Economical and convenient carbonyl transposition approach toward a 2-arylcycloheptanone derivative

Article abstract of DOI:10.1080/00397910500377149

A convenient, straightforward, and easy access to 2(2,3-dimethoxy-phenyl)- cycloheptanone, which employs an heteroatom-facilitated ortho-lithiation coupled to a carbonyl transposition strategy, is reported. The synthetic approach avoids using very expensi

Full text of DOI:10.1080/00397910500377149

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Economical and Convenient Carbonyl
Transposition Approach Toward a
2‐Arylcycloheptanone Derivative
Andrea B. J. Bracca a & Teodoro S. Kaufman a
a Instituto de Química Orgánica de Síntesis, IQUIOS (CONICET‐UNR) and
Facultad de Ciencias Bioquímicas y Farmacéuticas , Universidad Nacional de
Rosario , Argentina
Published online: 19 Aug 2006.
To cite this article: Andrea B. J. Bracca & Teodoro S. Kaufman (2006) Economical and Convenient
Carbonyl Transposition Approach Toward a 2‐Arylcycloheptanone Derivative, Synthetic Communications:
An International Journal for Rapid Communication of Synthetic Organic Chemistry, 36:3, 299-310, DOI:
10.1080/00397910500377149
To link to this article: http://dx.doi.org/10.1080/00397910500377149
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Synthetic Communicationsw, 36: 299–310, 2006
Copyright # Taylor & Francis LLC
ISSN 0039-7911 print/1532-2432 online
DOI: 10.1080/00397910500377149
Economical and Convenient Carbonyl
Transposition Approach Toward a
2-Arylcycloheptanone Derivative
Andrea B. J. Bracca and Teodoro S. Kaufman
´
´ ´
and Facultad de Ciencias Bioquımicas y Farmaceuticas, Universidad
´ ´
Instituto de Quımica Organica de Sıntesis, IQUIOS (CONICET-UNR)
Nacional de Rosario, Argentina
Abstract: A convenient, straightforward, and easy access to 2(2,3-dimethoxy-phenyl)-
cycloheptanone, which employs an heteroatom-facilitated ortho-lithiation coupled to a
carbonyl transposition strategy, is reported. The synthetic approach avoids using very
expensive reagents or difficult-to-prepare starting materials.
Keywords: 2-Arylcycloheptanone, carbonyl transposition, chemical synthesis,
epoxide rearrangement, ortho-lithiation
INTRODUCTION
Derivatives of 2-substituted cycloheptanone have been employed as synthetic
intermediates.[1] However, they are not easily available, because the efficient
synthesis of a-aryl alkanones and cycloalkanones is still a challenging
problem. Reagents and reactions employed for their preparation include diary-
liodonium salts,[2a–e] organobismuths,[2f,g] organoboron derivatives,[2h] iron
and chromium carbonyls,[3a,b] copper reagents,[3c–g] organoleads,[4a–c]
nickel,[4d] and palladium[4e–g] derivatives, as well as Grignard[5a] and organo-
cadmiums,[5b] photostimulated reactions[5c] with ketone enolates,[5d] and
arylation of enamines with highly reactive halides.[5e] Additional alternatives
Received in the USA July 28, 2005
Address correspondence to Teodoro S. Kaufman, Instituto de Quımica Organica de
´
Sıntesis, IQUIOS (CONICET-UNR) and Facultad de Ciencias Bioquımicas y Farma-
´
´
´
´
ceuticas, Universidad Nacional de Rosario, Suipacha 531, S2002LRK, Rosario,
Argentina. Tel./Fax: þ54-341-4370477; E-mail: tkaufman@fbioyf.unr.edu.ar
299

300
A. B. J. Bracca and T. S. Kaufman
involve arylmethylene insertion through aryldiazomethane,[6a–c] b-oxido car-
benoid,[6d] and 1-arylmethylbenzotriazole chemistry,[6e] as well as the
rearrangement of halohydrins, derived from the addition of benzylmagnesium
chloride to carbonyl compounds followed by a-bromination.[7]
Methods employed for accessing 2-aryl-substituted cycloheptanones
include ring expansion of cyclohexanone with aryldiazomethane[8] and aryl-
methyl benzotriazole derivatives.[6e]
Stephaoxocanidine (1), shown in Figure 1, is a novel natural product
isolated from Stephania cepharantha.[9] We have synthesized AC- and
ABC-ring analogs[10] of this tetracyclic compound and demonstrated that
certain tricyclic derivatives possess interesting acetylcholinesterase-inhibiting
activity.[10d,e]
For a project related to the total synthesis of stephaoxocanidine and struc-
tural analogs incorporating the D-ring of the natural product, we required a
simple, inexpensive, and reliable route to 2(2,3-dimethoxyphenyl) cyclohep-
tanone (2). However, the available methods require either expensive,
unstable, or highly toxic reagents; not easily available starting materials; or
special equipment or are limited to aromatics carrying electron-withdrawing
groups.
RESULTS AND DISCUSSION
Compound 2 was previously prepared by Gutsche[8] employing the corre-
sponding phenyldiazomethane, an unstable compound for the preparation
of which the hazardous, highly toxic, and currently not readily available
anhydrous hydrazine is required; in addition, the transformation demands
important quantities of mercury(II) oxide, which is added in excess as
oxidant.
We envisioned a new synthesis of 2 as the result from the 1,2-addition of
ortho-metallated 1,2-dimethoxybenzene (3) to cycloheptanone (4), followed
by a carbonyl transposition. For reviews on carbonyl transposition, see[11]
Figure 1. Stephaoxocanidine (1) and target compound (2).

Convenient Synthesis of a 2-Arylcycloheptanone
301
Thus, compound 3 was subjected to an heteroatom-facilitated ortho lithiation
with n-butyllithium in dry Et2O, and the resulting organometallic derivative
was treated with cycloheptanone, resulting in 65% of alcohol 5, which was
easily dehydrated with catalytic amounts of oxalic acid in refluxing
toluene,[1c] furnishing aryl-cycloheptene 6.
.
However, submission of 6 to hydroboration-oxidation with BH3 SMe2
gave mixtures of the expected secondary alcohol 7 and its epimer 8 (37%,
combined yield)[12] together with precursor 5, the latter being the most
abundant product.[12b,c] Despite literature precedents regarding product distri-
bution after hydroboration-oxidation of styrenes, the elevated proportion of 5
in the mixture was surprising, and consequently this approach was considered
inefficient.
Therefore, cycloheptene 6 was catalytically dihydroxylated with osmium
tetraoxide, employing NMO as stoichiometric co-oxidant. However, the trans-
formation proceeded sluggishly, and poor yields (30%) of diol 9 were realized
after prolonged exposure to the reaction conditions. Moreover, when 9 was
subjected to diol dehydration[13] with TsOH in toluene at 808C, the desired
ketone 2 and the rearranged aldehyde 10 were obtained as an approximate
1:6 mixture in 77% combined yield.
An analogous result was observed when 6 was epoxidized with m-CPBA
in chloroform and the resulting oxirane 11, obtained in 97% yield, was
.
rearranged with BF3 Et2O at 2508C or with ZnI2 at room temperature in
CH2Cl2 as solvent.[13a] In the former case, only 11% of 2 was obtained,
together with 57% of aldehyde 10.
Scheme 1: Reagents and conditions: a) 1. n-BuLi, Et2O, rt, overnight; 2.
Cycloheptanone (4), 30 min, rt (65%); b) (COOH)2 (cat.), PhMe, 1108C, 3 h
.
(70%); c) 1. BH3 SMe2, THF, 08C ! rt, overnight; 2. H2O2, NaOH, 508C
(7 þ 8, 37%); d) m-CPBA, Cl2CH2, NaHCO3, 08C, 1 h (97%); e) OsO4,
NMO, t-BuOH-H2O (2 : 1), 96 h, rt (30%); f) TsOH, PhMe, 808C, (77%); g)
ZnI2, CH2Cl2, rt, 2 h, (2, 27%; 10, 25%) or BF3Et2O, CH2Cl2, 2508C, 3 h
(2, 11%; 10, 57%); h) H2 (1 atm), 10% Pd/C (cat.), HCO2NH4, EtOH, rt,
1 h (78%); i) PCC/Al2O3, CH2Cl2, rt, overnight (88%).
The rearrangement of epoxides to carbonyl compounds is a useful
reaction; however, constitution of the rearranged product is determined by
the migratory aptitude of the substituents, as well as by the nature of the
Lewis acid and solvent employed. The mechanisms of the rearrangements
leading to both products are shown in Scheme 2. Coordination of the Lewis
acid to the oxygen of the epoxide in 11 results in weakening of the C–O
bond in intermediate 12, followed by cleavage of one of the C–O bonds to
give the most stable tertiary carbenium ion.
In this way, 12 can be rearranged through two alternative paths (a and b).
In path a, the oxirane is rearranged by way of a hydride shift giving intermedi-
ate 14, which provides ketone 2 after aqueous workup. However, when the
transformation takes place through competing path b probably for steric
reasons, a Meinwald rearrangement takes place, and alkyl migration to the

302
A. B. J. Bracca and T. S. Kaufman
Scheme 1.
tertiary carbenium center with concomitant ring contraction gives way to
cationic intermediate 13, which finally yields aldehyde 10.[14]
In view of the outcome of these transformations, epoxide 11 was submitted
to a catalytic hydrogenolysis in EtOH with 10% Pd/C and ammonium formate
as additive, easily furnishing a mixture of diastereomeric alcohols 7 and 8 in
combined 78% yield. Interestingly, the presence of ammonium formate[15]
was the key to avoid formation of undesirable side products.
Unexpectedly, however, the mixture of alcohols failed to oxidize under
Swern conditions (trifluoroacetic anhydride (TFAA), dimethyl sulfoxide
(DMSO), 2608C, then Et3N); therefore, it was conveniently treated with
pyridinium chlorochromate (PCC) supported on alumina, yielding 88% of
the ketone 2.
In conclusion, a simple and expedient synthesis of ketone 2 was
developed, based on an heteroatom-facilitated lithiation coupled with a
carbonyl transposition under conditions that avoid rearrangement to
aldehyde 11.

Convenient Synthesis of a 2-Arylcycloheptanone
303
Scheme 2.
EXPERIMENTAL
General Procedures
Melting points were taken on an Ernst Leitz Wetzlar model 350 hot-stage
microscope apparatus and are uncorrected. FT-IR spectra were determined
with a Shimadzu IR Prestige 21 spectrophotometer as thin films held
1
between NaCl cells or as dispersions in KBr disks. The H and 13C NMR
spectra were acquired in CDCl3 employing TMS as internal standard with a
Bruker AC200-E spectrometer operating at 200.13 and 50.33 MHz, respect-
ively. Distortionless enhancement by polarization transfer (DEPT) 135 and
DEPT 90 experiments aided the interpretation of the fully decoupled 13C
NMR spectra. HRMS data were obtained from Kent Electronics (UK). The
reactions were carried out under dry nitrogen or argon atmospheres,
employing oven-dried glassware. Commercial reagents were used without
further purification. Dry THF, Et2O, and toluene were prepared by distillation
from Na-benzophenone ketyl, and anhydrous CH2Cl2 was obtained by
refluxing 4 h over P2O5, followed by distillation. Anhydrous solvents were
stored in dry Schlenk bottles. All new compounds gave single spots on TLC
plates run in different hexane–EtOAc solvent systems. Spots were visualized
by exposure to UV light (254 and 365 nm), followed by spraying with ethanolic
p-anisaldehyde/sulfuric acid reagent and careful heating. Standard workup
procedures consisted of diluting the reaction with brine (5–10 mL) and
extracting the products with EtOAc (4 ꢀ 20–30 mL); the combined organic
extracts were washed once with brine, dried over Na2SO4, and concentrated
under reduced pressure, and the respective residues were chromatographed.
Flash column chromatographies were carried out with silica gel 60 H,

304
A. B. J. Bracca and T. S. Kaufman
eluting with hexane–EtOAc mixtures under positive pressure and employing
gradient techniques.
1-(20,30-Dimethoxyphenyl) Cycloheptene (6)
A solution of n-BuLi in hexanes (6.95 mL, 8 mmol) was added dropwise to an
ice-water-cooled solution of 3 (1000 mg, 7.25 mmol) in anhydrous Et2O
(10 mL). The reaction was stirred overnight at room temperature; then it
was cooled again and treated with 4 (0.895 mL, 7.6 mmol). After a reaction
period of 30 min, brine (10 mL) was added, and the reaction was submitted
to the conventional workup and chromatography procedure, giving 5
(1185 mg, 65%) as an oil. IR (film, n): 3515, 2925, 2857, 1581, 1473, 1385,
1
1298, 1168, 1075, and 746 cm21; H NMR (d): 1.15–2.35 (m, 13H, H-2,
H-3, H-4, H-5, H-6, H-7, and OH), 3.86 (s, 3H, OCH3), 3.96 (s, 3H, OCH3)
and 6.80–7.15 (m, 3H, ArH-40, ArH-50 and ArH-60); 13C NMR (d): 22.83
(C-3 and C-6), 29.83 (C-4 and C-5), 41.83 (C-2 and C-7), 55.65 (OCH3-30),
60.82 (OCH3-20), 77.59 (C-1), 111.30 (C-40), 117.86 (C-50), 123.42 (C-60),
142.61 (C-10), 146.60 (C-20), and 152.61 (C-30). Anal. calcd. for C15H22O3:
C, 71.97; H, 8.86. Found: C, 72.27; H, 8.68. Without further purification,
oxalic acid dihydrate (48 mg, 0.38 mmol) was added to a solution of 5
(1185 mg, 4.74 mmol) in dry toluene (10 mL), and the reaction was heated
at 1108C during 3 h until completed (TLC). Then most of the solvent was
removed under reduced pressure, and the remaining oil was chromatographed,
furnishing 6 (770 mg, 70%) as a solid; mp: 32–348C (Hexane–EtOAc). IR
(KBr, n): 2931, 2838, 1590, 1470, 1306, 1267, 1093, 1011, and 788 cm21
;
1H NMR (d): 1.50–1.90 (m, 6H, H-3 and H-6), 2.20–2.31 (m, 2H, H-7),
2.45–2.53 (m, 2H, H-3), 3.78 (s, 3H, OCH3), 3.85 (s, 3H, OCH3), 5.88
(t, 1H, J ¼ 6.6, H-2), 6.72 (dd, 1H, J ¼ 1.3 and 7.5, ArH-40), 6.79 (dd, 1H,
J ¼ 1.3 and 8.2, ArH-60) and 6.95 (dd, 1H, J ¼ 7.5 and 8.2, ArH-50); 13C
NMR (d): 26.83 (C-5), 26.95 (C-4), 28.94 (C-6), 32.66 (C-3), 34.45 (C-7),
55.73 (OCH3-30), 60.22 (OCH3-20), 110.77 (C-40), 121.49 (C-60), 123.37
(C-50), 131.36 (C-2), 140.98 (C-10), 143.74 (C-1), 146.05 (C-20), and
152.58 (C-30). HRMS: Found: m/z ¼ 232.14644; C15H20O2 requires
m/z ¼ 232.14633. Anal. calcd. for C15H20O2: C, 77.55; H, 8.68. Found: C,
77.42; H, 8.71.
1-(2,3-Dimethoxyphenyl)-8-oxabicyclo [5.1.0] Octane (11)
A 0.5 M sodium hydrogen carbonate solution (2.05 mL, 1.025 mmol) was
added to a solution of 6 (95 mg, 0.41 mmol) in CH2Cl2 (2.7 mL) cooled in
an ice-water bath. The biphasic system was treated with a solution of
mCPBA (72%, 147 mg, 0.614 mmol) in CH2Cl2 (1.45 mL), and the reaction
was stirred 1 h at 08C. The reaction was diluted with brine and submitted to
conventional workup and chromatography procedure, furnishing 11 (99 mg,
97%), as a solid; mp: 58–628C. IR (KBr, n): 2929, 2849, 1683, 1464, 1302,

Convenient Synthesis of a 2-Arylcycloheptanone
305
1268, 1069, 787, and 748 cm21; 1H NMR (d): 1.17–1.32 (m, 1H, H-4), 1.46–
1.75 and 2.00–2.12 (m, 8H, H-2, H-3, H-4, H-5, and H-6), 2.20–2.35 (m, 1H,
H-2), 3.12 (t, 1H, J ¼ 4.4, H-7), 3.85 (s, 3H, OCH3), 3.89 (s, 3H, OCH3), 6.82
(dd, 1H, J ¼ 2.0 and 7.6, ArH-40), 6.92 (dd, 1H, J ¼ 2.0 and 7.7, ArH-60) and
7.00 (dd, 1H, J ¼ 7.6 and 7.7, ArH-50); 13C NMR (d): 24.27 (C-4), 24.39 (C-
5), 28.69 (C-3), 30.88 (C-6), 34.32 (C-2), 55.61 (OCH3-30), 60.43 (OCH3-20),
62.44 (C-7), 63.37 (C-1), 111.47 (C-40), 119.01 (C-60), 123.65 (C-50), 137.97
(C-10), 146.50 (C-20), and 152.40 (C-30). HRMS: Found: m/z ¼ 248.14093;
C15H20O3 requires m/z ¼ 248.14125. Anal. calcd. for C15H20O3: C, 72.55;
H, 8.12. Found: C, 72.61; H, 8.15.
2-(20,30-Dimethoxyphenyl) Cycloheptanone (2)
Ten percent Pd/C (26 mg) was added to a solution of oxirane 11 (74 mg,
0.166 mmol) and ammonium formate (56.4 mg, 0.895 mmol) in EtOH
(5 mL), and the system was hydrogenated under atmospheric pressure until
complete consumption of the starting material. Then the catalyst was
filtered through a Celite pad, and the filtrate was concentrated in vacuo.
Chromatography of the residue afforded 7 (38 mg, 51%) and 8 (20 mg,
27%). Compound 7: IR (film, n): 3461, 2929, 2834, 1583, 1464, 1266,
1
1168, 1086, 785, and 747 cm21; H NMR (d): 1.50–1.88 (m, 10H, H-3,
H-4, H-5, H-6 and H-7), 1.91–2.06 (m, 1H, H-2), 3.04–3.15 (m, 1H, H-1),
3.84 (s, 3H, OCH3), 3.86 (s, 3H, OCH3), 6.78 (dd, 1H, J ¼ 1.4 and 6.7,
ArH-40), 6.82 (dd, 1H, J ¼ 1.4 and 6.7, ArH-60) and 7.05 (t, 1H, J ¼ 8,
ArH-50); 13C NMR (d): 21.83 (C-6), 27.37 (C-5), 27.72 (C-4), 31.92 (C-3),
35.76 (C-7), 47.56 (C-2), 55.54 (OCH3-30), 60.73 (OCH3-20), 76.83 (C-1),
110.20 (C-40), 119.12 (C-60), 124.40 (C-50), 139.57 (C-10), 146.70 (C-20),
and 152.72 (C-30). Compound 8: IR (film, n): 3482, 2927, 2857, 1583,
1
1476, 1275, 1072, 783, and 749 cm21; H NMR (d): 1.45–1.91 (m, 10H,
H-3, H-4, H-5, H-6, and H-7), 1.94–2.21 (m, 1H, H-2), 3.25 (dt, 1H,
J ¼ 2.1, 2.3, and 11.1, OH), 3.84 (s, 3H, OCH3), 3.86 (s, 3H, OCH3), 6.80
(dd, 1H, J ¼ 1.6 and 7.9, ArH-40), 6.86 (dd, 1H, J ¼ 1.6 and 7.9, ArH-60)
and 7.02 (t, 1H, J ¼ 7.9, ArH-50); 13C NMR (d): 21.72 (C-6), 27.01 (C-5),
27.97 (C-4), 28.39 (C-3), 35.34 (C-7), 44.71 (C-2), 55.58 (OCH3-30), 60.70
(OCH3-20), 72.53 (C-1), 110.50 (C-40), 120.80 (C-60), 123.80 (C-50), 139.27
(C-10), and 152.61 (C-20 and C-30). Without further purification, sodium
acetate (12.2 mg, 0.15 mmol) and PCC/Al2O3 (276 mg, 3 equiv.) were succes-
sively added to a mixture of 7 and 8 (19 mg) in CH2Cl2 (5 mL). The reaction
was stirred overnight at room temperature until completion; the solids were
separated by filtration through Celite, the filter was washed with CH2Cl2,
and the filtrate was concentrated under reduced pressure and chromato-
graphed, affording 2 (10.7 mg, 88%) as an oil. IR (film, n): 2931, 2855,
1
1696, 1585, 1453, 1276, 1169, 1084, and 747 cm21; H NMR (d): 1.39–
1.78, 1.89–2.02 and 2.59–2.85 (m, 10H, H-3, H-4, H-5, H-6, and H-7),
3.75 (s, 3H, OCH3), 3.84 (s, 3H, OCH3), 3.89–3.99 (m, 1H, H-2), 6.77

306
A. B. J. Bracca and T. S. Kaufman
(dd, 1H, J ¼ 1.5 and 7.5, ArH-40), 6.81 (dd, 1H, J ¼ 1.5 and 8.0, ArH-60), and
7.01 (dd, 1H, J ¼ 7.5 and 8.0, ArH-50); 13C NMR (d): 24.41 (C-6), 29.63
(C-4), 29.79 (C-3), 31.86 (C-5), 43.73 (C-7), 53.16 (C-2), 55.54 (OCH3-20),
59.98 (OCH3-30), 110.96 (C-40), 120.78 (C-60), 123.74 (C-50), 145.80 (C-20),
152.34 (C-30), and 214.35 (C-1). HRMS: Found: m/z ¼ 248.14115;
C15H20O3 requires m/z ¼ 248.14125. Anal. calcd. for C15H20O3: C, 72.55;
H, 8.12. Found: C, 72.67; H, 8.19.
Rearrangement of Epoxide 11 under Lewis Acid Assistance, Synthesis
of 1-(2,3-Dimethoxyphenyl)-cyclohexanecarbaldehyde (10)
Method 1: A solution of oxirane 11 (20 mg, 0.08 mmol) in CH2Cl2 (1 mL) was
.
cooled to 2508C and treated with a 0.76 M solution of BF3 Et2O in CH2Cl2
(0.03 mL, 0.023 mmol). After stirring at 2508C for 3 h, the reaction was
quenched with brine (5 mL), and after acquiring room temperature, the
products were submitted to the conventional workup and chromatography
procedure, furnishing aldehyde 10 (11.3 mg, 57%) as an oil. IR (film, n):
2931, 2858, 1722, 1580, 1456, 1301, 1225, 1148, 1095, 786, and 746 cm21
;
1H NMR (d): 1.50–1.83 (m, 8H, H-2ax, H-3, H-4, H-5, and H-6ax), 2.10–
2.30 (m, 2H, H-2eq, and H-6eq), 3.76 (s, 3H, OCH3), 3.94 (s, 3H, OCH3),
6.84 (dd, 1H, J ¼ 1.8 and 7.8, ArH-40), 6.94 (dd, 1H, J ¼ 1.8 and 8.2,
ArH-60), 7.02 (dd, 1H, J ¼ 7.8, and 8.2, H-50), and 9.75 (s, 1H, CHO);
13C NMR (d): 22.69 (C3 and C-5), 25.43 (C-4), 32.35 (C-2 and C-6), 51.93
(C-1), 55.58 (OCH3-30), 60.02 (OCH3-20), 111.39 (C-40), 118.91 (C-60),
123.72 (C-50), 138.34 (C-10), 146.27 (C-20), 152.54 (C-30), and 204.07
(CHO); HRMS: Found: m/z ¼ 249.14914; C15H21O3 (M þ 1) requires
m/z ¼ 248.14125. Anal. calcd. for C16H22O3: C, 72.55; H, 8.12. Found: C,
72.72; H, 8.20. Increasing solvent polarity furnished ketone 2 (2.2 mg,
11%). Method 2: Zinc iodide (31 mg) was added to a solution of 11 (16 mg,
0.065 mmol) in CH2Cl2. After stirring 2 h at room temperature, the mixture
was chromatographed, furnishing 10 (4.3 mg, 27%) and 2 (4.0 mg, 25%).
cis-1-(2,3-Dimethoxyphenyl)-cycloheptane-1,2-diol (9)
An OsO4 solution in t-BuOH (0.15 mL, 0.007 mmol) was added to an ice-
water-bath-cooled solution of olefin 6 (40 mg, 0.172 mmol) and NMO
(28 mg, 0.234 mmol) in 2 : 1 t-BuOH-H2O (3 mL). The reaction was left
overnight at room temperature, and then more NMO (28 mg) was added;
after 4 days the reaction was terminated by addition of 10% NaHSO3
(5 mL). The organics were extracted with EtOAc (4 ꢀ 25 mL), and the
combined organic phases were washed with brine (10 mL), dried (Na2SO4),
concentrated in vacuo, and chromatographed, furnishing diol 9 (13.5 mg,
30%) as a white solid; mp: 122–1248C (hexane–EtOAc). IR (KBr, n):
3448, 3249, 2924, 2859, 1582, 1472, 1253, 1182, 1054, 963, 833, and
1
753 cm21; H NMR (d): 1.50–2.15 (m, 10H, H-3, H-4, H-5, H-6 and H-7),

Convenient Synthesis of a 2-Arylcycloheptanone
307
3.36 (s, 3H, OCH3), 3.92 (s, 3H, OCH3), 4.18 (bd, 1H, J ¼ 10.8, OH-2), 4.26
(s, 1H, OH-1), 6.85 (dd, 1H, J ¼ 1.8 and 7.9, ArH-40), 7.11 (dd, 1H, J ¼ 7.8
and 8.0, ArH-50) and 7.14 (dd, 1H, J ¼ 1.8 and 8.0, ArH-60); 13C NMR (d):
19.93 (C-4), 22.52 (C-6), 26.69 (C-5), 30.32 (C-3), 37.91 (C-7), 55.64
(OCH3-30), 60.64 (OCH3-20), 77.11 (C-2), 78.50 (C-1), 111.45 (C-40),
118.77 (C-50), 123.61 (C-60), 140.14 (C-10), 146.26 (C-30), and 152.78 (C-
20). HRMS: Found: m/z ¼ 266.15206; C15H22O4 requires m/z ¼ 266.15181.
Anal. calcd. for C15H22O4: C, 67.64; H, 8.33. Found: C, 67.77; H, 8.29.
ACKNOWLEDGMENT
The authors gratefully acknowledge financial support provided by CONICET,
´
Fundacion Antorchas, and ANPCyT (Project 06-12532) and also thank
SECyT-UNR. A. B. J. B. especially acknowledges ANPCyT and CONICET
for her fellowship.
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