IPy2BF4-mediated rearrangements of 1,2-difunctionalized compounds and olefins

Article abstract of DOI:10.1002/chem.200500070

Acetal derivatives are easily obtained from 1,2-difunctionalized compounds by a new reaction mediated by IPy₂BF₄ with a mechanism based on a 1,2-migration of aryl or alkyl groups. A new oxidative rearrangement reaction of olefins is also described. Moreover, when this metal-free protocol is applied to cyclic olefins, interesting ring-contraction reactions are observed. The new methodologies described here are a clean and efficient alternative to known strategies that make use of potentially toxic metallic complexes.

Full text of DOI:10.1002/chem.200500070

DOI: 10.1002/chem.200500070
IPy2BF4-Mediated Rearrangements of 1,2-Difunctionalized Compounds and
Olefins
[a]
FranciscoJ. FaÇanµs,* Mónica lvarez-PØrez, and FØlix Rodríguez
Abstract: Acetal derivatives are easily obtained from 1,2-difunctionalized com-
pounds by a new reaction mediated by IPy2BF4 with a mechanism based on a 1,2-
migration of aryl or alkyl groups. A new oxidative rearrangement reaction of ole-
fins is also described. Moreover, when this metal-free protocol is applied to cyclic
olefins, interesting ring-contraction reactions are observed. The new methodolo-
gies described here are a clean and efficient alternative to known strategies that
make use of potentially toxic metallic complexes.
Keywords: 1,2-migration reactions ·
alkenes rearrangement ring
contraction · synthetic methods.
·
·
Introduction
The reagent bis(pyridine)iodonium(i) tetrafluoroborate
(IPy2BF4)[6] has been shown to be a versatile reagent in or-
ganic synthesis as it effects many useful and unique transfor-
mations.[7] During our investigations on the reactivity of this
reagent with 1,2-difunctionalized compounds we observed
that compounds such as 3 (X=I, Y=OMe) react with
IPy2BF4, under certain conditions, by a rearrangement reac-
tion to give products 1 (Scheme 1). Taking into account that
compounds 3 (X=I, Y=OMe) are easily available from a
well-established iodofunctionalization reaction of olefins 2
with IPy2BF4, we thought that compounds 1 should be di-
rectly obtainable from simple alkenes 2 by a tandem iodo-
functionalization/rearrangement process mediated by
IPy2BF4. This prompted us to initiate a deeper investigation
of the ability of IPy2BF4 to perform these unusual rear-
rangement reactions. On this basis, we describe here the re-
sults of these studies which have culminated in the develop-
ment of a new method for the formation of carbonylic deriv-
atives 1, or derivatives, from both 1,2-difunctionalized deriv-
atives 3 (X=I, Y=OMe) and olefins 2. An interesting ring-
contraction reaction promoted by IPy2BF4 is also reported.
Carbon skeletal rearrangement reactions in which a group
(H, alkyl, aryl) migrates to the adjacent position are power-
ful synthetic tools that give access to carbon frames not
easily available by other procedures.[1] These reactions,
when applied to cyclic compounds, lead to ring contraction
or expansion products.[2] These atom-economical processes
occur, in most cases, with very high selectivity, and therefore
they have been widely used in the total synthesis of many
natural products.[3] Although the variety of rearrangement
reactions of this type published in the few last years is very
broad, probably the most interesting processes are those
which imply the formation of a carbonyl compound such as
1 (Scheme 1). Depending on the starting material, these re-
actions can be divided into two main groups: 1) oxidative
rearrangement of olefins 2,[4] and 2) rearrangement of 1,2-di-
functionalized compounds 3 (Scheme 1).[5]
Scheme 1. Synthesis of carbonyl compounds 1 from either olefins 2 or
1,2-difunctionalized compounds 3 by rearrangement reactions.
Results and Discussion
IPy2BF4-mediated rearrangement reactions of 1,2-difunc-
tionalized compounds: 1,2-migration of aryl groups: As
mentioned above, our investigation began with the study of
the reactivity of the reagent IPy2BF4 with 1,2-difunctional-
ized compounds. Thus, (1S*,2R*)-2-iodo-1,3-dimethoxy-1-
phenylpropane (3a) was chosen as a model compound to in-
vestigate all the factors that play a role in the course of the
[a] Prof. Dr. F. J. FaÇanµs, M. lvarez-PØrez, Dr. F. Rodríguez
Instituto Universitario de Química Organometµlica “Enrique Moles”
Unidad Asociada al CSIC, Universidad de Oviedo
Juliµn Clavería 8, 33006 Oviedo (Spain)
Fax : (+34)985-103-446
E-mail: fjfv@uniovi.es
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FULL PAPER
reaction. After careful optimization studies we observed
that compound 3a reacts with 2.2 equivalents of IPy2BF4,
2.2 equivalents of BF3·OEt2,[8] and 2.2 equivalents of H2O, in
dry dichloromethane at room temperature, in five minutes,
to afford the aldehyde 1a in 86% yield (Scheme 2).[9] This
IPy2BF4 and BF3·OEt2 coordinates to the iodine atom of the
starting compound 3a, as shown in I. Subsequent elimina-
tion of a molecule of iodine assisted by the vicinal phenyl
group leads to the phenonium ion intermediate 5.[11] Attack
of the nucleophile present in the reaction medium (H2O or
MeOH) then occurs at the carbon bound to the methoxy
group to form the corresponding acetal derivative 4a or the
hemiacetal derivative 6. Hemiacetal 6 evolves into the alde-
hyde 1a by losing a molecule of MeOH (Scheme 3).
Once we had found the optimum conditions to obtain the
aldehyde 1a or the acetal 4a, we decided to investigate the
scope of the reaction. Thus, we carried out a set of experi-
ments, under those optimized conditions, starting from the
aryl-substituted 1,2-difunctionalized compounds 3b–g
(Scheme 4). Although aldehydes analogous to 1a are easily
Scheme 2. Rearrangement reactions mediated by IPy2BF4 on model com-
pound 3a. Yields of the reaction performed using only one equivalent of
IPy2BF4 and one equivalent of BF3·OEt2 are given in parentheses (see
reference [8]).
transformation implies the migration of the phenyl group to
the adjacent position and the incorporation of a molecule of
water.[9,10] Moreover, when this reaction was performed
under the same reaction conditions but with 2.2 equivalents
of MeOH instead of H2O, dimethyl acetal 4a was obtained
in 93% yield (Scheme 2).[8] In this case the final product in-
corporates a molecule of methanol instead of a molecule of
water.
Scheme 4. Synthesis of acetals 4b–g from 1,2-difunctionalized compounds
3b–g by 1,2-migration reactions of aryl groups.
available following the procedure described above, in some
cases their isolation was found to be difficult. For this
reason, and taking into account that these aldehydes are
easily available from the corresponding dimethyl acetals, we
decided to perform all the reactions in the presence of
MeOH. Under these conditions, the acetals 4b–g were
easily obtained in high yields (Scheme 4).
A plausible mechanism that explains the formation of
compounds 1a and 4a is depicted in Scheme 3. First, we be-
lieve that the iodonium ion generated from the mixture of
The most interesting results are highlighted in Table 1. A
phenyl group (Table 1, entries 1, 4, and 5) and also electron-
rich (Table 1, entry 2) and, surprisingly, electron-poor aryl
groups (Table 1, entry 3) undergo the 1,2-migration reaction.
Moreover, the aryl group can migrate to primary, secondary,
or tertiary carbons (Table 1, entries 1, 4, and 5). The result
shown in Table 1, entry 6 is noteworthy as it supposes that
the reaction proceeds when cyclic ethers such as 3g
[(2S*,3R*)-diastereoisomer] are used. Interestingly, this re-
action is totally diastereoselective, as only the formation of
Scheme 3. Proposed mechanism for the IPy2BF4-mediated rearrangement
reaction.
Abstract in Spanish: La reacción de compuestos 1,2-difun-
cionalizados con IPy2BF4 da lugar a acetales a travØs de un
proceso basado en una reacción de migración 1,2 de un
grupo arilo o alquilo. TambiØn se describe una nueva reac-
ción de reagrupamiento oxidativo de olefinas promovida por
IPy2BF4. Cuando este protocolo se aplica a olefinas cíclicas
se obtienen interesantes productos procedentes de una reac-
ción de contracción de anillo. Las nuevas metodologías aquí
descritas suponen una alternativa limpia yeficiente a los co-
nocidos mØtodos que utilizan complejos metµlicos potencial-
mente contaminantes.
Table 1. Synthesis of acetals 4b–g from 1,2-difunctionalized compounds
3b–g.
Entry
Starting
material
Ar
R
R1
R2
Product
Yield
[%][a]
1
2
3
4
5
6
3b
3c
3d
3e
Ph
4-MeC6H4
4-BrC6H4
Ph
Me
Me
Me
Me
Me
H
H
H
Me
Me
H
H
H
H
Me
H
4b
96
90
87
91
86
81
4c[b]
4d[c]
4e
3 f
Ph
Ph
4 f[b]
4g[b,e]
3g[d]
-(CH2)2-
[a] Yield based on starting iodide 3. [b] The reaction was performed at
À108C. [c] The reaction required 1h to complete. [d] (2 S*,3R*)-diaster-
eoisomer. [e] The (2S*,3R*)-diastereoisomer was formed exclusively.
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F. J. FaÇanµs et al.
diastereoisomer 4g [(2S*,3R*)-diastereoisomer] was ob-
served.
Taking advantage of our experience in the synthesis of
terpene derivatives such as 3h–j (Table 2),[12] we decided to
Scheme 5. Synthesis of acetals 4j–l from 1,2-difunctionalized compounds
3k–n by 1,2-migration reactions of alkyl groups.
Table 2. Synthesis of terpene-derived acetals 4h,i and aldehydes or ke-
tones 1b–d from the corresponding 1,2-difunctionalized terpene deriva-
tive 3h–j.
Entry Starting
material
Additional Product
nucleophile
Yield
[%][a]
investigate the 1,2-migration of alkyl groups. As shown in
Scheme 5, the reaction was carried out as described before
except that larger amounts of IPy2BF4 and BF3·EtO2
(2.7 equiv) were required to achieve complete conversion.
The most interesting results are collected in Table 3. First
of all, it should be noted that the reaction only proceeded in
those cases in which the carbon containing the iodine atom
1
MeOH
96
98
92
2
3
ent-3h
MeOH
MeOH
ent-4h
Table 3. Synthesis of acetals 4j–l from 1,2-difunctionalized compounds
3k–n.
Entry
Starting
material
Alk
R1
Product
Yield
[%][a]
4
5
6
3h
3i
H2O
H2O
H2O
83
1
2
3
4
3k
3 l
3m
3n
Pr
Pent
Me
H
Pr
Me
pentyl
cyclohexyl
4j
4k
4k
4l
90
85
61[b]
88
86
[a] Yield based on starting iodide 3. [b] 17% of 2-octanone was also iso-
lated.
was substituted. In contrast, when the R1 substituent was a
hydrogen atom (i.e., the carbon containing the iodine atom
was primary), the reaction did not work under any of the
different conditions attempted and the starting material was
recovered unchanged. Also remarkable are those examples
where a 1,2-migration reaction of a hydrogen atom was ob-
served (Table 3, entries 3 and 4). Although the main product
obtained when starting from compound 3m was that coming
from the 1,2-migration reaction of a methyl group (4k), a
small amount (17% yield) of 2-octanone was also isolated.
This minor product is thought to come from the 1,2-migra-
tion reaction of a hydrogen atom. This latter reaction was
the only one observed when the reaction was performed
with compound 3n (Table 3, entry 4).
Although the 1,2-migration reactions of alkyl groups de-
scribed here are a significant achievement, probably the
most interesting results were those obtained when using
cyclic compounds as starting materials. Thus, the treatment
of cyclic compounds 3o–t with IPy2BF4 under the conditions
described in Scheme 5 led to the new cyclic compounds 1e
or 4 m–q (Table 4). This transformation supposes an unpre-
cedented ring-contraction reaction mediated by IPy2BF4.
Thus, four-, six-, and seven-membered rings have been trans-
formed into the corresponding three-, five-, and six-mem-
bered rings, respectively (Table 4, entries 1–4). However, the
reaction did not proceed when it was attempted with five-
and eight-membered rings; in these cases the starting mate-
rial was recovered unchanged.[14]
43[b]
[a] Yield based on starting iodide 3. [b] 49% of the starting material was
recovered.
try the rearrangement reaction with these substrates. The
objectives of these studies were, on the one hand, to trans-
form the initial terpene derivatives into others with a differ-
ent substitution pattern,[13] and, on the other hand, as the in-
itial terpene derivatives 3h–j are enantiomerically pure, this
investigation could give us some information about the ste-
reochemical outcome of the rearrangement reaction. Thus,
terpene derivatives 3h–j, under the same reaction conditions
as those previously mentioned, gave the new terpene-de-
rived acetals 4h,i or aldehydes/ketones 1b–d in very high
yield and as single enantiomers in all cases (Table 2). The
structure of these compounds was determined by NMR
spectroscopy and confirmed by X-ray crystal-structure anal-
ysis in the case of 4h. The stereochemical outcome of the re-
action can be explained by a model similar to that shown in
Scheme 3.
IPy2BF4-mediated rearrangement reactions of 1,2-difunc-
tionalized compounds: 1,2-migration of alkyl groups and
ring-contraction reactions: Once the 1,2-migration reaction
of aryl groups had been perfectly established, we decided to
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IPy2BF4-Mediated Rearrangements
FULL PAPER
Table 4. Synthesis of cyclic compounds 1e and 4m–q by ring-contraction
reactions.
suppose an initial coordination of the iodonium ion to the
iodine atom of 3s to give an intermediate analogous to I
(see Scheme 3). At this point, the elimination of the mole-
cule of iodine can be assisted by one of two sections (a or b)
of the cyclohexane skeleton that lead, via intermediates II
or III, to the same diastereoisomer of the final product (4p,
or ent-4p). In contrast, starting from 3t, the migration of the
two possible branches (a or b) does not lead to the same di-
astereoisomer. Migration of branch b leads, via intermediate
IV, to diastereoisomer 4p, which is the minor isomer ob-
served in the reaction, whereas migration of branch a leads,
via intermediate V, to diastereoisomer 4q, which is the
major isomer observed in the reaction. Although we do not
have a clear justification for this, it is clear that migration of
the branch that contains the methoxy group in an equatorial
position (branch a, leading to 4q) is much more favored
than the migration of the branch that contains the methoxy
group in an axial position (branch b).
Entry
Starting
material
Product
Yield
[%][a]
1
2
3
68
62
70
4
5
86
81
IPy2BF4-mediated rearrangement reactions of olefins:
tandem
iodofunctionalization/rearrangement
reactions:
Bearing in mind that all the alkoxy-substituted iodides used
as starting materials in the previous sections can be easily
obtained from olefins by the well-established iodofunction-
alization reaction mediated by the reagent IPy2BF4,[15] we
believed that we could develop a tandem iodofunctionaliza-
tion/rearrangement method to transform olefins into acetals
directly. The scope of the reactions described previously in
this paper would be considerably extended if this tandem
process could be achieved. As shown in Scheme 7, the re-
agent IPy2BF4 would play a dual role in this process: firstly
it would act as an iodinating agent to favor the functionali-
zation of the olefin 2 to form intermediate 3, and secondly it
would mediate the 1,2-migration reaction that leads to the
final rearranged product 4.
6
76[e]
[a] Yield based on starting iodide 3. [b] The expected dimethyl acetal was
not observed, and under these reaction conditions the aldehyde 1e was
isolated. [c] Reaction performed at À408C. [d] The reaction was per-
formed at À408C for 90 min. The 1H NMR spectrum of the crude reac-
tion mixture shows a 15:1 mixture of 4q and 4p. [e] Yield of the major
diastereoisomer 4q based on 3t.
Interesting results from both a synthetic and mechanistic
point of view were observed from the reaction of the trisub-
stituted cyclohexane derivatives 3s and 3t. As reflected in
entries 5 and 6 of Table 4, these two diastereoisomers led to
two different disubstituted cyclopentane derivatives 4p and
4q, respectively. These observations can be rationalized ac-
cording to Scheme 6. Thus, starting from compound 3s we
Scheme 7. Synthesis of acetals 4 from olefins 2 by a tandem iodofunction-
alization/rearrangement process.
After some initial studies focused on finding the best re-
action conditions, we realized that the treatment of olefins 2
with 3.3 equivalents of IPy2BF4 and 3.7 equivalents of
BF3·EtO2 in dichloromethane, in the presence of five equiv-
alents of methanol, at room temperature for one hour, led
to the formation of acetals 4 in very high yields in most
cases (Scheme 7 and Table 5). The reaction was found to be
general and both styrene- (Table 5, entries 1–6) and alkyl-
substituted olefins (Table 5, entries 7 and 8) can be used as
starting materials. Highly functionalized olefins, such as the
Scheme 6. Proposed mechanism for the evolution of diastereoisomeric
compounds 3s and 3t.
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F. J. FaÇanµs et al.
Table 5. Synthesis of acetals 4 from olefins 2.
baths were prepared by cooling ethanol, 2-propanol, or acetone with
liquid nitrogen. Dichloromethane was continuously refluxed and freshly
distilled from calcium hydride under nitrogen. Solvents used in extraction
and purification (CH2Cl2, hexane, Et2O, AcOEt) were purchased from
Scharlau and used without further purification. BF3·OEt2 used to obtain
the acetals was dried by standard methods and stored under nitrogen.[9]
Compounds were visualized on analytical thin-layer chromatograms
(TLC) by UV light (254 nm) and/or by staining with an o-phosphomolyb-
dic acid solution (prepared by dissolving o-phosphomolybdic acid (5 g) in
ethanol (100 mL) and subsequent heating. Silica gel (230–240 mesh) was
used for flash chromatography. 1H NMR (200, 300, 400 MHz) and
13C NMR (50.5, 75.5, 100 MHz) spectra were measured at room tempera-
ture on Bruker AC-200, AC-300, and AMX-400 instruments, respectively,
with tetramethylsilane (d=0.0 ppm, 1H NMR) or CDCl3 (d=77.00 ppm,
13C NMR) as internal standard. Carbon multiplicities were assigned by
DEPT techniques. High-resolution mass spectra (HRMS) were deter-
mined on a Finnigan MAT 95 spectrometer. Elemental analyses were car-
ried out on a Perkin-Elmer 2400 microanalyzer. A Perkin Elmer 241po-
larimeter was used to measure optical rotations (sodium lamp).
Entry
Olefin
R1
R2
Product
Yield [%][a]
1
2
3
4
5
2a
2b
2c
2d
2e
Ph
Ph
4-MeC6H4
4-BrC6H4
Ph
CH2OMe
H
H
H
4a
4b
4c
4d
4e
84
91
89
93
82
Me
6
2 f
Ph
4h
93
7
8
2g
2h
Pr
pentyl
Pr
Me
4j
4k
88
66[b]
9
1e[c]
4n
71
67
10
1,2-Difunctionalized compounds 3 were synthesized as reported previous-
ly.[12,15]
General procedure for the rearrangement reaction of 1,2-difunctionalized
compounds 3 to give aldehydes or ketones 1: A solution of IPy2BF4
(0.41g, 1.1mmol) in dry CH 2Cl2 (2.5 mL) was prepared under nitrogen
and treated with dry BF3·OEt2 (3 mL of a 0.4m solution in CH2Cl2,
1.1 mmol) and H2O (20 mL, 1.1 mmol) at room temperature. A solution
of the corresponding compound 3 (0.5 mmol) in dry CH2Cl2 (2 mL) was
then added at the same temperature. A change in the color of the solu-
tion (red to violet) was observed immediately. The reaction was moni-
tored by TLC and quenched with a 5% solution of Na2S2O3·5H2O
(10 mL) when complete. Extraction with CH2Cl2 (2”10 mL) was per-
formed immediately, and the combined organic layers were washed with
water (2”10 mL) and dried with anhydrous sodium sulfate. The solvents
were carefully removed and the residue was purified by flash chromatog-
raphy (SiO2, hexane/diethyl ether, 40:1) to obtain pure aldehydes or ke-
tones 1.
11
12
4p/4q
55/32
88
4o
[a] Yield based on starting olefin 2. [b] 12% of 2-octanone was also iso-
lated. [c] The expected dimethyl acetal was not observed, and under
these reaction conditions the aldehyde 1e was isolated.
terpene derivative 2 f, also reacted without any problem
(entry 6). Interestingly, in this case the reaction was found
to be highly selective, leading to a single isomer of the rear-
ranged final product 4h. Finally, it should be noted that
cyclic alkenes 2i–l cleanly underwent ring-contraction reac-
tions to give compounds 1e and 4m–q (Table 5, entries 9–
12).
3-Methoxy-2-phenylpropanal (1a): Colorless oil. Rf =0.35 (hexane/ethyl
acetate, 5:1); 1H NMR (200 MHz, CDCl3): d=9.78 (d, J=1.6 Hz, 1H;
CHO), 7.50–7.10 (m, 5H; ArH), 4.06 (dd, J=8.9, 7.2 Hz, 1H;
CHHOMe), 3.88 (apparent td, J=7.2, 5.5, 1.6 Hz, 1H; PhCH), 3.74 (dd,
J=8.9, 5.5 Hz, 1H; CHHOMe), 3.39 (s, 3H; OMe) ppm; 13C NMR
(75 MHz, CDCl3): d=199.6, 133.8, 129.0, 128.8, 127.8, 71.7, 59.1,
58.7 ppm; HRMS (70 eV, EI): calcd for C10H12O2 ([M]+): 164.0837; found
164.0840; elemental analysis calcd (%) for C10H12O2: C 73.15, H 7.37;
found: C 73.28, H 7.49.
Conclusion
(1S,2S,3R,7R,9S)-3-[(S)-Formylphenylmethyl]-2,5,5,10,10-pentamethyl-
4,6-dioxatricyclo[7.1.1.02,7]undecane (1b): Colorless oil. Rf =0.37 (hexane/
ethyl acetate, 10:1); [a]D20 =+17.6 (c=2.0, CH2Cl2); 1H NMR (200 MHz,
CDCl3): d=9.71(d, J=4.3 Hz, 1H; HC=O), 7.50–7.10 (m, 5H; ArH),
4.60 (d, J=8.6 Hz, 1H; OCHCHPh), 3.74 (d, J=8.2 Hz, 1H; OCHCH2),
2.50–2.30 (m, 1H; aliphatic ring), 1.90–0.80 (m, 5H; aliphatic ring), 1.42,
1.38, 1.20, 0.95, 0.85 (5s, 15H; 5”Me) ppm; 13C NMR (75 MHz, CDCl3):
d=199.2, 135.0, 128.9, 128.8, 127.6, 100.7, 73.0, 71.1, 58.3, 48.6, 46.0, 39.2,
39.0, 34.7, 27.7, 26.6, 25.9, 24.0, 22.7, 20.4 ppm; HRMS (FAB): calcd for
C22H31O3 ([M+1]+): 343.2273; found 343.2277; elemental analysis calcd
(%) for C22H30O3: C 77.16, H 8.83; found: C 77.31, H 8.99.
We have developed a novel reaction with the reagent
IPy2BF4 that widens even further the synthetic possibilities
of this reagent. Following the protocol described here, it is
possible to synthesize aldehydes (or derivatives) from
alkoxy-substituted iodides by a 1,2-migration reaction of
aryl or alkyl groups. Moreover, a new oxidative rearrange-
ment reaction of olefins to give aldehyde/ketone derivatives
has been studied. Novel ring-contraction reactions are ob-
served when the process is applied to cyclic compounds. The
metal-free strategy described here represents a clean and
synthetically competitive alternative to the already estab-
lished use of metal complexes and it is likely to find many
applications in organic synthesis.
(1S,2S,4R,7R,8S)-8-[(R)-Formylphenylmethyl]-3,3,7,10,10-pentamethyl-
9,11-dioxatricyclo[5.4.0.02,4]undecane (1c): Colorless oil. Rf =0.48
(hexane/ethyl acetate, 5:1); [a]2D0 =À30.8 (c=3.0, CH2Cl2); 1H NMR
(300 MHz, CDCl3): d=9.73 (d, J=4.3 Hz, 1H; HC=O), 7.40–7.20 (m,
5H; ArH), 4.50 (d, J=7.4 Hz, 1H; OCHCHPh), 3.64 (dd, J=7.4, 4.3 Hz,
1H; PhCH), 3.39 (d, J=2.0 Hz, 1H; OCHCH), 1.70–0.50 (m, 6H; ali-
phatic ring), 1.51, 1.44, 1.05, 1.01, 0.91 (5s, 15H; 5”Me) ppm; 13C NMR
(75 MHz, CDCl3): d=199.4, 135.5, 129.0, 128.9, 127.7, 100.0, 75.0, 72.8,
58.4, 37.6, 31.5, 29.2, 25.9, 25.6, 25.2, 21.0, 20.1, 16.2, 15.3, 14.9 ppm;
HRMS (FAB): calcd for C22H31O3 ([M+1]+): 343.2273; found 343.2274;
elemental analysis calcd (%) for C22H30O3: C 77.16, H 8.83; found: C
77.32, H 9.02.
Experimental Section
General: Unless noted, all reactions were carried out under nitrogen in
oven-dried glassware. Temperatures are reported as bath temperatures;
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IPy2BF4-Mediated Rearrangements
FULL PAPER
(1S,2S,3S,7R,9S)-3,3,7,10,10-Pentamethyl-3-(phenylacetyl)-9,11-dioxatri-
cyclo[5.4.0.02,4]undecane (1d): Colorless oil. Rf =0.38 (hexane/ethyl ace-
tate, 10:1); 1H NMR (200 MHz, CDCl3): d=7.40–7.10 (m, 5H; ArH),
4.17 (s, 1H; OCHC=O), 3.95 (d, J=16.4 Hz, 1H; PhCHH), 3.80 (d, J=
16.4 Hz, 1H; PhCHH), 3.78 (d, J=7.8 Hz, 1H; OCHCH2), 2.50–0.80 (m,
6H; aliphatic ring), 1.47, 1.32, 1.24, 1.15, 0.92 (5s, 15H; 5”Me) ppm;
13C NMR (75 MHz, CDCl3): d=209.8, 134.1, 129.8, 128.2, 126.5, 100.8,
77.7, 70.9, 47.6, 47.4, 47.4, 39.5, 39.0, 34.4, 27.9, 26.2, 25.4, 24.1, 23.0,
20.3 ppm; HRMS (70 eV, EI): calcd for C22H30O3 ([M]+): 342.2195; found
342.2198; elemental analysis calcd (%) for C22H30O3: C 77.16, H 8.83;
found: C 77.28, H 8.69.
4.20 (s, 1H; CH(OMe)2), 3.38 (s, 6H; 2”OMe), 1.41 (s, 6H; 2”Me)
ppm; 13C NMR (75 MHz, CDCl3): d=146., 127.7, 126.7, 125.8, 113.6,
58.2, 43.4, 23.1ppm; HRMS (70 eV, EI): calcd for C 12H18O2 ([M]+):
194.1307; found 194.1312; elemental analysis calcd (%) for C12H18O2: C
74.19, H 9.34; found: C 74.35, H 9.22.
(2S*,3R*)-2-Methoxy-3-phenyltetrahydrofuran (4g): Colorless oil. Rf =
0.37 (hexane/ethyl acetate, 10:1); 1H NMR (300 MHz, CDCl3): d=7.40–
7.20 (m, 5H; ArH), 4.94 (d, J=2.0 Hz, 1H; CH(OMe)2), 4.14 (m, 1H;
CHHO), 4.06 (m, 1H; CHHO), 3.37 (s, 3H; OMe), 3.33 (m, 1H; CHPh),
2.47 (m, 1H; CHHCHPh), 2.05–1.90 (m, 1H; CHHCHPh) ppm;
13C NMR (75 MHz, CDCl3): d=142.3, 128.5, 127.2, 126.5, 110.5, 67.2,
54.8, 51.3, 26.9 ppm; HRMS (70 eV, EI): calcd for C11H14O2 ([M]+):
178.0994; found 178.0997; elemental analysis calcd (%) for C11H14O2: C
74.13, H 7.92; found: C 74.27, H 7.83.
General procedure for the rearrangement reaction of 1,2-difunctionalized
compounds 3 to give acetals 4 or aldehyde 1e: A solution of IPy2BF4
(0.41g, 1.1mmol) in dry CH 2Cl2 (2.5 mL) was prepared under nitrogen
and treated with dry BF3·OEt2 (3 mL of a 0.4m solution in the same sol-
vent, 1.1 mmol) and methanol (46 mL, 1.1 mmol) at room temperature. A
solution of the corresponding compound 3 (0.5 mmol) in CH2Cl2 (2 mL)
was then added at the same temperature. A change in the color of the so-
lution (red to violet) was observed immediately. The reaction was moni-
tored by TLC and quenched with a 5% solution of Na2S2O3·5H2O
(10 mL) when complete. Extraction with CH2Cl2 (2”10 mL) was per-
formed immediately, and the combined organic layers were washed with
water (2”10 mL) and dried with anhydrous sodium sulfate. Solvents
were carefully removed and the residue was purified by flash chromatog-
raphy (SiO2, hexane/diethyl ether, 40:1) to give pure acetals 4 or alde-
hyde 1e.
(1S,2S,3R,7R,9S)-3-[(1S)-2,2-Dimethoxy-1-phenylethyl]-2,5,5,10,10-pen-
tamethyl-4,6-dioxatricyclo[7.1.1.02,7]undecane (4h): Colorless solid. M.p.
156.2–156.48C (cold pentane); [a]2D0 =+1.6 (c=2.7, CH2Cl2); 1H NMR
(200 MHz, CDCl3): d=7.30–7.15 (m, 5H; ArH), 4.70 (d, J=3.1Hz, 1H;
CH(OMe)2), 4.42 (d, J=11.0 Hz, 1H; OCHCHPh), 3.66 (d, J=8.2 Hz,
1H; OCHCH2), 3.45 (s, 3H; OMe), 3.39 (s, 3H; OMe), 3.01(dd, J=11.0,
3.1Hz, 1H; PhC H), 2.42–2.28 (m, 1H; aliphatic ring), 1.80–0.30 (m, 5H;
aliphatic ring), 1.44, 1.39, 1.14, 0.78, 0.78 (5s, 15H; 5”Me) ppm;
13C NMR (50 MHz, CDCl3): d=137.7, 130.4, 127.4, 126.7, 106.7, 100.2,
71.7, 71.5, 56.6, 56.3, 48.7, 48.6, 46.4, 38.8, 38.6, 35.0, 27.7, 26.3, 26.0, 24.0,
23.0, 20.0 ppm; HRMS (FAB): calcd for C24H37O4 ([M+1]+): 389.2692;
found 389.2684; elemental analysis calcd (%) for C24H36O4: C 74.19, H
9.34; found: C 74.07, H 9.12.
1,1,3-Trimethoxy-2-phenylpropane (4a): Colorless oil. Rf =0.31(hexane/
ethyl acetate, 5:1); 1H NMR (200 MHz, CDCl3): d=7.40–7.20 (m, 5H;
ArH), 4.61(d, J=6.6 Hz, 1H; CH(OMe)2), 3.74 (d, J=5.8 Hz, 2H;
CH2OMe), 3.44 (s, 3H; OMe), 3.32 (s, 6H; 2”OMe), 3.19 (dd, J=6.6,
5.8 Hz, 1H; PhCH) ppm; 13C NMR (75 MHz, CDCl3): d=139.0, 128.6,
127.9, 126.4, 105.8, 73.0, 58.7, 54.6, 54.5, 49.0 ppm; HRMS (70 eV, EI):
calcd for C12H18O3 ([M]+): 210.1256; found 210.1254; elemental analysis
calcd (%) for C12H18O3: C 68.54, H 8.63; found: C 68.68, H 8.54.
(1R,2R,3S,7S,9R)-3-[(1R)-2,2-Dimethoxy-1-phenylethyl]-2,5,5,10,10-
pentamethyl-4,6-dioxatricyclo[7.1.1.02,7]undecane (ent-4h): Colorless
solid. The spectroscopic data for ent-4h were identical to those of 4h.
[a]2D0 =À1.6 (c=5.2, CH2Cl2).
(1S,2S,4R,7R,8S)-8-[(1R)-2,2-Dimethoxy-1-phenylethyl]-3,3,7,10,10-
pentamethyl-9,11-dioxatricyclo[5.4.0.02,4]undecane (4i): Colorless oil. Rf =
0.42 (hexane/ethyl acetate, 5:1); [a]2D0 =À3.4 (c=1.0, CH2Cl2); 1H NMR
(300 MHz, CDCl3): d=7.45–7.15 (m, 5H; ArH), 4.70 (d, J=3.1Hz, 1H;
CH(OMe)2), 4.27 (d, J=10.0 Hz, 1H; OCHCHPh), 3.44 (s, 3H; OMe),
3.36 (s, 3H; OMe), 3.29 (d, J=1.7 Hz, 1H; OCHCH), 3.06 (dd, J=10.0,
3.1Hz, 1H; PhC H), 1.70–0.50 (m, 6H; aliphatic ring), 1.50, 1.44, 0.98,
0.96, 0.87 (5s, 15H; 5”Me) ppm; 13C NMR (75 MHz, CDCl3): d=138.0,
130.7, 127.6, 126.8, 106.7, 99.7, 73.6, 72.4, 56.8, 56.2, 49.3, 38.5, 31.6, 29.2,
25.5, 25.4, 21.0, 19.4, 15.9, 15.5, 14.9 ppm; HRMS (FAB): calcd for
C24H37O4 ([M+1]+): 389.2692; found 389.2690; elemental analysis calcd
(%) for C24H36O4: C 74.19, H 9.34; found: C 74.26, H 9.40.
1,1-Dimethoxy-2-phenylethane (4b): Colorless oil. Rf =0.34 (hexane/
ethyl acetate, 20:1); 1H NMR (200 MHz, CDCl3): d=7.40–7.20 (m, 5H;
ArH), 4.58 (t, J=5.5 Hz, 1H; CH(OMe)2), 3.37 (s, 6H; 2”OMe), 2.94
(d, J=5.5 Hz, 2H; CH2) ppm; 13C NMR (75 MHz, CDCl3): d=137.0,
129.3, 128.2, 126.3, 105.2, 53.2, 39.6 ppm; HRMS (70 eV, EI): calcd for
C10H14O2 ([M]+): 166.0994; found 166.0997; elemental analysis calcd (%)
for C10H14O2: C 72.26, H 8.49; found: C 72.37, H 8.58
1,1-Dimethoxy-2-(4-methylphenyl)ethane (4c): Colorless oil. Rf =0.31
(hexane/ethyl acetate, 20:1); 1H NMR (300 MHz, CDCl3): d=7.20–7.00
(m, 4H; ArH), 4.54 (t, J=5.7 Hz, 1H; CH(OMe)2), 3.35 (s, 6H; 2”
OMe), 2.89 (d, J=5.7 Hz, 2H; CH2), 2.33 (s, 3H; Me) ppm; 13C NMR
(75 MHz, CDCl3): d=135.6, 133.8, 129.1, 128.9, 105.2, 53.1, 39.0,
20.9 ppm; HRMS (70 eV, EI): calcd for C11H16O2 ([M]+): 180.1150; found
180.1146; elemental analysis calcd (%) for C11H16O2: C 73.30, H 8.95;
found: C 73.46, H 8.81.
4-(Dimethoxymethyl)heptane (4j): Colorless oil. Rf =0.43 (hexane/ethyl
acetate, 10:1); 1H NMR (300 MHz, CDCl3): d=4.10 (d, J=6.0 Hz, 1H;
CH(OMe)2), 3.31 (s, 6H; 2”OMe), 1.65–1.10 (m, 9H; CH(CH2CH2)2),
0.85 (t, J=6.7 Hz, 6H; 2”Me) ppm; 13C NMR (75 MHz, CDCl3): d=
107.8, 54.2, 39.8, 31.1, 19.9, 14.4 ppm; HRMS (70 eV, EI): calcd for
C10H22O2 ([M]+): 174.1620; found 174.1625; elemental analysis calcd (%)
for C10H22O2: C 68.92, H 12.72; found: C 69.04, H 12.65.
2-(4-Bromophenyl)-1,1-dimethoxyethane (4d): Colorless oil. Rf =0.24
1
(hexane/ethyl acetate, 20:1); H NMR (300 MHz, CDCl3): d=7.40 (d, J=
2-(Dimethoxymethyl)heptane (4k): Colorless oil. Rf =0.36 (hexane/ethyl
acetate, 10:1); 1H NMR (300 MHz, CDCl3): d=4.01(d, J=6.6 Hz, 1H;
CH(OMe)2), 3.34 (s, 6H; 2”OMe), 2.45–2.35 (m, 1H; CHCH(OMe)2),
1.45–1.20 (m, 8H; 4”CH2), 1.00–0.80 (m, 6H; 2”Me) ppm; 13C NMR
(75 MHz, CDCl3): d=108.9, 53.9, 53.7, 35.6, 32.0, 31.5, 26.5, 22.5, 14.2,
13.9 ppm; HRMS (70 eV, EI): calcd for C10H22O2 ([M]+): 174.1620; found
174.1618; elemental analysis calcd (%) for C10H22O2: C 68.92, H 12.72;
found: C 69.02, H 12.58.
8.3 Hz, 2H; ArH), 7.10 (d, J=8.3 Hz, 2H; ArH), 4.49 (t, J=5.4 Hz, 1H;
CH(OMe)2), 3.33 (s, 6H; 2”OMe), 2.85 (d, J=5.4 Hz, 2H; CH2) ppm;
13C NMR (75 MHz, CDCl3): d=135.8, 131.2, 131.1, 120.2, 104.9, 53.3,
39.0 ppm; HRMS (70 eV, EI): calcd for C9H10BrO ([MÀ31]+): 212.9915;
found 212.9910; elemental analysis calcd (%) for C10H13BrO2: C 49.00, H
5.35; found: C 49.23, H 5.26.
1,1-Dimethoxy-2-phenylpropane (4e): Colorless oil. Rf =0.30 (hexane/
ethyl acetate, 20:1); 1H NMR (200 MHz, CDCl3): d=7.50–7.10 (m, 5H;
ArH), 4.40 (d, J=7.0 Hz, 1H; CH(OMe)2), 3.41, 3.28 (2s, 6H; 2”OMe),
3.05 (q, J=7.0 Hz, 1H; PhCH), 1.31 (d, J=7.0 Hz, 3H; Me) ppm;
13C NMR (75 MHz, CDCl3): d=142.9, 128.1, 127.8, 126.2, 108.4, 54.2,
53.8, 42.8, 16.6 ppm; HRMS (70 eV, EI): calcd for C11H16O2 ([M]+):
180.1150; found 180.1153; elemental analysis calcd (%) for C11H16O2: C
73.30, H 8.95; found: C 73.51, H 9.15.
2-Cyclohexyl-1,1-dimethoxyethane (4l): Colorless oil. Rf =0.37 (hexane/
ethyl acetate, 10:1); 1H NMR (300 MHz, CDCl3): d=4.45 (t, J=5.7 Hz,
1H; CH(OMe)2), 3.28 (s, 6H; 2”OMe), 1.76–0.80 (m, 13H) ppm;
13C NMR (75 MHz, CDCl3): d=102.6, 52.2, 39.8, 33.6, 33.4, 26.4,
26.1ppm; HRMS (70 eV, EI): calcd for C 10H20O2 ([M]+): 172.1463; found
172.1467; elemental analysis calcd (%) for C10H20O2: C 69.72, H 11.70;
found: C 69.79, H 11.56.
1,1-Dimethoxy-2-methyl-2-phenylpropane (4 f): Colorless oil. Rf =0.34
1
(hexane/ethyl acetate, 20:1); H NMR (300 MHz, CDCl3): d=7.50 (d, J=
exo-Bicyclo[4.1.0]heptane-7-carbaldehyde (1e): Colorless oil. Rf =0.30
1
8.0 Hz, 2H; ArH), 7.37 (t, J=8.0 Hz, 2H; ArH), 7.27 (m, 1H; ArH),
(hexane/ethyl acetate, 10:1); H NMR (200 MHz, CDCl3): d=8.99 (d, J=
Chem. Eur. J. 2005, 11, 5938 – 5944
ꢀ 2005 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.chemeurj.org
5943

F. J. FaÇanµs et al.
5.5 Hz, 1H; HC =O), 2.10–0.80 (m, 11H; bicyclic moiety) ppm;
13C NMR (50 MHz, CDCl3): d=201.4, 36.4, 22.4, 22.1, 20.7 ppm; HRMS
(70 eV, EI): calcd for C8H12O ([M]+): 124.0888; found 124.0892; elemen-
tal analysis calcd (%) for C8H12O: C 77.38, H 9.74; found: C 77.49, H
9.60.
3853), and the Ministerio de Educación y Cultura, Spain (grant to M.A.-
P.). F.R. is grateful for funding from the MCYT (Programa Ramón y
Cajal).
(Dimethoxymethyl)cyclopentane (4m): Colorless oil. Rf =0.25 (hexane/
ethyl acetate, 20:1); 1H NMR (300 MHz, CDCl3): d=4.10 (d, J=7.7 Hz,
1H; CH(OMe)2), 3.33 (s, 6H; 2”OMe), 2.20 (sextet, J=7.7 Hz, 1H;
CHCH(OMe)2), 2.00–1.10 (m, 8H; rest of the ring) ppm; 13C NMR
(75 MHz, CDCl3): d=108.2, 52.8, 41.6, 28.1, 25.6 ppm; HRMS (70 eV,
EI): calcd for C7H13O ([MÀ31]+): 113.0966; found 113.0968; elemental
analysis calcd (%) for C8H16O2: C 66.63, H 11.18; found: C 66.77, H
11.01
[1] Comprehensive Organic Synthesis, Vol. 3 (Eds.: B. M. Trost, I. Flem-
ing, G. Pattenden), Pergamon, Oxford (UK), 1991.
[2] L. F. Silva, Jr., Tetrahedron 2002, 58, 9137, and references therein.
[3] For some recent and representative examples, see: a) S. F. Oliver, K.
Hçgenauer, O. Simic, A. Antonello, M. D. Martin, S. V. Ley, Angew.
Chem. 2003, 115, 6178; Angew. Chem. Int. Ed. 2003, 42, 5996;
b) L. E. Overman, L. D. Pennington, J. Org. Chem. 2003, 68, 7143;
c) H. Wang, A. Ganesan, J. Org. Chem. 2000, 65, 4685.
1-(Dimethoxymethyl)indane (4n): Colorless oil. Rf =0.31(hexane/ethyl
acetate, 20:1); 1H NMR (300 MHz, CDCl3): d=7.50 (dd, J=5.6, 3.0 Hz,
1H; HC=C), 7.36–7.15 (m, 3H; ArH), 4.40 (d, J=7.4 Hz, 1H; CH-
(OMe)2), 3.60–3.40 (m, 1H; CHCH(OMe)2), 3.50 (s, 3H; OMe), 3.44 (s,
3H; OMe), 3.10–2.85 (m, 2H; CCH2), 2.25 (dtd, J=13.1, 8.3, 5.3 Hz, 1H;
CCH2CHH), 2.03 (ddt, J=13.1, 8.8, 7.1 Hz, 1H; CCH2CHH) ppm;
13C NMR (75 MHz, CDCl3): d=144.6, 142.7, 126.7, 126.0, 125.4, 124.2,
107.0, 54.0, 52.7, 47.3, 31.2, 27.2 ppm; HRMS (70 eV, EI): calcd for
C12H16O2 ([M]+): 192.1150; found 192.1156; elemental analysis calcd (%)
for C12H16O2: C 74.97, H 8.39; found: C 74.92, H 8.50
[4] Although oxidative rearrangement reactions of olefins have been
performed with complexes of lead(iv) or selenium(iv), the most
widely used reagents are undoubtedly thallium(iii) salts. For some
examples, see: a) H. M. C. Ferraz, L. F. Silva, Tetrahedron 2001, 57,
9939; b) H. M. C. Ferraz, L. F. Silva, T. O. Vieira, Tetrahedron 2001,
57, 1709; c) E. C. Taylor, A. McKillop, J. D. Hunt, F. Kienzle, E.
Bigham, J. Am. Chem. Soc. 1973, 95, 3635; d) J. Halpern, P. Abley,
J. E. Byrd, J. Am. Chem. Soc. 1973, 95, 2591.
[5] Representative examples of rearrangement reactions of 1,2-difunc-
tionalized compounds are the pinacol, semipinacol, benzilic acid, Fa-
vorskii, and Wolff rearrangement reactions. See ref. [1].
[6] IPy2BF4 is commercially available from either Novabiochem or Al-
drich.
[7] For some recent applications of this reagent, see: a) J. Barluenga,
M. Trincado, E. Rubio, J. M. Gonzµlez, Angew. Chem. 2003, 115,
2508; Angew. Chem. Int. Ed. 2003, 42, 2406; b) J. Barluenga, H.
Vµzquez-Villa, A. Ballesteros, J. M. Gonzµlez, J. Am. Chem. Soc.
2003, 125, 9028; c) J. Barluenga, F. Gonzµlez-Bobes, S. R. Anantho-
ju, M. A. García-Martín, J. M. Gonzµlez, Angew. Chem. 2001, 113,
3491; Angew. Chem. Int. Ed. 2001, 40, 3389. d) For a brief overall
review of early applications, see: J. Barluenga, Pure Appl. Chem.
1999, 71, 431.
[8] When the amount of IPy2BF4 and/or acid was reduced, slightly
lower yields of compounds 1a or 4a were obtained. For example,
when one equivalent of IPy2BF4 and one equivalent of BF3·OEt2
were used, compound 1a was isolated in 53% yield (65% conver-
sion). Under these conditions compound 4a was obtained in 65%
yield (72% conversion).
(Dimethoxymethyl)cyclohexane (4o): Colorless oil. Rf =0.35 (hexane/
ethyl acetate, 20:1); 1H NMR (200 MHz, CDCl3): d=3.97 (d, J=7.0 Hz,
1H; CH(OMe)2), 3.32 (s, 6H; 2”OMe), 1.85–1.50 (m, 6H; aliphatic
ring), 1.34–0.80 (m, 5H; aliphatic ring) ppm; 13C NMR (75 MHz, CDCl3):
d=108.4, 53.4, 39.9, 27.9, 26.3, 25.6 ppm; HRMS (70 eV, EI): calcd for
C9H18O2 ([M]+): 158.1307; found 158.1313; elemental analysis calcd (%)
for C9H18O2: C 68.31, H 11.47; found: C 68.45, H 11.56.
(1R*,2R*)-1-(Dimethoxymethyl)-2-methoxycyclopentane (4p): Colorless
oil. Rf =0.16 (hexane/ethyl acetate, 10:1); 1H NMR (200 MHz, CDCl3):
d=4.14 (d, J=7.0 Hz, 1H; CH(OMe)2), 3.70–3.55 (m, 1H; MeOCH),
3.37, 3.33, 3.29 (3s, 9H; 3xOMe), 2.30–2.10 (m, 1H; CHCH(OMe)2),
1.90–1.30 (m, 6H; rest of the ring) ppm; 13C NMR (75 MHz, CDCl3): d=
106.3, 84.3, 56.5, 53.9, 53.1, 48.1, 31.8, 26.2, 23.5 ppm; HRMS (70 eV, EI):
calcd for C9H18O3 ([M]+): 174.1256; found 174.1259; elemental analysis
calcd (%) for C9H18O3: C 62.04, H 10.41; found: C 62.15, H 10.30.
(1S*,2R*)-1-(Dimethoxymethyl)-2-methoxycyclopentane (4q): Colorless
oil. Rf =0.22 (hexane/ethyl acetate, 10:1); 1H NMR (300 MHz, CDCl3):
d=4.46 (d, J=8.5 Hz, 1H; CH(OMe)2), 3.69 (t, J=3.1Hz, 1H;
MeOCH), 3.39, 3.31, 3.25 (3s, 9H; 3xOMe), 2.10–1.97 (m, 1H; CHCH-
(OMe)2), 1.94–1.42 (m, 6H; rest of the ring) ppm; 13C NMR (75 MHz,
CDCl3): d=105.2, 82.9, 56.3, 54.1, 52.6, 47.8, 30.0, 25.0, 21.7 ppm; HRMS
(70 eV, EI): calcd for C9H18O3 ([M]+): 174.1256; found 174.1254; elemen-
tal analysis calcd (%) for C9H18O3: C 62.04, H 10.41; found: C 62.17, H
10.55.
[9] In the absence of water the reaction did not proceed and the start-
ing material was recovered unchanged. The solvent (CH2Cl2) and
the BF3·OEt2 were dried before use. When commercial BF3·OEt2
was used without any previous drying treatment, 72% of aldehyde
1a was isolated. In this case the water is thought to come from the
commercial BF3·OEt2.
[10] BF3·OEt2 was dried following reported methods and stored under
nitrogen: D. D. Perrin, W. L. F. Armarego, Purification of Laborato-
ryChemicals , Pergamon Press, Oxford, 1988.
[11] The color of the solution turns violet indicating the formation of
molecular iodine during the reaction.
[12] a) J. Barluenga, M. Alvarez-PØrez, F. Rodríguez, F. J. FaÇanµs, J. A.
Cuesta, S. García-Granda, J. Org. Chem. 2003, 68, 6583; b) J. Bar-
luenga, F. Rodríguez, J. Vadecard, M. Bendix, F. J. FaÇanµs, F.
López-Ortiz, M. A. Rodríguez, J. Am. Chem. Soc. 1999, 121, 8776.
[13] These functionalized terpene derivatives could find application as
chiral ligands in organometallic chemistry. For recent, related work,
see: J. M. Gardiner, P. D. Crewe, G. E. Smith, K. T. Veal, Chem.
Commun. 2003, 618.
General procedure for the rearrangement reaction of olefins 2 to give
acetals 4 or aldehyde 1e: A solution of IPy2BF4 (1.23 g, 3.3 mmol) in dry
CH2Cl2 (16 mL) was prepared under nitrogen and then treated with dry
BF3·OEt2 (0.46 mL, 3.7 mmol) and methanol (0.21mL, 5 mmol) at room
temperature. The corresponding olefin 2 (1.0 mmol) was then slowly
added, the red color of the mixture turning violet. The reaction was
monitored by TLC and quenched after 1h by addition of a 5% solution
of Na2S2O3·5H2O (10 mL). Extraction with CH2Cl2 (2”10 mL) was per-
formed immediately and the combined organic layers washed with water
(2”10 mL) and dried with anhydrous sodium sulfate. The solvents were
removed carefully and the residue was purified by flash chromatography
(SiO2, hexane/diethyl ether, 40:1) to obtain pure acetals 4 or aldehyde
1e.
[14] Starting from eight-membered carbocycles, the reaction led to the
formal substitution of the iodine atom by a methoxy group to give
the corresponding 1,2-dimethoxy derivative.
[15] J. Barluenga, J. M. Gonzµlez, P. J. Campos, G. Asensio, Angew.
Chem. 1985, 97, 341; Angew. Chem. Int. Ed. Engl. 1985, 24, 319; see
also ref [7d] and references therein.
Acknowledgment
Financial support for this work was provided by the Dirección General
de Investigación Científica y TØcnica (DGICYT), Spain (BQU-2001-
Received: January 20, 2005
Published online: June 23, 2005
5944
www.chemeurj.org
ꢀ 2005 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Chem. Eur. J. 2005, 11, 5938 – 5944