The reaction of spiroepoxycyclohexadienones towards cyanide nucleophiles

Article abstract of DOI:10.1016/j.tet.2004.03.007

The reaction of spiroepoxycyclohexadienones 1 with TMSCN in the presence of catalytic amounts of Bu₄NCN results in the formation of two diastereomeric cyanohydrins. Alternatively, the reaction of 1 with equimolecular amounts of Bu₄NC

Full text of DOI:10.1016/j.tet.2004.03.007

Tetrahedron 60 (2004) 3825–3830
The reaction of spiroepoxycyclohexadienones towards
cyanide nucleophiles
a
Ruben Cordoba, Aurelio G. Csaky¨, Joaquın Plumet, Fernando Lopez Ortiz,
a
a
b
,
,
*
*
´
´
´
Rafael Herrera, Hugo A. Jimenez-Vazquez and Joaquın Tamariz
´
´
c
d
d
´
´
´
a
´
´
´
´
Departamento de Quımica Organica, Facultad de Quımica, Universidad Complutense, 28040 Madrid, Spain
´
´ ´
Instituto de Investigaciones Quimicobiologicas, Universidad Michoacana de San Nicolas de Hidalgo, Edif. B-1, Ciudad Universitaria,
b
´
´
Area de Quımica Organica, Universidad de Almerıa, Carretera de Sacramento, 04120 Almerıa, Spain
c
F. J. Mujica S/N, 58066 Morelia, Mich., Mexico
d
´ ´
Escuela Nacional de Ciencias Biologicas, Instituto Politecnico Nacional, Prol. Carpio y Plan de Ayala, 11340 Mexico,
´
´
D.F., Mexico Mexico
Received 12 January 2004; revised 8 February 2004; accepted 2 March 2004
Abstract—The reaction of spiroepoxycyclohexadienones 1 with TMSCN in the presence of catalytic amounts of Bu4NCN results in the
formation of two diastereomeric cyanohydrins. Alternatively, the reaction of 1 with equimolecular amounts of Bu4NCN gave rise to products
arising from two other different reaction paths.
q 2004 Elsevier Ltd. All rights reserved.
1. Introduction
behaviour against 1 of a nucleophilic reagent, the cyanide
anion, arising from two different sources: TMSCN or
Bu4NCN.
Spiroepoxycyclohexadienones 1 (Fig. 1) have attracted
attention in the context of their reactivity as dienes in
Diels–Alder reactions.1 On the other hand, their use as
synthetic intermediates has also been reported by consider-
ing the reactivity of the carbonyl group towards organo-
lithium reagents.2 Additionally, differently substituted
spiroepoxycyclohexadienones 1 have been synthesised and
evaluated as irreversible inhibitors of neutral sphingo-
myelinase.3
2. Results and discussion
The reaction of spiroepoxycyclohexadienones 1 with
TMSCN (1.0 equiv.) in the presence5 of catalytic amounts
of Bu4NCN (0.1 equiv.) in CH2Cl2 at 0 8C for 45 min.
afforded cyanohydrins 2 in yields between 35 and 70% as
almost equimolecular mixtures of diastereomers (Scheme 1,
Table 1).
Figure 1.
Taking into account that compounds 1 show up to five
possible electrophilic reaction centres, this densely functio-
nalized structure may be considered as a suitable model to
test the site-selectivity of the attack of a single nucleophilic
agent. Considering that this type of process has not been
previously studied on compounds such as 1, with the
exception of two isolated reports,4 we decided to explore the
Keywords: Epoxides; Catalysis; Cyanides.
*
Corresponding authors. Tel.: þ34-394-5030; fax: þ34-394-4103
(A.G.C.); tel./fax: þ34-91-394-4100 (J.P.);
e-mail addresses: csaky@quim.ucm.es; plumety@quim.ucm.es
Scheme 1.
0040–4020/$ - see front matter q 2004 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2004.03.007

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R. Cordoba et al. / Tetrahedron 60 (2004) 3825–3830
3826
Table 1. Reaction of compound 1 with TMSCN (1.0 equiv.) and Bu4NCN
(0.1 equiv.)
No.
1
R1
R2
R3
R4
2 (%) a
drb
1
2
3
4
1a
1b
1c
1d
Br
Br
H
MeO
MeO
H
Br
Br
Br
H
H
MeO
H
2a (71)
2b (55)
2c (50)
2d (55)
1.0:1.3
1.0:1.0
1.0:1.4
1.0:1.6
H
MeO
H
a
Percent yield in the pure isolated mixture of diastereomeric 2. The
remaining starting material was recovered unchanged.
Diastereomer ratio, evaluated by GC–MS. See Section 3.
b
The structural assignment of cyanohydrins 2 was possible
by NOE measurements on the 1H NMR spectra of the
mixture of diastereomers (Fig. 2): selective irradiation
(experiments carried out in toluene-d8 and CDCl3 at
500 MHz) of the methyl signal of the TMS group of the
major isomer 2a-I (9H, s, d¼0.22 ppm in toluene-d8,
d¼0.32 ppm in CDCl3) gave an enhancement of one of
the diastereotopic hydrogen atoms of the epoxide moiety
(1H, d, 3J¼5.0 Hz, d¼2.98 ppm in toluene-d8, d¼3.46 ppm
in CDCl3). This puts forward the cis stereochemical
relationship between the OTMS group and the epoxidic
CH2 in 2a-I. On the other hand, no NOE effect was observed
upon irradiation of the methyl signal of the TMS group of
the minor isomer 2a-II (9H, s, d¼0.28 ppm in toluene-d8,
d¼0.29 ppm in CDCl3).
Scheme 2.
KI in acetone (24 h, rt) also affords 3 in 79% isolated yield
(Scheme 3).
Scheme 3.
With respect to compounds 4 and 5, they have not been
observed in nucleophilic addition reactions to these kind of
spiroepoxycyclohexadienones, although the related alcohol
6 (Scheme 4) is the main product in the reactions of 1a both
with NaBH4/CeCl3 in MeOH4b (70%) or LiAlH4 in THF
(70%), which indicates that also in these cases compound 5
may be formed and overreduced to 6.
Figure 2.
Efforts to achieve the chromatographic separation of these
diastereomers at preparative scale were unsuccessful.
However, treatment of the mixture of compounds 2a with
TsOH (1.0 equiv.) in MeOH (0 8C, 2 h) resulted in a clean
transformation of the minor isomer 2a-II back into 1a,
whereas the major isomer 2a-I remained unaltered6 under
these reaction conditions.
Scheme 4.
In order to gain more information on this process, we
submitted compound 1a to reaction, in two independent
experiments, with either equimolecular amounts of TMSCN
or Bu4NCN. Whereas the reaction of 1a with TMSCN under
these new reaction conditions gave rise to the full recovery
of the starting material, the reaction with Bu4NCN
(1.0 equiv., CH2Cl2, 0 8C, 45 min) afforded a mixture of
compounds 3, 4 and 5, which were obtained in a ratio 3:
4:5¼5.5:1.0:3.5 (evaluated by GC–MS) in 75% overall
yield (Scheme 2).
In an attempt to gain more insight into the factors that
control the outcome of these reactions, we decided to carry
out an ab initio MO study of compound 1a. The
determination of atomic coefficients in the frontier
molecular orbitals, particularly in the LUMO, along with
the atomic charges, should give a better idea of the sites
more amenable to suffer nucleophilic attack. The data
obtained from the HF/6-31G calculation of the most stable
conformer of 1a are shown in Table 2.
The formation of benzodioxole 3 from 1a has been
previously reported under different experimental con-
ditions: (a) by a 1,3-sigmatropic shift analogous to the
rearrangement of vinylcyclopropanes to cyclopentenes;4b
(b) by reaction with NaCN in DMSO or Et2AlCN in toluene,
albeit in low yield (20%);4b (c) by reaction with tBuMe2SiCl
in the presence of Et3N in DMF.4a,7 In an additional
experiment, we have observed that the reaction of 1a with
These results indicate that: (a) the epoxide moiety should
not be reactive towards nucleophilic reagents, as both
charges and LUMO-coefficients at C2 and C3 are smaller
than the same parameters on C4 and C8; (b) for a charge-
controlled reaction, the carbonyl carbon C4 is clearly the
preferred centre for nucleophilic attack; (c) for an orbital-
controlled reaction, C8 is the preferred centre for
nucleophilic attack.

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3827
Table 2. HF/6-31G** calculations of energies (eV) and coefficientsa of the
frontier molecular orbitals, and charge distribution, of compound 1ab
Ci
HOMO E¼29.1763
LUMO E¼1.1404
Chargesb
C2
C3
C4
C8
20.0760
20.0627
20.0237
0.2497
20.1276
0.0194
0.1875
0.2410
0.060
0.077
0.594
20.050
Values of the pz coefficients. The relative p1z contributions and their DCi
a
are analogues.
Mu¨lliken.
b
Therefore, the experimental outcome when 1a was made to
react with TMSCN (1.0 equiv.) in the presence of Bu4NCN
as catalyst (Scheme 5) may be explained on the basis of the
formation of an hypervalent silicon intermediate8 (note that
no reaction took place with TMSCN alone, vide supra)
which delivers a hard cyanide species that preferentially
attacks the CvO group, giving rise to an intermediate
ammonium salt plus TMSCN. Trapping of the ammonium
salt with TMSCN affords the final product 2 and regenerates
the catalyst.
Scheme 6.
Scheme 5.
Scheme 7.
On the other hand, when the reaction was carried out with
equimolecular amounts of Bu4NCN (Scheme 6), a soft
cyanide species is delivered, which attacks on C8 affording
an intermediate A. Intramolecular nucleophilic attack on C2
takes place with cleavage of the C2–C3 bond instead of the
expected C2–O bond due to the formation a delocalized
pentadienyl carbanion which is protonated on workup to
give B, which finally aromatises by [1,5]-H shift9 followed
by loss of either HCN or HBr, affording the final products 3
and 4 respectively.
A similar reaction pathway may also account for the
formation of 3 with I2 as nucleophile, when 1a was treated
with KI in acetone (Scheme 3). That the attack to C8 by
CN2 is the initial event of the reaction with equimolecular
amounts of Bu4NCN can also be deduced from the results
obtained using 1b as starting material (Scheme 7). In this
case, a mixture of compounds 7 and 8 was obtained in a ratio
7:8¼1:3 (evaluated by GC–MS) and 72% overall yield.
Finally, the formation of aldehyde 5 may be interpreted by
two different reaction paths: (i) by initial CN attack on C8
Scheme 8.

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3828
(Scheme 8, path A) followed by CN migration to afford
intermediate D, which upon loss of HCN to give
intermediate E and final aromatization affords 5; or (ii) by
initial CN attack on C4 (Scheme 8, path B) followed by CN
migration to afford intermediate D, which evolves to the
final product as previously stated.
3.2. Typical procedure for the cyanosilylation of
6-spiroepoxycyclohexadienones
To a solution of the carbonyl compound (0.37 mmol) in dry
CH2Cl2 (0.5 mL) was added, under argon and at 0 8C,
TMSCN (0.046 mL, 0.37 mmol) followed by a solution of
the ammonium salt (10 mg, 0.037 mmol) in dry CH2Cl2
(0.5 mL). The mixture was stirred at 0 8C for 15 min. A
saturated solution of NaHCO3 (3 mL) was added and the
mixture was extracted with CH2Cl2. Drying of the combined
organic phases with MgSO4 was followed by evaporation of
the solvent under vacuum. The products were purified by
chromatography on silica gel (ethyl acetate/hexane).
However, the path B can be ruled out because, in an
independent essay, cyanohydrins 2 did not afford com-
pounds 5 after reaction with Bu4NCN or TMSCN–Bu4NCN
(2.5 h, 0 8C).
In summary in this paper the different behaviour of the
epoxide moiety of spiroepoxycyclohexadienone towards
cyanide nucleophiles has been described. A competitive
reaction pathway was proposed in order to account for the
different results obtained.
3.2.1. 5,7-Dibromo-6-methoxy-4-trimethylsilanyloxy-1-
oxaspiro[2.5]octa-5,7-diene-4-carbonitriles, 2a. Data for
2a-I, 1H NMR: (CDCl3, 500 MHz) d 0.32 (s, 9H, 3CH3–Si),
2.92 (d, J¼5.0 Hz, 1H, CH2–O), 3.46 (d, J¼5.0 Hz, 1H,
1
CH2–O), 3.81 (s, 3H, OCH3), 6.19 (s, 1H, CH) ppm; H
NMR: (toluene-d8, 500 MHz) d 0.22 (s, 9H, 3CH3–Si), 2.01
(d, J¼5.0 Hz, 1H, CH2–O), 2.98 (d, J¼5.0 Hz, 1H, CH2–
O), 3.30 (s, 3H, OCH3), 5.58 (s, 1H, CH) ppm; 13C NMR:
(CDCl3, 75 MHz) d 0.00 (3CH3–Si), 50.16 (CH2–CN),
58.87 (OCH3), 59.46 (O–C–CH2), 73.70 (O–C–CN),
109.10 (CBr), 114.68 (CN), 119.27 (CBr), 129.01 (CH),
148.87 (C–OCH3) ppm; MS (70 eV, EI) m/z (%): 407/409/
411 (5/10/5) [Mþz], 362/364/366 (11/22/11) [M245], 352/
354/356 (5/8/4) [M255], 347/349/351 (3/7/4) [M260],
337/339/341 (4/6/3) [M270], 229/231 (18/18), 201/203
(7/7), 137/139 (5/5), 122 (5), 103 (6), 89 (8), 75 (34), 74
(10), 73 (100), 59 (9), 45 (30), 44 (5), 43 (10). Data for
3. Experimental
3.1. General
All reactions were carried out under argon atmosphere.
Column chromatography was performed on silica gel Merck
230–400 mesh. NMR spectra were recorded on Bruker 200-
AM (200 MHz), Bruker AM300 (300 MHz) and on a Bruker
AM500 (500 MHz) instruments, using CDCl3 and toluene-
d8 as solvents. Chemical shifts are in ppm relative to TMS.
Mass spectra were recorded on a mass spectrometer HP
5890. GC/MS analyses were performed with a capillary
column 95% dimethyl 5% diphenylpolysiloxane, using a
gradient of temperature 45–290 8C. Ab initio calculations
were carried out using the Gaussian 94 program package10
in personal computers running under the Linux operating
system. The initial structure of 1a was optimized using the
semiempirical AM1 model, and the resulting geometry was
employed as the starting structure for optimisation at the
HF/6-31G** level. The 6-31G** atomic orbitals for
bromine, as implemented in Gaussian 94, are incomplete,
and they were supplemented with a d polarization function
formed by a single gaussian primitive with a scale factor of
1.00, an exponent of 0.389, and a contraction factor of 1.00,
giving a total of 30 basis functions.11 Additional optimis-
ations were carried out in order to locate the most stable
conformer of 1a, with respect to the methoxy group. This
conformer turned out to be that with the MeO group syn to
the epoxide oxygen, and perpendicular to the plane of the
six-membered ring. Spiroepoxycyclohexadienone 1a was
synthesized using the method described by K. Hinterding
et al.4b Compound 1c was obtained using the method
described by V. Bonnarme et al.1b Spiroepoxycyclo-
hexadienone 1d was synthesized using the method
described by E. J. Corey et al.2 Compound 1b was obtained
following the analogous synthetic route used by
K. Hinterding et al.4b to synthesize 1a, in a four step
sequence using 2,4,6-trimethoxybenzaldehyde as the start-
ing material. Compounds 3, 5 and 6 have been previously
described by K. Hinterding et al.4bThe rest of chemicals
were obtained from commercial sources and were used
without further purification. Solvents were distilled and
dried over molecular sieves.
1
2a-II: H NMR: (CDCl3, 500 MHz) d 0.29 (s, 9H, 3CH3–
Si), 3.06 (d, J¼5.0 Hz, 1H, CH2–O), 3.45 (d, J¼5.0 Hz, 1H,
1
CH2–O), 3.81 (s, 3H, OCH3), 6.12 (s, 1H, CH) ppm; H
NMR: (toluene-d8, 500 MHz) d 0.28 (s, 9H, 3CH3–Si), 2.05
(d, J¼5.0 Hz, 1H, CH2–O), 2.95 (d, J¼5.0 Hz, 1H, CH2–
O), 3.35 (s, 3H, OCH3), 5.50 (s, 1H, CH) ppm; 13C NMR:
(CDCl3, 75 MHz) d 0.00 (3CH3–Si), 51.75 (CH2–CN),
58.00 (O–C–CH2), 58.87 (OCH3), 74.28 (O–C–CN),
108.50 (CBr), 115.27 (CN), 118.93 (CBr), 128.72 (CH),
148.87 (C– OCH3) ppm; MS (70 eV, EI) m/z (%): 407/409/
411 (7/15/8) [Mþz], 363/365/367 (11/15/9) [M244], 362/
364/366 (39/78/40) [M245], 352/354/356 (7/12/6)
[M255], 347/349/351 (6/13/8) [M260], 229/231 (14/14),
201/203 (7/8), 137/139 (10/9), 103 (13), 89 (8), 75 (32), 74
(11), 73 (100), 59 (14), 47 (11), 45 (32), 43 (12). Anal. calcd
for C12H15Br2NO3Si: C, 35.23; H, 3.70; N, 3.42. Found: C,
35.35; H, 3.75; N, 3.61.
3.2.2. 5,7-Dibromo-6,8-dimethoxy-4-trimethylsilanyl-
oxy-1-oxaspiro[2.5]octa-5,7-diene-4-carbonitriles,
2b.
1
Data for 2b-I: H NMR: (CDCl3, 200 MHz) d 0.14 (s, 9H,
3CH3–Si), 3.09 (d, 1H, J¼5.4 Hz, CH2–O), 3.22 (d, 1H,
J¼5.4 Hz, CH2–O), 3.61 (s, 3H, OCH3), 3.73 (s, 3H, OCH3)
ppm; MS (70 eV, EI) m/z (%): 437/439/481 (20/40/21)
[Mþz], 392/394/396 (10/18/11) [M245], 377/379/381
(10/21/12) [M260], 358/360 (47/47) [M2Br], 335/337/
339 (12/20/12) [M2104], 259/261 (49/50) [M2Br–
TMSCN], 231/233 (22/21), 75 (46), 73 (100), 59 (27), 45
(25), 43 (26). Data for 2b-II: 1H NMR: (CDCl3, 200 MHz) d
0.15 (s, 9H, 3CH3–Si), 3.05 (d, 1H, J¼5.6 Hz, CH2–O),
3.22 (d, 1H, J¼5.6 Hz, CH2–O), 3.61 (s, 3H, OCH3), 3.70
(s, 3H, OCH3) ppm; MS (70 eV, EI) m/z (%): 437/439/481

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R. Cordoba et al. / Tetrahedron 60 (2004) 3825–3830
3829
(22/47/23) [Mþz], 392/394/396 (24/48/96) [M245], 377/
379/381 (17/34/16) [M260], 358/360 (34/34) [M2Br],
335/337/339 (16/32/15) [M2104], 259/261 (52/50)
[M2Br–TMSCN], 231/233 (21/19), 75 (28), 73 (100), 59
(28), 45 (32). Anal. calcd for C13H17Br2NO4Si: C, 35.55; H,
3.90; N, 3.19. Found: C, 35.71; H, 3.99; N, 3.27.
3.3.3. 5,7-Dibromo-6-methoxy-benzo[1,3]dioxole-4-car-
1
bonitrile, 8. H NMR (200 MHz, CDCl3) d 3.79 (s, 3H,
OMe), 6.15 (s, 2H, O–CH2–O) ppm; MS (70 eV) m/z (%):
338/340/342 (51/100/48) [Mþz], 323/325/327 (41/83/39)
[M2CH3], 293/295/297 (3/9/6) [M245], 267/269/271 (7/9/
4) [M271], 244/246 (4/4), 131/133 (5/5), 92 (5), 59 (16).
3.2.3. 7-Bromo-4-trimethylsilanyloxy-1-oxaspiro[2.5]-
octa-5,7-diene-4-carbonitriles, 2c. Data for 2c-I: 1H
NMR: (CDCl3, 200 MHz) d 0.19 (s, 9H, 3CH3–Si), 2.89
(d, 1H, J¼5.0 Hz, CH2–O), 3.25 (d, 1H, J¼4.9 Hz, CH2–
O), 5.70–5.90 (m, 2H, H-5, H-8), 6.21 (dd, 1H, J¼9.8 Hz,
J¼1.5 Hz, H-6) ppm; MS (70 eV, EI) m/z (%): 254/256
(79/81) [M245], 103 (25), 75 (26), 73 (100), 45 (32). Data
for 2c-II: 1H NMR: (CDCl3, 200 MHz) d 0.20 (s, 9H,
3CH3–Si), 2.83 (d, 1H, J¼4.9 Hz, CH2–O), 3.28 (d, 1H,
J¼4.9 Hz, CH2–O), 5.70–5.90 (m, 2H, H-5, H-8), 6.21 (dd,
1H, J¼9.8 Hz, J¼1.5 Hz, H-6) ppm; MS (70 eV, EI) m/z
(%): 254/256 (18/19) [M245], 244/246 (10/10) [M255],
103 (17), 75 (20), 73 (100), 45 (66). Anal. calcd for
C11H14BrNO2Si: C, 44.01; H, 4.70; N, 4.67. Found: C,
44.09; H, 4.81; N, 4.83.
3.4. Addition of KI to spiroepoxycyclohexadienone 1a
To a solution of 1a (19 mg, 0.06 mmol) in dry acetone
(10 mL) was added potassium iodide (100 mg, 0.60 mmol).
The reaction was stirred for 72 h at room temperature. The
residue was diluted with acetone and filtered to eliminate the
excess of salt. Drying with MgSO4 was followed by
evaporation of the solvent under vacuum. The crude product
was purified by chromatography on silica gel (ethyl acetate/
hexane) to yield compound 34b (15 mg, 0.05 mmol) as a
white solid.
3.5. Addition of LiAlH4 to spiroepoxycyclohexadienone
1a
A solution of 1a (100 mg, 0.32 mmol) in THF (0.5 mL) was
added, dropwise, to a solution of LiAlH4 (13 mg,
0.32 mmol) in THF (1 mL) at 0 8C. The mixture was stirred
at 0 8C for 30 min. The reaction was quenched by the
dropwise addition of water, and the mixture was extracted
with Et2O. Drying of the combined organic phases with
MgSO4 was followed by evaporation of the solvent under
vacuum. The products were purified by chromatography on
3.2.4. 6-Methoxy-4-trimethylsilanyloxy-1-oxaspiro-
1
[2.5]octa-5,7-diene-4-carbonitriles, 2d. Data for 2d-I: H
NMR: (CDCl3, 200 MHz) d 0.18 (s, 9H, 3CH3–Si), 2.93 (d,
1H, J¼4.9 Hz, CH2–O), 3.50 (d, 1H, J¼4.9 Hz, CH2–O),
4.81 (d, 1H, J¼2.5 Hz, H-2), 5.55 (d, 1H, J¼10.1 Hz, H-5),
6.08 (dd, 1H, J¼10.1, 2.5 Hz, H-4) ppm. Data for 2d-II: 1H
NMR: (CDCl3, 200 MHz) d 0.02 (s, 9H, 3CH3–Si), 2.94 (d,
1H, J¼4.9 Hz, CH2–O), 3.45 (d, 1H, J¼4.9 Hz, CH2–O),
4.87 (d, 1H, J¼2.5 Hz, H-5), 5.55 (d, 1H, J¼10.1 Hz, H-8),
6.05 (dd, 1H, J¼10.1, 2.5 Hz, H-7) ppm. Anal. calcd for
C12H17NO3Si: C, 57.34; H, 6.82; N, 5.57. Found: C, 57.25;
H, 6.71; N, 5.65.
1
silica gel (ethyl acetate/hexane) and characterized by H
NMR and mass spectrometry. The reaction yielded
compound 6 as the major product (70 mg, 0.22 mmol) and
2,4-dibromo-3-methoxy-phenol as a minor product (13 mg,
0.05 mmol).
3.3. Typical procedure for the addition of Bu4NCN to
6-spiroepoxycyclohexadienones 1
Acknowledgements
To a solution of the spiroepoxycyclohexadienone 1
(0.22 mmol) in dry CH2Cl2 (1.1 mL) was added, under
argon and at 0 8C, a solution of Bu4NCN (0.22 mmol) in dry
CH2Cl2 (1.1 mL). The mixture was stirred at 0 8C for
45 min. A saturated solution of NaHCO3 (5 mL) was added
and the mixture was extracted with CH2Cl2. Drying of the
combined organic phases with MgSO4 was followed by
evaporation of the solvent under vacuum. The products
were purified by chromatography on silica gel (ethyl
acetate/hexane).
´
Ministerio de Educacion, Cultura y Deporte, Project BQU
2000-0653 is gratefully thanked for financial support.
References and notes
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32, 324–333. (b) Bonnarme, V.; Bachmann, C.; Cousson, A.;
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also: (c) Purdeau, S.; Pougsegu, L. Org. Prep. Proc. Int. 1999,
31, 617–680.
3.3.1. 7-Bromo-6-methoxy-benzo[1,3]dioxole-4-carbo-
nitrile, 4. 1H NMR (CDCl3, 200 MHz) d 3.98 (s, 3H,
OCH3), 6.09 (s, 2H, O–CH2–O), 6.83 (s, 1H, CH) ppm; MS
(70 eV, EI) m/z (%): 255/257 (100/97) [Mþz], 240/242
(59/60) [M215], 227/229 (19/19) [M228], 210/212 (7/7),
182/184 (6/9), 131/133 (5/6), 75 (15), 53 (9), 29 (14).
2. See for instance: Corey, E. J.; Dittami, J. P. J. Am. Chem. Soc.
1985, 107, 256–257. For a selected report, see: Danishefsky,
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3.3.2. 4,6-Dibromo-5,7-dimethoxy-benzo[1,3]dioxole, 7.
1H NMR (200 MHz, CDCl3) d 3. 82 (s, 3H, OMe), 3.84 (s,
3H, OMe), 5.99 (s, 2H, O–CH2–O) ppm; MS (70 eV) m/z
(%): 333/335/337 (47/95/46) [Mþz], 318/320/322 (50/100/
47) [M2CH3], 262/264/266 (7/9/5) [M271], 131/133 (9/9),
102 (7), 86 (7), 78 (7), 74 (7).
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5. The original purpose of this reaction was to try the ring-
opening of the epoxide functionality, based on the known

´
R. Cordoba et al. / Tetrahedron 60 (2004) 3825–3830
3830
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the literature, and is currently under active research in our
laboratories.
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11. The values that define this polarization function were taken
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