Bis(pyridine)iodonium tetrafluoroborate (IPy2BF4): A versatile oxidizing reagent

Article abstract of DOI:10.1002/chem.200400136

The use of bis(pyridine)iodonium tetrafluoroborate (IPy₂BF ₄) as an oxidizing agent towards different types of alcohols is reported. The observed reactivity involves different reaction pathways, as a function both of the structures of the starting materials and of the experimental conditions. Interestingly, the title iodine-containing compound is capable of a tuneable reaction with simple cycloalkanols, providing straight and selective access either to ω-iodocarbonyl compounds or to ketones, a previously unreported and chemoselective range of oxidation potential. Furthermore, appropriate conditions for the preparation of aldehydes and esters from primary alcohols by easily performed experimental procedures were also established. The β-scission reactions of cycloalkanols and the α-oxidation processes of primary, secondary and benzylic alcohols are discussed.

Full text of DOI:10.1002/chem.200400136

FULL PAPER
Bis(pyridine)iodonium Tetrafluoroborate (IPy2BF4): A Versatile Oxidizing
Reagent
Josÿ Barluenga,* Francisco Gonzµlez-Bobes, Marcelo C. MurguÌa,
Sreenivasa R. Ananthoju, and Josÿ M. Gonzµlez[a]
Abstract: The use of bis(pyridine)iodo-
nium tetrafluoroborate (IPy2BF4) as an
oxidizingagent towards different types
of alcohols is reported. The observed
reactivity involves different reaction
pathways, as a function both of the
structures of the startingmaterials and
of the experimental conditions. Inter-
estingly, the title iodine-containing
compound is capable of a tuneable re-
action with simple cycloalkanols, pro-
vidingstrahigt and selective access
either to w-iodocarbonyl compounds or
to ketones, a previously unreported
and chemoselective range of oxidation
potential. Furthermore, appropriate
conditions for the preparation of alde-
hydes and esters from primary alcohols
by easily performed experimental pro-
cedures were also established. The b-
scission reactions of cycloalkanols and
the a-oxidation processes of primary,
secondary and benzylic alcohols are
discussed.
Keywords: aldehydes ¥ cleavage re-
actions ¥ esters ¥ ketones ¥ oxidation
Introduction
chemical or thermal conditions, leadingto b-scission reac-
tions of cycloalkanols,[12] and oxidation processes of alcohols
and diols (Scheme 1).
The development of new approaches to oxidation reactions
of alcohols has become a central area of research in chemis-
try. In this field, the use of iodine(v) derivatives such as
Dess Martin reagent (DMP)[1] or o-iodoxybenzoic acid
(IBX)[2] is a testament to this valuable transformation. How-
ever, the atmospheric instability of some of these iodine(v)
compounds[3] and the potential explosiveness of others,[4]
have driven the search for new competitive alternatives. Poly-
mer-bonded reagents,[5] water-soluble derivatives,[6] and the
use of iodine(iii)[7] and iodine(i)[8] compounds are amongst
the agents that have focused interest in this field in stoichio-
metric approaches.[9]
Recently, the synthetic dominance of reagents such as
DMP and IBX has been further highlighted by their capabil-
ity to effect new chemoselective synthetic chemical transfor-
mations.[10]
Scheme 1. IPy2BF4 as an oxidizingreagent.
We report here on the use of bis(pyridine)iodonium tetra-
fluoroborate (IPy2BF4)[11] as a reagent for the execution of
interestingoxidation chemistry of alcohols under photo-
Results and Discussion
Our initial studies on the interaction of IPy2BF4 with alco-
hols resulted in general and previously unreported b-scission
processes of secondary and tertiary cycloalkanols, which
gave rise to w-iodofunctionalized systems.[12,13] The main fea-
tures of this novel procedure are briefly summarized in
Table 1.
The reactions were conducted at room temperature and
took place under photochemical conditions (irradiation with
a 100 W lamp). The corresponding w-iodinated derivative
was obtained as the major or even as the single reaction
[a] Prof. Dr. J. Barluenga, F. Gonzµlez-Bobes, Dr. M. C. MurguÌa,
Dr. S. R. Ananthoju, Dr. J. M. Gonzµlez
Instituto Universitario de QuÌmica Organometµlica ™Enrique Moles∫
Unidad Asociada al C.S.I.C., Universidad de Oviedo
C/Juliµn ClaverÌa, 8, 33006 Oviedo (Spain)
Fax : (+34)98-510-3450
E-mail: barluenga@uniovi.es
Supportinginformation for this article is available on the WWW
under http://www.chemeurj.org/ or from the author.
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DOI: 10.1002/chem.200400136
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J. Barluenga et al.
FULL PAPER
product from the transformation of the startingalcohol 1.[14]
The reaction takes place with secondary and tertiary cycloal-
kanols of different sizes (Table 1). The tools employed to
control the outcome of the reported transformation are the
reaction time, the concentration of the reagents and the use
of a heterogeneous base (Cs2CO3).[15] This b-scission process
is regioselective: as a rule, the more highly substituted car-
bon carbon bond adjacent to the alcohol functionality un-
dergoes this oxidative cleavage process (see Table 1).
process.[17] Interestingly, the addition even of sub-stoichio-
metric amounts of iodine has been found to be appropriate
to achievingthis goal (Scheme 2).
The reactivity of 1,2-diols under those experimental con-
ditions was also tested. In this case, a,w-dialdehydes are
generated as the sole reaction product (Table 2).[16]
Scheme 2. Initial observation of a-oxidation of alcohols promoted by
IPy2BF4-I2. Reaction conditions: IPy2BF4 (2.5 equiv), I2 (0.4 equiv), 12 h.
As can be observed, the outcome of the reaction does not
depend on the stereochemistry of the startingsubstrate, and
the process can be executed in a satisfactory manner with
diols of different sizes, providingthe correspondingalde-
hydes in high purity after a simple extraction (Table 2).
Exploratory studies to improve this reaction sequence
were conducted with the use of 2-octanol (1r) as model
compound. Thermal rather than photochemical conditions
were found more efficient to accomplish this alternative oxi-
dation mode. Furthermore, careful optimization of the stoi-
chiometry, the selection of an appropriate solvent and the
presence of a base were required to carry out the desired
oxidation reaction (Table 3).
Table 2. Synthesis of a,w-dialdehydes 2 from cyclic diols 1.[a]
The combination of IPy2BF4 and I2 under thermal condi-
tions affords the correspondingketones in rather good iso-
lated yields and in reasonable reaction times (Table 3).
Benzyl alcohol derivatives also reacted well with this com-
bination of reagents. In this case, addition of potassium car-
bonate (K2CO3) gave better experimental results than the
correspondingcesium salt, so it was routinely employed
(Table 4).
The described conditions allow for the satisfactory oxida-
tion of several benzylic alcohols bearingdifferent substitu-
ents (entries 4 8, Table 4). The correspondingcarbonyl com-
pounds were obtained as single reaction products. Even
benzyl alcohol (4b) was cleanly oxidized to afford benzalde-
hyde (5b) without any noticeable evidence of over-oxida-
tion[2a] takingplace (entry 2, Table 4).
Primary alkanols react under these conditions to afford
either aldehydes or esters. Interestingly, a simple modifica-
tion of the experimental conditions can be nicely used to
drive the formation of the observed products selectively
(Table 5).
As shown, the concentration of the reagents, the reaction
temperature, the addition of an inorganic base[18] and the
presence of different additives[19,20] were optimized to direct
this unconventional reaction range,[21] to produce both fami-
lies of oxidation products exclusively (Table 5).
Entry
Substrate
Time
[h]
Product
Yield
[%][b]
1
2
1
2
24
24
18
63
66
77
3
4
18
12
12
79
91
92
5
6
In terms of reaction mechanism, the different oxidation
processes could be interpreted as involvingthe generation
of several intermediate species in a sequential manner
(Scheme 3).
[a] Two equivalents of IPy2BF4 and a 0.04m concentration of the corre-
spondingdiol were employed. [b] Isolated yield based on startingdiols.
The reported yields have not been optimized.
A reasonable proposal could invoke the initial formation
of the oxonium ion (A), resultingfrom interaction between
the alkanol and IPy2BF4.[22] Subsequent deprotonation in the
presence of the base affords the iodane (B).[23] Different
pathways might be operative as a function of the experimen-
tal conditions, accountingfor the different observed reaction
products. Thus, homolytic decomposition of B under photo-
chemical conditions would form the alkoxyl radical (C),[24]
which could undergo the well established b-scission pro-
cess,[13] affordingthe carbon-centered radical ( D). The reac-
When the b-scission reaction of cyclohexanol (1c) was
studied, the formation of small amounts of cyclohexanone
(3c) as a function of the experimental conditions was noted.
This initial observation prompted us to explore the oxidizing
capability of IPy2BF4 further, in search of a suitable reaction
medium that would allow selective preparation of the car-
bonyl product resultingfrom an alternative a-oxidation
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Bis(pyridine)iodonium Tetrafluoroborate
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Table 3. Oxidation of secondary alcohols 1 to ketones 3 with IPy2BF4-I2.[a]
would furnish the resultingke-
tones and regenerate iodine in
the
reaction
medium
(Scheme 3).[27]
Entry
Substrate
Time
[h]
Product
Yield
[%][b]
The observed formation of
esters with the oxidation of pri-
mary alcohols could be ex-
plained by assuminga prior
generation of an aldehyde (F),
in agreement with the sequence
discussed above. The evolution
of F through the hemiketal-like
intermediate (G) and its even-
tual oxidation would furnish
esters (Scheme 4).[28]
1
2
1
2
2
6
92
87
3
4
3
4
91
98
Conclusion
It has been demonstrated that
IPy2BF4 is able to promote dif-
ferent oxidation processes of al-
cohols in a clean and satisfacto-
ry manner, just by appropriate
choice of reaction conditions.
All materials employed in
these transformations are com-
mercially available and easy to
handle and store. In addition,
simple variations in the experi-
mental procedure allow for the
selective preparation of differ-
ent families of carbonyl deriva-
5
6
7
7
92
92
[a] Reactions were performed with the followingstoichiometry: IPy 2BF4 (3 equiv), I2 (0.5 equiv) and Cs2CO3
(5 equiv). A 0.06m concentration of The relevant alcohol (1 equiv) was employed. [b] Yield of isolated product
relative to the startingalkanol 1.
tion of D and the previously formed bis(pyridine)iodanyl
radical would lead to the bifunctional derivative
(Scheme 3).[12]
Conversely, an oxidative ligand-exchange reaction with
molecular iodine might drive the conversion of B into the
bis(iodo)alkoxy-l3-iodane E.[25] Lastly, a hydrogen elimina-
Scheme 4. Mechanistic proposal for the formation of esters from primary
alkanols.
tion reaction, common in the chemistry of these species,[26]
Scheme 3. Proposed reaction pathways.
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J. Barluenga et al.
FULL PAPER
Table 4. Oxidation of benzylic alcohols 4 with IPy2BF4-I2.[a]
ments with tetramethylsilane (1H NMR) or CDCl3 (13C NMR) as internal
standards. Carbon multiplicities were assigned by DEPT techniques.
High-resolution mass spectra (HRMS) were determined on a Finnigan
MATT 95 spectrometer. Elemental analyses were carried out on
a
Perkin Elmer 2400 microanalyzer. Meltingpoints were determined on a
B¸chi Tottoli machine and have not been corrected. Optical rotation was
measured on a Perkin Elmer 241 polarimeter.
Entry
1
Substrate 4
Time
[h]
Product 5
Yield
[%][b]
General procedure for the preparation of 2a, 2b, and 2k (Table 1): The
relevant alcohol (2 mmol, 1 equiv) was added to a solution of IPy2BF4
(2.5 mmol, 1.25 equiv, 0.93 g) in CH2Cl2 (20 mL), and the mixture was ir-
radiated for 12 hours. Na2S2O3 (5% solution in water, 40 mL) was added,
and the mixture was extracted with CH2Cl2 (4î20 mL). The organic
layer was washed with H2SO4 (1m, 2î50 mL) and water (2î50 mL) and
dried (Na2SO4). Evaporation of the solvents afforded the w-iodoalde-
hydes essentially pure.
4-Iodobutanal (2a): yellow oil. Rf = 0.55 (hexane/ethyl acetate 3:1); 1H
NMR (300 MHz, CDCl3): d = 9.81 (t, J = 1.2 Hz, 1H), 3.23 (t, J =
6.5 Hz, 2H), 2.60 (td, J = 6.9, 1.2 Hz, 2H), 2.15 (m, 2H) ppm; 13C NMR
14
14
86
88
2
3
14
3
80
94
91
(75 MHz, CDCl3):
d = 200.5 (CH), 44.1 (CH2), 25.3 (CH2), 5.6
(CH2) ppm; IR (neat): n˜ = 1722 cmÀ1; elemental analysis calcd (%) for
C4H7IO: C 24.26, H 3.56; found: C 24.42, H 3.57.
1
5-Iodopentanal (2b): yellow oil. Rf = 0.58 (hexane/ethyl acetate 3:1); H
NMR (300 MHz, CDCl3): d = 9.67 (t, J = 1.4 Hz, 1H), 3.11 (t, J =
6.5 Hz, 2H), 2.60 (td, J = 7.1, 1.4 Hz, 2H), 1.75 1.60 (m, 4H) ppm; 13C
NMR (75 MHz, CDCl3): d = 201.5 (CH), 42.2 (CH2), 32.2 (CH2), 22.5
4
5
(CH2), 6.1 (CH2) ppm; IR (neat): n˜
=
1724 cmÀ1; elemental analysis
calcd (%) for C5H9IO: C 28.32, H 4.27; found: C 28.18, H 4.13.
5-Iodohexanal (2k): yellow oil. Rf = 0.40 (hexane/ethyl acetate 4:1); 1H
NMR (300 MHz, CDCl3): d = 9.71 (t, J = 1.5 Hz, 1H), 4.13 (m, 1H),
2.46 (dt, J = 6.6, 1.5 Hz, 2H), 1.87 (d, J = 6.9 Hz, 3H), 1.76 (m, 2H),
1.65 (m, 2H) ppm; 13C NMR (75 MHz, CDCl3): d = 201.6 (CH), 42.5
(CH2), 41.6 (CH2), 29.2 (CH), 28.5 (CH3), 22.0 (CH2) ppm; IR (neat): n˜
= 1723 cmÀ1; HRMS: calcd for C6H11O [MÀI]+: 99.0809; found 99.0804.
General procedure for the preparation of 2c, 2d, and 2n (Table 1):
Cs2CO3 (10 mmol, 10 equiv, 3.25 g) was added to a solution containing
IPy2BF4 (2.5 mmol, 2.5 equiv, 0.93 g) and the alkanol (1 mmol, 1 equiv) in
CH2Cl2 (50 mL). The resulting heterogeneous mixture was vigorously
stirred and irradiated (100 W) for the time indicated in Table 1. The reac-
tion mixture was cooled in an ice-water bath, hydrolysed with H2SO4
(1m, 50 mL) and allowed to warm to room temperature. The mixture was
extracted with CH2Cl2 (4î20 mL), and the combined organic layers were
washed with Na2S2O3 (5% solution in water, 2î50 mL) and water (2î
50 mL) and dried (Na2SO4). Evaporation of the solvent and column chro-
matography (hexane/ethyl acetate) gives pure samples of the bifunctional
compounds.
3
6
7
8
36
21
24
73
85
64
6-Iodohexanal (2c): yellow oil. Rf
= 0.63 (hexane/ethyl acetate 3:1);
1
chromatography: hexane/ethyl acetate 15:1; H NMR (300 MHz, CDCl3):
d = 9.73 (t, J = 1.4 Hz, 1H), 3.12 (t, J = 6.8 Hz, 2H), 2.43 (td, J = 7.3,
1.4 Hz, 2H), 1.81 (m, 2H), 1.62 (m, 2H), 1.42 (2H) ppm; 13C NMR
(75 MHz, CDCl3): d = 202.0 (CH), 43.3 (CH2), 32.9 (CH2), 29.7 (CH2),
20.7 (CH2), 6.4 (CH2) ppm; IR (neat): n˜ = 1724 cmÀ1; HRMS: calcd for
C6H11O [MÀI]+: 99.0809; found 99.0806.
[a] Reactions were performed with the followingstoichiometry: IPy 2BF4
(3 equiv), I2 (0.5 equiv) and K2CO3 (2.5 equiv). A 0.06m concentration of
The relevant alcohol (1 equiv) was employed. [b] Yield of isolated prod-
uct relative to the startingalkanol 4.
12-Iodododecanal (2d): yellow oil. Rf = 0.85 (CH2Cl2); chromatography:
hexane/CH2Cl2 1:1; 1H NMR (300 MHz, CDCl3): d
= 9.76 (t, J =
tives in a straightforward manner. Overall, the given trans-
formations constitute a new example of the versatility of
this reagent and expand its application profile.
1.7 Hz, 1H), 3.18 (t, J = 7.1 Hz, 2H), 2.60 (td, J = 7.4, 1.7 Hz, 2H), 1.81
(c, J = 6.8 Hz, 2H), 1.63 (m, 2H), 1.27 (14H) ppm; 13C NMR (75 MHz,
CDCl3): d = 202.8 (CH), 43.8 (CH2), 33.4 (CH2), 30.4 (CH2), 29.3 (CH2 î
3), 29.2 (CH2), 29.0 (CH2), 28.4 (CH2), 21.9 (CH2), 7.2 (CH2) ppm; IR
(neat): n˜
found 183.1749.
=
1725 cmÀ1; HRMS: calcd for C12H23O [MÀI]+: 183.1748;
Experimental Section
(3R)-3,7-Dimethyl-6-iodooctanal (2n): yellow oil. Rf
= 0.22 (hexane/
CH2Cl2 3:1); chromatography: hexane/CH2Cl2, 3:1; 1H NMR (300 MHz,
CDCl3) for the mixture of epimers: d = 9.75 (s, 2H), 4.1 4.06 (m, 2H),
2.44 2.12 (m, 4H), 2.10 1.83 (m, 4H), 1.74 0.98 (m, 8H), 0.97 0.89 (m,
18H) ppm; 13C NMR (75 MHz, CDCl3) for the mixture of epimers: d =
202.3 (CH), 51.7 (CH), 51.6 (CH), 51.0 (CH2), 50.5 (CH2), 36.8 (CH2 î2),
35.9 (CH2), 35.7 (CH2), 34.8 (CH), 34.5 (CH), 27.5 (CH), 27.2 (CH), 23.0
(CH3), 20.0 (CH3), 19.8 (CH3), 19.7 (CH3), 19.5 (CH3) ppm; IR (neat): n˜
= 1724 cmÀ1; elemental analysis calcd (%) for C10H19IO: C 42.57, H 6.79;
found: C 42.71, H 6.75.
General: All reactions were carried out under positive nitrogen atmos-
phere. CH2Cl2 and CH3CN were distilled from CaH2 and stored under ni-
trogen. Analytical thin-layer chromatography plates were Merck UV-
active silica gel 60 F254 on aluminium. Flash column chromatography was
carried out on silica gel 60, 230 240 mesh, with appropriate mixtures of
1
hexane and ethyl acetate or methylene chloride as eluent. H NMR (200,
300, 400 MHz) and 13C NMR (50, 75, 100 MHz) spectra were measured
at room temperature on Bruker AC 200, AC 300 and AMX 400 instru-
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Bis(pyridine)iodonium Tetrafluoroborate
4206 4213
Table 5. Oxidation of primary alcohols 6 with IPy2BF4-I2.
13-Iodotridecan-2-one (2i): yellow oil.
Rf = 0.53 (hexane/ethyl acetate 3:1);
chromatography: hexane/ethyl acetate
1
10:1; H NMR (200 MHz, CDCl3): d =
3.16 (t, J = 7.0 Hz, 2H), 2.39 (t, J =
7.4 Hz, 2H), 2.1 (s, 3H), 1.81 1.74 (m,
2H), 1.63 1.24 (16H) ppm; 13C NMR
(50 MHz, CDCl3): d = 209 (C), 43.6
(CH2), 33.2 (CH2), 30.3 (CH2), 29.7
(CH3), 29.3 (CH2), 29.2 (CH2 î3), 28.9
(CH2), 28.3 (CH2), 23.6 (CH2), 7.1
Entry
1[d]
Substrate
Conc.
T
t
Product
7 or 8
Yield
[%][c]
6
[m][a] [8C][b] [h]
0.02
0.02
60
60
14
14
83
85
(CH2) ppm; IR (neat): n˜ = 1704 cmÀ1
;
2[d]
elemental analysis calcd (%) for
C13H25IO: C 48.15, H 7.77; found: C
48.22, H 7.50.
3[e]
0.4
0.4
40
40
24
24
90
75
6-Iodoheptanal (2l): yellow oil. Rf
=
0.57 (hexane/ethyl acetate 3:1); chro-
matography: hexane/ethyl acetate
1
4[e]
10:1; H NMR (300 MHz, CDCl3): d =
9.75 (t, J = 1.5 Hz, 1H), 4.12 (m, 1H),
2.42 (td, J = 7.2, 1.5 Hz, 2H), 1.87 (d,
J
=
6.9 Hz, 3H), 1.82 1.29 (m,
6H) ppm; 13C NMR (75 MHz, CDCl3):
202.1 (CH), 43.5 (CH2), 42.3
5[e]
0.4
40
20
70
d
=
(CH2), 29.7 (CH3), 29.1 (CH2), 28.7
(CH), 20.9 (CH2) ppm; IR (neat): n˜ =
[a] Concentration of the alcohol 6. [b] Oil bath temperature. [c] Yield of isolated product relative to the start-
ingalkanol 6. [d] Experiments conducted with the followingstoichiometry: IPy 2BF4 (3 equiv), I2 (4 equiv),
K2CO3 (5 equiv). [e] Experiments conducted with the followingstoichiometry: IPy 2BF4 (3 equiv), I2
(0.5 equiv), K2CO3 (2 equiv), tBuOH (2.5 equiv).
1723 cmÀ1
;
elemental analysis calcd
(%) for C7H13IO: 35.02, 5.45;
found: C 35.11, H 5.38.
C
H
cis-(1R,3S)-3-(3’-Iodobutyl)-2,2-dime-
thylcyclopropanecarbaldehyde (2 m):
General procedure for the preparation of 2e 2i, 2 l, and 2 m (Table 1):
Cs2CO3 (10 mmol, 5 equiv, 3.25 g) was added to a solution containing
IPy2BF4 (2.5 mmol, 1.25 equiv, 0.93 g) and the alkanol (2 mmol, 1 equiv)
in CH2Cl2 (20 mL). In all cases the workup was equivalent to that report-
ed above.
yellow oil. Rf
=
0.65 (hexane/ethyl acetate 3:1); chromatography:
1
hexane/ethyl acetate 10:1; H NMR (400 MHz, CDCl3) for the mixture of
epimers: d = 9.53 (d, J = 5.6 Hz, 1H), 9.50 (d, J = 5.9 Hz, 1H), 4.15
(m, 2H), 2.04 1.50 (m, 10H), 1.90 (d, J = 6.8 Hz, 6H), 1.44 1.23 (m,
2H), 1.33 (d, J = 2.5 Hz, 6H), 1.55 (s, 6H) ppm; 13C NMR (100 MHz,
CDCl3) for the mixture of epimers: d = 201.7 (CH), 42.9 (CH2), 42.6
(CH2), 38.4 (CH), 38.3 (CH), 36.6 (CH), 36.4 (CH), 29.9 (C), 29.8 (C),
29.2 (CH), 29.1 (CH), 28.9 (C), 28.8 (C), 24.7 (CH2), 24.4 (CH2), 15.0
6-Iodohexan-2-one (2e): yellow oil. Rf = 0.42 (hexane/ethyl acetate 3:1);
1
chromatography: hexane/ethyl acetate 10:1; H NMR (300 MHz, CDCl3):
d = 3.07 (t, J = 6.8 Hz, 2H), 2.36 (t, J = 7.2 Hz, 2H), 2.03 (s, 3H), 1.70
(m, 2H), 1.55 (m, 2H) ppm; 13C NMR (75 MHz, CDCl3): d = 207.7 (C),
41.9 (CH2), 32.3 (CH2), 29.6 (CH3), 24.3 (CH2), 5.6 (CH2) ppm; IR
(CH3), 14.9 (CH3) ppm; IR (neat): n˜
= ; HRMS: found:
1693 cmÀ1
280.0326 [M]+; C10H17IO calcd 280.0324.
(neat): n˜
99.0809.
=
1712 cmÀ1; HRMS: found 99.0803 [MÀI]+; C6H11O calcd
Preparation of 2j (Table 1): An equivalent procedure to that above was
followed, but with use of 10 equiv of Cs2CO3.
7-Iodoheptan-2-one (2 f): yellow oil. Rf
=
0.57 (hexane/ethyl acetate
7-Iodomethylbicyclo[3.3.1]nonan-3-one (2j): yellow oil. Rf = 0.35
3:1); chromatography: hexane/ethyl acetate 10:1; 1H NMR (200 MHz,
(hexane/ethyl acetate 3:1); chromatography: hexane/ethyl acetate 10:1;
1
CDCl3): d = 3.12 (t, J = 6.9 Hz, 2H), 2.39 (t, J = 7.2 Hz, 2H), 2.07 (s,
m.p. = 71 738C (decomp); H NMR (200 MHz, CDCl3): d = 2.95 (d, J
3H), 1.76 (q, J
=
6.9 Hz, 2H), 1.50 1.10 (m, 4H) ppm; 13C NMR
= 6.8 Hz, 2H), 2.60 2.34 (m, 4H), 2.29 2.09 (m, 2H), 1.91 1.56 (m, 3H),
(50 MHz, CDCl3): d = 208.3 (C), 43.1 (CH2), 32.9 (CH2), 29.7 (CH3),
29.7 (CH2), 22.3 (CH2), 6.5 (CH2) ppm; IR (neat): n˜ = 1714 cmÀ1; ele-
mental analysis calcd (%) for C7H13IO: C 35.02, H 5.45; found: C 35.17,
H 5.31.
0.87 (m, 2H) ppm; 13C NMR (50 MHz, CDCl3): d
= 212.0 (C), 50.1
(CH2), 34.3 (CH2), 32.0 (CH2), 28.4 (CH), 28.2 (CH2), 14 (CH2) ppm; IR
(KBr): n˜ = 1708 cmÀ1; elemental analysis calcd (%) for C10H15IO: C
43.18, H 5.48; found: C 42.91, H 5.51.
7-Iodo-3-methyloctan-2-one (2 g): yellow oil. Rf
=
0.32 (hexane/ethyl
General procedure for the preparation of 2o 2q (Table 2): The appropri-
ate diol (2 mmol, 1 equiv) was added to a magnetically stirred solution of
IPy2BF4 (2.5 mmol, 1.25 equiv, 0.93 g) in CH2Cl2 (50 mL), and the result-
ingmixture was irradiated for the time indicated in Table 2. Na 2S2O3
(5% solution in water, 40 mL) was added, and the mixture was extracted
with CH2Cl2 (4î20 mL). The organic layer was washed with H2SO4 (1m,
2î50 mL) and water (2î50 mL) and dried (Na2SO4). Evaporation of the
solvents afforded the a,w-dialdehydes in high purity. Analytical samples
were prepared by column chromatography (hexane/ethyl acetate).
acetate 20:1); chromatography: hexane/ethyl acetate 20:1; 1H NMR
(300 MHz, CDCl3) for the mixture of diastereoisomers: d = 4.2 4.07 (m,
2H), 2.49 2.44 (m, 2H), 2.10 (s, 3H), 2.09 (s, 3H), 1.87 (d, J = 6.9 Hz,
3H), 1.85 (d, J = 6.9 Hz, 3H), 1.79 1.25 (m, 12H), 1.05 (d, J = 7.0 Hz,
3H), 1.04 (d, J = 7.0 Hz, 3H) ppm; 13C NMR (75 MHz, CDCl3) for the
mixture of diastereoisomers: d = 212.1 (C), 46.6 (CHî2), 42.5 (CH2),
42.4 (CH2), 31.5 (CH2), 31.3 (CH2), 29.8 (CH), 28.7 (CH3), 27.9 (CH3),
27.2 (CH3), 27.2 (CH2), 27.0 (CH2), 16.1 (CH3), 16.0 (CH3) ppm; IR
(neat): n˜
=
1710 cmÀ1; elemental analysis calcd (%) for C9H17IO: C
General procedure for the preparation of compounds 3 (Table 3): The
relevant alcohol (2 mmol, 1 equiv), I2 (1 mmol, 0.5 equiv, 0.25 g) and
Cs2CO3 (10 mmol, 5 equiv, 3.25 g) were sequentially added to a stirred
solution of IPy2BF4 (6 mmol, 3 equiv, 2.23 g) in CH3CN (30 mL). The het-
erogeneous mixture was heated (608C) for the time specified in Table 3.
The crude reaction mixture was then allowed to cool, filtered through
Celite and washed with CH2Cl2 (25 mL). The filtrate was concentrated
under vacuum, redissolved in CH2Cl2 (25 mL) and stirred with HCl (1n,
25 mL) for 15 min. The reaction mixture was then transferred to a sepa-
ration funnel, and the aqueous layer was further extracted with CH2Cl2
40.31, H 6.39; found: C 40.12, H 6.65.
8-Iodooctan-2-one (2h): yellow oil. Rf = 0.37 (hexane/ethyl acetate 5:1);
1
chromatography: hexane/ethyl acetate 10:1; H NMR (300 MHz, CDCl3):
d = 3.18 (t, J = 6.9 Hz, 2H), 2.43 (t, J = 7.4 Hz, 2H), 2.14 (s, 3H), 1.81
(q, J = 6.9 Hz, 2H), 1.57 (q, J = 7.4 Hz, 2H), 1.45 1.24 (m, 4H) ppm;
13C NMR (75 MHz, CDCl3): d = 208.5 (C), 43.2 (CH2), 32.9 (CH2), 29.9
(CH2), 29.6 (CH3), 27.6 (CH2), 23.1 (CH2), 6.9 (CH2) ppm; IR (neat): n˜
= 1714 cmÀ1; elemental analysis calcd (%) for C8H15IO: C 37.81, H 5.95;
found: C 37.97, H 5.99.
Chem. Eur. J. 2004, 10, 4206 4213
www.chemeurj.org
¹ 2004 Wiley-VCH VerlagGmbH & Co. KGaA, Weinheim
4211

J. Barluenga et al.
FULL PAPER
(5î15 mL). The combined organic phases were sequentially washed with
Na2S2O3 (5% solution in water, 2î50 mL) and H2O (2î50 mL) and
dried (Na2SO4). Pure ketones were isolated after concentration of the
solvent and column chromatography, and displayed data identical with
those of commercial samples.
here. For a general overview, see: a) R. Sheldon, I. W. C. E. Arends,
G.-J. ten Brink, A. Dijksman, Acc. Chem. Res. 2002, 35, 774;
b) R. A. Sheldon, I. W. C. E. Arends, A. Dijksman, Catalysis Today
2000, 57, 157.
[10] For a concise review, see: a) T. Wirth, Angew. Chem. 2001, 113,
2893; Angew. Chem. Int. Ed. 2001, 40, 2812. For some representative
references: b) K. C. Nicolaou, T. Montagnon, P. S. Baran, Y.-L.
Zhong, J. Am. Chem. Soc. 2002, 124, 2245; c) K. C. Nicolaou, T.
Montagnon, P. S. Baran, Angew. Chem. 2002, 114, 1035; Angew.
Chem. Int. Ed. 2002, 41, 993; d) K. C. Nicolaou, P. S. Baran, Y.-L.
Zhong, J. Am. Chem. Soc. 2001, 123, 3183; e) K. C. Nicolaou, P. S.
Baran, Y.-L. Zhong, J. Am. Chem. Soc. 2000, 122, 7596.
[11] For recent applications, see: a) G. EspuÊa, G. Arsequell, G. Valen-
cia, J. Barluenga, J. M. Alvarez-Gutiÿrez, A. Ballesteros, J. M. Gon-
zµlez, Angew. Chem. 2004, 116, 329; Angew. Chem. Int. Ed. 2004, 43,
325; b) J. Barluenga, H. Vµzquez-Villa, A. Ballesteros, J. M. Gon-
zµlez, J. Am. Chem. Soc. 2003, 125, 9028; c) J. Barluenga, M. Trinca-
do, E. Rubio, J. M. Gonzµlez, Angew. Chem. 2003, 115, 2508;
Angew. Chem. Int. Ed. 2003, 42, 2406.
General procedure for the preparation of 5a 5h (Table 4): The proce-
dure was totally equivalent to that described above, except for the use of
K2CO3 (5 mmol, 2.5 equiv, 0.7 g) instead of Cs2CO3.
General procedure for the preparation of 7a 7b (Table 5): The relevant
alcohol (1 mmol, 1 equiv), I2 (4 mmol, 4 equiv, 1 g), MS (4 ä, 4 g), and
K2CO3 (10 mmol, 5 equiv, 0.7 g) were sequentially added to a stirred solu-
tion of IPy2BF4 (3 mmol, 3 equiv, 1.1 g) in CH3CN (50 mL). The hetero-
geneous mixture was heated (608C) for 16 h. The crude reaction mixture
was then allowed to cool, filtered through Celite and washed with
CH2Cl2 (12 mL). The filtrate was concentrated under vacuum, redissolved
in CH2Cl2 (12 mL) and stirred with HCl (1n, 12 mL) for 15 min. The re-
action mixture was then transferred to a separatingfunnel, and the aque-
ous layer was further extracted with CH2Cl2 (5î15 mL). The combined
organic phases were sequentially washed with Na2S2O3 (5% solution in
water, 2î50 mL) and H2O (2î50 mL) and dried (Na2SO4). Removal of
the solvent under vacuum and column chromatography (hexane/ethyl
acetate) gave pure aldehydes.
[12] For an initial communication, see: J. Barluenga, F. Gonzµlez-Bobes,
S. R. Ananthoju, M. A. GarcÌa-MartÌn, J. M. Gonzµlez, Angew.
Chem. 2001, 113, 3491; Angew. Chem. Int. Ed. 2001, 40, 3389.
[13] For a recent review focused on b-scission reactions, see: E. Suµrez,
M. S. RodrÌguez in Radicals in Organic Chemistry, (Eds.: P. Renaud,
M. P. Sibi), Wiley-VCH, Weinheim, 2001, pp. 440 454.
General procedure for the preparation of 8a 8c (Table 5): IPy2BF4
(6 mmol, 3 equiv, 2.23 g) was dissolved in CH3CN (5 mL) at 408C. The al-
cohol (2 mmol, 1 equiv), tBuOH (5 mmol, 2.5 equiv, 0.5 mL), I2 (1 mmol,
0.5 equiv, 0.25 g), MS (4 ä, 1 g), and K2CO3 (4 mmol, 2 equiv, 0.56 g)
were added sequentially. The mixture was heated at 408C for the time in-
dicated in Table 5. Workup was equivalent to that described for the prep-
aration of 7a and 7b. The esters were isolated by column chromatogra-
phy (hexane/ethyl acetate).
[14] All compounds give NMR and analytical data in accordance with
the proposed structures.
[15] The effect of Cs2CO3 has been discussed previously and seems to be
related to the deprotonation reaction of one of the plausible inter-
mediates. This deprotonation would be crucial when the b-scission
process was not a particularly favoured reaction. See reference [12].
[16] The cleavage of vicinal diols to produce a,w-dialdehydes is a widely
employed transformation. For a general overview, see: T. K. M.
Shingin Comprehensive Organic Synthesis, Vol. 7 (Eds.: B. M. Trost,
I. Fleming, S. V. Ley), Pergamon Press, Oxford, 1991, pp. 703 717.
[17] For a related a-oxidation employingbromine( i) salts, see: a) G.
Rousseau, S. Robin, Tetrahedron Lett. 2000, 41, 8881; b) L. K. Blair,
S. Hobbs, N. Bagnoli, L. Husband, N. Badika, J. Org. Chem. 1992,
57, 1600.
Acknowledgement
This research was partially supported by the Principado de Asturias (PR-
01-GE-9) and the Spanish DGI (MCT-01-BQU-3853). Generous support
from Merck, Sharp & Dohme is also gratefully acknowledged. F.G.-B.
thanks the Principado de Asturias for a predoctoral fellowship and M. C.
M. thanks CONICET for financial support. The authors are grateful to
the referees for the useful comments and suggestions.
[18] K2CO3 was found to be uniquely effective for this oxidation process.
Cs2CO3, KHCO3, Na2CO3, Li2CO3, Mg(CO3)¥4Mg(OH)2¥5H2O,
Al2O3 and MgO were also tested, affording worse results in all
cases.
[19] In the absence of molecular sieves (MS 4 ä), small amounts (5
10%) of the correspondingacids were detected in the crude reac-
tion mixtures.
[20] In the absence of tBuOH the desired esters were obtained in lower
yields.
[21] Esters are commonly observed as by-products in the oxidation of
primary alcohols, although their selective preparation in this kind of
homo-couplingprocess has rarely been reported and is normally re-
stricted to intramolecular reactions. For leadingreferences see: H.
Tohma, T. Maegawa, Y. Kita, Synlett 2003, 723; b) T. Suzuki, K.
Morita, Y. Matsuo, K. Hiroi, Tetrahedron Lett. 2003, 44, 2003; c) T.
Suzuki, K. Morita, M. Tsuchida, K. Hiroi, Org. Lett. 2002, 4, 2361;
d) S. Kajigaeshi, T. Nakagawa, N. Nagasaki, H. Yamasaki, S. Fujisa-
ki, Bull. Chem. Soc. Jpn. 1986, 59, 747; e) S. O. Nwaukwa, P. M.
Keehn, Tetrahedron Lett. 1982, 23, 35; f) L. Farkas, O. Sch‰tater, J.
Am. Chem. Soc. 1949, 71, 2827. See also Ref. [7a].
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[22] This proposal assumes a different initial pathway for the interaction
of the bis(pyridine)iodonium cation with an alcohol than with an
alkene. In the latter case, earlier work on related bromonium re-
agents has nicely shown that one of the pyridine ligands has to dis-
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[9] Alternative catalytic approaches based on the use of metallic com-
pounds together with diverse stoichiometric oxidants are currently
of interest. A detailed discussion of this field cannot be presented
+
sociate off first and that the remainingPyBr species is responsible
for reaction with the alkene; for leadingwork see: a) A. A. Neverov,
H. X. Feng, K. Hamilton, R. S. Brown, J. Org. Chem. 2003, 68, 3802,
and references therein. The differences between alcohols and al-
kenes as nucleophiles and, importantly, the participation of the inor-
ganic base and its likely role of irreversibly removing a proton are
amongthe reasons that may play a key role favouringthe alterna-
tive path postulated here.
4212
¹ 2004 Wiley-VCH VerlagGmbH & Co. KGaA, Weinheim
www.chemeurj.org
Chem. Eur. J. 2004, 10, 4206 4213

Bis(pyridine)iodonium Tetrafluoroborate
4206 4213
[23] The formation of these types of intermediates through the interac-
tion of iodine-containing reagents and hydroxy groups is widely ac-
cepted. For spectroscopic evidence, see: a) J. Madsen, C. Viuf, M.
Bols, Chem. Eur. J. 2000, 6, 1140; b) J. L. Courtneidge, J. Lusztyc, D.
Pagÿ, Tetrahedron Lett. 1994, 35, 1003.
[26] For
a
general overview, see: M. Ochiai in Hypervalent Iodine
Chemistry: Modern Developments in Organic Synthesis, (Ed.: T.
Wirth), Springer, Berlin, 2003, pp. 5 68.
[27] This explains why only sub-stoichiometric amounts of this element
were required to execute some of these transformations.
[28] This kind of mechanism has previously been proposed in related se-
quences: C. McDonald, H. Holdcomb, K. Kennedy, E. Kirkpatrick,
P. Vanemon, J. Org. Chem. 1989, 54, 1213. See also: refs.[7a] and
[21a].
[24] For a review on the chemistry of alkoxy radicals, see: J. Hartung, T.
Gottwald, K. Spehar, Synthesis 2002, 1469.
[25] The generation of alkoxybis(chloro)-l3-iodanes related to E has
been already postulated: D. D. Tanner, G. C. Gidley, N. Das, J. E.
Rowe, A. Potter, J. Am. Chem. Soc. 1984, 106, 5261. On the basis of
these studies, the presence of different dimeric compounds cannot
be discounted. For the sake of simplicity these plausible intermedi-
ates are not shown.
Received: February 10, 2004
Published online: July 9, 2004
Chem. Eur. J. 2004, 10, 4206 4213
www.chemeurj.org
¹ 2004 Wiley-VCH VerlagGmbH & Co. KGaA, Weinheim
4213