]heptan-2-one (14h). (0.73 g, 1.96
1
mmol, 65%) A white solid: mp 67−68 °C; H NMR (400 MHz,
Data for 4,4,6-Trimethyl-1-(((3-(phenanthren-9-yl)prop-2-yn-1-
yl)oxy)-methyl)-7-oxabicyclo[4.1.0]heptan-2-one (14c). (0.72 g, 1.81
CDCl3) δ 7.58−7.49 (m, 6H), 7.43 (d, J = 7.5 Hz, 2H), 7.34 (t, J = 7.5
Hz, 1H), 4.51 (d, J = 16.0 Hz, 1H), 4.42 (d, J = 16.0 Hz, 1H), 4.31 (d,
J = 10.0 Hz, 1H), 3.71 (d, J = 10.0 Hz, 1H), 2.65 (d, J = 14.8 Hz, 1H);
2.10 (d, J = 14.8 Hz, 1H), 1.94 (dd, J = 14.9, 2.0 Hz, 1H), 1.73 (dd, J =
14.8, 2.0 Hz, 1H), 1.55 (s, 3H), 1.00 (s, 3H), 0.95 (s, 3H); 13C NMR
(100 MHz, CDCl3) δ 206.2, 141.0, 140.0, 132.0 (2C), 128.7 (2C),
127.5, 126.8 (4C), 121.4, 86.3, 85.5, 67.3, 65.0, 63.5, 59.5, 48.4, 44.1,
34.3, 30.5, 27.6, 21.3 cm−1; IR (CH2Cl2) 2957, 1716, 1487, 1358,
1224, 1088 cm−1; MS (ESI) m/e 375.2, 303.2, 276.1, 265.1, 121.1;
HRMS (ESI) calcd for C25H27O3 [M + H]+ 375.1960, found 375.1951.
General Experimental Procedure for Synthesis of Isoquino-
linone 2. To a solution of 1a (0.05 g, 0.12 mmol) in 1.2 mL of
CH2Cl2 at room temperature under nitrogen, NHTf2 (3 mg, 0.01
mmol) was added. The reaction mixture was heated to 40 °C for 70
min until no starting material was detected by TLC. The reaction
mixture was cooled to room temperature and was quenched with
saturated aqueous NaHCO3 (20 mL). The organic phase was
separated, and the aqueous phase was extracted with CH2Cl2 (20
mL × 3). The combined organic layers were washed with brine (50
mL × 3), dried over anhydrous MgSO4 (5.0 g), and filtered. The
filtrate was concentrated under reduced pressure to give the crude
mixture.
1
mmol, 60%) A white solid: mp 96−97 °C; H NMR (400 MHz,
CDCl3) δ 8.67−8.66 (m, 2H), 8.44−8.42 (m, 1H), 7.98 (s, 1H), 7.83
(d, J = 8.0 Hz, 1H), 7.68−7.56 (m, 4H), 4.66 (d, J = 16.0 Hz, 1H),
4.58 (d, J = 16.0 Hz, 1H), 4.39 (d, J = 10.0 Hz, 1H), 3.80 (d, J = 10.0
Hz, 1H), 2.67 (d, J = 14.6 Hz, 1H), 2.11 (d, J = 14.8 Hz, 1H), 1.96
(dd, J = 14.6, 1.6 Hz, 1H), 1.74 (dd, J = 14.8, 1.6 Hz, 1H), 1.56 (s,
3H), 0.99 (s, 3H), 0.96 (s, 3H); 13C NMR (100 MHz, CDCl3) δ
206.4, 132.2, 131.0, 130.3, 130.0, 128.5, 127.5, 127.1, 126.9, 126.8,
122.7, 122.6, 118.9, 89.4, 84.7, 67.5, 65.3, 63.7, 59.9, 48.6, 44.3, 34.5,
30.7, 27.7, 21.5; IR (CH2Cl2) 2915, 1712, 1384, 1354, 1084 cm−1; MS
(ESI) m/e 421.2 [M + Na]+ (35), 292.1 (22), 291.1 (100); HRMS
(ESI) calcd for C27H26O3Na [M + Na]+ 421.1780, found 421.1771.
Data for 1-(((3-(4-Bromophenyl)prop-2-yn-1-yl)oxy)methyl)-
4,4,6-trimethyl-7-oxabicyclo[4.1.0]heptan-2-one (14d). (0.81 g,
2.28 mmol, 75%) A white solid: mp 58−59 °C; 1H NMR (400
MHz, CDCl3) δ 7.44 (d, J = 8.8 Hz, 2H), 7.29 (d, J = 8.8 Hz, 2H),
4.45 (d, J = 16.0 Hz, 1H), 4.38 (d, J = 16.0 Hz, 1H), 4.25 (d, J = 10.0
Hz, 1H), 3.67 (d, J = 10.0 Hz, 1H), 2.65 (d, J = 13.6 Hz, 1H), 2.10 (d,
J = 14.8 Hz, 1H), 1.93 (dd, J = 13.6, 2.0 Hz, 1H), 1.74 (dd, J = 14.8,
2.0 Hz, 1H), 1.53 (s, 3H), 1.00 (s, 3H), 0.94 (s, 3H); 13C NMR (100
MHz, CDCl3) δ 206.4, 133.1 (2C), 131.6 (2C), 122.7, 121.6, 86.1,
85.4, 67.5, 65.2, 63.7, 59.6, 48.6, 44.3, 34.4, 30.6, 27.7, 21.4; IR
(CH2Cl2) 2958, 1714, 1634, 1486, 1089 cm−1; MS (ESI) m/e 379.1,
377.1, 359.1, 321.2, 199.1; HRMS (ESI) calcd for C19H22BrO3 [M +
H]+ 377.0752, found 377.0745.
Data for 4-Benzoyl-2-tosyl-1,2,3,4,6,7-hexahydroisoquinolin-
8(5H)-one (2a). In the typical procedure, to a solution of 1a (0.05
g, 0.12 mmol) in 1.2 mL of CH2Cl2 at 40 °C was added HNTf2 (3.0
mg, 0.01 mmol). The reaction mixture was stirred for 70 min. The
crude mixture was purified by silica gel column chromatography (ethyl
acetate/hexanes 1:2) to give 2a (0.041 g, 0.10 mmol, 83%) as colorless
crystals: mp 210−211 °C; 1H NMR (400 MHz, CDCl3) δ 7.98 (d, J =
7.6 Hz, 2H), 7.69−7.61 (m, 3H), 7.54 (d, J = 6.0 Hz, 2H), 7.29 (d, J =
8.0 Hz, 2H), 4.59 (dd, J = 7.3, 5.5 Hz, 1H), 4.09 (d, J = 16.5 Hz, 1H),
3.76 (ddd, J = 12.3, 5.5, 1.0 Hz, 1H), 3.56 (ddd, J = 16.4, 4.9, 2.5 Hz,
1H), 3.09 (dd, J = 12.0, 7.6 Hz, 1H), 2.46−2.39 (m, 2H), 2.41 (s, 3H),
2.30 (m, 1H), 2.12−1.84 (m, 3H); 13C NMR (100 MHz, CDCl3) δ
197.6, 196.5, 152.2, 144.0, 136.0, 134.2, 133.1, 131.2, 129.8 (2C),
129.2 (2C), 128.6 (2C), 127.8 (2C), 48.7, 46.1, 43.1, 37.6, 29.3, 22.2,
21.5; IR (CH2Cl2) 2961, 1670, 1646, 1594, 1346, 1164 cm−1; MS
(ESI) m/e 432.1 ([M + Na]+, 100), 410.1 (6), 380.6 (3), 341.6 (6);
HRMS (ESI) calcd for C23H23NO4NaS [M + Na]+ 432.1245, found
432.1236. Crystals suitable for X-ray diffraction analysis were grown
from a solution of CH2Cl2/hexanes.
Data for 4-(3-Methylbenzoyl)-2-tosyl-1,2,3,4,6,7-hexahydroiso-
quinolin-8(5H)-one (2b). In the typical procedure, to a solution of
1b (0.11 g, 0.25 mmol) in 2.5 mL of CH2Cl2 was added HNTf2 (9.0
mg, 0.03 mmol). The reaction mixture was stirred for 60 min at 40 °C.
The crude mixture was purified by flash column chromatography
(silica gel, ethyl acetate/hexanes 1:3) to give 2b (90 mg, 0.21 mmol,
84%) as a white solid: mp 106−107 °C; 1H NMR (400 MHz, CDCl3)
δ 7.77 (d, J = 7.5 Hz, 2H), 7.64 (d, J = 8.1 Hz, 2H), 7.47 (d, J = 7.4
Hz, 1H), 7.42 (t, J = 7.4 Hz, 1H), 7.29 (d, J = 7.9 Hz, 2H), 4.58 (br s,
1H), 4.06 (d, J = 16.3 Hz, 1H), 3.74 (m, 1H), 3.58 (d, J = 16.4 Hz,
1H), 3.12 (m, 1H), 2.44−2.25 (m, 9H), 2.09−1.87 (m, 3H); 13C
NMR (100 MHz, CDCl3) δ 197.7, 196.5, 152.3, 143.9, 139.0, 135.9,
134.9, 132.9, 130.9, 129.7, 128.9, 128.9, 127.6, 125.7, 48.4, 45.9, 42.9,
37.4, 29.2, 22.0, 21.4, 21.3; IR (CH2Cl2) 2926, 2359, 1671, 1390, 1349,
1165 cm−1; MS (ESI) m/e 446.1 ([M + Na]+, 100), 441.2, 384.1,
Data for 4,4,6-Trimethyl-1-(((3-(m-tolyl)prop-2-yn-1-yl)oxy)-
methyl)-7-oxabicyclo-[4.1.0]heptan-2-one (14e). (0.72 g, 2.30
1
mmol, 77%) A yellow oil: H NMR (400 MHz, CDCl3) δ 7.26 (s,
1H), 7.25 (d, J = 10.0 Hz, 1H), 7.18 (t, J = 7.2 Hz, 1H), 7.12 (d, J =
7.2 Hz, 1H), 4.47 (d, J = 16.0 Hz, 1H), 4.38 (d, J = 16.0 Hz, 1H), 4.26
(d, J = 10.0 Hz, 1H), 3.67 (d, J = 10.0 Hz, 1H), 2.65 (d, J = 13.6 Hz,
1H), 2.31 (s, 3H), 2.10 (d, J = 15.2 Hz, 1H), 1.93 (dd, J = 13.6, 2.0 Hz,
1H), 1.74 (dd, J = 14.8, 2.0 Hz, 1H), 1.53 (s, 3H), 0.99 (s, 3H), 0.94
(s, 3H); 13C NMR (100 MHz, CDCl3) δ 206.4, 137.9, 132.3, 129.3,
128.8, 128.2, 122.4, 86.7, 84.5, 67.5, 65.1, 63.7, 59.6, 48.6, 44.3, 34.5,
30.7, 27.8, 21.5, 21.2; IR (CH2Cl2) 2956, 1716, 1602, 1576, 1471,
1357, 1090 cm−1; MS (ESI) m/e 335.2, 291.1, 248.1, 199.0; HRMS
(ESI) calcd for C20H24O3Na [M + Na]+ 335.1623, found 335.1628.
Data for 4,4,6-Trimethyl-1-(((3-(naphthalene-1-yl)prop-2-yn-1-
yl)oxy)methyl)-7-oxabicyclo[4.1.0]heptan-2-one (14f). (0.58 g, 1.68
mmol, 56%) A yellow oil: 1H NMR (400 MHz, CDCl3) δ 8.33 (d, J =
8.0 Hz, 1H), 7.81 (d, J = 7.6 Hz, 2H), 7.66 (d, J = 6.8 Hz, 1H), 7.55
(dd, J = 7.6, 1.2 Hz, 1H), 7.50 (dd, J = 7.2, 0.8 Hz, 1H), 7.39 (d, J =
7.6 Hz, 1H),4.63 (d, J = 16.0 Hz, 1H), 4.55 (d, J = 16.0 Hz, 1H), 4.36
(d, J = 10.0 Hz, 1H), 3.76 (d, J = 10.0 Hz, 1H), 2.65 (d, J = 13.6 Hz,
1H), 2.09 (d, J = 14.8 Hz, 1H), 1.93 (dd, J = 13.6, 2.0 Hz, 1H), 1.74
(dd, J = 14.8, 2.0 Hz, 1H), 1.53 (s, 3H), 0.98 (s, 3H), 0.94 (s, 3H); 13C
NMR (100 MHz, CDCl3) δ 206.3, 133.2, 133.0, 130.6, 128.8, 128.2,
126.7, 126.3, 126.0, 125.1, 120.2, 89.7, 84.6, 67.5, 65.2, 63.7, 59.7, 48.5,
44.2, 34.4, 30.6, 27.7, 21.4; IR (CH2Cl2) 2956, 1714, 1644, 1395, 1085
cm−1; MS (ESI) m/e 371.2, 366.2, 337.2; HRMS (ESI) calcd for
C23H24O3Na [M + Na]+ 371.1623, found 371.1615.
Data for 1-(((3-(3-Methoxyphenyl)prop-2-yn-1-yl)oxy)methyl)-
4,4,6-trimethyl-7-oxabicyclo[4.1.0]heptan-2-one (14g). (0.67 g,
2.05 mmol, 68%) A yellow oil: 1H NMR (400 MHz, CDCl3) δ
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Article
309.1; HRMS (ESI) calcd for C24H25NO4S [M + Na]+ 446.1402,
found 446.1396.
196.6, 152.1, 143.9, 134.9, 134.1, 133.8, 132.8, 131.0, 130.4, 129.8,
128.6, 128.5, 127.9, 127.8, 127.0, 125.6, 124.3, 52.1, 45.9, 43.2, 37.6,
29.7, 22.2, 21.5; IR (CH2Cl2) 2925, 1670, 1596, 1349, 1166, 1091
cm−1; MS (FAB) m/e (%) 460.2 ([M + H]+, 100), 443.2 (15), 427.4
(21), 424.1 (8), 419.3 (4); HRMS (FAB) [M + H]+ C27H26NO4S
calcd 460.1583, found 460.1579.
Data for 4-(4-Methylbenzoyl)-2-tosyl-1,2,3,4,6,7-hexahydroiso-
quinolin-8(5H)-one (2c). In the typical procedure, to a solution of
1c (0.05 g, 0.12 mmol) in 1.2 mL of CH2Cl2 was added HNTf2 (3.0
mg, 0.01 mmol). The reaction mixture was stirred for 10 min at 40 °C.
The crude mixture was purified by flash column chromatography
(silica gel, ethyl acetate/hexanes 1:3) to give 2c (32 mg, 0.076 mmol,
Data for Ethyl 2-(8-Oxo-2-tosyl-1,2,3,4,5,6,7,8-octahydroisoqui-
noline-4-carbonyl)benzoate (2g). In the typical procedure, to a
solution of 1g (0.10 g, 0.21 mmol) in 2.1 mL of CH2Cl2 was added
HNTf2 (6.0 mg, 0.02 mmol). The reaction mixture was stirred at 40
°C for 30 min. The crude mixture was purified by flash column
chromatography (silica gel, 1:5 ethyl acetate/hexanes) to give 2g (5.0
mg, 0.01 mmol, 5%) as a white solid: mp 206−207 °C; 1H NMR (500
MHz, CDCl3) δ 8.01 (d, J = 7.6 Hz, 1H), 7.92 (d, J = 7.9 Hz, 1H),
7.84 (t, J = 7.9 Hz, 1H), 7.70 (d, J = 8.2 Hz, 2H), 7.63 (t, J = 7.6 Hz,
1H), 7.34 (d, J = 8.2 Hz, 2H), 5.01 (d, J = 14.5 Hz, 1H), 4.49 (dd, J =
8.5, 5.0 Hz, 1H), 4.21 (d, J = 17.0 Hz, 1H), 3.89 (d, J = 14.5 Hz, 1H),
3.53 (d, J = 17.0 Hz, 1H), 3.50−3.41 (m, 2H), 2.43 (s, 3H), 2.42−2.35
(m, 1H), 2.14−2.03 (m, 2H), 2.03−1.95 (m, 1H), 1.91−1.81 (m, 1H),
1.77−1.66 (m, 1H), 1.11 (t, J = 7.0 Hz, 3H) ; 13C NMR (125 MHz,
CDCl3) δ 204.3, 165.6, 144.5, 141.5, 138.2, 135.1, 133.0, 130.1, 130.0,
127.8, 126.3, 125.0, 123.6, 122.6, 91.9, 66.5, 62.7, 56.7, 45.9, 33.7, 31.5,
22.3, 21.6, 15.2; IR (CH2Cl2) 2925, 1783, 1726, 1598, 1351, 1164,
1092 cm−1; MS (ESI) m/e (%) 504.1 ([M + Na]+, 100), 433.1 (20);
HRMS (ESI) C26H27NO6NaS [M + Na]+ calcd 504.1457, found
504.1448.
General Experimental Procedure for Synthesis of Hetero-
tetracyclic Compound 4. To a solution of 1a (0.10 g, 0.25 mmol) in
2.5 mL of CH2Cl2 at −15 °C under nitrogen was added FeCl3 (0.082
g, 0.50 mmol). The reaction mixture was stirred for 1.5 h at −15 °C
until no 1a was detected by TLC. The reaction mixture was quenched
with saturated aqueous NaHCO3 (20 mL). The organic phase was
separated, and the aqueous phase was extracted with ethyl ether (20
mL × 3). The combined organic layers were washed with brine (50
mL × 3), dried over anhydrous MgSO4 (5 g), and concentrated to give
the crude mixture.
Data for (4R,4aS,12bS)-4,8-Dichloro-6-tosyl-1,2,3,4,4a,5,6,7-oc-
tahydroindeno-[2,1-d]isoquinolin-4a-ol (4a). In the typical proce-
dure, to a solution of 1a (0.10 g, 0.25 mmol) in 2.5 mL of CH2Cl2 at
−15 °C under nitrogen was added FeCl3 (0.082 g, 0.50 mmol). The
reaction mixture was stirred at −15 °C for 1.5 h. The crude mixture
was purified by flash column chromatography (silica gel, ethyl acetate/
hexanes 1:3) to give 4a (0.089 g, 0.19 mmol, 77%) as colorless
crystals: mp 164−165 °C; 1H NMR (400 MHz, CDCl3) δ 7.77 (d, J =
8.4 Hz, 2H), 7.59 (d, J = 7.6 Hz, 1H), 7.48 (d, J = 7.6 Hz, 1H), 7.40
(d, J = 7.2 Hz, 1H), 7.37 (d, J = 8.4 Hz, 2H),7.29 (td, J = 8.4, 1.2 Hz,
1H), 4.91 (dd, J = 13.2, 1.5 Hz, 1H), 4.81 (dd, J = 13.2, 5.2 Hz, 1H),
4.05 (dd, J = 13.2, 1.6 Hz, 1H), 3.33 (d, J = 12.8 Hz, 1H), 3.12 (d, J =
13.2 Hz, 1H), 2.45−2.40 (m, 4H), 2.19 (br s, 1H, OH), 2.10 (tt, J =
13.2, 4.4 Hz, 1H), 1.98−1.87 (m, 2H), 1.81 (dq, J = 13.6, 2.4 Hz, 1H),
1.09 (dq, J = 14.0, 1.6 Hz, 1H); 13C NMR (100 MHz, CDCl3) δ 145.6,
144.1, 140.9, 135.9, 133.9, 129.9, 128.8, 127.8, 127.7, 126.4, 124.5,
120.5, 75.4, 64.1, 58.9, 46.8, 41.7, 33.7, 30.3, 21.8, 21.6; IR (CH2Cl2)
3445, 2952, 1642, 1441, 1159 cm−1; MS (ESI) m/e (%) 486.0 ([M +
Na]+, 100), 468.1 (5), 392.1 (14), 356.1 (6), 313.1 (9), 300.6 (3);
HRMS (ESI) calcd for C23H23NO3NaSCl2 [M + Na]+ 486.0673,
found 486.0670. Crystals suitable for X-ray diffraction analysis were
grown from CH2Cl2 and hexanes.
1
63%) as colorless crystals: mp 207−208 °C; H NMR (400 MHz,
CDCl3) δ 7.89 (d, J = 8.2 Hz, 2H), 7.65 (d, J = 8.2 Hz, 2H), 7.34 (d, J
= 8.0 Hz, 2H), 7.29 (d, J = 8.0 Hz, 2H), 4.60 (m, 1H), 4.14 (d, J =
16.4 Hz, 1H), 3.80 (dd, J = 12.1 Hz, 5.5 Hz, 1H), 3.50 (d, J = 17.9 Hz,
1H), 3.01 (dd, J = 12.1 Hz, 8.2 Hz, 1H), 2.46 (s, 3H), 2.45−2.39 (m,
2H), 2.41 (s, 3H), 2.39−2.26 (m, 1H), 2.11−1.86 (m, 3H); 13C NMR
(100 MHz, CDCl3) δ 197.2, 196.6, 152.4, 145.4, 143.9, 135.5, 131.0,
130.1, 129.8, 129.7, 128.7, 127.8, 48.6, 46.2, 43.1, 37.5, 29.2, 22.1, 21.7,
21.5; IR (CH2Cl2) 2925, 1672, 1606, 1350, 1165 cm−1; MS (ESI) m/e
(%) 446.1 ([M + Na]+, 100), 314.1 (12), 313.6 (25), 309 (22); HRMS
(ESI) [M + Na]+ C24H25NO4NaS calcd 446.1402, found 446.1401.
Crystals suitable for X-ray diffraction analysis were grown from
CH2Cl2 and hexanes.
Data for 4-(4-Methoxybenzoyl)-2-tosyl-1,2,3,4,6,7-hexahydroiso-
quinolin-8(5H)-one (2d). In the typical procedure, to a solution of 1d
(0.05 g, 0.11 mmol) in 1.1 mL of CH2Cl2 was added HNTf2 (3.0 mg,
0.01 mmol). The reaction mixture was stirred at 40 °C for 5 min. The
crude mixture was purified by flash column chromatography (silica gel,
ethyl acetate/hexanes 1:3) to give 2d (30 mg, 0.069 mmol, 60%) as a
white solid: mp 77−78 °C; 1H NMR (400 MHz, CDCl3) δ 7.89 (d, J
= 8.8 Hz, 2 H), 7.65 (d, J = 8.1 Hz, 2 H), 7.30 (d, J = 8.1 Hz, 2 H),
7.00 (d, J = 8.8 Hz, 2 H), 4.59 (m, 1H), 4.18 (d, J = 16.4 Hz, 1 H),
3.92 (s, 3H), 3.84 (m, 1H), 3.46 (d, J = 16.4 Hz, 1H), 2.96 (dd, J =
12.0, 8.5 Hz, 1H), 2.45−2.38 (m, 2H), 2.41 (s, 3H), 2.32 (m, 1H),
2.10−1.84 (m, 3H); 13C NMR (100 MHz, CDCl3) δ 196.6, 195.9,
164.4, 152.6, 143.9, 133.0, 131.1, 130.0, 129.8, 129.0, 127.7, 114.3,
55.6, 48.2, 46.3, 43.1, 37.5, 29.1, 22.1, 21.5; IR (CH2Cl2) 2926, 2852,
1668, 1600, 1348, 1260 cm−1; MS (ESI) m/e (%) 462.1 ([M + Na]+,
100), 440.2 (8), 398.2 (14), 398.1 (100), 388.2 (12), 319.2 (10);
HRMS (ESI) [M + Na]+ C24H25NO5NaS calcd 462.1351, found
462.1361.
Data for 4-([1,1′-Biphenyl]-4-carbonyl)-2-tosyl-1,2,3,4,6,7-
hexahydroisoquinolin8(5H)-one (2e). In the typical procedure, to a
solution of 1e (0.05 g, 0.10 mmol) in 1.0 mL of CH2Cl2 was added
HNTf2 (3.0 mg, 0.01 mmol). The reaction mixture was stirred at 40
°C for 25 min. The crude mixture was purified by flash column
chromatography (silica gel, 1:2 ethyl acetate/hexanes) to give 2e (0.04
g, 0.08 mmol, 80%) as a white solid: mp 182−183 °C; 1H NMR (400
MHz, CDCl3) δ 8.05 (d, J = 8.3 Hz, 2H), 7.76 (d, J = 8.3 Hz, 2H),
7.66 (d, J = 7.9 Hz, 4H), 7.50 (d, J = 7.3 Hz, 2H), 7.44 (t, J = 7.3 Hz,
1H), 7.29 (d, J = 7.9 Hz, 2H), 4.64 (m, 1H), 4.12 (d, J = 16.1 Hz, 1H),
3.81 (dd, J = 12.0, 5.6 Hz, 1H), 3.57 (d, J = 16.1 Hz, 1H), 3.11 (dd, J =
12.0 Hz, 7.8 Hz, 1H), 2.47−2.30 (m, 3H), 2.40 (s, 3H), 2.15−1.85 (m,
3H); 13C NMR (100 MHz, CDCl3) δ 197.1, 196.5, 152.2, 146.9,
143.9, 139.3, 134.5, 133.0, 131.1, 129.8, 129.2, 129.0, 128.6, 127.7,
127.7, 127.3, 48.6, 46.1, 43.0, 37.5, 29.2, 22.1, 21.5; IR (CH2Cl2) 2923,
2853, 1674, 1601, 1349, 1165 cm−1; MS (ESI) m/e (%) 508.2 ([M +
Na]+, 100), 507.3 (17), 490.4 (12), 463.3 (8), 457.3 (12), 454.3 (27),
449.4 (28), 443.2 (8), 433.2 (8), 432.2 (32); HRMS (ESI) [M + Na]+
C29H27NO4NaS calcd 508.1559, found 508.1552.
Data for 4-(1-Naphthoyl)-2-tosyl-1,2,3,4,6,7-hexahydroisoquino-
lin-8(5H)-one (2f). In the typical procedure, to a solution of 1f (0.05 g,
0.11 mmol) in 1.1 mL of CH2Cl2 was added HNTf2 (3.0 mg, 0.01
mmol). The reaction mixture was stirred at 40 °C for 15 min. The
crude mixture was purified by flash column chromatography (silica gel,
1:3 ethyl acetate/hexanes) to give 2f (0.03 g, 0.065 mmol, 60%) as a
pale yellow liquid: 1H NMR (400 MHz, CDCl3) δ 8.50 (d, J = 8.4 Hz,
1H), 8.08 (d, J = 8.2 Hz, 1H), 7.94 (t, J = 8.2 Hz, 2H), 7.67−7.55 (m,
5H), 7.30−7.25 (m, 2H), 4.53 (m, 1H), 3.91 (d, J = 16.3 Hz, 1H),
3.76 (d, J = 16.3 Hz, 1H), 3.55 (dd, J = 12.8, 5.3 Hz, 1H), 3.37 (dd, J =
12.8, 6.6 Hz, 1H), 2.52−2.42 (m, 3H), 2.31 (s, 3H), 2.23−2.13 (m,
1H), 2.08−1.88 (m, 2H); 13C NMR (100 MHz, CDCl3) δ 200.9,
Data for (4R,4aS,12bS)-4,8-Dichloro-10-methyl-6-tosyl-
1,2,3,4,4a,5,6,7-octahydroindeno[2,1-d]isoquinolin-4a-ol (4c). In
the typical procedure, to a solution of 1c (0.21 g, 0.50 mmol) in 5.0
mL of CH2Cl2 at −15 °C under nitrogen was added FeCl3 (0.163 g,
1.00 mmol). The reaction mixture was stirred at −15 °C for 1.5 h. The
crude mixture was purified by flash column chromatography (silica gel,
1:3 ethyl acetate/hexanes) to give 4c (0.181 g, 0.38 mmol, 76%) as a
white solid: mp 246−247 °C; 1H NMR (400 MHz, CDCl3) δ 7.77 (d,
J = 8.0 Hz, 2H), 7.39−7.34 (m, 4H), 7.20 (d, J = 7.6 Hz, 1H), 4.88 (d,
J = 13.2 Hz, 1H), 4.82 (dd, J = 13.2, 4.8 Hz, 1H), 4.05 (dd, J = 13.2,
1.6 Hz, 1H), 3.33 (d, J = 12.8 Hz, 1H), 3.12 (d, J = 12.8 Hz, 1H), 2.46
(s, 3H), 2.45 (m, 1H), 2.43 (s, 3H), 2.20 (br s, 1H, OH), 2.10 (tt, J =
12390
dx.doi.org/10.1021/jo402025z | J. Org. Chem. 2013, 78, 12381−12396

The Journal of Organic Chemistry
Article
13.2, 4.4 Hz, 1H), 1.98−1.87 (m, 2H), 1.81−1.78 (m, 1H), 1.11−1.08
(m, 1H); 13C NMR (100 MHz, CDCl3) δ 145.8, 144.1, 138.3, 136.4,
134.6, 129.9, 128.8, 128.6, 127.7, 125.7, 120.2, 75.3, 63.9, 58.7, 46.8,
41.8, 33.7, 30.3, 21.8, 21.7, 21.6; IR (CH2Cl2) 3549, 2943, 1587, 1578,
1351, 1159 cm−1; MS (ESI) m/e (%) 500.1 ([M + Na]+, 100), 478.1
(30), 293.1 (3), 212.1 (18); HRMS (ESI) calcd for C24H25NO3NaSCl2
[M + Na]+ 500.0829, found 500.0830.
(0.0053 mL, 0.006 mmol). The reaction mixture was stirred at room
temperature for 1 h. After cooling to 0 °C, the reaction was added 1.5
mL of 2 M NaOH in MeOH. The mixture was stirred at room
temperature for an additional 2 h. The reaction mixture was diluted
with 20 mL of water and extracted with ethyl acetate (20 mL × 3).
The combined organic layers were washed with brine (50 mL × 3),
dried over anhydrous MgSO4 (10 g), and concentrated to give the
crude mixture. The crude oil was purified by flash column
chromatography (silica gel, ethyl acetate/hexanes 1:3) to give 9
Data for (4R,4aS,14bS)-4,8-Dichloro-6-tosyl-1,2,3,4,4a,5,6,7-oc-
tahydrobenzo-[4,5]indeno[2,1-d]isoquinolin-4a-ol (4f). In the typi-
cal procedure, to a solution of 1f (0.23 g, 0.50 mmol) in 5.0 mL of
CH2Cl2 at −15 °C under nitrogen was added FeCl3 (0.163 g, 1.00
mmol). The reaction mixture was stirred at −15 °C for 2.0 h. The
crude mixture was purified by flash column chromatography (silica gel,
1:3 ethyl acetate/hexanes) to give 4f (0.119 g, 0.23 mmol, 46%) as a
white solid: mp 227−228 °C; 1H NMR (400 MHz, CDCl3) δ 9.19 (d,
J = 8.4 Hz, 1H), 7.88 (d, J = 8.4 Hz, 1H), 7.81−7.78 (m, 4H), 7.55 (td,
J = 8.0, 1.2 Hz, 1H), 7.50 (t, J = 7.6 Hz, 1H), 7.38 (d, J = 8.0 Hz, 2H),
5.05−4.97 (m, 2H), 4.99 (dd, J = 12.8, 1.2 Hz, 1H), 3.38 (d, J = 13.2
Hz, 1H), 3.17 (d, J = 12.8 Hz, 1H), 2.52 (m, 1H), 2.45 (s, 3H), 2.26
(m, 2H), 2.0 (m, 2H), 1.84 (m, 1H), 1.12 (m, 1H); 13C NMR (100
MHz, CDCl3) δ 145.4, 144.1, 137.8, 134.4, 133.9, 133.5, 129.9, 129.1,
128.6, 128.5, 127.7, 127.1, 126.5, 125.9, 123.3, 122.3, 75.9, 64.0, 58.2,
47.1, 41.8, 33.8, 30.6, 21.9, 21.6; IR (CH2Cl2) 3380, 2988, 1602, 1597,
1340, 1159 cm−1; MS (EI) m/e (%) 536.0 ([M + Na]+, 100), 516.1
(6), 333.6 (7), 263.1 (18), 174.1 (8), 138.5 (3); HRMS (ESI) calcd
for C27H25NO3NaSCl2 [M + Na]+ 536.0830, found 536.0822.
Data for (4R,4aS,12bS)-4,8-Dichloro-11-methoxy-6-tosyl-
1,2,3,4,4a,5,6,7-octahydroindeno[2,1-d]isoquinolin-4a-ol (4i). In
the typical procedure, to a solution of 1i (0.22 g, 0.50 mmol) in 5.0
mL of CH2Cl2 at −15 °C under nitrogen was added FeCl3 (0.163 g,
1.00 mmol). The reaction mixture was stirred at −15 °C for 2.5 h. The
crude mixture was purified by flash column chromatography (silica gel,
ethyl acetate/hexanes 1:3) to give 4i (0.171 g, 0.35 mmol, 69%) as a
white solid: mp 235−236 °C; 1H NMR (400 MHz, CDCl3) δ 7.77 (d,
J = 8.4 Hz, 2H), 7.48 (d, J = 8.4 Hz, 1H), 7.37 (d, J = 8.4 Hz, 2H),
7.02 (d, J = 2.4 Hz, 1H), 6.80 (dd, J = 8.4, 2.4 Hz, 1H), 4.89 (dd, J =
12.8, 1.6 Hz, 1H), 4.75 (dd, J = 12.8, 4.8 Hz, 1H), 4.04 (dd, J = 12.8,
1.6 Hz, 1H), 3.85 (s, 3H), 3.33 (d, J = 13.2 Hz, 1H), 3.12 (d, J = 13.2
Hz, 1H), 2.45 (s, 3H), 2.40 (m, 1H), 2.06 (tt, J = 13.6, 4.0 Hz, 1H),
1.98−1.87 (m, 2H), 1.81 (dquin, J = 13.6, 2.0 Hz, 1H), 1.11−1.07 (m,
1H); 13C NMR (100 MHz, CDCl3) δ 159.9, 144.1, 142.6, 137.5,
137.2, 130.1, 129.9, 128.5, 127.7, 125.2, 112.2, 106.2, 75.4, 64.2, 58.3,
55.6, 46.7, 41.7, 33.8, 30.8, 21.9, 21.6; IR (CH2Cl2) 3321, 2915, 1616,
1447, 1162 cm−1; MS (ESI) m/e (%) 516.0 ([M + Na]+, 100), 494.1
(21), 337.6 (12), 121.1 (13); HRMS (ESI) calcd for
C24H25NO4NaSCl2 [M + Na]+ 516.0779, found 516.0774.
1
(0.079 g, 0.19 mmol, 79%) as a white solid: mp 94−95 °C; H NMR
(400 MHz, CDCl3) δ 7.74 (d, J = 8.2 Hz, 2H), 7.28−7.22 (m, 5H),
7.16−7.14 (m, 2H), 4.38 (s, 4H), 2.70 (q, J = 6.7 Hz, 1H), 2.36 (s,
3H), 2.34−2.29 (m, 2H), 1.97−1.84 (m, 2H), 1.73−1.66 (m, 1H),
1.35 (s, 3H); 13C NMR (100 MHz, CDCl3) δ 216.2, 201.2, 143.7,
136.0, 131.5 (2C), 129.6 (2C), 128.5, 128.1 (2C), 127.5 (2C), 121.9,
86.0, 81.5, 62.7, 51.1, 38.2, 38.0, 33.8, 21.4, 20.6, 19.2; IR (CH2Cl2)
3053, 2970, 1715, 1440, 1349, 1162 cm−1; MS (MALDI) m/e (%)
446.1 ([M + Na]+, 73), 406.1 (10); HRMS (MALDI) calcd for
C24H25NO4SNa [M + Na]+ 446.1420, found 446.1414.
Experimental Procedure for TMSOTf-Promoted Cycloisome-
rization Reaction of 10a. Formation of 11a, 12a, and 13a. To a
solution of 10a (0.10 g, 0.22 mmol) in 2.2 mL of CH2Cl2 at room
temperature under nitrogen was added TMSOTf (0.019 mL, 0.11
mmol). The reaction mixture was stirred at room temperature for 24
h, after which time to the reaction mixture was added 10 mL of water.
The mixture was extracted with ethyl acetate (20 mL × 3). The
combined organic layers were washed with brine (50 mL × 3), dried
over anhydrous MgSO4 (10 g) and concentrated to give the crude
mixture. The residue was purified by flash column chromatography
using a mixture of EtOAc/hexanes (1/2) as eluent to afford 11a (29
mg, 0.064 mmol, 29%), 12a (22 mg, 0.048 mmol, 22%) and 13a (24
mg, 0.062 mmol, 28%).
Data for 4-Methyl-N-(2-oxo-2-(1,4,4-trimethyl-2-oxocyclopentyl)-
ethyl)-N-(3-phenyl-prop-2-yn-1-yl)benzenesulfonamide (11a). A
1
white solid: mp 108−109 °C; H NMR (400 MHz, CDCl3) δ 7.75
(d, J = 8.2 Hz, 2H), 7.29−7.23 (m, 5H), 7.16−7.14 (m, 2H), 4.49−
4.40 (m, 4H), 2.80 (d, J = 13.7 Hz, 1H), 2.36 (s, 3H), 2.23 (d, J = 17.6
Hz, 1H), 2.17 (d, J = 17.6 Hz, 1H), 1.55 (d, J = 13.7 Hz, 1H), 1.43 (s,
3H), 1.11 (s, 3H), 1.00 (s, 3H); 13C NMR (100 MHz, CDCl3) δ
215.9, 200.9, 143.6, 136.0, 131.5 (2C), 129.6 (2C), 128.5, 128.1 (2C),
127.5 (2C), 121.9, 86.1, 81.5, 63.5, 53.0, 50.8, 46.7, 38.1, 33.4, 29.6,
29.0, 24.1, 21.4; IR (CH2Cl2) 2959, 2872, 1739, 1724, 1598, 1351
cm−1; MS (ESI) m/e (%) 474.2 ([M + Na]+, 100), 469.2 (10), 452.2
(5); HRMS (ESI) calcd for C26H29NO4SNa [M + Na]+ 474.1715,
found 474.1724. Crystals suitable for X-ray diffraction analysis were
slow recrystallization from dichloromethane and hexanes.
Data for (4R,4aS,12bS)-4,8-Dibromo-6-tosyl-1,2,3,4,4a,5,6,7-oc-
tahydroindeno-[2,1-d]isoquinolin-4a-ol (7). In the typical procedure,
to a solution of 1a (0.10 g, 0.25 mmol) in 2.5 mL of CH2Cl2 at −15
°C under nitrogen was added FeBr3 (0.15 g, 0.50 mmol). The reaction
mixture was stirred at −15 °C for 1 h. The crude mixture was purified
by flash column chromatography (silica gel, ethyl acetate/hexanes 1:3)
to give 7 (93 mg, 0.17 mmol, 67%) as a white solid: mp 205−206 °C;
1H NMR (400 MHz, CDCl3) δ 7.78 (d, J = 8.0 Hz, 2H), 7.61 (d, J =
7.6 Hz, 1H), 7.45 (d, J = 6.8 Hz, 1H), 7.40 (d, J = 7.2 Hz, 1H), 7.37
(d, J = 8.4 Hz, 2H), 7.26 (td, J = 7.2, 1.2 Hz, 1H), 4.95 (dd, J = 12.8,
4.8 Hz, 1H), 4.86 (dd, J = 13.2, 1.6 Hz, 1H), 4.12 (dd, J = 13.2, 1.6 Hz,
1H), 3.37 (d, J = 13.2 Hz, 1H), 3.18 (d, J = 13.2 Hz, 1H), 2.55−2.45
(m, 4H), 2.18−2.05 (m, 3H), 1.96 (td, J = 13.6, 4.0 Hz, 1H), 1.79−
1.73 (m, 1H), 1.09 (dd, J = 12.4, 1.6 Hz, 1H); 13C NMR (100 MHz,
CDCl3) δ 145.5, 144.1, 141.8, 139.7, 133.9, 129.9 (2C), 127.9, 127.7
(2C), 126.4, 124.5, 121.7, 118.9, 74.9, 59.9, 57.6, 48.5, 43.2, 34.7, 30.3,
22.8, 21.6; IR (CH2Cl2) 3321, 2915, 1623, 1348, 1162 cm−1; MS
(ESI) m/e 577.9, 575.9, 573.9, 504.1, 482.1, 266.0, 263.1, 219.0;
HRMS (ESI) calcd for C23H23NO3NaSBr2 [M + Na]+ 573.9663,
found 573.9672. Crystals suitable for X-ray diffraction analysis were
grown from CH2Cl2 and hexanes.
Data for 2-(4-Benzoyl-1-tosyl-1H-pyrrol-3-yl)-2,4,4-trimethylcy-
clopentanone (12a). A pale yellow oil: 1H NMR (500 MHz,
CDCl3) δ 7.75 (d, J = 8.4 Hz, 2H), 7.72 (d, J = 7.2 Hz, 2H), 7.57 (t, J
= 7.4 Hz, 1H), 7.47 (d, J = 7.8 Hz, 2H), 7.43 (s, 1H), 7.28 (d, J = 8.2
Hz, 2H), 7.07 (s, 1H), 2.68 (d, J = 18.8 Hz, 1H), 2.43 (s, 3H), 2.34 (d,
J = 18.8 Hz, 1H), 2.26 (d, J = 13.6 Hz, 1H), 1.91 (d, J = 13.6 Hz, 1H),
1.53 (s, 3H), 1.21 (s, 3H), 1.11 (s, 3H); 13C NMR (125 MHz, CDCl3)
δ 220.6, 190.9, 145.9, 139.4, 134.9, 133.4, 132.2, 130.3 (2C), 129.1
(2C), 128.4 (2C), 127.3 (2C), 124.6, 119.3, 53.0, 52.0, 50.4, 32.9, 31.8,
31.0, 25.7, 21.6; IR (CH2Cl2) 2952, 1734, 1649, 1598, 1343, 1174
cm−1; MS (ESI) m/e 472.1 [M + Na]+, 450.1, 434.1, 383.1, 374.2,
358.1, 306.1, 190.0; HRMS (ESI) calcd for C26H27NO4NaS [M +
Na]+ 472.1559, found 472.1556.
Data for 2-(4-Benzoyl-1H-pyrrol-3-yl)-2,4,4-trimethylcyclopenta-
1
none (13a). A white solid: mp 195−196 °C; H NMR (400 MHz,
CDCl3) δ 9.00 (br s, 1H), 7.63 (d, J = 7.3 Hz, 2H), 7.47 (t, J = 7.3 Hz,
1H), 7.38 (dd, J = 7.5, 7.3 Hz, 2H), 6.95 (s, 1H), 6.57 (s, 1H), 2.82 (d,
J = 18.8 Hz, 1H), 2.42 (d, J = 13.4 Hz, 1H), 2.40 (d, J = 19.1 Hz, 1H),
1.94 (d, J = 13.4 Hz, 1H), 1.55 (s, 3H), 1.25 (s, 3H), 1.17 (s, 3H); 13C
NMR (100 MHz, CDCl3) δ 222.9, 191.2, 140.9, 131.0, 129.8, 129.6,
128.7 (2C), 128.0 (2C), 120.6, 118.3, 53.6, 52.2, 50.8, 32.7, 32.2, 31.2,
25.6; IR (CH2Cl2) 3272, 2955, 1725, 1629, 1384 cm−1; MS (ESI) m/e
(%) 318.1 ([M + Na]+, 100), 311.2 (3), 296.7 (24); HRMS (ESI)
calcd for C19H21NO2Na [M + Na]+ 318.1470, found 318.1473.
Procedure for TMSOTf-Promoted Semipinacol Rearrange-
ment of 8 to 9. To a solution of 8 (0.10 g, 0.24 mmol) in 2.3 mL of
CH2Cl2 at room temperature under nitrogen was added TMSOTf
12391
dx.doi.org/10.1021/jo402025z | J. Org. Chem. 2013, 78, 12381−12396

The Journal of Organic Chemistry
Article
1
Crystals suitable for X-ray diffraction analysis were grown from ethyl
acetate and hexanes.
solid: mp 178−179 °C; H NMR (400 MHz, CDCl3) δ 9.02 (br s,
1H), 7.76 (d, J = 8.2 Hz, 2H), 7.62−7.60 (m, 4H), 7.45−7.49 (m,
2H), 7.38−7.42 (m, 1H), 7.08−7.09 (m, 1H), 6.64 (s, 1H), 2.86 (d, J
= 18.8 Hz, 1H), 2.46−2.41(m, 2H), 1.98 (d, J = 13.4 Hz, 1H), 1.59 (s,
3H), 1.28 (s, 3H), 1.21 (s, 3H); 13C NMR (100 MHz, CDCl3) δ
222.9, 190.8, 143.9, 140.2, 139.6, 129.6, 129.4, 128.8, 127.9, 127.2,
126.7, 120.7, 118.3, 53.6, 52.2, 50.8, 32.7, 32.2, 31.2, 25.6; IR
(CH2Cl2) 2958, 2356, 1728, 1622, 1258, 1174 cm−1; MS (ESI) m/e
(%)370.2 ([M − H]−, 100), 368.2 (28), 239.1 (10), 203.1 (32), 87.1
(17); HRMS (ESI) calcd for C25H24NO2 [M − H]− 370.1807, found
370.1801.
General Procedure for TMSOTf-Promoted Cycloisomeriza-
tion Reaction of 10 Followed by Basic Treatments. Formation
of 13. To a solution of 10a (0.10 g, 0.22 mmol) in 2.2 mL of CH2Cl2
at room temperature under nitrogen was added TMSOTf (0.048 mL,
0.27 mmol). The reaction mixture was stirred at room temperature for
24 h, after which time the reaction mixture was cooled at 0 °C and 1.5
mL of 2 M NaOH in MeOH was added. The reaction was allowed to
stir at room temperature for 2 h. The reaction mixture was treated with
10 mL of water. The mixture was extracted with ethyl acetate (20 mL
× 3). The combined organic layers were washed with brine (50 mL ×
3), dried over anhydrous MgSO4 (10 g), and concentrated to give the
crude mixture.
Data for 2-(4-Benzoyl-1H-pyrrol-3-yl)-2,4,4-trimethylcyclopenta-
none (13a). In the typical procedure, to a solution of 10a (0.11 g, 0.22
mmol) in 2.2 mL of CH2Cl2 at room temperature under nitrogen was
added TMSOTf (0.048 mL, 0.27 mmol). The reaction mixture was
stirred for 4 h. After cooling to 0 °C, the reaction mixture was treated
with 2 M NaOH in MeOH (1.5 mL). The reaction was stirred at room
temperature for 2 h. The crude mixture was purified by flash column
chromatography (silica gel, ethyl acetate/hexanes 1:2) to give 13a (40
mg, 0.14 mmol, 62%) as colorless crystals. All analytical data for 13a
are identical to those of the previous experiment.
Data for 2,4,4-Trimethyl-2-(4-(4-methylbenzoyl)-1H-pyrrol-3-yl)-
cyclopentanone (13b). In the typical procedure, to a solution of 10b
(0.10 g, 0.22 mmol) in 2.2 mL of CH2Cl2 at room temperature under
nitrogen was added TMSOTf (0.048 mL, 0.27 mmol). The reaction
mixture was stirred for 2 h. After cooling to 0 °C, the reaction mixture
was treated with 2 M NaOH in MeOH (1.5 mL). The reaction was
stirred at room temperature for 2 h. The crude mixture was purified by
flash column chromatography (silica gel, ethyl acetate/hexanes 1:2) to
give 13b (46 mg, 0.15 mmol, 67%) as a white solid: mp 189−190 °C;
1H NMR (400 MHz, CDCl3) δ 8.76 (br s, 1H), 7.60 (d, J = 7.5 Hz,
2H), 7.20 (d, J = 7.8 Hz, 2H), 7.02 (d, J = 1.8 Hz, 1H), 6.61 (d, J = 1.9
Hz, 1H), 2.79 (d, J = 18.8 Hz, 1H), 2.42−2.35 (m, 5H), 1.94 (d, J =
13.5 Hz, 1H), 1.56 (s, 3H), 1.24 (s, 3H), 1.15 (s, 3H); 13C NMR (100
MHz, CDCl3) δ 222.7, 191.1, 141.5, 138.2, 129.7, 129.3, 129.0, 128.7,
120.8, 118.1, 53.6, 52.2, 50.7, 32.8, 32.0, 31.1, 25.7, 21.5; IR (CH2Cl2)
3270, 2957, 1725, 1606, 1451, 1383 cm−1; MS (ESI) m/z 332.2 ([M +
Na]+, 100), 311.2 (5), 310.2 (32), 235.0 (5); HRMS (ESI) calcd for
C20H23NO2Na [M + Na]+ 332.1626, found 332.1618.
Data for 2-(4-(1-Naphthoyl)-1H-pyrrol-3-yl)-2,4,4-trimethylcyclo-
pentanone (13e). In the typical procedure, to a solution of 10e (0.11
g, 0.22 mmol) in 2.2 mL of CH2Cl2 at room temperature under air was
added TMSOTf (0.048 mL, 0.27 mmol). The reaction mixture was
stirred for 1 h. After cooling to 0 °C, the reaction mixture was treated
with 2 M NaOH in MeOH (1.5 mL). The reaction was stirred at room
temperature for 2 h. The crude mixture was purified by flash column
chromatography (silica gel, ethyl acetate/hexanes 1:2) to give 13e (47
mg, 0.14 mmol, 62%) as a pale yellow oil: 1H NMR (400 MHz,
CDCl3) δ 8.49 (br s, 1H), 7.92 (d, J = 8.0 Hz, 1H), 7.87 (d, J = 8.0 Hz,
1H), 7.84 (dd, J = 7.5, 1.5 Hz, 1H), 7.47−7.39 (m, 4H), 6.72 (dd, J =
2.9, 2.0 Hz, 1H), 6.64 (t, J = 2.2 Hz, 1H), 2.88 (d, J = 19.0 Hz, 1H),
2.59 (d, J = 13.3 Hz, 1H), 2.45 (d, J = 19.0 Hz, 1H), 2.00 (d, J = 13.3
Hz, 1H), 1.60 (s, 3H), 1.30 (s, 3H), 1.26 (s, 3H); 13C NMR (100
MHz, CDCl3) δ 222.2, 192.2, 139.2, 133.6, 130.8, 130.7, 129.7, 129.6,
128.0, 126.8, 126.2, 125.8, 125.2, 124.3, 122.7, 118.5, 53.6, 52.2, 50.9,
32.8, 32.4, 31.4, 25.2; IR (CH2Cl2) 3247, 2958, 2347, 1725, 1631,
1380, 1325 cm−1; MS (ESI) m/e (%) 368.2 ([M + Na]+, 89), 347.2
(23), 246.2 (100), 293.1 (10), 242.3 (10); HRMS (ESI) calcd for
C23H23NO2Na [M + Na]+ 368.1626, found 368.1620.
Data for 2,4,4-Trimethyl-2-(4-(phenanthrene-9-carbonyl)-1H-
pyrrol-3-yl)-cyclopentanone (13f). In the typical procedure, to a
solution of 10f (0.12 g, 0.22 mmol) in 2.2 mL of CH2Cl2 at room
temperature under air was added TMSOTf (0.048 mL, 0.27 mmol).
The reaction mixture was stirred for 5 h. After cooling to 0 °C, the
reaction mixture was treated with 2 M NaOH in MeOH (1.5 mL).
The reaction was stirred at room temperature for 2 h. The crude
mixture was purified by flash column chromatography (silica gel, ethyl
acetate/hexanes 1:2) to give 13f (49 mg, 0.12 mmol, 56%) as a pale
yellow oil: 1H NMR (400 MHz, CDCl3) δ 8.88 (br s, 1H), 8.59 (d, J =
8.4 Hz, 1H), 8.55 (d, J = 8.2 Hz, 1H), 7.84 (d, J = 8.2 Hz, 1H), 7.73
(d, J = 7.8 Hz, 1H), 7.65 (td, J = 7.2, 1.1 Hz, 1H), 7.59 (s, 1H), 7.52−
7.55 (m, 1H), 7.50−7.46 (m, 1H), 7.38−7.42 (m, 1H), 6.53 (s, 1H),
6.50 (s, 1H), 2.88 (d, J = 19.2 Hz, 1H), 2.56 (d, J = 13.3 Hz, 1H), 2.45
(d, J = 19.2 Hz, 1H), 1.95 (d, J = 13.3 Hz, 1H), 1.54 (s, 3H), 1.30 (s,
3H), 1.26 (s, 3H); 13C NMR (100 MHz, CDCl3) δ 222.8, 192.2,
127.5, 131.3, 130.4, 130.2, 129.2, 129.1, 127.5, 126.9, 126.8, 126.8,
126.3, 125.9, 122.5, 122.4, 121.9, 118.9, 53.6, 52.0, 51.0, 32.6, 31.6,
24.9; IR (CH2Cl2) 3255, 2956, 2366, 2339, 1730, 1630 cm−1; MS
(ESI) m/e (%) 394.2 ([M + H]−, 44), 354.2 (3),345.0 (4), 310.1 (3),
295.0 (3); HRMS (ESI) calcd for C27H24NO2 [M − H]− 394.1807,
found 394.1814.
Data for 2,4,4-Trimethyl-2-(4-(3-methylbenzoyl)-1H-pyrrol-3-yl)-
cyclopentanone (13c). In the typical procedure, to a solution of 10c
(0.10 g, 0.22 mmol) in 2.2 mL of CH2Cl2 at room temperature under
air was added TMSOTf (0.048 mL, 0.27 mmol). The reaction mixture
was stirred for 12 h. After cooling to 0 °C, the reaction mixture was
treated with 2 M NaOH in MeOH (1.5 mL). The reaction was stirred
at room temperature for 2 h. The crude mixture was purified by flash
column chromatography (silica gel, 1:2 ethyl acetate/hexanes) to give
1
13c (34 mg, 0.11 mmol, 49%) as a white solid: mp 187−188 °C; H
NMR (400 MHz, CDCl3) δ 8.60 (br s, 1H), 7.51 (s, 1H), 7.47 (d, J =
6.3 Hz, 1H), 7.30−7.26 (m, 2H), 7.07 (s, 1H), 6.66 (s, 1H), 2.80 (d, J
= 18.8 Hz, 1H), 2.42 (d, J = 13.4 Hz, 1H), 2.39 (d, J = 18.4 Hz, 1H),
2.38 (s, 3H), 1.96 (d, J = 13.4 Hz, 1H), 1.57 (s, 3H), 1.25 (s, 3H), 1.18
(s, 3H); 13C NMR (100 MHz, CDCl3) δ 222.6, 191.4, 141.0, 137.8,
131.8, 129.7, 129.3, 127.8, 126.0, 120.8, 118.2, 53.6, 52.2, 50.7, 32.7,
32.1, 31.2, 25.6, 21.3; IR (CH2Cl2) 3720, 3258, 2952, 2359, 2343,
1717, 1623 cm−1; MS (ESI) m/e (%) 332.2 ([M + Na]+, 100), 310.2
(10), 269.1 (1), 263.1 (2); HRMS (ESI) calcd for C20H23NO2Na [M
+ Na]+ 332.1626, found 332.1622.
Data for 2-(4-(3-Methoxybenzoyl)-1H-pyrrol-3-yl)-2,4,4-trime-
thylcyclopentanone (13g). In the typical procedure, to a solution
of 10g (0.10 g, 0.22 mmol) in 2.2 mL of CH2Cl2 at room temperature
under air was added TMSOTf (0.048 mL, 0.27 mmol). The reaction
mixture was stirred for 4 h. After cooling to 0 °C, the reaction mixture
was treated with 2 M NaOH in MeOH (1.5 mL). The reaction was
stirred at room temperature for 2 h. The crude mixture was purified by
flash column chromatography (silica gel, ethyl acetate/hexanes 1:2) to
give 13g (47 mg, 0.15 mmol, 65%) as colorless crystals: mp 176−177
Data for 2-(4-([1,1′-Biphenyl]-4-carbonyl)-1H-pyrrol-3-yl)-2,4,4-
trimethyl-cyclopentanone (13d). In the typical procedure, to a
solution of 10d (0.12 g, 0.22 mmol) in 2.2 mL of CH2Cl2 at room
temperature under air was added TMSOTf (0.048 mL, 0.27 mmol).
The reaction mixture was stirred for 4 h. After cooling to 0 °C, the
reaction mixture was treated with 2 M NaOH in MeOH (1.5 mL).
The reaction was stirred at room temperature for 2 h. The crude
mixture was purified by flash column chromatography (silica gel, ethyl
acetate/hexanes 1:2) to give 13d (44 mg, 0.12 mmol, 53%) as a white
1
°C; H NMR (400 MHz, CDCl3) δ 9.03 (br s, 1H), 7.27 (d, J = 8.4
Hz, 1H), 7.20 (d, J = 8.4 Hz, 2H), 7.03−7.00 (m, 2H), 6.58 (s, 1H),
3.81 (s, 3H), 2.81 (d, J = 18.9 Hz, 1H), 2.42 (s, 1H), 2.38 (d, J = 3.8
Hz, 1H), 1.94 (d, J = 13.4 Hz, 1H), 1.55 (s, 3H), 1.25 (s, 3H), 1.17 (s,
3H); 13C NMR (100 MHz, CDCl3) δ 222.8, 190.9, 159.3, 142.2,
129.8, 129.6, 129.0, 121.4, 120.5, 118.3, 117.4, 113.4, 55.4, 53.6, 52.2,
50.7, 32.7, 32.1, 31.2, 25.6; IR (CH2Cl2) 2957, 1713, 1598, 1576, 1351,
1290 cm−1; MS (ESI) m/e (%) 348.2 ([M + Na]+, 100), 327.2 (10),
12392
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Article
326.22 (50), 235.0 (10); HRMS (ESI) calcd for C20H23NO3Na [M +
Na]+ 348.1576, found 348.1582. Crystals suitable for X-ray diffraction
analysis were grown from ethyl acetate and hexanes.
3H), 2.20 (s, 2H), 1.55 (d, J = 13.7 Hz, 1H), 1.44 (s, 3H), 1.11 (s,
3H), 1.00 (s, 3H); 13C NMR (100 MHz, CDCl3) δ 215.9, 200.8,
147.9, 144.0, 137.3, 136.0, 129.7, 129.3, 127.6, 126.4, 123.7, 123.3,
84.5, 83.5, 63.6, 53.0, 51.0, 46.6, 37.9, 33.4, 29.6, 29.0, 24.1, 21.4; IR
(CH2Cl2) 2956, 2928, 1716, 1532, 1351, 1264, 1163 cm−1; MS (ESI)
m/e (%) 519.2 ([M + Na]+, 100), 497.2 (6), 482.3 (4), 320.6 (3),
181.1 (3); HRMS (ESI) calcd for C26H28N2O6SNa [M + Na]+
519.1566, found 519.1569.
General Experimental Procedure for BF3-Promoted Cyclo-
isomerization of 14 under Nitrogen. Synthesis of Dihydrofur-
an 15. To a solution of 14a (0.08 g, 0.25 mmol) in 10.0 mL of
CH2Cl2 at room temperature under an atmosphere of nitrogen was
added BF3·OEt2 (0.032 mL, 0.25 mmol). The reaction mixture was
stirred at room temperature for 3 h. The reaction mixture was
quenched with saturated aqueous NaHCO3 The organic phase was
separated, and the aqueous phase was extracted with CH2Cl2 (20 mL
× 3 mL). The combined organic layers were washed with brine (50
mL × 3), dried over anhydrous MgSO4 (10 g), and concentrated to
give the crude mixture.
Data for 2-(4-(4-Bromobenzoyl)-1H-pyrrol-3-yl)-2,4,4-trimethyl-
cyclopentanone (13h). In the typical procedure, to a solution of 10h
(0.12 g, 0.22 mmol) in 2.2 mL of CH2Cl2 at room temperature under
air was added TMSOTf (0.048 mL, 0.27 mmol). The reaction mixture
was stirred for 23 h. After cooling to 0 °C, the reaction mixture was
treated with 2 M NaOH in MeOH (1.5 mL). The reaction was stirred
at room temperature for 2 h. The crude mixture was purified by flash
column chromatography (silica gel, ethyl acetate/hexanes 1:2) to give
13h (0.040 g, 0.11 mmol, 48%) as a white solid: mp 193−194 °C; 1H
NMR (400 MHz, CDCl3) δ 8.79 (br s, 1H), 7.54 (s, 4H), 7.01−7.00
(m, 1H), 6.64−6.63 (m, 1H), 2.79 (d, J = 18.8 Hz, 1H), 2.40 (d, J =
18.8 Hz, 1H), 2.37 (d, J = 13.4 Hz, 1H), 1.95 (d, J = 13.4 Hz, 1H),
1.55 (s, 3H), 1.26 (s, 3H), 1.17 (s, 3H); 13C NMR (100 MHz, CDCl3)
δ 222.5, 189.9, 139.6, 131.3, 130.4, 129.9, 129.4, 125.8, 120.5, 118.4,
53.5, 52.2, 50.7, 32.8, 32.1, 31.2, 25.6; IR (CH2Cl2) 3269, 2958, 1723,
1627, 1453, 1397 cm−1; MS (ESI) m/e (%) 374.1 ([M + H]+, 100),
293.1 (2), 288.6 (7), 269.1 (4); HRMS (ESI) C19H21NO2Br [M + H]+
374.0756, found 374.0751.
Data for 2,4,4-Trimethyl-2-(4-(thiophene-2-carbonyl)-1H-pyrrol-
3-yl)cyclopentanone (13i). In the typical procedure, to a solution of
10i (0.10 g, 0.22 mmol) in 2.2 mL of CH2Cl2 at room temperature
under air was added TMSOTf (0.048 mL, 0.27 mmol). The reaction
mixture was stirred for 4 h. After cooling to 0 °C, the reaction mixture
was treated with 2 M NaOH in MeOH (1.5 mL). The reaction was
stirred at room temperature for 2 h. The crude mixture was purified by
flash column chromatography (silica gel, ethyl acetate/hexanes 1:2) to
give 13i (35 mg, 0.12 mmol, 52%) as yellow crystals: mp 164−165 °C;
1H NMR (400 MHz, CDCl3) δ 8.66 (br s, 1H), 7.60 (d, J = 3.5 Hz,
Data for 2-(4-Benzoyl-2,5-dihydrofuran-3-yl)-2,4,4-trimethylcy-
clopentanone (15a). In the typical procedure, to a solution of 14a (80
mg, 0.25 mmol) in 10.0 mL of CH2Cl2 at room temperature under
nitrogen was added BF3·OEt2 (0.032 mL, 0.25 mmol). The reaction
mixture was stirred for 3 h, and the crude mixture was purified by flash
column chromatography (silica gel, ethyl acetate/dichloromethane/
hexanes 1:1:9) to give 15a (64 mg, 0.20 mmol, 79%) as a pale yellow
oil: 1H NMR (500 MHz, CDCl3) δ 7.85 (dd, J = 7.2, 1.2 Hz, 2H), 7.59
(t, J = 7.5 Hz, 1H), 7.49 (t, J = 7.5 Hz, 2H), 4.94−4.89 (m, 2H), 4.82−
4.76 (m, 2H), 2.27 (d, J = 18.0 Hz, 1H), 2.21 (d, J = 18.0 Hz, 1H),
2.18 (d, J = 13.5 Hz, 1H), 2.02 (d, J = 13.5 Hz, 1H), 1.36 (s, 3H), 1.11
(s, 3H), 1.09 (s, 3H); 13C NMR (125 MHz, CDCl3) δ 218.9, 194.6,
145.6, 137.1, 133.7, 132.3, 128.9, 128.8, 78.7, 52.6, 51.7, 50.8, 33.6,
30.3, 30.2, 25.8; IR (CH2Cl2) 2957, 1734, 1653, 1539, 1447, 1265
cm−1; MS (ESI) m/e 299.2, 298.2, 251.2, 237.1; HRMS (ESI) calcd for
C19H22O3Na [M + Na]+ 321.1467, found 321.1460.
Data for 2,4,4-Trimethyl-2-(4-(4-methylbenzoyl)-2,5-dihydrofur-
an-3-yl)cyclopentanone (15b). In the typical procedure, to a solution
of 14b (80 mg, 0.25 mmol) in 10.0 mL of CH2Cl2 at room
temperature under nitrogen was added BF3·OEt2 (0.032 mL, 0.25
mmol). The reaction mixture was stirred for 2 h, and the crude
mixture was purified by flash column chromatography (silica gel, ethyl
acetate/dichloromethane/hexanes 1:1:9) to give 15b (55 mg, 0.18
mmol, 69%) as a pale yellow oil: 1H NMR (500 MHz, CDCl3) δ 7.76
(d, J = 8.0 Hz, 2H), 7.28 (d, J = 8.0 Hz, 2H), 4.93−4.88 (m, 2H),
4.81−4.76 (m, 2H), 2.43 (s, 3H), 2.26 (d, J = 18.0 Hz, 1H), 2.19 (d, J
= 18.0 Hz, 1H), 2.18 (d, J = 13.0 Hz, 1H), 2.02 (d, J = 13.0 Hz, 1H),
1.35 (s, 3H), 1.10 (s, 3H), 1.08 (s, 3H); 13C NMR (125 MHz, CDCl3)
δ 218.9, 194.6, 144.8, 144.6, 134.5, 132.5, 129.5, 129.1, 78.7, 52.6, 51.6,
50.7, 33.6, 30.2, 30.1, 25.8, 21.7; IR (CH2Cl2) 2915, 1738, 1655, 1605,
1384, 1266 cm−1; MS (ESI) m/e 335.2, 313.2, 311.2, 299.2; HRMS
(ESI) calcd for C20H24O3Na [M + Na]+ 335.1623, found 335.1614.
Data for 2,4,4-Trimethyl-2-(4-(phenanthrene-9-carbonyl)-2,5-
dihydrofuran-3-yl)cyclopentanone (15c). In the typical procedure,
to a solution of 14c (0.10 g, 0.25 mmol) in 10.0 mL of CH2Cl2 at
room temperature under nitrogen was added BF3·OEt2 (0.032 mL,
0.25 mmol). The reaction mixture was stirred for 1 h, and the crude
mixture was purified by flash column chromatography (silica gel, 1:1:9
ethyl acetate/dichloromethane/hexanes) to give 15c (69 mg, 0.17
mmol, 69%) as a pale yellow oil: 1H NMR (500 MHz, CDCl3) δ 8.73
(d, J = 8.1 Hz, 1H), 8.69 (d, J = 8.5 Hz, 1H), 8.46 (dd, J = 8.5, 1.5 Hz,
1H), 7.99 (s, 1H), 7.95 (d, J = 7.5 Hz, 1H), 7.76 (t, J = 7.0 Hz, 1H),
7.72−7.63 (m, 3H), 4.98−4.76 (m, 4H), 2.47 (d, J = 18.5 Hz, 1H),
2.41 (d, J = 13.5 Hz, 1H), 2.32 (d, J = 18.5 Hz, 1H), 1.97 (d, J = 13.5
Hz, 1H), 1.44 (s, 3H), 1.22 (s, 3H), 1.17 (s, 3H); 13C NMR (125
MHz, CDCl3) δ 218.9, 194.4, 151.9, 134.9, 132.3, 131.9, 130.7, 130.3,
129.9, 129.8, 129.0, 128.0, 127.7, 127.4, 127.2, 126.0, 122.9, 122.7,
78.1, 77.7, 52.6, 52.5, 51.7, 33.5, 31.1, 30.9, 24.8; IR (CH2Cl2) 2952,
1738, 1645, 1579, 1447, 1388, 1251 cm−1; MS (ESI) m/e 421.2, 400.2,
399.2, 342.2; HRMS (ESI) calcd for C27H26O3Na [M + Na]+,
421.1780, found 421.1775.
1H), 7.57 (d, J = 5.0 Hz, 1H), 7.36 (s, 1H), 7.09 (t, J = 4.2 Hz, 1H),
6.65 (s, 1H), 2.72 (d, J = 18.7 Hz, 1H), 2.38 (d, J = 13.3 Hz, 1H), 2.36
(d, J = 18.7 Hz, 1H), 1.98 (d, J = 13.5 Hz 1H), 1.56 (s, 3H), 1.22 (s,
3H), 1.12 (s, 3H); 13C NMR (100 MHz, CDCl3) δ 222.7, 182.3,
145.8, 131.9, 131.8, 129.7, 127.5, 127.4, 120.8, 118.1, 53.5, 52.3, 50.5,
32.9, 31.8, 30.9, 26.1; IR (CH2Cl2) 2960, 1728, 1608, 1516, 1417,
1381 cm−1; MS (ESI) m/e (%) 324.1 ([M + Na]+, 100), 303.1 (5),
302.1 (40), 232.1 (3); HRMS (ESI) calcd for C17H19NO2SNa [M +
Na]+ 324.1034, found 324.1036. Crystals suitable for X-ray diffraction
analysis were grown from ethyl acetate and hexanes.
Data for 4-Methyl-N-(3-(4-nitrophenyl)prop-2-yn-1-yl)-N-(2-oxo-
2-(1,4,4-trimethyl-2-oxocyclopentyl)ethyl)benzenesulfonamide
(11j). In the typical procedure, to a solution of 10j (0.11 g, 0.22 mmol)
in 2.2 mL of CH2Cl2 at room temperature under air was added
TMSOTf (0.048 mL, 0.27 mmol). The reaction mixture was stirred for
2 h, and the crude mixture was purified by flash column
chromatography (silica gel, 1:3 ethyl acetate/hexanes) to give 11j
1
(0.073 g, 0.15 mmol, 66%) as a white solid: mp 120−121 °C; H
NMR (400 MHz, CDCl3) δ 8.14 (d, J = 8.7 Hz, 2H), 7.75 (d, J = 8.1
Hz, 2H), 7.35−7.21 (m, 4H), 4.56−4.37 (m, 4H), 2.81 (d, J = 13.7
Hz, 1H), 2.38 (s, 3H), 2.21 (s, 2H), 1.56 (d, J = 13.7 Hz, 1H), 1.45 (s,
3H), 1.12 (s, 3H), 1.01 (s, 3H); 13C NMR (100 MHz, CDCl3) δ
215.9, 200.8, 147.3, 143.9, 136.1, 132.4, 129.7, 128.8, 127.6, 123.5,
87.3, 84.1, 63.7, 53.1, 51.0, 46.6, 38.0, 33.5, 29.7, 29.1, 24.1, 21.5; IR
(CH2Cl2) 2959, 2871, 1716, 1596, 1520, 1344, 1267 cm−1; MS (ESI)
m/e (%) 495.2 ([M − H]−, 70), 388.2 (13), 364.1 (10), 362 (13),
350.1 (38); HRMS (ESI) calcd for C26H27N2O6S [M − H]− calcd
495.1590, found 495.1582.
Data for 4-Methyl-N-(3-(3-nitrophenyl)prop-2-yn-1-yl)-N-(2-oxo-
2-(1,4,4-trimethyl-2-oxocyclopentyl)ethyl)benzenesulfonamide
(11k). In the typical procedure, to a solution of 10k (0.11 g, 0.22
mmol) in 2.2 mL of CH2Cl2 at room temperature under air was added
TMSOTf (0.048 mL, 0.27 mmol). The reaction mixture was stirred for
2 h, and the crude mixture was purified by flash column
chromatography (silica gel, 1:3 ethyl acetate/hexanes) to give 11k
1
(0.098 g, 0.20 mmol, 89%) as a pale yellow oil: H NMR (400 MHz,
CDCl3) δ 8.15 (dq, J = 8.0, 1.3 Hz, 1H), 7.95 (s, 1H), 7.75 (d, J = 8.2
Hz, 2H), 7.50−7.42 (m, 2H), 7.31 (d, J = 8.0 Hz, 2H), 4.52 (d, J =
20.4 Hz, 1H), 4.48−4.35 (m, 3H), 2.81 (d, J = 13.7 Hz, 1H), 2.37 (s,
12393
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Data for 2-(4-(4-Bromobenzoyl)-2,5-dihydrofuran-3-yl)-2,4,4-tri-
methylcyclopentanone (15d). In the typical procedure, to a solution
of 14d (94 mg, 0.25 mmol) in 10.0 mL of CH2Cl2 at room
temperature under nitrogen was added BF3·OEt2 (0.032 mL, 0.25
mmol). The reaction mixture was stirred for 3 h, and the crude
mixture was purified by flash column chromatography (silica gel, ethyl
acetate/dichloromethane/hexanes 1:1:9) to give 15d (71 mg, 0.19
mmol, 75%) as a pale yellow oil: 1H NMR (500 MHz, CDCl3) δ 7.71
(dd, J = 8.5, 2.0 Hz, 2H), 7.49 (dd, J = 8.5, 2.0 Hz, 2H), 4.93−4.86 (m,
2H), 4.82−4.74 (m, 2H), 2.28 (d, J = 18.0 Hz, 1H), 2.22 (d, J = 18.0
Hz, 1H), 2.15 (d, J = 13.5 Hz, 1H), 1.82 (d, J = 13.5 Hz, 1H), 1.34 (s,
3H), 1.13 (s, 3H), 1.11 (s, 3H); 13C NMR (125 MHz, CDCl3) δ
218.9, 193.5, 146.1, 135.8, 132.2, 131.7, 130.4, 128.9, 78.5, 52.6, 51.7,
50.8, 33.6, 30.4, 30.3, 25.7; IR (CH2Cl2) 2952, 1738, 1660, 1587, 1399,
1263 cm−1; MS (ESI) m/e 379.1, 377.1, 375.1, 347.2, 231.1; HRMS
(ESI) calcd for C19H22BrO3 [M + H]+, 377.0752, found 377.0749.
Data for 2,4,4-Trimethyl-2-(4-(3-methylbenzoyl)-2,5-dihydrofur-
an-3-yl)cyclopentanone (15e). In the typical procedure, to a solution
of 14e (80 mg, 0.25 mmol) in 10.0 mL of CH2Cl2 at room
temperature under nitrogen was added BF3·OEt2 (0.032 mL, 0.25
mmol). The reaction mixture was stirred for 3 h, and the crude
mixture was purified by flash column chromatography (silica gel, ethyl
acetate/dichloromethane/hexanes 1:1:9) to give 15e (59 mg, 0.19
mmol, 76%) as a pale yellow oil: 1H NMR (500 MHz, CDCl3) δ 7.66
(s, 1H), 7.64 (d, J = 7.5 Hz, 1H), 7.41 (d, J = 8.0 Hz, 1H), 7.37 (t, J =
7.5 Hz, 1H), 4.94−4.89 (m, 2H), 4.82−4.76 (m, 2H), 2.42 (s, 3H),
2.28 (d, J = 18.0 Hz, 1H), 2.21 (d, J = 18.0 Hz, 1H), 2.18 (d, J = 13.5
Hz, 1H), 1.82 (d, J = 13.5 Hz, 1H), 1.36 (s, 3H), 1.11 (s, 3H), 1.09 (s,
3H); 13C NMR (125 MHz, CDCl3) δ 219.0, 194.8, 145.4, 138.7,
137.1, 134.5, 132.4, 129.2, 128.7, 126.3, 78.7, 52.6, 51.7, 50.8, 33.6,
30.2, 30.1, 25.8, 21.3; IR (CH2Cl2) 2957, 1738, 1660, 1601, 1583,
1455, 1273 cm−1; MS (ESI) m/e 335.2, 313.2, 291.1, 199.0; HRMS
(ESI) calcd for C20H24O3Na [M + Na]+ 335.1623, found 335.1615.
Data for 2-(4-(1-Naphthoyl)-2,5-dihydrofuran-3-yl)-2,4,4-trime-
thylcyclopentanone (15f). In the typical procedure, to a solution of
14f (90 mg, 0.25 mmol) in 10.0 mL of CH2Cl2 at room temperature
under nitrogen was added BF3·OEt2 (0.032 mL, 0.25 mmol). The
reaction mixture was stirred for 1 h, and the crude mixture was purified
by flash column chromatography (silica gel, ethyl acetate/dichloro-
methane/hexanes 1:1:9) to give 15f (62 mg, 0.18 mmol, 76%) as a
J = 18.6 Hz, 1H), 2.42 (d, J = 18.7 Hz, 1H), 2.37 (d, J = 13.6 Hz, 1H),
2.02 (d, J = 13.6 Hz, 1H), 1.59 (s, 3H), 1.26 (s, 3H), 1.18 (s, 3H); 13C
NMR (100 MHz, CDCl3) δ 220.7, 190.3, 151.7, 141.7, 139.6, 132.4,
129.9, 128.9, 128.5, 123.9, 52.6, 52.1, 49.1, 33.1, 31.7, 30.9, 25.8; IR
(CH2Cl2) 2958, 1730, 1712, 1647, 744 cm−1; MS (ESI) m/e 319.1,
297.2, 223.1; HRMS (ESI) calcd for C19H20O3Na [M + Na]+
319.1310, found 319.1313. Crystals suitable for X-ray diffraction
analysis were grown from ehyl acetate and hexanes.
Data for 2,4,4-Trimethyl-2-(4-(4-methylbenzoyl)furan-3-yl)-
cyclopentanone (16b). In the typical procedure, to a solution of
14b (80 mg, 0.25 mmol) in 10.0 mL of CH2Cl2 at 70 °C under oxygen
was added BF3·OEt2 (0.032 mL, 0.25 mmol). The reaction mixture
was stirred for 48 h, and the crude mixture was purified by flash
column chromatography (silica gel, ethyl acetate/dichloromethane/
hexanes 1:1:9) to give 16b (41 mg, 0.13 mmol, 53%) as a white solid:
1
mp 84−85 °C; H NMR (400 MHz, CDCl3) δ 7.72 (d, J = 1.2 Hz,
1H), 7.70 (d, J = 8.0 Hz, 2H), 7.35 (d, J = 1.2 Hz, 1H), 7.26 (d, J = 8.0
Hz, 2H), 2.67 (d, J = 18.4 Hz, 1H), 2.42 (s, 3H), 2.39 (d, J = 18.4 Hz,
1H), 2.34 (d, J = 13.6 Hz, 1H), 2.00 (d, J = 13.6 Hz, 1H), 1.57 (s, 3H),
1.23 (s, 3H), 1.15 (s, 3H); 13C NMR (100 MHz, CDCl3) δ 220.8,
190.0, 151.2, 143.2, 141.5, 136.9, 129.9, 129.2, 129.1, 124.0, 52.6, 52.1,
49.0, 33.1, 31.6, 30.9, 25.8, 21.6; IR (CH2Cl2) 2958, 1738, 1651, 1609,
1528, 1372 cm−1; MS (ESI) m/e 311.2, 308.1, 342.3; HRMS (ESI)
calcd for C20H23O3 [M + H]+ 311.1647, found 311.1646.
Data for 2,4,4-Trimethyl-2-(4-(phenanthrene-9-carbonyl)furan-
3-yl)cyclopentanone (16c). In the typical procedure, to a solution of
14c (0.10 g, 0.25 mmol) in 10.0 mL of CH2Cl2 at 70 °C under oxygen
was added BF3·OEt2 (0.032 mL, 0.25 mmol). The reaction mixture
was stirred for 24 h, and the crude mixture was purified by flash
column chromatography (silica gel, ethyl acetate/dichloromethane/
hexanes 1:1:9) to give 16c (52 mg, 0.13 mmol, 52%) as a pale yellow
oil: 1H NMR (400 MHz, CDCl3) δ 8.72 (d, J = 8.4 Hz, 1H), 8.69 (d, J
= 8.4 Hz, 1H), 8.10 (dd, J = 8.4, 0.8 Hz, 1H), 7.91 (d, J = 8.4, 0.8 Hz,
1H), 7.89 (s, 1H), 7.74 (ddd, J = 8.0, 6.8, 1.2 Hz, 1H), 7.69 (ddd, J =
8.0, 6.8, 1.2 Hz, 1H), 7.67−7.64 (m, 2H), 7.61 (ddd, J = 8.0, 6.8, 1.2
Hz, 1H), 7.40 (d, J = 2.0 Hz, 1H), 2.83 (d, J = 18.8 Hz, 1H), 2.56 (d, J
= 13.6 Hz, 1H), 2.49 (d, J = 18.8 Hz, 1H), 2.09 (d, J = 13.6 Hz, 1H),
1.57 (s, 3H), 1.33 (s, 3H), 1.29 (s, 3H); 13C NMR (100 MHz, CDCl3)
δ 220.7, 191.6, 153.7, 142.2, 136.5, 131.2, 130.6, 129.9, 129.7, 129.4,
128.8, 128.3, 127.9, 127.3, 127.2, 127.1, 126.3, 126.0, 122.8, 122.6,
52.7, 51.9, 49.4, 33.0, 32.1, 31.5, 31.3, 25.2; IR (CH2Cl2) 2944, 1738,
1651, 1612, 1528, 1373 cm−1; MS (ESI) m/e 419.2, 397.2, 336.2,
321.2; HRMS (ESI) calcd for C27H24O3Na [M + Na]+ 419.1623,
found 419.1616.
1
pale yellow oil: H NMR (500 MHz, CDCl3) δ 8.47 (d, J = 8.0 Hz,
1H), 7.99 (d, J = 8.0 Hz, 1H), 7.89 (d, J = 8.0 Hz, 1H), 7.74 (d, J = 7.0
Hz, 1H), 7.61 (t, J = 7.0 Hz, 1H), 7.55 (t, J = 7.5 Hz, 1H), 7.51 (t, J =
7.5 Hz, 1H), 4.98−4.69 (m, 4H), 2.43 (d, J = 18.5 Hz, 1H), 2.36 (d, J
= 18.5 Hz, 1H), 2.30 (d, J = 13.5 Hz, 1H), 1.94 (d, J = 13.5 Hz, 1H),
1.42 (s, 3H), 1.21 (s, 3H), 1.16 (s, 3H); 13C NMR (125 MHz, CDCl3)
δ 218.9, 194.8, 151.0, 135.7, 133.8, 132.9, 132.5, 129.9, 128.6, 128.5,
128.2, 126.7, 125.2, 124.5, 78.1, 76.7, 52.7, 52.5, 51.6, 33.6, 30.9, 30.8,
24.9; IR (CH2Cl2) 2952, 1738, 1653, 1590, 1388, 1277 cm−1; MS
(ESI) m/e 371.2, 349.2, 321.2, 280.2; HRMS (ESI) calcd for
C23H24O3Na [M + Na]+, 371.1623, found 371.1614.
General Experimental Procedure for BF3-Promoted Cycliza-
tion of 14 under Oxygen. Synthesis of Furan 16. To a solution of
14a (80 mg, 0.25 mmol) in 10.0 mL of CH2Cl2 at room temperature
under an oxygen was added BF3·OEt2 (0.032 mL, 0.25 mmol). The
reaction mixture was stirred at 70 °C for 16 h until no 14a was
detected by TLC. The reaction mixture was quenched with saturated
aqueous NaHCO3. The organic phase was separated, and the aqueous
phase was extracted with CH2Cl2 (3 × 20 mL). The combined organic
layers were washed with brine (50 mL × 3), dried over anhydrous
MgSO4 (10 g), and concentrated to give the crude mixture.
Data for 2-(4-(4-Bromobenzoyl)furan-3-yl)-2,4,4-trimethylcyclo-
pentanone (16d). In the typical procedure, to a solution of 14d (90
mg, 0.25 mmol) in 10.0 mL of CH2Cl2 at 70 °C under oxygen was
added BF3·OEt2 (0.032 mL, 0.25 mmol). The reaction mixture was
stirred for 15 h, and the crude mixture was purified by flash column
chromatography (silica gel, ethyl acetate/dichloromethane/hexanes
1:1:9) to give 16d (42 mg, 0.11 mmol, 45%) as a white solid: mp 80−
1
82 °C (ethyl acetate/hexanes); H NMR (500 MHz, CDCl3) δ 7.71
(d, J = 1.2 Hz, 1H), 7.65 (d, J = 8.0 Hz, 2H), 7.61 (d, J = 8.0 Hz, 2H),
7.38 (d, J = 1.2 Hz, 1H), 2.69 (d, J = 18.5 Hz, 1H), 2.41 (d, J = 18.5
Hz, 1H), 2.31 (d, J = 13.5 Hz, 1H), 1.99 (d, J = 13.5 Hz, 1H), 1.56 (s,
3H), 1.25 (s, 3H), 1.16 (s, 3H); 13C NMR (125 MHz, CDCl3) δ
220.6, 189.1, 151.4, 141.9, 138.3, 131.8, 130.5, 129.9, 127.4, 123.8,
52.6, 52.0, 49.1, 33.1, 31.7, 30.9, 25.7; IR (CH2Cl2) 2952, 1738, 1651,
1583, 1528, 1365 cm−1; MS (ESI) m/e 377.1, 375.1, 338.3, 321.2;
HRMS (ESI) calcd for C19H20O3Br [M + H]+ 375.0596, found
375.0600.
Data for 2-(4-Benzoylfuran-3-yl)-2,4,4-trimethylcyclopentanone
(16a). In the typical procedure, to a solution of 14a (80 mg, 0.25
mmol) in 10.0 mL of CH2Cl2 at 70 °C under oxygen was added BF3·
OEt2 (0.032 mL, 0.25 mmol). The reaction mixture was stirred for 16
h, and the crude mixture was purified by flash column chromatography
(silica gel, ethyl acetate/dichloromethane/hexanes 1:1:9) to give 16a
(41 mg, 0.14 mmol, 56%) as a colorless powder: mp 99−100 °C; H
NMR (400 MHz, CDCl3) δ 7.79 (d, J = 7.8 Hz, 2H), 7.75 (s, 1H),
7.59 (t, J = 7.3 Hz, 1H), 7.48 (t, J = 7.5 Hz, 2H), 7.39 (s, 1H), 2.71 (d,
Data for 2,4,4-Trimethyl-2-(4-(3-methylbenzoyl)furan-3-yl)-
cyclopentanone (16e). In the typical procedure, to a solution of
14e (80 mg, 0.25 mmol) in 10.0 mL of CH2Cl2 at 70 °C under oxygen
was added BF3·OEt2 (0.032 mL, 0.25 mmol). The reaction mixture
was stirred for 12 h, and the crude mixture was purified by flash
column chromatography (silica gel, ethyl acetate/dichloromethane/
hexanes 1:1:9) to give 16e (51 mg, 0.16 mmol, 65%) as a pale yellow
1
1
oil: H NMR (500 MHz, CDCl3) δ 7.72 (d, J = 1.2 Hz, 1H), 7.58 (s,
1H), 7.56 (d, J = 7.5 Hz, 1H), 7.38−7.32 (m, 3H), 2.68 (d, J = 18.5
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The Journal of Organic Chemistry
Article
Hz, 1H), 2.41 (s, 3H), 2.39 (d, J = 18.4 Hz, 1H), 2.35 (d, J = 13.5 Hz,
1H), 2.00 (d, J = 13.5 Hz, 1H), 1.57 (s, 3H), 1.24 (s, 3H), 1.17 (s,
3H); 13C NMR (125 MHz, CDCl3) δ 220.8, 190.6, 151.7, 141.6,
139.7, 138.4, 129.9, 129.4, 128.3, 126.2, 124.0, 52.6, 52.1, 49.0, 33.1,
31.7, 30.9, 25.7, 21.3; IR (CH2Cl2) 2959, 1738, 1651, 1601, 1524,
1369 cm−1; MS (ESI) m/e 311.2, 293.2, 283.2; HRMS (ESI) calcd for
C20H23O3 [M + H]+ 311.1647, found 311.1646.
AUTHOR INFORMATION
Corresponding Author
*E-mail: cheyeh@ntnu.edu.tw.
Notes
■
The authors declare no competing financial interest.
Data for 2-(4-(1-Naphthoyl)furan-3-yl)-2,4,4-trimethylcyclopen-
tanone (16f). In the typical procedure, to a solution of 14f (90 mg,
0.25 mmol) in 10.0 mL of CH2Cl2 at 70 °C under oxygen was added
BF3·OEt2 (0.032 mL, 0.25 mmol). The reaction mixture was stirred for
12 h, and the crude mixture was purified by flash column
chromatography (silica gel, 1:1:9 ethyl acetate/dichloromethane/
hexanes) to give 16f (53 mg, 0.15 mmol, 62%) as a pale yellow oil: 1H
NMR (500 MHz, CDCl3) δ 8.07 (dd, J = 6.0, 3.5 Hz, 1H), 7.96 (d, J =
8.0 Hz, 1H), 7.88 (dd, J = 6.0, 3.5 Hz, 1H), 7.61 (dd, J = 7.0, 0.5 Hz,
1H), 7.54−7.47 (m, 4H), 7.37 (d, J = 1.5 Hz, 1H), 2.80 (d, J = 18.5
Hz, 1H), 2.52 (d, J = 13.5 Hz, 1H), 2.47 (d, J = 18.5 Hz, 1H), 2.07 (d,
J = 13.5 Hz, 1H), 1.63 (s, 3H), 1.31 (s, 3H), 1.26 (s, 3H); 13C NMR
(125 MHz, CDCl3) δ 220.7, 191.7, 153.7, 142.1, 137.7, 133.7, 131.1,
130.5, 129.7, 128.3, 127.3, 126.5, 126.4, 126.1, 125.4, 124.2, 52.7, 51.9,
49.4, 33.1, 32.0, 31.3, 25.3; IR (CH2Cl2) 2959, 1738, 1651, 1530, 1372,
1145 cm−1; MS (ESI) m/e 447.2, 321.2, 275.2, 242.1; HRMS (ESI)
calcd for C23H23O3 [M + H]+ 347.1647, found 347.1641.
ACKNOWLEDGMENTS
■
This work has been supported by the National Council (NSC
101-2113-M-003-002-MY3) and National Taiwan Normal
University.
REFERENCES
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clopentanone (16g). In the typical procedure, to a solution of 14g
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1:1:9) to give 16g (38 mg, 0.12 mmol, 47%) as a pale yellow oil: H
NMR (500 MHz, CDCl3) δ 7.74 (d, J = 1.4 Hz, 1H), 7.39−7.33 (m,
3H), 7.31−7.30 (m, 1H), 7.12 (dt, J = 7.2, 2.2 Hz, 1H), 3.85 (s, 3H),
2.40 (d, J = 18.6 Hz, 1H), 2.34 (d, J = 13.6 Hz, 1H), 2.01 (d, J = 13.6
Hz, 1H), 2.01 (d, J = 13.7 Hz, 1H), 1.58 (s, 3H), 1.24 (s, 3H), 1.16 (s,
3H); 13C NMR (125 MHz, CDCl3) δ 220.8, 190.0, 159.7, 151.7,
141.6, 140.9, 129.9, 129.4, 123.9, 121.6, 118.9, 113.4, 55.5, 52.6, 52.1,
49.1, 33.1, 31.6, 30.9, 25.8; IR (CH2Cl2) 2957, 2366, 1739, 1654, 1530,
1372 cm−1; MS (ESI) m/e (%) 349.1 ([M + Na]+, 100), 327.2, 307.1,
256.1; HRMS (ESI) calcd for C20H23O4 [M + H]+, 327.1596, found
327.1587.
Data for 2-(4-([1,1′-Biphenyl]-3-carbonyl)furan-3-yl)-2,4,4-trime-
thylcyclopentanone (16h). In the typical procedure, to a solution of
14h (90 mg, 0.25 mmol) in 10.0 mL of CH2Cl2 at 70 °C under oxygen
was added BF3·OEt2 (0.032 mL, 0.25 mmol). The reaction mixture
was stirred for 24 h, and the crude mixture was purified by flash
column chromatography (silica gel, ethyl acetate/dichloromethane/
hexanes 1:1:9) to give 16h (46 mg, 0.12 mmol, 50%) as a pale yellow
oil: 1H NMR (500 MHz, CDCl3) δ 7.86 (d, J = 8.2 Hz, 2H), 7.78 (d, J
= 1.4 Hz, 1H), 7.68 (d, J = 8.3 Hz, 2H), 7.62 (d, J = 8.4 Hz, 2H), 7.46
(t, J = 7.4 Hz, 2H), 7.40−7.37 (m, 2H), 2.69 (d, J = 18.6 Hz, 1H), 2.41
(d, J = 18.4 Hz, 1H), 2.37 (d, J = 13.5 Hz, 1H), 2.01 (d, J = 13.6 Hz,
1H), 1.59 (s, 3H), 1.24 (s, 3H), 1.17 (s, 3H); 13C NMR (125 MHz,
CDCl3) δ 220.6, 189.8, 151.3, 145.2, 141.6, 139.8, 138.1, 130.0, 129.6,
128.9, 128.1, 127.2, 127.1, 123.9, 52.6, 52.0, 49.0, 33.0., 31.6, 30.9,
25.7; IR (CH2Cl2) 2952, 1737, 1649, 1603, 1462, 1375 cm−1; MS
(ESI) m/e 311.2, 373.2, 342.2, 292.2, 222.1; HRMS (ESI) calcd for
C25H24O3Na [M + Na]+ 395.1623, found 395.1622.
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ASSOCIATED CONTENT
■
S
* Supporting Information
NMR spectra for compounds 1a−i, 2a−g, 4a,c,f,i, 7, 8, 9, 10a−
k, 11a,j,k, 12a, 13a−i, 14a−h, 15a−f, and 16a−h and X-ray
crystallographic information files for compounds 2a,c, 4a, 7,
11a, 13a,g,i, 16a. This material is available free of charge via the
Internet at http://pubs.acs.org.
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(15) The structure elucidation of the compound was accomplished
by X-ray diffraction analysis. CCDC 946897 (2a), CCDC 946898
(2c), CCDC 946899 (4a), CCDC 946900 (7), CCDC 946901 (11a),
CCDC 946902 (13a), CCDC 946904 (13g), CCDC 946903 (13i),
and CCDC 946905 (16a) contain the supplementary crystallographic
data for this paper. These data can be obtained free of charge from
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