2-Iodoxybenzoic Acid Tosylates: the Alternative to Dess–Martin Periodinane Oxidizing Reagents

Article abstract of DOI:10.1002/adsc.201700776

Two powerful hypervalent iodine(V) oxidants, DMP-OTs (1-tosyloxy-1,1-diacetoxy-1H-1λ⁵-benzo[d][1,2]iodoxol-3-one) and IBX-OTs (1-tosyloxy-1-oxo-1H-1λ⁵-benzo[d][1,2]iodoxol-3-one) show high reactivity in the oxidation of structurally complex primary and secondary alcohols, which are highly functionalized polyketide or terpene fragments or steroids. The yields of the corresponding carbonyl compounds are even higher for the protocol that uses pyridine as additive. The oxidations proceed very rapidly at room temperature leaving the protective groups and π-systems intact and affording the corresponding carbonyl compounds in good to excellent yields. Moreover, IBX-OTs is an efficient reagent for the oxidative dehydrogenation of steroidal alcohols to the corresponding enones. (Figure presented.).

Full text of DOI:10.1002/adsc.201700776

Title: 2-Iodoxybenzoic Acid Tosylates: the Alternative to Dess-Martin
Periodinane Oxidizing Reagents
Authors: Mekhman Yusubov, Pavel Postnikov, Roza Yusubova, Akira
Yoshimura, Gerrit Jürjens, Andreas Kirschning, and Viktor
Zhdankin
This manuscript has been accepted after peer review and appears as an
Accepted Article online prior to editing, proofing, and formal publication
of the final Version of Record (VoR). This work is currently citable by
using the Digital Object Identifier (DOI) given below. The VoR will be
published online in Early View as soon as possible and may be different
to this Accepted Article as a result of editing. Readers should obtain
the VoR from the journal website shown below when it is published
to ensure accuracy of information. The authors are responsible for the
content of this Accepted Article.
To be cited as: Adv. Synth. Catal. 10.1002/adsc.201700776
Link to VoR: http://dx.doi.org/10.1002/adsc.201700776

10.1002/adsc.201700776
Advanced Synthesis & Catalysis
FULL PAPER
DOI: 10.1002/adsc.201((will be filled in by the editorial staff))
2-Iodoxybenzoic Acid Tosylates: the Alternative to Dess-Martin
Periodinane Oxidizing Reagents
Mekhman S. Yusubov,a* Pavel S. Postnikov,a Roza Ya. Yusubova,a Akira Yoshimura,b
Gerrit Jürjens,c,d Andreas Kirschning,d* and Viktor V. Zhdankine*
a
The Tomsk Polytechnic University, 634050 Tomsk, Russia; e-mail: yusubov@mail.ru
Department of Chemistry, Southern Methodist University, Dallas, TX, 75275
Institute for Medicinal Chemistry, Helmholtz Zentrum München, German Research Center for Environmental Health,
b
c
Schneiderberg 1b, 30167 Hannover, Germany
Institute of Organic Chemistry and Center of Biomolecular Drug Research (BMWZ), Leibniz University Hannover,
d
Schneiderberg 1b, 30167 Hannover, Germany; e-mail: andreas.kirschning@oci.uni-hannover.de
Department of Chemistry and Biochemistry, University of Minnesota Duluth, Duluth, Minnesota, 55812; e-mail:
e
vzhdanki@d.umn.edu
Received: ((will be filled in by the editorial staff))
Supporting information for this article is available on the WWW under http://dx.doi.org/10.1002/adsc.201######.
Abstract. Two powerful hypervalent iodine(V) oxidants, The oxidations proceed very fast at room temperature
DMP-OTs
benzo[d][1,2]iodoxol-3-one) and IBX-OTs (1-tosyloxy-1- affording the corresponding carbonyl compounds in good to
oxo-1H-1λ5-benzo[d][1,2]iodoxol-3-one)
show high excellent yields. Moreover, IBX-OTs is an efficient reagent
(1-tosyloxy-1,1-diacetoxy-1H-1λ5- leaving the protective groups and π-systems intact and
reactivity in the oxidation of structurally complex primary for the oxidative dehydrogenation of steroidal alcohols to
and secondary alcohols, which are highly functionalized the corresponding enones.
polyketide or terpene fragments or steroids. The yields of the
corresponding carbonyl compounds are even higher for
protocol that uses pyridine as additive.
Keywords: Iodine; Oxidation; Alcohols; Synthetic
methods; Terpenoids
Recently, we have reported the preparation and
structural study of new tosylate derivatives of IBX,
namely, the tosylate derivative of DMP (DMP-OTs,
2) and the tosylate derivative of IBX (IBX-OTs, 3).4
These compounds are prepared by simple treatment
of IBX (1) with TsOH•H2O in acetic anhydride at
room temperature (Scheme 1).
Introduction
Oxidizing reagents are essential constituents of
synthetic organic methodology.[1] Selective oxidation
of a hydroxyl group to carbonyl often represents a
key step in total synthesis of complex natural
products. Hypervalent iodine compounds have
emerged as versatile and environmentally benign
oxidizing reagents.[2] Particularly useful hypervalent
iodine oxidants are 2-iodoxybenzoic acid (IBX) and
the product of its acetylation Dess-Martin
periodinane (DMP), which are now employed
extensively in organic synthesis as mild and highly
selective reagents for the oxidation of alcohols to
carbonyl compounds as well as for a variety of other
synthetically useful oxidative transformations.[3] IBX
and DMP are mild oxidants with a relatively low
reactivity towards some substrates. In particular,
oxidations of primary alcohols with these reagents
often require elevated temperatures or extended
periods of time, which is undesirable in the reactions
with sensitive substrates. There is a clear need in the
development of more powerful but still selective
oxidizing reagents.
Scheme 1. Preparation of tosylate derivatives of IBX.
Preliminary studies[4] have shown that tosylate 3
has a higher reactivity toward alcohols compared
with IBX or DMP. In particular, we have found that
the oxidation of simple primary alcohols (1-octanol
and substituted benzyl alcohols) with 1 equiv of IBX-
OTs 3 in general is complete within 3-10 min at room
temperature with a quantitative conversion to the
respective carbonyl compounds.4 We explain the
1
This article is protected by copyright. All rights reserved.

10.1002/adsc.201700776
Advanced Synthesis & Catalysis
enhanced reactivity of compound 3 compared to the
DMP or IBX by the electron-withdrawing properties
of the tosylate substituent and consequently the
higher electrophilicity of the central iodine atom. In
the present paper, we have investigated the
applicability of the tosylate derivatives of IBX to the
oxidation of structurally complex alcohols, some of
which serve as key intermediates in total syntheses of
terpenes and polyketide antibiotics.[5-8]
could be detected by TLC after three minutes (entries
10 and 11). The new iodine(V) reagents 2 and 3
turned out to be very powerful oxidants in
dichloromethane and in selected cases also in
acetonitrile. Pyridine can be used as an additive
(entries 5 and 7). Both reagents demonstrate superior
oxidation properties compared to DMP, the most
prominent oxidant in natural product synthesis
(entries 8 and 9). IBX (1) itself as well as the
common reagent system DIB/TEMPO[9] are
inefficient under the conditions employed (entries 10
and 11). Likewise, a physical mixture of IBX and
TsOH•H2O is inactive due to insolubility of both
components in dichloromethane. A physical mixture
of DMP with TsOH•H2O has low stability and
inconsistent reactivity.
Next, we extended the scope of the oxidation
property of IBX-OTs monohydrate 3 to several
structurally complex alcohols 4a-e (Scheme 2). These
alcohols contain an olefinic double bond or an alkyne
moiety. While alcohols 4a and 4b[6] yield aldehydes
that are conjugated with a π-system, the oxidation of
alcohols 4c and 4d yields aldehydes 5c and 5d that
contain an isolated π-system,[6] in case of 5d bearing
a vinyl bromide. Finally, a secondary alcohol 4e[10]
was also included into this series of oxidations. The
oxidations proceeded extremely rapidly and within 10
minutes the transformation went to completion
leaving the π-systems intact and isolated yields were
generally good to excellent.
Results and Discussion
We have initially investigated the oxidation of known
allylic alcohol 4a5 as a model substrate for optimizing
the reaction conditions that are applicable in natural
product synthesis (Table 1).
Table 1. Optimization and comparison studies for
iodine(V)-promoted
oxidations
of
(S,E)-5-((tert-
butyldiphenylsilyl)oxy)-2,4-dimethylpent-2-en-1-ol 4a.a)
Entry Conditions
Ratio
reagent/
Solvent Conversion
(%)b)
substrate
1
2
3
4
5
3, rt, 3 min
3, rt, 3 min
3, rt, 3 min
3, rt, 3 min
3, pyridine,
rt, 3 min
1.06
1.06
1.06
1.06
1.06
CH2Cl2 96
CH3CN 94
DMSO 72
EtOAc 32
CH2Cl2 96
6
7
2, rt, 3 min
2, pyridine,
rt, 3 min
1.1
1.1
CH2Cl2 100
CH2Cl2 100
8
DMP, rt, 3
min
DMP, rt, 3
min
IBX, rt, 10
min
PhI(OAc)2-
TEMPO, rt,
10 min
1.1
1.1
1.1
1.2
CH2Cl2 63
CH3CN 64
9
10
11
CH2Cl2
CH2Cl2
0
6
a)
b)
For detailed procedures, see Experimental Section.
Determined by 1H NMR spectroscopy.
A stoichiometric amount of IBX-OTs 3 was able to
almost quantitatively transform alcohol 4a into
aldehyde 5a[5] at room temperature within 3 minutes.
Consequently, we carried out a series of oxidations in
different solvents or with other hypervalent iodine
reagents and terminated the reaction after three
minutes by adding aqueous solutions of NaHSO3 and
NaHCO3 and diethyl ether to the reaction mixture.
Only in the case of the reagent systems IBX (1) and
(diacetoxyiodo)benzene (DIB)/TEMPO the reaction
was terminated after 10 minutes as no transformation
Scheme 2. Oxidation of alcohols 4a-4e using IBX-OTs 3
(isolated yields are shown).
2
This article is protected by copyright. All rights reserved.

10.1002/adsc.201700776
Advanced Synthesis & Catalysis
In a second series of oxidations we extended the
reactions to other natural product fragments testing
different methods (Scheme 3).
ansamitocin[5] (alcohols 4k and 4l) and the
elansolids[7] (alcohols 4h-4j) as well as diterpene
tonantzitlolone[6] (alcohol 4g) using three following
procedures. Method A: IBX-OTs 3 was added to a
mixture of 4 and pyridine in CH2Cl2 at room
temperature. Method B: IBX-OTs 3 was mixed with
pyridine in CH2Cl2 and evaporated to give an oily
complex, which was then mixed with alcohol 4 in
CH2Cl2. Method C: DMP-OTs 2 was mixed with
pyridine in CH2Cl2 and evaporated to give an oily
complex,[11b] which was then mixed with alcohol 4 in
CH2Cl2. All these oxidations proceeded quickly at
room temperature affording the corresponding
oxidation products in good to excellent yields. In
general, the yields were higher for protocols that use
preformed complexes IBX-OTs/Py or DMP-OTs/Py
(methods B and C). Compared to IBX-OTs 3, DMP-
OTs 2 affords the oxidation products in slightly
higher yields; however, IBX-OTs is a practically
more convenient reagent because of its higher
stability to moisture.
Substrates 4a-l represent the very expensive and
difficult to obtain synthons available only in
submillimolar quantities. In order to test the
applicability of reagents 2 and 3 on a larger scale, we
performed oxidation of a common natural alcohol,
geraniol 5m, in a millimolar quantity. We have found
that the reaction of geraniol with IBX-OTs 3 was
excessively exothermic leading to a complex mixture
of products. In contrast, the reaction of geraniol with
DMP-OTs 2 in the presence of pyridine selectively
produced the expected citral as an inseparable
mixture of E- and Z-isomers 5m and 5m' (1.0 : 0.4
ratio) isolated by column chromatography in 89%
yield (Scheme 4). This result is similar to the
chromium(VI)-mediated oxidations of geraniol,[12]
however, our reaction conditions are milder and the
product yield is significantly higher.
Scheme 3. Oxidation of alcohols 4f-4l using IBX-
OTs/pyridine or DMP-OTs/pyridine (isolated yields
are shown).
Scheme 4. Oxidation of geraniol 4m on millimolar scale
using DMP-OTs/pyridine.
In the initial experiments (Table 1), we have shown
that both IBX-OTs 3 and DMP-OTs 2 demonstrate
strong oxidative reactivity towards alcohols. During
the optimizations we observed that their high
reactivity is not affected when a base like pyridine is
added in stoichiometric amount.[11] Mildly basic
conditions can be important in oxidations of acid
sensitive natural products and advanced synthetic
intermediates, and therefore we decided to further
explore the reactivity of structurally complex
alcohols 4f-l. In these studies, we selected
compounds 4f-l, advanced synthetic intermediates in
the total synthesis of the two polyketides
Finally, we studied the oxidation of several steroidal
alcohols 4n-4p using IBX-OTs as oxidant (Scheme 5).
The reactions of steroidal alcohols 4n-4p with 1
equiv IBX-OTs in CH2Cl2 (procedure 1, Scheme 5)
selectively afforded the corresponding ketones 5n-5p
in 70-89% isolated yields. For steroids 4o and 4p
containing hydroxyl in the A ring at position 4, this
oxidation was also accompanied in part with
desaturation of one or both α,β-positions of the
keto group yielding enones 5o' and 5p' as well as
dienone 5o". The preparative yields of enones 5o',
5o" and 5p' can be improved by using excess IBX-
3
This article is protected by copyright. All rights reserved.

10.1002/adsc.201700776
Advanced Synthesis & Catalysis
2-Iodobenzoic acid, p-toluenesulfonic acid and other
common reagents and solvents were from commercial
sources and used without further purification from freshly
OTs in acetonitrile at room temperature (procedures
2-4, Scheme 5). This result is in agreement with the
oxidative dehydrogenation of steroidal alcohols 4n
and 4o to the corresponding enones 5o', 5o" and 5p'
1
opened containers. H NMR spectra were recorded at 400
MHz and 13C NMR spectra were recorded at 100 MHz.
1
o
Chemical shifts are reported in parts per million (ppm). H
using IBX at 65-85 C (DMSO, 24-48 h) reported by
and 13C chemical shifts are referenced relative to
tetramethylsilane. Mass spectra (EI) were obtained at 70
eV or LCT (ESI). Analytical thin-layer chromatography
was performed using precoated silica gel plates and the
spots were visualized with UV light at 254 nm or by
staining with H2SO4/2,4-dinitrophenylhydrazine or
H2SO4/4-methoxybenzaldehyde in ethanol. Alcohols 4
were prepared according to known procedures or obtained
from commercial sources: Alcohols 4b, 4n and 4o[14] are
commercially available. Substrates 4a and 4l were
prepared according to Frenzel et al. starting from methyl
(R)-(−)-3-hydroxy-2-methylpropionate.[5b] Alcohols 4c and
4d were prepared from 4b according to known procedures
from the Kirschning group.[6d] Substrate 4e was prepared
according to Beckmann et al. starting from Hajos-Wiechert
ketone.[10] Alcohols 4f and 4k were obtained following a
multistep procedure which started from acrolein and allyl
methyl ether.[5a] Compound 4g was prepared from methyl
geranoate in several steps[6d] and 4h is available from
methyl (R)-(−)-3-hydroxy-2-methylpropionate.[7b] Finally,
alcohol 4i was synthesized from methyl isobutyrate and 1-
{[(2-(chloromethyl)allyl)oxy]methyl}-4-
Nicolaou.[13] In contrast to the Nicolaou's work, the
oxidations of 4o and 4p with IBX-OTs smoothly
proceed in acetonitrile at room temperature, however,
the isolated yields of enones 5o', 5o" and 5p' are
slightly lower.
methoxybenzene.[8] IBX (1) was prepared by oxidation of
2-iodobenzoic acid with Oxone.[15] IBX-OTs monohydrate
(3) was prepared by treating IBX with p-TsOH•H2O in
acetic anhydride according to the published procedure.[4]
1-Tosyloxy-1,1-diacetoxy-1H-1λ5-
benzo[d][1,2]iodoxol-3-one (DMP-OTs, 2); modified
procedure.[4] A mixture of IBX 1 (1.68 g, 6.0 mmol), p-
TsOH•H2O (3.42 g, 18.0 mmol), and acetic anhydride (20
mL) was magnetically stirred at room temperature. A
formation of clear, colorless solution was observed after 40
min of stirring and then a white, microcrystalline
precipitate started to form. After stirring the mixture for
additional 4 h, the precipitate was filtered and washed on
filter in dry atmosphere with a mixture of Et2O/Ac2O =
20:1 (20 mL) and dried in vacuum at room temperature
during 6 h to give 2.60 g (81%) of DMP-OTs 2, as a white,
Scheme 5. Oxidation of steroids 4n-4p (isolated yields are
shown).
1
microcrystalline solid. Mp: 99-100 °C (dec.). H NMR
(400 MHz, DMSO-d6): δ 8.16 (d, J = 8.0 Hz, 1H), 8.04 (d,
J = 7.6 Hz, 1H), 7.85 (t, J = 7.6 Hz, 1 H), 7.49 (d, J = 8.0
Hz, 2H), 7.13 (d, J = 8.0 Hz, 2H), 2.29 (s, 3H), 1.91 (s,
6H).
Conclusion
In summary, we have demonstrated that DMP-OTs 2
and IBX-OTs 3 are superior reagents for the
oxidation of structurally complex alcohols, which
serve as key intermediates in total syntheses of
terpenes and polyketide antibiotics. The oxidations
proceed extremely rapidly at room temperature
leaving the protective groups and π-systems intact
and affording the corresponding carbonyl compounds
in good to excellent yields. In general, the yields of
the corresponding oxidation products are higher for
protocol that uses pyridine as additive. Compared to
IBX-OTs 3, DMP-OTs 2 generally affords the
oxidation products in slightly higher yields; however,
IBX-OTs is practically more convenient reagent
because of its higher stability to moisture. Moreover,
IBX-OTs 3 is an efficient reagent for the oxidative
dehydrogenation of steroidal alcohols to the
corresponding enones.
Optimization and comparison studies for
iodine(V)-promoted oxidations of (S,E)-5-((tert-
butyldiphenylsilyl)oxy)-2,4-dimethylpent-2-en-1-ol 4a
(Table 1).
Oxidation with IBX-OTs 3 (Table 1, entries 1-4): To a
solution of 4a (37 mg, 0.1 mmol) in 1.0 mL of the
appropriate solvent (see Table 1), IBX-OTs•H2O 3 (48 mg,
0.106 mmol) was added and was stirred 3 min at rt. Then
Et2O (3 mL) and aqueous solutions of NaHSO3 (5%, 1 mL)
and NaHCO3 (5%, 3 mL) were added and the mixture was
vigorously stirred 5 min. Organic layer was separated,
dried by Na2SO4 and solvent removed in vacuum.
1
Conversion of alcohol to aldehyde was controlled by H
NMR spectra (see Supporting Information for actual NMR
spectra).
Oxidation with IBX-OTs 3 in the presence of pyridine
(Table 1, entry 5): To a solution of 4a (37 mg, 0.1 mmol)
and pyridine (8 mg, 0.1 mmol) in CH2Cl2 (1.0 mL), IBX-
OTs 3 (48 mg, 0.11 mmol) was added and the mixture was
stirred 3 min at rt. Then Et2O (3 mL) and aqueous
solutions of NaHSO3 (5%, 1 mL) and NaHCO3 (5%, 3 mL)
were added and the mixture was vigorously stirred 5 min.
Organic layer was separated, dried by Na2SO4 and solvent
removed in vacuum. Conversion of alcohol to aldehyde
was controlled by 1H NMR spectra (see Supporting
Information for actual NMR spectra).
Experimental Section
General experimental remarks
4
This article is protected by copyright. All rights reserved.

10.1002/adsc.201700776
Advanced Synthesis & Catalysis
Oxidation with DMP-OTs 2 (Table 1, entry 6): To a
6H), 6.29 (dd, J = 9.6 Hz, 1.6 Hz, 1H), 3.69-3.65 (m, 1H),
3.62-3.58 (m, 1H), 2.98-2.90 (m, 1H), 1.73 (s, 3H), 1.07 (d,
J = 6.8 Hz, 3H), 1.05 (s, 9H); 13C NMR (100 MHz,
CDCl3): δ 195.6, 157.3, 139.4, 135.75, 135.7, 133.6,
133.56, 129.9, 129.87, 129.84, 67.7, 36.5, 27.0, 19.4, 16.2,
9.5. HRMS (ESI) m/z: [M + Na]+ Calcd for C23H30O2NaSi
389.1913; Found: 389.1909.
solution of 4a (37 mg, 0.1 mmol) in CH2Cl2 (1.0 mL),
DMP-OTs 2 (59 mg, 0.11 mmol) was added and the
mixture was stirred 3 min at rt. Then Et2O (3 mL) and
aqueous solutions of NaHSO3 (5%, 1 mL) and NaHCO3
(5%, 3 mL) were added and the mixture was vigorously
stirred 5 min. Organic layer was separated, dried by
Na2SO4 and solvent removed in vacuum. Conversion of
1
alcohol to aldehyde was controlled by H NMR spectra
3-(Trimethylsilyl)propynal (5b). Following the
general procedure, the reaction of alcohol 4b (44 mg, 0.35
mmol) with IBX-OTs 3 (169 mg, 0.37 mmol) in CH2Cl2
(see Supporting Information for actual NMR spectra).
1
Oxidation with DMP-OTs 2 in the presence of
pyridine (Table 1, entry 7): To a solution of 4a (37 mg, 0.1
mmol) and pyridine (8 mg, 0.1 mmol) in CH2Cl2 (1.0 mL),
DMP-OTs 2 (59 mg, 0.11 mmol) was added and the
mixture was stirred 3 min at rt. Then Et2O (3 mL) and
aqueous solutions of NaHSO3 (5%, 1 mL) and NaHCO3
(5%, 3 mL) were added and the mixture was vigorously
stirred 5 min. Organic layer was separated, dried by
Na2SO4 and solvent removed in vacuum. Conversion of
(2.2 mL) afforded product 5b as an oil (39 mg, 90%). H
NMR (400 MHz, CDCl3): δ 9.16 (s, 1H), 0.26 (s, 9H); 13C
NMR (100 MHz, CDCl3): δ 176.9, 103.2, 102.3, 0.8.
HRMS (ESI) m/z: [M + Na]+ Calcd for C6H10ONaSi
149.0399; Found: 149.0391.
3(R)-2-methyl-5-(trimethylsilyl)pent-4-ynal
(5c).
Following the general procedure, the reaction of alcohol 4c
(42.5 mg, 0.25 mmol) with IBX-OTs 3 (135 mg, 0.30
mmol) in CH2Cl2 (2.5 mL) afforded product 5c as an oil
(39.5 mg, 94%). 1H NMR (400 MHz, CDCl3): δ 9.7 (d, J =
0.8 Hz, 1H), 2.57-2.51 (m, 2H), 2.51-2.35 (m, 1H), 1.21 (d,
J = 6.8 Hz, 3H), 0.13 (s, 9H); 13C NMR (100 MHz,
CDCl3): δ 203.4, 103.5, 87.2, 45.3, 21.3, 13.2, 0.14.
HRMS (ESI) m/z: [M + Na]+ Calcd for C9H16ONaSi
191.0868; Found: 191.0868.
1
alcohol to aldehyde was controlled by H NMR spectra
(see Supporting Information for actual NMR spectra).
Oxidation with DMP (Table 1, entries 8 and 9): To a
solution of 4a (37 mg, 0.1 mmol) 1.0 mL of the
appropriate solvent (see Table 1), DMP (47 mg, 0.11
mmol) was added and the mixture was stirred 3 min at rt.
Then Et2O (3 mL) and aqueous solutions of NaHSO3 (5%,
1 mL) and NaHCO3 (5%, 3 mL) were added and the
mixture was vigorously stirred 5 min. Organic layer was
separated, dried by Na2SO4 and solvent removed in
vacuum. Conversion of alcohol to aldehyde was controlled
by 1H NMR spectra (see Supporting Information for actual
NMR spectra).
(S)-4-bromo-2-methylpent-4-enal (5d). Following the
general procedure, the reaction of alcohol 4d (24 mg,
0.134 mmol) with IBX-OTs 3 (66.7 mg, 0.147 mmol) in
CH2Cl2 (1.2 mL) afforded product 5d as an oil (18 mg,
1
76%). H NMR (400 MHz, CDCl3-TMS): δ 9.64 (d, J =
0.8 Hz, 1H), 5.59-5.58 (m, 1H), 5.43 (m, 1H), 2.86-2.80
(m, 1H), 2.74-2.68 (m, 1H), 2.35-2.29 (m, 1H), 1.06 (d, J =
6.8 Hz, 3H). 13C NMR (100 MHz, CDCl3): δ 203.2, 131.1,
119.4, 44.6, 42.1, 12.7. HRMS (ESI) m/z: [M + Na]+ Calcd
for C6H9BrONa 198.9734; Found: 198.9719.
Oxidation with IBX 1 (Table 1, entry 10): To a
solution of 4a (37 mg, 0.1 mmol) in CH2Cl2 (1.0 mL), IBX
1 (31 mg, 0.11 mmol) was added and the mixture was
stirred 10 min at rt. Then Et2O (3 mL) and aqueous
solutions of NaHSO3 (5%, 1 mL) and NaHCO3 (5%, 3 mL)
were added and the mixture was vigorously stirred 5 min.
Organic layer was separated, dried by Na2SO4 and solvent
removed in vacuum. Conversion of alcohol to aldehyde
was controlled by 1H NMR spectra (see Supporting
Information for actual NMR spectra).
(7aS)-7a-methyl-2,3,5,6,7,7a-hexahydro-1H-inden-1-
one (5e). Following the general procedure, the reaction of
alcohol 4e (53 mg, 0.35 mmol) with IBX-OTs 3 (174 mg,
0.385 mmol) in CH2Cl2 (2 mL) afforded product 5e as a
1
volatile oil (37 mg, 70%). H NMR (400 MHz, CDCl3): δ
5.55 (dd, J = 6 Hz, 2.8 Hz, 1H), 2.70-2.61 (m, 1H), 2.54-
2.44 (m, 2H), 2.24-2.14 (m, 1H), 2.08-1.92 (m, 2H), 1.78-
1.58 (m, 3H), 1.32-1.24 (m, 1H), 1.11 (s, 3H). 13C NMR
(100 MHz, CDCl3): δ 221.3, 141.7, 120.7, 47.5, 37.0, 28.9,
27.1, 24.8, 22.0, 18.3. HRMS (ESI) m/z: [M + Na]+ Calcd
for C10H14ONa 173.0942; Found: 173.0941.
Oxidation with PhI(OAc)2-TEMPO (Table 1, entry
11): To a solution of 4a (37 mg, 0.1 mmol) in CH2Cl2 (1.0
mL), PhI(OAc)2 (39 mg, 0.12 mmol) and TEMPO (3.2 mg,
0.02 mmol) were added and the mixture was vigorously
stirred 10 min at rt. Then Et2O (3 mL) and aqueous
solutions of NaHSO3 (5%, 1 mL) and NaHCO3 (5%, 3 mL)
were added and the mixture was stirred 5 min. Organic
layer was separated, dried by Na2SO4 and solvent removed
in vacuum. Conversion of alcohol to aldehyde was
controlled by 1H NMR spectra (see Supporting Information
for actual NMR spectra).
General Experimental Procedures for Oxidation of
Alcohols by IBX-OTs or DMP-OTs in the presence of
Pyridine (Scheme 3).
General Method A: To a solution of alcohol 4 (0.1-
0.3 mmol) and pyridine (1.2 equiv) in CH2Cl2 (1-3 mL),
IBX-OTs 3 (1.11-1.5 equiv) was added and the mixture
was stirred at rt. The reaction was monitored by TLC and
GC-MS until full disappearance of the alcohol. Then Et2O
(3 mL) and aqueous solutions of NaHSO3 (5%, 1 mL) and
NaHCO3 (5%, 3 mL) were added and the mixture was
vigorously stirred 5 min. Organic layer was separated,
dried by Na2SO4 and solvent removed in vacuum. The
analytically pure product 5 was isolated by filtration of
reaction mixture through a short silica gel column using
dichloromethane as eluent.
General Experimental Procedure for Oxidation of
Alcohols by IBX-OTs 3 (Scheme 2). To a solution of
alcohol 4 (0.1-0.35 mmol) in CH2Cl2 (1-3 mL), IBX-OTs 3
(1.05-1.2 equiv) was added under stirring at room
temperature. Reaction mixture was stirred 5-10 min (see
Table 2; monitored by TLC and GC-MS). Then Et2O (3
mL) and aqueous solutions of NaHSO3 (5%, 1 mL) and
NaHCO3 (5%, 3 mL) were added and the mixture was
vigorously stirred 5 min. Organic layer was separated,
dried by Na2SO4 and solvent removed in vacuum. The
analytically pure product 5 was isolated by filtration of
reaction mixture through a short silica gel column using
dichloromethane as eluent.
General Method B: IBX-OTs 3 (1.2 equiv) was
mixed with pyridine (1.2 equiv) in CH2Cl2 (1-2 mL) and
the solvent was immediately evaporated. To the resulting
oily residue, a solution of alcohol 4 (0.1 mmol) in CH2Cl2
(1 mL) was added and the mixture was stirred at rt. The
reaction was monitored by TLC and GC-MS until full
disappearance of the alcohol. Then Et2O (3 mL) and
aqueous solutions of NaHSO3 (5%, 1 mL) and NaHCO3
(5%, 3 mL) were added and the mixture was vigorously
stirred 5 min. Organic layer was separated, dried by
(S,E)-5-((tert-butyldiphenylsilyl)oxy)-2,4-
dimethylpent-2-enal (5a). Following the general procedure,
the reaction of alcohol 4a (87 mg, 0.236 mmol) with IBX-
OTs 3 (120 mg, 0.265 mmol) in CH2Cl2 (2.2 mL) afforded
1
product 5a as an oil (81 mg, 93%). H NMR (400 MHz,
CDCl3): δ 9.37 (s, 1H), 7.66-7.64 (m, 4H), 7.47-7.37 (m,
5
This article is protected by copyright. All rights reserved.

10.1002/adsc.201700776
Advanced Synthesis & Catalysis
Na2SO4 and solvent removed in vacuum. The analytically
Method B: the reaction of IBX-OTs 3 (106 mg, 0.234
mmol) with pyridine (19 mg, 0.235 mmol) followed by
addition of alcohol 4j (80 mg 0.213 mmol) in CH2Cl2 (2
mL) after stirring for 30 min afforded product 5j as an oil
(74 mg, 93%). Method C: DMP-OTs 2 (36.4 mg, 0.068
mmol) was mixed with pyridine (5.5 mg, 0.068 mmol) in
CH2Cl2 (1 mL) and the solvent was immediately
evaporated. To the resulting oily residue, a solution of
alcohol 4j (23.8 mg 0.063 mmol) in CH2Cl2 (1 mL) was
added and the mixture was stirred at rt for 30 min. Then
Et2O (3 mL) and aqueous solutions of NaHSO3 (5%, 1 mL)
and NaHCO3 (5%, 3 mL) were added and the mixture was
vigorously stirred 5 min. Organic layer was separated,
dried by Na2SO4 and solvent removed in vacuum. The
analytically pure product 5j was isolated by filtration of
reaction mixture through a short silica gel column using
dichloromethane as eluent. The quantitative conversion of
pure product 5 was isolated by filtration of reaction
mixture through
a short silica gel column using
dichloromethane as eluent.
(3R,4R)-3-(benzyloxy)-4-methoxyhex-5-enal
(5f).
Method A: the reaction of alcohol 4f (70 mg, 0.297 mmol)
with IBX-OTs 3 (203 mg, 0.45 mmol) and pyridine (28 mg,
0.35 mmol) in CH2Cl2 (3 mL) after stirring for 3 h afforded
product 5f as an oil (45 mg, 64%). Method B: the reaction
of IBX-OTs 3 (122 mg, 0.27 mmol) with pyridine (22 mg,
0.275 mmol) followed by addition of alcohol 4f (58 mg
0.246 mmol) in CH2Cl2 (2 mL) after stirring for 0.5 h
1
afforded product 5f as an oil (44 mg, 83%). H NMR (400
MHz, CDCl3): δ 9.67 (s, 1H), 7.29-7.21 (m, 5H), 5.74-5.65
(m, 1H), 5.28-5.22 (m, 2H), 4.64 (d, J = 11.6 Hz, 1H), 4.55
(d, J = 11.6 Hz, 1H), 4.01-3.97 (m, 1H), 3.69-3.66 (m, 1H),
3.23 (s, 3H), 2.62-2.47 (m, 2H). 13C NMR (100 MHz,
CDCl3): δ 201.1, 138.2, 134.4, 128.5, 128.1, 127.9, 119.5,
83.9, 76.0, 73.2, 57.0, 45.3. HRMS (ESI) m/z: [M + Na]+
Calcd for C14H18O3Na 257.1154; Found: 257.1156.
1
substrate 4j to the product 5j was confirmed by H NMR
(see Supporting Information for actual spectra). Product 5j
was isolated as an oil (22.6 mg, 96%). 1H NMR (400 MHz,
CDCl3): δ 9.68 (s, 1H), 7.69-7.67 (m, 4H), 7.44-7.35 (m,
6H), 7.28-7.26 (m, 2H), 6.86 (d, J = 8.4 Hz, 2H), 5.67-5.62
(m, 1H), 5.48-5.41 (dt, J = 15.6 Hz, 5.2 Hz, 1H), 4.42 (dd,
J = 29.2 Hz, 10.8 Hz, 2H), 4.14 (dd, J = 5.2 Hz, 1.6 Hz,
2H), 3.79 (s, 3H), 1.85 (dd, J = 18 Hz, 14.8 Hz, 2H), 1.58-
1.51 (m, 1H), 1.33 (s, 3H), 1.09-1.04 (m, 15H). 13C NMR
(100 MHz, CDCl3): δ 205.8, 159.2, 141.3, 135.7, 134.0,
130.7, 129.7, 128.9, 127.7, 125.3, 113.9, 83.7, 65.7, 64.9,
55.4, 50.2, 35.8, 29.8, 28.8, 26.9, 20.5, 19.4. HRMS (ESI)
m/z: [M + Na]+ Calcd for C34H44O4NaSi 567.2907; Found:
567.2905.
2-((2S,5S)-5-((S)-2,2-dimethyl-1,3-dioxolan-4-yl)-5-
methyltetrahydrofuran-2-yl)-2-methylpropanal
(5g).
Method A: the reaction of alcohol 4g (52 mg, 0.201 mmol)
with IBX-OTs 3 (96 mg, 0.212 mmol) and pyridine (18 mg,
0.215 mmol) in CH2Cl2 (2 mL) after stirring for 25 min
afforded product 5g as an oil (45 mg, 87%). Method B: the
reaction of IBX-OTs 3 (95 mg, 0.21 mmol) with pyridine
(17 mg, 0.21 mmol) followed by addition of alcohol 4g
(39.5 mg 0.152 mmol) in CH2Cl2 (1 mL) after stirring for
1
20 min afforded product 5g as an oil (39 mg, 93%). H
(4S,5S,7R,8R,E)-7-(benzyloxy)-5-((tert-
NMR (400 MHz, CDCl3): δ 9.60 (s, 1H), 4.08-4.03 (m,
2H), 3.98-3.95 (m, 1H), 2.02-1.92 (m, 2H), 1.76-1.63 (m,
3H), 1.42 (s, 3H), 1.34 (s, 3H), 1.10 (s,3H), 1.05 (s, 3H),
1.03 (s, 1H). 13C NMR (100 MHz, CDCl3): δ .206.6, 109.5,
84.2, 83.5, 81.2, 66.1, 48.9, 33.9, 27.0, 26.4, 25.2, 22.7,
19.5, 16.9. HRMS (ESI) m/z: [M + Na]+ Calcd for
C14H24O4Na 279.1572; Found: 279.1569.
butyldimethylsilyl)oxy)-8-methoxy-2,4-dimethyldeca-2,9-
dienal (5k). Method A: the reaction of alcohol 4k (45 mg,
0.1 mmol) with IBX-OTs 3 (50 mg, 0.11 mmol) and
pyridine (9 mg, 0.115 mmol) in CH2Cl2 (1 mL) after
stirring for 12 h afforded product 5k as an oil (32 mg,
71%). Method B: the reaction of IBX-OTs 3 (95 mg, 0.21
mmol) with pyridine (17 mg, 0.215 mmol) followed by
addition of alcohol 4k (90 mg 0.2 mmol) in CH2Cl2 (2 mL)
after stirring for 30 min afforded product 5k as an oil (80
mg, 90%). Method C: DMP-OTs 2 (54 mg, 0.1 mmol) was
mixed with pyridine (8.7 mg, 0.11 mmol) in CH2Cl2 (1
mL) and the solvent was immediately evaporated. To the
resulting oily residue, a solution of alcohol 4k (41 mg 0.09
mmol) in CH2Cl2 (1 mL) was added and the mixture was
stirred at rt for 30 min. Then Et2O (3 mL) and aqueous
solutions of NaHSO3 (5%, 1 mL) and NaHCO3 (5%, 3 mL)
were added and the mixture was vigorously stirred 5 min.
Organic layer was separated, dried by Na2SO4 and solvent
removed in vacuum. The analytically pure product 5k was
isolated by filtration of reaction mixture through a short
silica gel column using dichloromethane as eluent. The
quantitative conversion of substrate 4k to the product 5k
5-((tert-butyldimethylsilyl)oxy)-2,4,4-
trimethylpentanal (5h). Method A: the reaction of alcohol
4h (52 mg, 0.201 mmol) with IBX-OTs 3 (135 mg, 0.299
mmol) and pyridine (24 mg, 0.3 mmol) in CH2Cl2 (2 mL)
after stirring for 2 h afforded product 5h as an oil (32 mg,
62%). Method B: the reaction of IBX-OTs 3 (79 mg, 0.175
mmol) with pyridine (15 mg, 0.18 mmol) followed by
addition of alcohol 4h (39.5 mg 0.152 mmol) in CH2Cl2 (1
mL) after stirring for 30 min afforded product 5h as an oil
(33 mg, 84%). 1H NMR (400 MHz, CDCl3): δ 9.53 (s, 1H),
3.22 (s, 2H), 2.46-2.37 (m, 1H), 1.85 (dd, J = 14.4 Hz, 8.0
Hz, 1H), 1.18 (dd, J = 14.4 Hz, 3.6 Hz, 1H), 1.07 (d, J =
7.2 Hz, 3H), 0.88 (s, 9H), 0.84 (s, 3H), 0.83 (s, 3H), 0.02 (s,
6H). 13C NMR (100 MHz, CDCl3): δ 205.8, 71.3, 42.9,
39.8, 35.8, 26.0, 25.0, 24.7, 18.4, 16.6, -5.4, -5.43. HRMS
(ESI) m/z: [M + Na]+ Calcd for C14H30O2NaSi 281.1913;
Found: 281.1913.
1
was confirmed by H NMR (see Supporting Information
for actual spectra). Product 5k was isolated as an oil (39
1
mg, 97%). H NMR (400 MHz, CDCl3): δ 9.33 (s, 1H),
7.31-7.26 (m, 5H), 6.36 (dd, J = 9.6 Hz, 1.2 Hz, 1H), 5.78-
5.69 (m, 1H), 5.33-5.26 (m, 2H), 4.75 (d, J = 8.8 Hz, 1H),
4.53 (d, J = 8.8, 1H), 3.82-3.78 (m, 1H), 3.70-3.67 (m, 1H),
3.55-3.50 (m, 1H), 3.30 (s, 1H), 2.82-2.77 (m, 1H), 1.88-
1.81 (m, 1H), 1.61 (d, J = 1.2 Hz, 3H), 1.99 (d, J = 6.8 Hz,
3H), 0.88 (s, 9H), 0.01 (s, 6H). 13C NMR (100 MHz,
CDCl3): δ 195.76, 158.3, 138.8, 138.1, 135.0, 128.4, 127.9,
127.7, 119.0, 84.7, 77.9, 72.9, 71.6, 56.9, 38.1, 36.0, 26.0,
18.2, 13.6, 9.5, -3.9, -4.5. HRMS (ESI) m/z: [M + Na]+
Calcd for C26H42O4NaSi 469.2750; Found: 469.2750.
5-((tert-butyldimethylsilyl)oxy)-2,4,4-
trimethylpentanal (5i). Method A: the reaction of alcohol 4i
(63 mg, 0.208 mmol) with IBX-OTs 3 (113 mg, 0.25
mmol) and pyridine (20 mg, 0.25 mmol) in CH2Cl2 (2 mL)
after stirring for 2 h afforded product 5i as an oil (44 mg,
71%). Method B: the reaction of IBX-OTs 3 (68 mg, 0.15
mmol) with pyridine (11 mg, 0.15 mmol) followed by
addition of alcohol 4i (37 mg 0.122 mmol) in CH2Cl2 (1
mL) after stirring for 30 min afforded product 5i as an oil
1
(34.5 mg, 94%). H NMR (400 MHz, CDCl3): δ 9.53 (s,
1H), 5.63-5.59 (m, 1H), 5,46-5.41 (m, 1H), 4.11 (d, J = 4.8
Hz, 2H), 1.94 (d, J = 14.8 Hz, 1H), 1.85 (d, J = 14.8 Hz,
1H), 1.20 (s, 3H), 1.08 (s, 3H), 1.02 (s, 3H), 0.91 (d, J = 16
Hz, 9H), 0.07 (s, 1H). 13C NMR (100 MHz, CDCl3): δ
204.4, 139.8, 127.2, 79.0, 63.8, 35.9, 29.5, 28.2, 26.1, 26.0,
25.8, 18.6, -3.4, -5.0, -5.03. HRMS (ESI) m/z: [M + Na]+
Calcd for C16H32O3NaSi 323.2018; Found: 323.2017.
(3S,6S,E)-3-((tert-butyldimethylsilyl)oxy)-7-((tert-
butyldiphenylsilyl)oxy)-4,6-dimethylhept-4-enal
(5l).
Method B: the reaction of IBX-OTs 3 (50 mg, 0.11 mmol)
with pyridine (9 mg, 0.115 mmol) followed by addition of
alcohol 4l (53 mg 0.1 mmol) in CH2Cl2 (1 mL) after
stirring for 30 min afforded product 5l as an oil (33 mg,
1
62%). H NMR (400 MHz, CDCl3): δ 9.72 (s, 1H), 7.67-
7.64 (m, 5H), 7.40-7.37 (m, 7H), 5.31 (d, J = 9.2 Hz, 1H),
4.46 (dd, J = 8.4 Hz, 4 Hz, 1H), 3.53-3.49 (m, 1H), 3.46-
3.40 (m, 1H), 2.64-2.54 (m, 1H), 2.41-2.36 (m, 1H), 1.54
(R,E)-7-((tert-butyldiphenylsilyl)oxy)-2-((4-
methoxybenzyl)oxy)-2,4,4-trimethylhept-5-enal
(5j).
6
This article is protected by copyright. All rights reserved.

10.1002/adsc.201700776
Advanced Synthesis & Catalysis
(d, J = 1.2 Hz, 3H), 1.05 (s, 9H), 0.97 (d, J = 6.4 Hz, 3H),
0.83 (s, 9H). 13C NMR (100 MHz, CDCl3): δ 202.2, 136.5,
135.75, 135.7, 134.0, 129.7, 129.68, 129.2, 127.7, 73.8,
68.3, 50.3, 35.1, 27.0, 25.8, 19.4, 18.2, 17.4, 12.0, -4.4., -
5.1. HRMS (ESI) m/z: [M + Na]+ Calcd for C26H48O3NaSi
547.3040; Found: 547.3039.
(5S,8R,9S,10S,13S,14S)-10,13-
dimethyltetradecahydro-3H-cyclopenta[a]phenanthrene-
3,17(2H)-dione (5p). Following the general Procedure 1,
the reaction of 5α-cholestane-17β-ol-3-one 4p (60 mg,
0.207 mmol) with IBX-OTs 3 (94 mg, 0.207 mmol) in
CH2Cl2 (2 mL) afforded product 5p as a white solid 50 mg
o
1
(84%), mp 127-129 C. H NMR (400 MHz, CDCl3): δ
2.48-2.24 (m, 4H), 2.13-1.90 (m, 4H), 1.85-1.81 (m, 2H),
1.71-1.48 (m, 4H), 1.43-1.25 (m, 6H), 1.05-0.96 (m, 4H),
0.88 (s, 3H), 0.82-0.76 (m, 1H). 13C NMR (100 MHz,
CDCl3): δ 221.1, 211.8, 54.01, 51.4, 47.9, 46.7, 44.7, 38.6,
38.2, 36.0, 35.9, 35.1, 31.6, 30.7, 28.8, 21.9, 20.8, 13.9,
11.6. HRMS (ESI) m/z: [M + Na]+ Calcd for C19H28O2Na
311.1987; Found: 311.1985.
Oxidation of geraniol 4m on a millimolar scale (Scheme
4).
DMP-OTs 2 (590 mg, 1.1 mmol) was added to a
solution of geraniol 4m (154 mg, 1.0 mmol) and pyridine
o
(90 mg, 1.14 mmol) in CH2Cl2 (6 mL) at 0 C and the
Oxidative Dehydrogenation of 5α-cholestane-3β-ol
4o (Scheme 5).
mixture was stirred for 5 min (the reaction was monitored
by TLC and GC-MS until full disappearance of geraniol).
Then Et2O (5 mL), petroleum ether (5 mL) and aqueous
solutions of NaHSO3 (5%, 5 mL) and NaHCO3 (5%, 5 mL)
were added and the mixture was vigorously stirred 5 min.
Organic layer was separated, dried by Na2SO4 and solvent
removed in vacuum. The analytically pure product was
isolated as an inseparable mixture of E- and Z-isomers 5m
and 5m' (1.0 : 0.4 ratio) by filtration of reaction mixture
through a short silica gel column using petroleum ether as
Procedure 2: To a solution of steroid 4o (55 mg,
0.142 mmol) in CH3CN (2 mL), IBX-OTs 3 (203 mg, 0.45
mmol) was added and stirred for 10 h. Then additional
IBX-OTs 3 (68 mg, 0.15 mmol) was added and the stirring
was continued for 2 h. Then Et2O (3 mL) and aqueous
solutions of NaHSO3 (5%, 1 mL) and NaHCO3 (5%, 3 mL)
were added and the mixture was vigorously stirred 5 min.
Organic layer was separated, dried by Na2SO4 and solvent
removed in vacuum. The resulting oil was separated by
column chromatography to afford product 5o' (17 mg,
31%) and product 5o" (28 mg, 51%) isolated as white
solids.
1
eluent; oil (135 mg, 89%); H NMR and 13C NMR (see
Supporting Information) identical to the spectra of
commercially available sample of citral.
Oxidation of Steroids 4m-4o by IBX-OTs 3 (Scheme 5).
Procedure 3: To a solution of steroid 4o (39 mg, 0.1
mmol) in CH3CN (3 mL), IBX-OTs 3 (48 mg, 0.106
mmol) was added and stirred for 10 h. Then additional
IBX-OTs 3 (136 mg, 0.3 mmol) was added by portions in
the course of 2 h and the stirring was continued for 10 h.
Then Et2O (3 mL) and aqueous solutions of NaHSO3 (5%,
1 mL) and NaHCO3 (5%, 3 mL) were added and the
mixture was vigorously stirred 5 min. Organic layer was
separated, dried by Na2SO4 and solvent removed in
vacuum. The resulting oil was separated by column
chromatography to afford product 5o' (23 mg, 61%) and
product 5o" (6 mg, 16%) isolated as white solids.
General Procedure 1: To a solution of steroid 4 (0.1-
0.2 mmol) in CH2Cl2 (1-2 mL), IBX-OTs 3 (1.05-1.2
equiv) was added under stirring at room temperature.
Reaction mixture was stirred 0.5-6 h (see Table 4;
monitored by TLC and GC-MS). Then Et2O (3 mL) and
aqueous solutions of NaHSO3 (5%, 1 mL) and NaHCO3
(5%, 3 mL) were added and the mixture was vigorously
stirred 5 min. Organic layer was separated, dried by
Na2SO4 and solvent removed in vacuum. The analytically
pure product 5 was isolated by filtration of reaction
mixture through a short silica gel column using petroleum
ether-ethyl acetate (9:1, 4:1) as eluent.
(1S,2R,10S,11S,14R,15R)-14-[(R)-1,5-
Dimethylhexyl]-2,15-
(5R,8R,9S,10S,13S,14S)-10,13-
dimethyltetracyclo[8.7.0.02,7.011,15]heptadeca-3,6-dien-5-
dimethylhexadecahydro-17H-cyclopenta[a]phenanthren-
17-one (5n). Following the general Procedure 1, the
4n (42 mg, 0.152
o
1
one (5o'); mp 110-112 C. H NMR (400 MHz, CDCl3): δ
7.14 (d, J = 10 Hz, 1H), 5.84 (d, J = 10 Hz, 1H), 2.4-2.32
(m, 1H), 2.23-2.17 (m, 1H), 2.03 (dt, J = 12.8 Hz, 3.2 Hz,
1H), 1.94-1.78 (m, 2H), 1.7 (dt, J = 13.2 Hz, 3.6 Hz, 2H),
1.56-1.32 (m, 9H), 1.17-1.04 (m, 9H), 0.99 (s, 4H), 0.92 (d,
J = 6.4 Hz, 3H), 0.85 (dd, J = 6.8 Hz, 2 Hz, 7H), 0.68 (s,
3H). 13C NMR (100 MHz, CDCl3): δ 200.5, 158.8, 127.5,
56.5, 56.3, 50.1, 44.4, 42.8, 41.2, 40.0, 39.6, 39.1, 36.3,
35.9, 35.8, 31.5, 28.4, 28.2, 27.8, 24.3, 24.0, 23.0, 22.7,
18.8, 13.1, 12.3. HRMS (ESI) m/z: [M + Na]+ Calcd for
C27H44ONa 407.3290; Found: 407.3290.
mmol) with IBX-OTs 3 (82 mg, 0.186 mmol) in CH2Cl2 (2
mL) afforded product 5n as a white solid (37 mg, 70%),
mp 114-115 oC. 1H NMR (400 MHz, CDCl3): δ 2.45-2.38
(m, 1H), 2.07-2.00 (m, 1H), 1.94-1.88 (m, 1H), 1.79-1.74
(m, 2H), 1.67-1.64 (m, 3H), 1.55-1.44 (m, 4H), 1.29-1.17
(m, 8H), 1.06-1.04 (m, 1H), 0.98-0.87 (m, 2H), 0.84 (s,
3H), 0.79 (s, 3H), 0.73-0.70 (m, 1H). 13C NMR (100 MHz,
CDCl3): δ 221.7, 55.0, 51.7, 48.0, 47.2, 38.8, 36.6, 36.0,
35.2, 31.8, 31.1, 29.1, 28.9, 26.9, 22.3, 21.9, 20.2, 14.0,
12.4. HRMS (ESI) m/z: [M + Na]+ Calcd for C19H30ONa
297.2194; Found: 297.2199.
(1S,2S,7S,10R,11S,15S)-2,15-
Dimethyltetracyclo[8.7.0.02,7.011,15]heptadecane-5,14-
dione (5o"); mp 109-111 oC. 1H NMR (400 MHz, CDCl3):
δ 7.05 (d, J = 10 Hz, 1H), 6.22 (dd, J = 10 Hz, 2 Hz, 1H),
6.06 (t, J = 1.6 Hz, 1H), 2.43-2.35 (m, 1H), 2.31-2.26 (m,
1H), 1.99-1.94 (m, 1H), 1.91-1.72 (m, 2H), 1.63-1.41 (m,
6H) 1.32-1.19 (m, 4H), 1.16 (s, 3H), 1.11-0.90 (m, 9H),
0.83 (d, J = 6.4 Hz, 3H), 0.79 (dd, J = 6.4 Hz, 1.6 Hz, 6H),
0.67 (s, 3H). 13C NMR (100 MHz, CDCl3): δ 186.6, 169.7,
156.2, 127.6, 123.9, 56.2, 55.6, 52.5, 43.8, 42.8, 39.64,
39.62, 36.2, 35.9, 35.7, 33.8, 33.1, 28.3, 28.2, 24.5, 24.0,
23.0, 22.96, 22.7, 18.8, 18.7, 12.2. HRMS (ESI) m/z: [M +
H]+ Calcd for C27H43O 383.3314; Found: 383.3315.
(8R,9S,10S,13R,14S,17R)-10,13-dimethyl-17-((R)-6-
methylheptan-2-yl)hexadecahydro-3H-
cyclopenta[a]phenanthren-3-one (5o). Following the
general Procedure 1, the reaction of 5α-cholestane-3β-ol 4o
(84 mg, 0.216 mmol) with IBX-OTs 3 (90 mg, 0.2 mmol)
in CH2Cl2 (2 mL) afforded product 5o as a white solid (69
mg, 89%), mp 127-128 oC. 1H NMR (400 MHz, CDCl3): δ
2.42-2.35 (m, 1H), 2.31-2.22 (m, 2H), 2.10-1.96 (m, 3H),
1.84-1.82 (m, 1H), 1.71-1.67 (m, 1H), 1.59-1.48 (m, 5H),
1.49-1.25 (m, 10H), 1.09-1.02 (m, 7H), 1.00 (s, 3H), 0.89
(d, J = 6.8 Hz, 3H), 0.86 (d, J = 1.6 Hz, 3H), 0.85 (d, J = 2
Hz, 3H), 0.67 (s, 3H). 13C NMR (100 MHz, CDCl3): δ
212.4, 56.42, 56.4, 53.9, 46.9, 44.9, 42.7, 40.0, 39.6, 38.7,
38.4, 36.3, 35.9, 35.8, 35.5, 31.9, 29.1, 28.4, 28.2, 24.4,
24.0, 22.7, 21.6, 18.8, 12.2, 11.6. HRMS (ESI) m/z: [M +
H]+ Calcd for C27H47O 387.3627; Found: 387.3617.
Oxidative Dehydrogenation of 5α-cholestane-17β-
ol-3-on 4p (Scheme 5).
Procedure 4: To a solution of steroid 4p (58.5 mg,
0.2 mmol) in CH2Cl2 (3 mL), IBX-OTs 3 was added 3
7
This article is protected by copyright. All rights reserved.

10.1002/adsc.201700776
Advanced Synthesis & Catalysis
times every 2.5 h by portions (3 x 90.5 mg, total 0.6 mmol)
and the stirring was continued for 10 h. Then Et2O (3 mL)
and aqueous solutions of NaHSO3 (5%, 1 mL) and
NaHCO3 (5%, 3 mL) were added and the mixture was
vigorously stirred 5 min. Organic layer was separated,
dried by Na2SO4 and solvent removed in vacuum. The
resulting oil was separated by column chromatography to
afford product 5p (26 mg, 45%) and product 5p' (10 mg,
17%) isolated as white solids.
[5] Ansamitocin: a) G. Jurjens, A. Kirschning, Org. Lett.
2014, 16, 3000-3003; b) T. Frenzel, M. Bruenjes, M.
Quitschalle, A. Kirschning, Org. Lett. 2006, 8, 135-138.
[6] Tonantzitlolon: a) C. Jasper, R. Wittenberg, M.
Quitschalle, J. Jakupovic, A. Kirschning, Org. Lett.
2005, 7, 479-482; b) C. Jasper, A. Adibekian, T. Busch,
M. Quitschalle, R. Wittenberg, A. Kirschning, Chem. -
Eur. J. 2006, 12, 8719-8734; c) G. Draeger, F. Jeske, E.
Kunst, E. G. Lopez, H. V. Sanchez, F. Tsichritzis, A.
Kirschning, J. Jakupovic, Eur. J. Org. Chem. 2007,
5020-5026; d) T. Busch, G. Draeger, E. Kunst, H.
Benson, F. Sasse, K. Siems, A. Kirschning, Org.
Biomol. Chem. 2016, 14, 9040-9045; e) T. J. Pfeffer, F.
Sasse, C. F. Schmidt, S. Lakaemper, A. Kirschning, T.
Scholz, Eur. J. Med. Chem. 2016, 112, 164-170.
(5S,8R,9S,10R,13S,14S)-10,13-dimethyl-
5,6,7,8,9,10,11,12,13,14,15,16-dodecahydro-3H-
cyclopenta[a]phenanthrene-3,17(4H)-dione (5p'); mp 139-
140 oC. 1H NMR (400 MHz, CDCl3): δ 7.13 (d, J = 10. Hz,
1H), 5.87 (d, J = 10 Hz, 1H), 2.50-2.42 (m, 1H), 2.39-2.34
(m, 1H), 2.27-2.21 (m, 1H), 2.13-2.04 (m, 1H), 1.98-1.83
(m, 4H), 1.67-1.59 (m, 2H), 1.57-1.43 (m, 4H), 1.36-1.30
(m, 2H), 1.08-1.01 (m, 5H), 0.90 (s, 3H). 13C NMR (100
MHz, CDCl3): δ 220.6, 200.0, 157.9, 127.8, 51.4, 50.2,
48.0, 44.4, 41.0, 39.2, 35.9, 35.4, 31.6, 30.3, 27.5, 21.8,
20.7, 14.0, 13.2. HRMS (ESI) m/z: [M + Na]+ Calcd for
C19H26O2Na 309.1830; Found: 309.1824.
[7] Elansolid: a) A. Weber, R. Dehn, N. Schlaeger, B.
Dieter, A. Kirschning, Org. Lett. 2014, 16, 568-571; b)
L. L. Wang, D. Candito, G. Draeger, J. Herrmann, R.
Mueller, A. Kirschning, Chem. - Eur. J. 2017, 23,
5291-5298.
Acknowledgements
This work was supported by research grants from the Russian
Science Foundation (RSF-16-13-10081) and the National Science
Foundation (CHE-1262479).
[8]R. Dehn, Y. Katsuyama, A. Weber, K. Gerth, R. Jansen,
H. Steinmetz, G. Hoefle, R. Mueller, A. Kirschning,
Angew. Chem. 2011, 123, 3968-3973; Angew. Chem.,
Int. Ed. 2011, 50, 3882-3887; b) S. L. Boulet, L. A.
Paquette, Synthesis 2002, 895-900.
References
[9]a) A. De Mico, R. Margarita, L. Parlanti, A. Vescovi, G.
Piancatelli, J. Org. Chem. 1997, 62, 6974-6977; b) G.
Piancatelli, F. Leonelli, N. Do, J. Ragan, Org. Synth.
2006, 83, 18-23.
[1] Modern Oxidation Methods (Ed.: J.-E. Backvall),
Wiley-VCH, Weinheim, 2011.
[2] For selected books and recent reviews, see: a) Iodine
Chemistry And Applications (Ed.: T. Kaiho), John
Wiley & Sons, Inc.: Chichester (UK), 2015; b) V. V.
Zhdankin, Hypervalent Iodine Chemistry: Preparation,
Structure and Synthetic Application of Polyvalent
Iodine Compounds; John Wiley & Sons Ltd: Chichester
(UK), 2014; c) Hypervalent Iodine Chemistry [In: Top.
Curr. Chem., 2016; 373] (Ed.: T. Wirth), 2016; d) A.
Yoshimura, V. V. Zhdankin, Chem. Rev. 2016, 116,
3328-3435; e) A. Yoshimura, M. S. Yusubov, V. V.
Zhdankin, Org. Biomol. Chem. 2016, 14, 4771-4781; f)
K. Aradi, B. L. Toth, G. L. Tolnai, Z. Novak, Synlett
2016, 27, 1456-1485; g) T. Dohi, Y. Kita, Curr. Org.
Chem. 2016, 20, 580-615; h) S. V. Kohlhepp, T. Gulder,
Chem. Soc. Rev. 2016, 45, 6270-6288; i) J. Waser,
Synlett 2016, 27, 2761-2773; j) M. S. Yusubov, A.
Yoshimura, V. V. Zhdankin, ARKIVOC 2016, (i), 342-
374; k) J. Charpentier, N. Fruh, A. Togni, Chem. Rev.
2015, 115, 650-682; l) E. A. Merritt, B. Olofsson,
Synthesis 2011, 517-538.
[10] For conversion of alcohol 4e to ketone 5e, see: M.
Beckmann, T. Meyer, F. Schulz, E. Winterfeldt, Chem.
Ber. 1994, 127, 2505-2509.
[11] a) For the oxidation of alcohols with IBX-pyridine,
see: I. M. Kumanyaev, M. A. Lapitskaya, L. L.
Vasiljeva, K. K. Pivnitsky, Mendeleev Commun. 2012,
22, 129-131; b) For complexes of hypervalent iodine
compounds with pyridine and other nitrogen ligands,
see: V. V. Zhdankin, A. Y. Koposov, N. V. Yashin,
Tetrahedron Lett. 2002, 43, 5735-5737, and references
cited therein.
[12] a) J. Muzart, A. N. A. Ajjou, S. Ait-Mohand,
Tetrahedron Lett. 1994, 35, 1989-1990; b) R. Barret, M.
Daudon, Tetrahedron Lett. 1991, 32, 2133-2134.
[13] K. C. Nicolaou, Y. L. Zhong, P. S. Baran, J. Am.
Chem. Soc. 2000, 122, 7596-7597.
[14] J. A. R. Salvador, M. L. Sa e. Melo, A. S. C. Neves,
Tetrahedron Lett. 1993, 34, 361-362.
[3] For selected reviews, see: a) A. Duschek, S. F. Kirsch,
Angew. Chem. 2011, 123, 1562–1590; Angew. Chem.,
Int. Ed. 2011, 50, 1524-1552; b) V. V. Zhdankin, J.
Org. Chem. 2011, 76, 1185-1197; c) V. Satam, A.
Harad, R. Rajule, H. Pati, Tetrahedron 2010, 66, 7659-
7706.
[15] M. Frigerio, M. Santagostino, S. Sputore, J. Org.
Chem. 1999, 64, 4537-4538.
[4] M. S. Yusubov, D. Y. Svitich, A. Yoshimura, V. N.
Nemykin, V. V. Zhdankin, Chem. Commun. 2013, 49,
11269-11271.
8
This article is protected by copyright. All rights reserved.

10.1002/adsc.201700776
Advanced Synthesis & Catalysis
FULL PAPER
2-Iodoxybenzoic Acid Tosylates: the Alternative to
Dess-Martin Periodinane Oxidizing Reagents
Adv. Synth. Catal. Year, Volume, Page – Page
Mekhman S. Yusubov,* Pavel S. Postnikov, Roza
Ya. Yusubova, Akira Yoshimura, Gerrit Jürjens,
Andreas Kirschning,* and Viktor V. Zhdankin*
9
This article is protected by copyright. All rights reserved.