Bidentate Nitrogen-Ligated I(V) Reagents, Bi(N)-HVIs: Preparation, Stability, Structure, and Reactivity

Article abstract of DOI:10.1021/acs.joc.1c00375

Hypervalent iodine(V) reagents are a powerful class of organic oxidants. While the use of I(V) compounds Dess-Martin periodinane and IBX is widespread, this reagent class has long been plagued by issues of solubility and stability. Extensive effort has been made for derivatizing these scaffolds to modulate reactivity and physical properties but considerable room for innovation still exists. Herein, we describe the preparation, thermal stability, optimized geometries, and synthetic utility of an emerging class of I(V) reagents, Bi(N)-HVIs, possessing datively bound bidentate nitrogen ligands on the iodine center. Bi(N)-HVIs display favorable safety profiles, improved solubility, and comparable to superior oxidative reactivity relative to common I(V) reagents. The highly modular synthesis and in situ generation of Bi(N)-HVIs provides a novel and convenient screening platform for I(V) reagent and reaction development.

Full text of DOI:10.1021/acs.joc.1c00375

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Article
Bidentate Nitrogen-Ligated I(V) Reagents, Bi(N)‑HVIs: Preparation,
Stability, Structure, and Reactivity
Xiao Xiao, Jessica M. Roth, Nathaniel S. Greenwood, Maria K. Velopolcek, Jordan Aguirre, Mona Jalali,
Alireza Ariafard, and Sarah E. Wengryniuk*
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ABSTRACT: Hypervalent iodine(V) reagents are a powerful class of
organic oxidants. While the use of I(V) compounds Dess−Martin
periodinane and IBX is widespread, this reagent class has long been
plagued by issues of solubility and stability. Extensive effort has been
made for derivatizing these scaffolds to modulate reactivity and physical
properties but considerable room for innovation still exists. Herein, we
describe the preparation, thermal stability, optimized geometries, and
synthetic utility of an emerging class of I(V) reagents, Bi(N)-HVIs,
possessing datively bound bidentate nitrogen ligands on the iodine center. Bi(N)-HVIs display favorable safety profiles, improved
solubility, and comparable to superior oxidative reactivity relative to common I(V) reagents. The highly modular synthesis and in situ
generation of Bi(N)-HVIs provides a novel and convenient screening platform for I(V) reagent and reaction development.
can require linear and sometimes lengthy synthetic sequences,
making individual reaction optimization using these handles
impractical.7a Therefore, the continued development of new
scaffolds and, in particular, those capable of generating soluble,
stable, low-cost, and readily tunable I(V) reagents remains of
considerable interest.
In 2002, Zhdankin reported a bidentate nitrogen-ligated
I(V) species with a 2,2′-bipyridine ligand (Figure 1B, 10, R =
H);9 however, no further studies on its reactivity or potential
synthetic utility were described. Based on the work of our
laboratory and others regarding (bis)cationic nitrogen-ligated
I(III) reagents, or N-HVIs (9), which display enhanced and
unique reactivity relative to typical ArIX2 reagents,10 we
hypothesized that the analogous nitrogen-ligated I(V)
compounds, which we have termed Bi(N)-HVIs (10),
warranted further study. In addition to their potential novel
reactivity, our prior work indicated that the bidentate nitrogen
ligands could provide a convenient and modular handle for
tuning reactivity and thus offer a practical advantage over
current I(V) scaffolds.
INTRODUCTION
■
Hypervalent iodine reagents (HVIs) have received tremendous
attention from the synthetic community in recent years. HVIs,
commonly seen in both the I(III) and I(V) oxidation state, are
environmentally benign, inexpensive, and versatile oxidants,
providing an attractive alternative to metal-based reagents
across a wide range of transformations.1 I(V) species are
effective reagents for heteroatom oxidation,1e arene dearoma-
tization,1f and ketone desaturation;1g however, their applica-
tions have long been plagued by practical and safety
limitations.1,2 The simplest I(V) reagents, the acyclic
iodylbenzene (1, PhIO2) or cyclic IBX2c,d (5), are polymeric
in nature due to intermolecular I···X interactions, resulting in
generally poor solubility in most common organic solvents.2b,3
Furthermore, the low thermal and shock stability of PhIO2 and
IBX has been well-documented, posing a significant safety
hazard and limiting their scalability (Figure 1A).2,4 In an effort
to address these limitations, an array of pseudocyclic (2−4)
and cyclic (6−8) I(V) derivatives have been developed that
possess intramolecular I···X bonding interactions that disrupt
the polymeric nature, or arene, X-ligand, or benziodoxolone
variations to tune reactivity, leading to more soluble, practical,
and efficient oxidants.5−7 In particular, the venerable Dess−
Martin periodinane (DMP, 6), derived upon acylation of IBX
with Ac2O,8 has seen broad application in natural product
synthesis due to its superior solubility, selective reactivity, and
commercial availability; however, the high cost and moisture
sensitivity pose challenges for its large-scale preparation and
storage. While it has been demonstrated that these strategies
are effective in modulating reactivity and stability of I(V)
scaffolds, the derivatives often still possess safety concerns and
We recently reported the first synthetic application of Bi(N)-
HVIs in the oxidative dearomatization of electron-deficient
phenols to o-quinones (11 to 12, Figure 1B).11 These
substrates have proven resistant to oxidation with almost all
Received: February 15, 2021
Published: April 19, 2021
https://doi.org/10.1021/acs.joc.1c00375
© 2021 American Chemical Society
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RESULTS AND DISCUSSION
Synthesis of Bi(N)-HVIs. Bi(N)-HVIs can be synthesized
in accordance with Zhdankin’s originally reported procedure,
starting from commercial iodylbenzene (1).9 Due to its
insolubility, iodylbenzene must first be converted to the
bis(acetoxy)iodylbenzene (PhI(O)(OAc)2, 13) by stirring in
neat acetic anhydride followed by concentration (Scheme 1).
■
Scheme 1. Synthesis and Isolation of I(V) Bi(N)-HVIs
Figure 1. Common I(V) reagents and Bi(N)-HVI synthesis and
reactivity.
known oxidants, demonstrating the novel reactivity of Bi(N)-
HVIs.12 The Bi(N)-HVIs could be isolated or prepared in situ
from iodylbenzene, and commercially available bidentate
nitrogen ligands were found to be soluble in common organic
solvents and, as we had postulated, modulating the nitrogen
ligand had a marked effect on reactivity. Given these promising
preliminary findings, we conducted a more detailed study on
the synthesis and reactivity of Bi(N)-HVI to probe their
general utility as synthetic oxidants.
Herein, we report on the synthesis, isolation, and stability of
Bi(N)-HVI derivatives as well as their reactivity in a panel of
representative oxidative transformations. The Bi(N)-HVIs can
be isolated or used in situ, display good solubility, have
favorable safety profiles, and exhibit robust reactivity.
Thermogravimetric analysis (TGA) indicates that Bi(N)-
HVIs possess superior thermal stability to common I(V)
reagents, addressing a long-standing liability of this reagent
class. Computationally derived structures for isolable deriva-
tives are reported, which provide insights into the coordination
environment and geometry around the iodine center to aide in
further reagent design. Their reactivity in alcohol and sulfide
oxidation as well as ketone desaturation is found to be
equivalent or superior to current I(V) reagents. Across these
transformations, a different N-ligand was found to be the most
effective in each case, further demonstrating the role of the N-
ligands in tuning and modulating reactivity and demonstrating
the potential of Bi(N)-HVIs as a convenient, operationally
simple I(V) platform for reaction screening and development.
This has been performed in our laboratory on up to 1.5 g scale
to give 13 in quantitative yield, which can then be stored at
−20 °C under argon for up to 1 month; however, it is prone to
loss of −OAc with reversion back to PhIO2, so purity should
1
be checked by H NMR prior to use. Treatment of 13 with
TMSOTf, presumed to give a highly active triflate
intermediate,13 is followed by the addition of nitrogen ligand
to give the desired Bi(N)-HVI. To date, we have investigated a
range of bidentate nitrogen ligands (14−26) in this Bi(N)-
HVI synthesis. In our previous report, Bi(N)-HVIs incorporat-
ing ligands 14−26 were all synthesized and used in situ and
their presence was inferred by the successful subsequent
1
reaction or by H NMR without isolation. In this study, the
focus was on identifying and fully characterizing isolable
derivatives. Of the compounds previously synthesized, only
four Bi(N)-HVIs proved consistently isolable; two bipyridine
(27 and 28) and two phenanthroline (29 and 30) derivatives
were isolated in good-to-high yields after crystallization
(Scheme 1). Even within the scope of the isolable compounds,
identity of the nitrogen ligand did have a notable effect on
stability; Bi(bipy)-HVI 27 and Bi(4-MeO-bipy)-HVI 28 can be
stored at −20 °C for up to 1 month, whereas Bi(phen)-HVI 29
and Bi(5-Mephen)-HVI 30 have to be used immediately or
isolated and stored in a glovebox, due to significant moisture
sensitivity. Several practical considerations could be taken from
our studies: (1) the Bi(N)-HVIs display good solubility in a
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Figure 2. TGA for decomposition of I(V) reagents: Bi(bipy)-HVI 27 (red), Bi(4-MeObipy)-HVI 28 (green), precursor PhI(O)(OAc)2 13 (black),
and IBX 5 (blue).
Figure 3. Optimized geometries for Bi(bipy)HVI (27-min, 1−4).
range of common organic solvents including CH3CN, dimethyl
sulfoxide (DMSO), MeOH, CH2Cl2, and CHCl3, a broader
and more practical selection than many common I(V)
reagents. (2) Decomposition back to PhIO2 and free ligand
was the primary method of degradation, occurring during
attempts at crystallization, trituration, or upon prolonged
exposure to moisture and with the propensity affected by the
identity of the N-ligand.
Thermal Stability of Bi(N)-HVIs. A common concern
when using hypervalent iodine reagents, and in particular I(V)
compounds, is their thermal instability. PhIO2 and IBX have
both been reported to undergo violent exothermic decom-
position at temperatures around 200 °C, leading to significant
concerns when working on scale.1a−d,4 As the stability of
Bi(N)-HVIs had yet to be studied, we sought to establish their
thermal safety profiles. For these studies, only Bi(bipy)-HVI
(27) and Bi(4-MeObipy)-HVI (28) were bench-stable for long
enough periods of time to perform reliable analyses. The
thermal decomposition profiles of 27 and 28, as well as
PhI(O)(OAc)2 (13) and IBX (5), were examined using TGA
(Figure 2). IBX (5) experienced two-stage degradation with
initial onset temperature at 103 °C and a second and steeper
decomposition at 230 °C, which is consistent with the reported
decomposition temperature of 233 °C.4 PhI(O)(OAc)2 (13)
underwent a steep and single stage decomposition at an onset
temperature of 227 °C with an abrupt decomposition at 240
°C. In contrast, we were pleased to see that both Bi(N)-HVI
reagents displayed gradual decomposition profiles; the onset
points for Bi(bipy)-HVI 27 and Bi(4-MeO-bipy)-HVI 28 were
164 °C and 179 °C, respectively, with relatively gradual
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degradation curves in the range 200−600 °C. These results
indicate that while the PhI(O)(OAc)2 (13) precursor should
be handled with caution, Bi(N)-HVI reagents seem to offer
improved thermal stability relative to IBX (5), potentially
providing safer I(V) alternatives. A complete description of the
samples’ thermal properties can be found in the Supporting
Information.
Optimized Geometries of Bi(N)-HVIs. Due to the
potential implications on reactivity and subsequent reagent
design, we were interested in gaining insights into the
geometry and coordination environment at the I(V) center
of Bi(N)-HVIs. Despite extensive efforts, all attempts to obtain
crystals for X-ray structural analysis were unsuccessful. In lieu
of crystallographic data, we turned to the computational study
of the reagent scaffolds. We have undertaken the density
functional theory calculations at the SMD/M06-2X/def2-
TZVP//SMD/M06-2X/LANL2DZ(d),6-31G(d) level of
theory for obtaining structure and energy of various isomers
of bipyridine-ligated Bi(bipy)-HVI (27).14
should not be presumed that 27-min1 would be the
predominant reactive isomer in solution.14
Reactivity Profiling. With reliable syntheses and en-
couraging safety data in hand, attention turned for establishing
the utility of Bi(N)-HVIs as practical synthetic oxidants. As
previously mentioned, the reactivity of Bi(N)-HVIs in the
dearomatization of electron-deficient phenols to o-quinones
has already been reported by our laboratory and the results are
briefly summarized in Scheme 2. I(V) reagents have emerged
Scheme 2. Dearomatization of Electron-Poor Phenols to
ortho-Quinones with Bi(4-CO2Etbipy)-HVI11
The four lowest energy isomers for Bi(bipy)-HVI (27-
min1−27-min4) are shown in Figure 3, with selected bond
distances and angles for the lowest energy isomer 27-min1,
presented in Table 1. 27-min1 adopts a distorted octahedral
Table 1. Selected Bond Distances and Angles in 27-min1
bond lengths
distance [Å]
bond angles
degree (deg)
I1−C1
I1−O1
I1−O2
I1−O3
I1−N1
I1−N2
2.106
1.763
2.231
2.732
2.235
2.567
C1−I1−N1
C1−I1−N2
C1−I1−O2
C1−I1−O3
O1−I1−N2
O2−I1−N1
N1−I1−N2
86.2
82.8
84.5
151.3
157.3
170.1
67.7
geometry around the iodine(V) center, with the oxo (O1),
bidentate nitrogen ligand (N1 and N2), and a triflate anion
(O2) occupying equatorial positions.15 The aryl ring occupies
one axial position while another, more weakly bound, triflate
anion is bound in a pseudoaxial position, with a distortion
toward the heterocyclic ligand. All of the equatorial ligands
form slightly acute bond angles with an I1−C1 iodine−carbon
bond with bond angles ranging from 82.8166 to 86.2108°. This
basic ligand geometry, with equatorial positioning of X-ligands
and an axial carbon substituent, is in accordance with
previously reported X-ray structures of I(V) reagents.3a,14−16
Closer examination of 27-min1 reveals that the binding of the
bipyridine ligand is unsymmetrical, with significantly different
bond lengths of I1−N1 2.235 Å and I1−N2 2.567 Å for those
trans to the triflate and oxo, respectively. The two heterocycles
of the bipyridine ligand are also not completely coplanar, with
a dihedral angle of 10.8° between the two nitrogens. The other
isomers, 27-min2−27-min4, range from 3.3 to 10.6 kcal mol−1
less stable than 27-min1. 27-min2 results from an axial-
equatorial isomerization of a triflate (O3) and one of the
bipyridine nitrogens (N2). 27-min3 shows dissociation of the
axial nitrogen in 27-min2, and 27-min4 has only one bound
triflate anion (unbound −OTf has been omitted for clarity),
but otherwise the coordination geometry most closely
resembles that of 27-min1. It should be noted that recent
computational studies on IBX-mediated oxidations have
indicated that isomerization to a less stable isomer precedes
either ligand exchange or substrate oxidation, and thus, it
a
Yields reported are of combined C2/C6 oxidation products as they
were inseparable. The C2/C6 ratio is reported in parentheses.
as leading oxidants for the regioselective dearomatization of
phenols to o-quinones and o-quinols; however, phenols lacking
electron-donating groups are typically unreactive.1f Through
the use of Bi(N)-HVIs, we described the first general method
for the dearomatization of electron-deficient phenols to o-
quinones. In situ Bi(4-CO2Etbipy)-HVI 31 was found to be the
most effective and general reagent; however, other derivatives
also showed significant activity against these challenging
substrates.11 Computational studies to further understand the
mechanism and unique reactivity of Bi(N)-HVIs in these
oxidations are currently underway and will be reported in due
course. Building on these findings, we now examine their
reactivity in alcohol oxidation, sulfide oxidation, and ketone
desaturation, all common transformations mediated by I(V)
reagents.
Oxidation of Alcohols. We began by investigating the
reactivity of Bi(N)-HVIs in the oxidation of alcohols. While
the use of DMP for this transformation is ubiquitous due to its
commercial availability, solubility, and mild reaction con-
ditions, it is also expensive and prone to hydrolysis, and its
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reactivity is not tunable, leaving room for potential
improvement.1e,2 Initial screening consisted of using both the
isolated and in situ-generated Bi(bipy)-HVI 27 alongside
several common I(V) reagents in the oxidation of 1-
phenylethanol (57) to acetophenone (58) (Table 2). As
Table 3. Ligand Screening for In Situ Bi(N)-HVI Oxidation
of 1-Phenylethanol
a
a
Table 2. Oxidation of 1-Phenylethanol
b
entry
reagents
time
yield (%)
97
1
2
3
4
5
6
7
8
DMP
IBX
PhIO2
30 min
24 h
24 h
24 h
2 h
2 h
24 h
24 h
c
33 (82)
trace
de
,
o-tBuSO2PhIO2 (59)
27 (isolated)
27 (in situ)
PhIO(OAc)2 (13)
PhIO(OAc)2, TMSOTf
87
90
a
All the reactions were carried out with the 0.2 mmol scale in CH2Cl2
e
1
90 (88)
0
(0.2 M) and reported yields were determined by HNMR with 1,2-
dibromoethane as the internal standard.
f
10
a
Reactions were carried out on the 0.2 mmol scale in CH2Cl2 (0.2
Table 4. Alcohol Scope with In Situ Bi(bipy)-HVI
Oxidation
b
a
M). NMR yields, determined with 1,2-dibromoethane as the internal
standard. DMSO was used as a solvent. Low yield in CH2Cl2 due to
limited solubility. Nitromethane was used as a solvent. Isolated
yield. Complex mixture of products.
c
d
e
f
expected, DMP (6) gave the desired product with excellent
yield after just 30 min (entry 1). Both IBX (5) and PhIO2 (1)
performed poorly in CH2Cl2 due to insolubility (entries 2, 3),
which could be alleviated in the case of IBX by running the
reaction in DMSO to give 82% yield. Oxidation with
pseudocyclic iodylarene o-tBuSO2PhIO2 (59) gave good yields
but only when performed in NO2Me, in accordance with the
literature.5 We were pleased to see that both the isolated (entry
5) and in situ (entry 6) Bi(bipy)-HVI (27) performed
comparably to DMP, giving ketone 58 in 90% yield after 2
h. Low conversions obtained from control experiments with
Bi(N)-HVI precursors, PhIO(OAc)2 (13) (entry 7), and the
highly active intermediate generated upon treatment with
TMSOTf (entry 8) supported that the Bi(bipy)-HVI complex
was the active oxidant under the in situ conditions.
To identify the most efficient Bi(N)-HVI, a ligand screen
was then conducted under in situ conditions (Table 3). In
almost all cases, good-to-high yields were obtained, with
electron-deficient 4-NO2-bipy (16) and 5,5′-Clphen (25)
ligands giving the lowest yields, at least in part due to poor
solubility of the resulting Bi(N)-HVIs. Along with simple
bipyridine (14), 4-CO2Etbipy (15) and 5,5′-Mephen (26) gave
the best yields at greater than 90% in all cases. The use of
monodentate pyridine did not afford any desired product, as
seen in our prior dearomatization report,11 supporting the
importance of a bidentate ligand. Due to the low cost and
commercial availability, bipyridine was selected as the optimal
ligand for further studies of Bi(N)-HVI alcohol oxidation.
The substrate scope was then examined using in situ
Bi(bipy)-HVI 27 (Table 4). Efficient oxidation of cyclic,
acyclic, aliphatic, and aromatic secondary alcohols proceeded
in good-to-excellent yields to give 58−66. Controlled
oxidation of 2-phenyl-ethanol to aldehyde 67 could also be
achieved in 71% yield. Steroid derivatives 68 and 69 possessing
a tertiary alcohol, enone, and free carboxylic acid between
them were also oxidized in 93 and 80%, respectively, including
a
All the reactions were carried out on the 0.2 mmol scale in CH2Cl2
1
(0.2 M) and reported yields were determined by HNMR with 1,2-
dibromoethane as the internal standard unless otherwise noted.
b
c
Isolated yield. 2.2 equiv in situ Bi(bipy)-HVI was used.
a double oxidation in the case of 69. This study demonstrates
the utility of in situ Bi(bipy)-HVI 27 as a cost-effective,
practical alternative to DMP or IBX for alcohol oxidation.
Sulfide oxidation. I(V) reagents have also found broad
application in the controlled oxidation of sulfides to
sulfoxides.1,6a,f,17 Screening of in situ Bi(N)-HVIs in the
oxidation of thioanisole revealed that the more electron-rich
Bi(4-MeObipy)-HVI 28 provided the best and most consistent
yields of sulfoxide products (Table 5).18 Applying the
optimized conditions to a panel of electronically diverse aryl
sulfides, a similar trend emerged to that of Bi(N)-HVI-
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very short reaction times to achieve high yields. The small
scope study shown in Table 6 demonstrates that while
Bi(phen)-HVI 29 is capable of achieving desaturation, its utility
is somewhat limited relative to other I(V) reagents such as
IBX. The reason for the inferior reactivity in this case remains
unclear; however, based on Nicolaou’s proposed mechanism,1g
we propose two possible explanations: (1) Bi(N)-HVIs are
less-efficient single-electron oxidants than other I(V) species or
(2) the lack of dissociating hydroxyl ligands to act as a base
hinders the desaturation process.
Table 5. Sulfide Oxidation with In Situ Bi(4-MeObipy)-
HVI
a
CONCLUSIONS
■
In conclusion, we have reported on the synthesis, stability, and
reactivity profiling of novel derivatives of bidentate nitrogen-
ligated I(V) reagents, or Bi(N)-HVIs. These reagents can be
synthesized and used in situ, or we have now identified four
isolable derivatives some of which can be stored for extended
periods. Bi(N)-HVIs have improved solubility in common
organic solvents relative to traditional I(V) reagents and TGA
analysis revealed favorable thermal stability profiles for
Bi(bipy)-HVI 27 and Bi(4-MeObipy)-HVI 28 relative to
PhI(O)(OAc)2 or IBX, providing a practical and potentially
safer alternative to long-standing I(V) reagents. Computational
study of Bi(bipy)-HVI 27 revealed the four lowest energy
geometries and provided the first insights into the coordination
environment and geometry at the iodine center. In addition to
our prior report on phenol dearomatization, Bi(N)-HVI
reactivity has now been demonstrated in alcohol and sulfide
oxidation, as well as ketone desaturation, with each process
optimized to use a different bidentate nitrogen ligand. With the
exception of ketone desaturation, Bi(N)-HVIs performed
equivalently or superior to I(V) oxidants such as IBX, DMP,
or pseudocyclic analogues, while often enabling the use of a
more convenient solvent or milder temperature. As a result of
their facile synthesis and breadth of available bidentate
heterocyclic scaffolds, Bi(N)-HVIs provide an I(V) reagent
design platform with unprecedented modularity and tunability.
Studies to further elucidate the structure, mechanism, and
synthetic applications of these reagents are ongoing in our
laboratory.
a
All the reactions were carried out with the 0.1 mmol scale in CDCl3
(0.05 M) and yields were determined by 1HNMR with 1,2-
dibromoethane as the internal standard. Isolated yield. −78 °C in
CH2Cl2.
b
c
mediated phenol dearomatization; the more electron-deficient
aryl sulfides 70−72 were oxidized to sulfoxides in high yields,
whereas the more reactive, electron-rich derivatives 73−75
gave low-to-moderate yields along with unidentified by-
products. The electronic trend was counteracted to some
extent by lowering the reaction temperatures; however, yields
remained low. This trend is opposite to that of other I(V)-
mediated sulfide oxidations, wherein more electron-rich
substrates are more readily and cleanly oxidized.1,6a,f,17
Ketone Desaturation. Since Nicolaou and Baran’s pioneer-
ing reports on the use of IBX/DMSO,1g,19a,b the use of this and
other I(V) reagents for ketone desaturation has become a
staple of organic synthesis.1,19c Upon screening in situ Bi(N)-
HVIs in this transformation, it was found that in situ 1,10-
phenanthroline-ligated Bi(phen)-HVI 29 was effective in the
desaturation of cyclohexanone, while other Bi(N)-HVIs
showed markedly lower activity (Table 6).18 Several other
notable reaction features included the use of acetonitrile as a
solvent, which was previously ineffective, as well as the need for
EXPERIMENTAL SECTION
a
■
Table 6. Ketone Desaturation with In Situ Bi(phen)-HVIs
General Information. 1H and 13C NMR spectra were recorded at
500 MHz and 125 MHz on a Bruker ADVANCE 500, 500 MHz and
125 MHz on a Bruker ADVANCE III HD, or 400 and 100 MHz on a
1
Bruker ADVANCE 400. H NMR chemical shifts were reported in
parts per million (ppm) from the solvent resonance (CDCl3 7.26
ppm, CD3CN 1.94 ppm, DMSO-d6 2.50 ppm). The data were
reported as follows: chemical shift number, multiplicity (s = singlet, d
= doublet, t = triplet, sept = septet, dd = doublet of doublets, dt =
doublet of triplets, td = triplet of doublets, m = multiplet, and br =
broad signal). Proton decoupled attached proton test 13C NMR shifts
were reported in ppm from the solvent resonance (CDCl3 77.16 ppm,
CD3CN 1.32 ppm, 118.26 ppm, DMSO-d6 39.52 ppm). The reaction
solvent CDCl3 was neutralized through basic alumina and CD3CN
was used from commercial sources without further purification. All
the other reaction solvents were anhydrous (HPLC-grade solvent
passed through an activated-alumina column). TMSOTf and pyridine
were freshly distilled over CaH2 and stored over molecular sieves
under Ar. All other reagents were used without further purification
unless otherwise noted. Flash chromatography was carried out using
Sorbent Technologies silica gel 60 Å (40−63 μm) in the solvent
system listed in the individual experiments. The reactions were
monitored by 1H NMR or analytical thin-layer chromatography
(TLC) on Merck silica gel (60 F2s4) plates. Accurate masses for
a
All the reactions were carried out on the 0.1 mmol scale in CD3CN
(0.05 M) and yields were determined by 1H NMR with 1,2-
dibromoethane as the internal standard. Isolated yield.
b
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derivatized products were conducted on an Agilent 6520 Accurate-
Mass Q-TOF LC/MS. Samples were taken up in a suitable solvent for
analysis. The signals were mass measured against an internal lock
mass reference of perfluorotributylamine for EI-GCMS and leucine
enkephalin for ESI-LCMS. Waters software calibrates the instruments
and reports measurements, by the use of neutral atomic masses. The
mass of the electron is not included. Infrared spectra were obtained
using a Thermo Nicolet iS5 FTIR spectrometer with an iD5 ATR
accessory. Melting points were obtained on a Standford Research
Systems MPA100 OptiMelt automated melting point system and are
uncorrected.
Hz, 2H), 9.10 (dd, J = 8.5, 1.5 Hz, 2H), 8.38 (s, 2H), 8.25 (dd, J =
8.5, 4.5 Hz, 2H), 8.08−18.05 (m, 2H), 7.73−7.63 (m, 3H); 13C{1H}
NMR (125 MHz, DMSO-d6): δ 149.7, 147.7, 142.1, 137.4, 133.1,
130.1, 129.7, 127.7, 127.1, 125.9, 120.8 (q, J = 320.3 Hz); Anal. Calcd
for C20H15F6IN2O7S2·2H2O: C, 32.62; H, 2.60; N, 3.80. Found: C,
32.17; H, 2.86; N, 3.83.
1,10-(5,5′-Me)Phenathrolyl λ5-Iodane Bistriflate; Bi(Mephen)-HVI
(30). Prepared according to general procedure A. After removing the
reaction solvent in vacuo, the resulting solids were washed with
CH2Cl2 (1 × 20 mL, 2 × 5 mL) to give 30 as a white solid (0.463 g,
1
61% yield). H NMR (500 MHz, DMSO-d6): δ 8.92 (d, J = 8.5 Hz,
Hypervalent iodine reagents PhIO2,20 2-t-BuSO2PhIO2,6e and
ligand 1621 and 2522 were synthesized according to the corresponding
literature procedures.
2H), 8.25 (s, 2H), 8.09 (d, J = 8.0 Hz, 2H), 8.09−8.07 (m, 2H),
7.72−7.64 (m, 3H), 3.04 (s, 6H); 13C{1H} NMR (125 MHz, DMSO-
d6): δ 159.1, 149.7, 141.5, 137.2, 136.6, 132.9, 130.7, 129.9, 127.8,
127.7, 127.0, 126.8, 126.6, 120.7 (q, J = 320.1 Hz), 22.9; Anal. Calcd
for C22H19F6IN2O7S2·2H2O: C, 34.57; H, 2.60; N, 3.66. Found: C,
34.29; H, 2.30; N, 3.17.
General Procedure B: Oxidation of Alcohols with Bi(N)-HVI.
To a flame-dried flask with a stir bar were added bis(acetoxy)-
iodylbenzene (13) (74.4 mg, 0.22 mmol) in dry CH2Cl2 (0.1 M, 2
mL) followed by dry TMSOTf (80.0 μL, 0.44 mmol), generating a
clear solution which was stirred for 5 min. 2,2′-Bipyridine (34.4 mg,
0.22 mmol) was then added, followed by desired alcohol (0.2 mmol).
Reactions were monitored by TLC. In cases where yield was
determined by 1H NMR yields, the crude reaction mixtures were
filtered to remove a white solid (bipy·OTf), concentrated in vacuo,
and dissolved in CDCl3, and 1,2-dibromoethane (8.7 μL, 0.1 mmol,
internal standard) was added. For isolated yields, the crude reaction
mixtures were concentrated in vacuo and purified by flash
chromatography.
Acetophenone (58). Prepared according to general procedure B
from 1-phenyl-1-ethanol. Purified via flash chromatography (5%
EtOAc/Hex) and isolated as colorless oil (21.1 mg, 88% yield). A
large-scale reaction was performed on 3.95 mmol 1-phenyl-1-ethanol
to give 58 (0.411 g, 87% yield). The spectroscopic data for 58 are
consistent with that previously reported.24 1H NMR (500 MHz,
CDCl3): δ 7.97−7.95 (m, 2H), 7.57 (d, J = 7.5 Hz, 1H), 7.49−7.45
(m, 2H), 2.61 (t, 3H).
Cyclohexanone (59). Prepared according to general procedure B
from cyclohexanol (82% NMR yield). The spectroscopic data for 59
are consistent with that previously reported.25 1H NMR (500 MHz,
CDCl3): δ 2.34 (t, J = 6.5 Hz, 4H), 1.89−1.84 (m, 4H), 1.75−1.69
(m, 2H).
2-Methyl Cyclohexanone (60). Prepared according to general
procedure B from 2-methyl cyclohexanol (84% NMR yield). The
spectroscopic data for 60 are consistent with that previously
reported.26 1H NMR (500 MHz, CDCl3): δ 2.43−2.34 (m, 2H),
2.33−2.25 (m, 1H), 2.12−2.08 (m, 2H), 1.89−1.80 (m, 1H), 1.72−
1.61 (m, 2H), 1.43−1.33 (m, 1H), 1.02 (d, J = 6.5 Hz, 3H).
2-Isopropyl Cyclohexanone (61). Prepared according to general
procedure B from cis-2-isopropyl cyclohexanol (68% NMR yield).
The spectroscopic data for 61 are consistent with that previously
reported.27 1H NMR (500 MHz, CDCl3): δ 2.44−2.31 (m, 2H),
2.29−2.23 (m, 1H), 2.11 (sep, J = 6.5 Hz, 1H), 2.00−1.90 (m, 2H),
1.89−1.81 (m, 1H), 1.77−1.68 (m, 1H), 1.65−1.51 (m, 2H), 0.89 (d,
J = 4.4 Hz, 3H), 0.87 (d, J = 4.3 Hz, 3H).
Cyclohexenone (62). Prepared according to general procedure B
from cyclohexanol (68% NMR yield). The spectroscopic data for 62
are consistent with that previously reported.28 1H NMR (500 MHz,
CDCl3): δ 7.00 (dt, J = 10.5, 4.0 Hz, 1H), 6.03 (dt, J = 10.5, 2.0 Hz,
1H), 2.44 (t, J = 6.5 Hz, 2H), 2.38−2.34 (m, 2H), 2.05−1.99 (m,
2H).
The dearomatization of electron-poor phenols with Bi(N)-HVIs
(Scheme 2) was previously reported by our group and a summary of
the key findings was included here for the sake of completion.
Detailed experimental procedures and full characterization for
compounds 32−56 can be found in our prior publication.11
Synthesis of Bis(acetoxy)iodylbenzene (13). Procedure is in
accordance with that reported by Yagupolski.23 To a 100 mL round-
bottom flask containing iodylbenzene (0.5 g, 2.1 mmol) was added
acetic anhydride (60 mL), and the mixture was stirred at room
temperature for 3 h. Acetic anhydride was then removed in vacuo to
give PhIO(OAc)2 (13) as white powder in quantitative yield. Note:
PhI(O)(OAc)2 can be reliably stored for up to ∼1 month at −20 °C
1
under argon. H NMR (500 MHz, CDCl3/TFA): δ 8.33−8.03 (m,
2H), 7.93−7.60 (m, 3H), 2.17 (s, 6H); 13C{1H} NMR (125 MHz,
DMSO-d6): δ 172.0, 150.9, 131.4, 129.0, 126.5, 21.1.
General Procedure A: Synthesis of Isolable Bi(N)-HVI
Reagents (27−30). Procedure is in accordance with that reported
by Zhdankin.9 To a flame-dried flask under argon were added
bis(acetoxy)iodylbenzene (13) (0.388 g, 1.0 mmol) and dry CH2Cl2
(20 mL) to generate a white suspension. Distilled TMSOTf (0.36 mL,
2.0 mmol) in 10 mL of dry CH2Cl2 was then added, to generate a
homogenous, clear solution. A solution of nitrogen ligand (1.0 mmol)
in 20 mL of dry CH2Cl2 was then added slowly and the reaction
mixture was stirred for 30 min followed by the removal of solvent via
a rotary evaporator. The residue was then treated with dry CH2Cl2
(∼30 mL) with gentle heating to 38 °C. The solution was carefully
decanted to a new flask to avoid any insoluble byproducts. This
solution was then treated with hexanes (∼20 mL) and placed in a
freezer, affording the desired Bi(N)-HVI as a white solid.
2,2′-Bipyridyl λ5-Iodane Bistriflate; Bi(bipy)-HVI (27). Prepared
according to general procedure A to give 27 as a white solid (0.505 g,
75% yield). The spectroscopic data for Bi(bipy)-HVI (27) are
consistent with that previously reported.9,11 1H NMR (500 MHz,
1:20 TFA/CDCl3): δ 9.15 (d, J = 5.6 Hz, 2H), 8.93 (t, J = 8.0 Hz,
2H), 8.70 (d, J = 8.0 Hz, 2H), 8.37 (dd, J = 7.8, 5.9 Hz, 2H), 8.10−
8.04 (m, 2H), 7.81−7.70 (m, 3H); 1H NMR (500 MHz, DMSO-d6):
δ 8.82 (d, J = 5.0 Hz, 2H), 8.56 (d, J = 8.0 Hz, 2H), 8.26 (dt, J = 8.0,
1.5 Hz, 2H), 8.37 (dt, J = 8.0, 1.5 Hz, 2H), 7.75−7.71 (m, 2H), 7.70−
7.63 (m, 3H); 13C{1H} NMR (125 MHz, DMSO-d6): δ 149.7, 148.8,
147.1, 142.0, 132.8, 129.8, 127.0, 126.7, 123.2; Anal. Calcd for
C18H13F6IN2O7S2·2H2O: C, 30.44; H, 2.41; N, 3.94. Found: C, 30.94;
H, 2.10; N, 3.44.
2,2′-(4,4′-MeO)Bipyridyl λ5-Iodane Bistriflate; Bi(4-MeObipy)-HVI
(28). Prepared according to general procedure A to give 28 as a white
1
solid (0.410 g, 56% yield). H NMR (500 MHz, DMSO-d6): δ 8.69
(d, J = 6.5 Hz, 2H), 8.24 (d, J = 2.5 Hz, 2H), 8.07 (dd, J = 8.5, 1.5 Hz,
2H), 7.71−7.63 (m, 3H), 7.44 (dd, J = 6.0, 2.5 Hz, 2H), 4.09 (s, 6H);
Anal. 13C{1H} NMR (126 MHz, DMSO): δ 169.8, 149.8, 148.8,
147.6, 137.2 132.7, 130.7, 129.8, 127.8, 127.0, 120.7 (q, J = 320.3
Hz), 112.6, 110.0, 57.3; Calcd for C20H17F6IN2O9S2·2H2O: C, 31.18;
H, 2.75; N, 3.64. Found: C, 31.48; H, 2.39; N, 3.31.
(2R,5R)-5-Isopropyl-2-methylcyclohexan-1-one (63). Prepared
according to general procedure B from (2R,5R)-2-methyl-5-
(isopropyl)cyclohexan-1-ol. Purified via flash chromatography (5%
EtOAc/Hex) and isolated as colorless oil (23.7 mg, 77% yield). The
spectroscopic data for 63 are consistent with that previously
reported.29 1H NMR (500 MHz, CDCl3): δ 2.35 (ddd, J = 13.0,
4.0, 2.0 Hz, 1H), 2.17−2.10 (m, 1H), 2.08−1.95 (m, 3H), 1.93−1.81
1,10-Phenathrolyl λ5-Iodane Bistriflate; Bi(phen)-HVI (29).
Prepared according to general procedure A. After removing the
reaction solvent in vacuo, the resulting solids were washed with
CH2Cl2 (1 × 20 mL, 2 × 5 mL) to give 29 as a white solid (0.518 g,
71% yield). 1H NMR (500 MHz, DMSO-d6): δ 9.32 (dd, J = 5.0, 1.5
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(m, 2H), 1.42−1.29 (m, 2H), 1.00 (d, J = 6.0 Hz, 3H), 0.91 (d, J =
6.5 Hz, 3H), 0.85 (d, J = 7.0 Hz, 3H).
1,3-Dihydro-2H-inden-2-one (64). Prepared according to general
procedure B from 2,3-dihydro-1H-inden-2-ol (98% NMR yield). The
spectroscopic data for 64 are consistent with that previously
reported.30 1H NMR (500 MHz, CDCl3): δ 7.32−7.27 (m, 5H),
3.58 (s, 4H).
3,4-Dihydronaphthalen-1(2H)-one (65). Prepared according to
general procedure B from 1,2,3,4-tetrahydronaphthalen-1-ol (79%
NMR yield). The spectroscopic data for 65 are consistent with that
previously reported.31 1H NMR (500 MHz, CDCl3): δ 7.04 (dd, J =
8.5, 1.5 Hz, 1H), 7.47 (td, J = 6.5, 1.5 Hz, 1H), 7.33−7.29 (m, 1H),
7.26−7.23 (m, 1H), 2.97 (t, J = 6.5 Hz, 2H), 2.67 (t, J = 6.5 Hz, 2H),
2.17−2.11 (m, 2H).
4-Phenylbutan-2-one (66). Prepared according to general
procedure B from 4-phenylbutan-2-ol (93% NMR yield). The
spectroscopic data for 66 are consistent with that previously
reported.32 1H NMR (500 MHz, CDCl3): δ 7.29−7.26 (m, 2H),
7.21−7.17 (m, 3H), 2.89 (d, J = 7.5 Hz, 2H), 2.76 (d, J = 8.0 Hz,
2H), 2.14 (s, 3H).
carried out at room temperature to give 71 (92% NMR yield). The
reaction mixture was concentrated and purified by flash chromatog-
raphy (10% EtOAc/Hex) to give 71 as a white solid (14.2 mg, 86%
yield). The spectroscopic data for 71 are consistent with that
previously reported.37 1H NMR (500 MHz, CDCl3): δ 7.84 (dt, J =
8.5, 2.0 Hz, 2H), 7.77 (dt, J = 8.5, 1.5 Hz, 2H), 2.77 (s, 3H).
4-Bromophenyl Methyl Sulfoxide (72). Prepared according to
general procedure C from 4-bromo-thioanisole. The reaction was
carried out at −40 °C to give 72 (76% NMR yield). The
spectroscopic data for 72 are consistent with that previously
reported.38 1H NMR (500 MHz, CDCl3): δ 7.67 (dt, J = 8.5, 2.0
Hz, 2H), 7.52 (dt, J = 8.5, 2.0 Hz, 2H), 2.72 (s, 3H).
Methyl Phenyl Sulfoxide (73). Prepared according to general
procedure C from thioanisole. The reaction was carried out at −40 °C
to give 73 (73% NMR yield). The spectroscopic data for 73 are
consistent with that previously reported.37 1H NMR (500 MHz,
CDCl3): δ 7.56−7.51 (m, 3H), 7.18 (dd, J = 6.5, 2.0 Hz, 2H), 2.82 (s,
3H).
4-Methylphenyl Methyl Sulfoxide (74). Prepared according to
general procedure C from 4-methyl-thioanisole. The reaction was
carried out at −40 °C to give 74 (44% NMR yield). The
spectroscopic data for 74 are consistent with that previously
reported.37 1H NMR (500 MHz, CDCl3): δ 7.54 (dt, J = 8.5, 2.0
Hz, 2H), 7.33 (d, J = 9.0 Hz, 2H), 2.70 (s, 3H), 2.41 (s, 3H).
4-Methoxyphenyl Methyl Sulfoxide (75). Prepared according to
general procedure C from 4-methoxy-thioanisole. The reaction was
carried out at −78 °C in CH2Cl2 (2 mL) to give 75 (30% NMR
yield). The spectroscopic data for 75 are consistent with that
previously reported.37 1H NMR: δ 7.59 (dd, J = 9.0, 1.0 Hz, 2H), 7.02
(dd, J = 9.0, 1.0 Hz, 2H), 3.85 (s, 3H), 2.70 (s, 3H).
2-Phenylacetaldehyde (67). Prepared according to general
procedure B from 2-phenylethan-1-ol (71% NMR yield). The
spectroscopic data for 67 are consistent with that previously
reported.33 1H NMR (500 MHz, CDCl3): δ 9.75 (t, J = 2.5 Hz,
1H), 7.37 (t, J = 7.0 Hz, 2H), 7.31 (t, J = 7.5 Hz, 1H), 7.22 (d, J = 8.0
Hz, 2H), 3.69 (d, J = 2.5 Hz, 2H).
Cortisone acetate (68). Prepared according to general procedure B
from hydrocortisone acetate. Purified via flash chromatography (70%
EtOAc/Hex) and isolated as a gray solid (74.8 mg, 93% yield). The
spectroscopic data for 68 are consistent with that previously
reported.34 1H NMR (500 MHz, CDCl3): δ 5.73 (s, 1H), 5.09 (d,
J = 17.5 Hz, 1H), 4.66 (d, J = 17.5 Hz, 2H), 2.76 (d, J = 8.0 Hz, 2H),
2.14 (s, 3H), 2.87 (d, J = 12.5 Hz, 1H), 2.85−2.74 (m, 2H), 2.68−
2.57 (m, 1H), 2.52−2.23 (m, 6H), 2.16 (s, 3H), 2.02−1.89 (m, 4H),
1.10−1.60 (m, 2H), 1.50−1.44 (m, 1H), 1.40 (s, 3H), 0.68 (s, 3H).
(4R)-4-((5R,8R,9S,10S,13R,14S)-10,13-Dimethyl-3,12 Dioxohexa-
decahydro-1H-cyclopenta[a]phenanthren-17-yl)pentanoic acid
(69). Prepared according to general procedure B from (4R)-4-
((5R,8R,9S,10S,13R,14S)-3,12-dihydroxy-10,13-dimethylhexadecahy-
dro-1H-cyclopenta[a]phenanthren-17-yl)pentanoic acid, using 2.2
equiv of in situ 27. Purified via flash chromatography (50% EtOAc/
Hex) and isolated as a white solid (62.2 mg, 80% yield). The
spectroscopic data for 69 are consistent with that previously
reported.35 1H NMR (500 MHz, CDCl3): δ 2.67−2.54 (m, 2H),
2.50−2.27 (m, 3H), 2.21−2.03 (m, 4H), 1.98−1.74 (m, 8H), 1.67−
1.59 (m, 1H), 1.50−1.25 (m, 8H), 1.11 (s, 3H), 1.06 (s, 3H), 0.88 (d,
J = 8.0 Hz, 3H).
General Procedure D: Ketone Desaturation with Bi(N)-HVI.
To a flame-dried flask with PhIO(OAc)2 (13) (33.8 mg, 0.1 mmol)
and 1.0 mL of CD3CN was added TMSOTf (36.2 μL, 0.2 mmol)
dropwise under argon, generating a clear solution which was stirred
for 5 min. Phenanthroline (18.0 mg, 0.1 mmol) was added in one
portion and stirred for another 5 min. The resulting solution of
Bi(phen)-HVI (29) was then transferred via a syringe into a solution
of ketone (0.1 mmol) in 1.0 mL of CD3CN dropwise over 30 min.
The reaction mixture was stirred for another 30 min, 1,2-
dibromoethane (4.35 μL, 0.05 mmol) was added as the internal
1
standard and yields were determined by H NMR.
Cyclohex-2-en-1-one (76). Prepared according to general
procedure D from cyclohexanone to give 76 (70% NMR yield).
The spectroscopic data for 76 are consistent with that previously
reported.39 1H NMR (400 MHz, CD3CN): δ 7.09 (dt, J = 10.0, 4.0
Hz, 1H), 5.94 (dt, J = 10.4, 2.0 Hz, 1H), 2.37 (t, J = 8.0 Hz, 2H),
2.36−2.32 (m, 2H), 2.00−1.96 (m, 2H).
General Procedure C: Oxidation of Sulfides with Bi(N)-HVI.
To a flame-dried flask with a stir bar was added bis(acetoxy)-
iodylbenzene (13) (33.8 mg, 0.1 mmol). With stirring, CDCl3 (2 mL)
was added to form a cloudy white suspension. To this suspension was
added TMSOTf (36.2 μL, 0.2 mmol) resulting in a colorless solution.
After 5 min, 4,4′-dimethoxybipyridine (21.6 mg, 0.1 mmol) was
added to the mixture which was then stirred at temperature indicated
for oxidation (23 °C, −40 °C, or −78 °C) for 5 min before sulfide
was added (0.1 mmol). After 1 h, the reaction vessel was removed
from the cold bath (unless at 23 °C) and immediately quenched with
water and rapidly stirred while coming to room temperature. Water
was removed and the organic layer was dried with sodium sulfate,
filtered, and concentrated in vacuo. 1,2-Dibromoethane (4.35 μL, 0.05
mmol) was then added as an internal standard and yields were
4-Methylcyclohex-2-en-1-one (77). Prepared according to general
procedure D from 4-methylcyclohexanone to give 77 (51% NMR
yield). The spectroscopic data for 77 are consistent with that
previously reported.19c 1H NMR (500 MHz, CD3CN): δ 6.89 (dq, J =
10.0, 1.5 Hz, 1H), 5.87 (ddd, J = 10.0, 2.5, 1.0 Hz, 1H), 2.58−2.52
(m, 1H), 2.39−2.33 (m, 2H), 2.13−2.07 (m, 1H), 1.66−1.58 (m,
1H), 1.12 (d, J = 7.5 Hz, 3H).
4-(tert-Butyl)-cyclohex-2-en-1-one (78). Prepared according to
general procedure D from 4-(tert-butyl)-cyclohexanone to give 78
(53% NMR yield). The spectroscopic data for 78 are consistent with
that previously reported.19c 1H NMR (500 MHz, CD3CN): δ 7.11
(dt, J = 10.5, 2.0 Hz, 1H), 5.95 (ddd, J = 10.5, 3.0, 1.0 Hz, 1H), 2.39−
2.30 (m, 2H), 2.27−2.22 (m, 1H), 2.10−2.07 (m, 1H), 1.75−1.68
(m, 1H), 0.96 (s, 9H).
4-Phenylcyclohex-2-en-1-one (79). Prepared according to general
procedure D from 4-phenylcyclohexanone (52% NMR yield). The
reaction mixture was concentrated and directly purified via flash
chromatography (10% EtOAc/Hex) to give 79 as a white solid (8.3
mg, 48% yield). The spectroscopic data for 79 are consistent with that
previously reported.19c 1H NMR (400 MHz, CDCl3): δ 7.38−7.35
(m, 2H), 7.30−7.27 (m, 1H), 7.24−7.21 (m, 2H), 7.00 (ddd, J =
10.0, 2.5, 1.5 Hz, 1H), 6.17 (dd, J = 10.0, 2.5, Hz, 1H), 3.75−3.71 (m,
1H), 2.59−2.45 (m, 2H), 2.40−2.34 (m, 1H), 2.09−2.01 (m, 1H).
1
determined by H NMR.
4-Nitrophenyl Methyl Sulfoxide (70). Prepared according to
general procedure C from 4-nitrothioanisole. The reaction was carried
out at room temperature to give 70 (93% NMR yield). The
spectroscopic data for 70 are consistent with that previously
reported.36 1H NMR (500 MHz, CDCl3): δ 8.39 (dt, J = 9.0, 2.0
Hz, 2H), 7.84 (dt, J = 9.0, 2.0 Hz, 2H), 2.79 (s, 3H).
4-Cyanophenyl Methyl Sulfoxide (71). Prepared according to
general procedure C from 4-cyano-thioanisole. The reaction was
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4,4-Dimethylcyclohex-2-en-1-one (80). Prepared according to
general procedure D from 4,4-dimethylcyclohexanone to give 80
(70% NMR yield). The spectroscopic data for 80 are consistent with
that previously reported.19c 1H NMR (500 MHz, CD3CN): δ 6.74
(dt, J = 10.0, 1.0 Hz, 1H), 5.76 (d, J = 10.0 Hz, 1H), 2.40 (t, J = 7.0
Hz, 1H), 1.85 (td, J = 6.5, 1.0 Hz, 1H),1.14 (s, 6H).
TGA Characterization. TGA was performed on samples with a
Hi-Res TGA 2950 (TA Instruments), taking care to keep exposure to
air to a minimum (<120 s). Measurements were conducted under
nitrogen gas, at a heating rate of 10 °C/min, from room temperature
to 800 °C. For full description of thermal decomposition of Bi(N)-
HVIs, see associated Supporting Information.
thank the Australian Research Council (ARC) for project
funding (DP180100904) and the Australian National
Computational Infrastructure and the University of Tasmania
for the generous allocation of the computing time.
REFERENCES
■
(1) (a) The Chemistry of Hypervalent Halogen Compounds; Olofsson,
B., Marek, I., Rappoport, Z., Eds.; John Wiley & Sons: Chichester,
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ASSOCIATED CONTENT
* Supporting Information
The Supporting Information is available free of charge at
https://pubs.acs.org/doi/10.1021/acs.joc.1c00375.
■
sı
Computational details for structural elucidation, details
on thermal decomposition studies, optimization of
alcohol oxidation, sulfide oxidation, and ketone desatu-
ration, and 1H NMR and 13C{1H} NMR spectra (PDF)
AUTHOR INFORMATION
Corresponding Author
■
(2) For reviews on I(V) reagents, see: (a) Zhdankin, V. V.
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Reagents in Organic Synthesis. Arkivoc 2006, 2006, 26. (c) Satam, V.;
Harad, A.; Rajule, R.; Pati, H. 2-Iodoxybenzoic acid (IBX): an
efficient hypervalent iodine reagent. Tetrahedron 2010, 66, 7659.
(d) Duschek, A.; Kirsch, S. F. 2-Iodoxybenzoic Acid− A Simple
Oxidant with a Dazzling Array of Potential Applications. Angew.
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Sarah E. Wengryniuk − Department of Chemistry, Temple
University, Philadelphia, Pennsylvania 19122, United States;
orcid.org/0000-0002-4797-0181; Email: sarahw@
temple.edu
Authors
Xiao Xiao − Department of Chemistry, Temple University,
Philadelphia, Pennsylvania 19122, United States
Jessica M. Roth − Department of Chemistry, Temple
University, Philadelphia, Pennsylvania 19122, United States
Nathaniel S. Greenwood − Department of Chemistry, Temple
University, Philadelphia, Pennsylvania 19122, United States
Maria K. Velopolcek − Department of Chemistry, Temple
University, Philadelphia, Pennsylvania 19122, United States
Jordan Aguirre − Department of Chemistry, Temple
University, Philadelphia, Pennsylvania 19122, United States
Mona Jalali − School of Natural SciencesChemistry,
University of Tasmania, Hobart TAS 7001, Australia
Alireza Ariafard − School of Natural SciencesChemistry,
University of Tasmania, Hobart TAS 7001, Australia
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Koposov, A. Y.; Netzel, B. C.; Yashin, N. V.; Rempel, B. P.; Ferguson,
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Complete contact information is available at:
https://pubs.acs.org/10.1021/acs.joc.1c00375
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
■
The authors are grateful to the National Institutes of Health
(NIH R01 GM123098) for financial support of this work, and
the authors would like to acknowledge the Donors of the
American Chemical Society Petroleum Research Fund for
partial support of this research (DNI-56603). We are thankful
to Dr. Stephanie Wunder for the use of her instrumentation for
TGA studies. We thank Bilal Hoblos for running a large-scale
oxidation during revision. We thank Dr. Charles DeBrosse
(Temple University) for NMR spectroscopic assistance and
Dr. Charles W. Ross III, Director: Automated Synthesis and
Characterization at University of Pennsylvania Chemistry for
providing high-resolution mass spectral data. A.A. and M.J. also
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Article
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