N-heterocyclic carbene-promoted rauhutcurrier reactions between vinyl sulfones and α,β-unsaturated aldehydes

Article abstract of DOI:10.1071/CH11264

N-heterocyclic carbenes (NHCs) promote the addition of 1,1- bis(phenylsulfonyl)ethylene to the α-position of α,β- unsaturated aldehydes. The proposed reaction pathway for this RauhutCurrier-type reaction includes an unusual conjugate addition of an NHC to

Full text of DOI:10.1071/CH11264

RESEARCH FRONT
Full Paper
CSIRO PUBLISHING
Aust. J. Chem. 2011, 64, 1158–1164
www.publish.csiro.au/journals/ajc
N-Heterocyclic Carbene-Promoted Rauhut Currier
]
Reactions between Vinyl Sulfones and a,b-Unsaturated
Aldehydes
A
A B
,
Roxanne L. Atienza and Karl A. Scheidt
A
Department of Chemistry, Center for Molecular Innovation and Drug Discovery,
Chemistry of Life Processes Institute, Silverman Hall, Northwestern University,
2145 Sheridan Road, Evanston, IL 60208, USA.
B
Corresponding author. Email: scheidt@northwestern.edu
N-heterocyclic carbenes (NHCs) promote the addition of 1,1-bis(phenylsulfonyl)ethylene to the a-position of a,b-
unsaturated aldehydes. The proposed reaction pathway for this Rauhut–Currier-type reaction includes an unusual
conjugate addition of an NHC to a bis-vinyl sulfone.
Manuscript received: 8 July 2011.
Manuscript accepted: 19 July 2011.
Introduction
with an atypical NHC electrophile (non-carbonyl containing),
resulting in the RC product of a,b-unsaturated aldehydes.
Vinyl sulfones are versatile electrophiles in organic synthesis
because of their high reactivity in organometallic and organo-
catalyis.[11] Our group has recently reported the use of vinyl
sulfones as substrates in a carbene-catalyzed reaction with 1,3-
dipolar electrophiles to form cycloaddition products with an
unusual sulfonyl transposition.[12] In our initial investigations
exploring homoenolate equivalent cycloadditions with vinyl
sulfones, we discovered that NHCs promoted an unexpected
process to deliver the apparent RC product (Scheme 1).
Metal-free catalysis is an attractive field of methodology
development because of its biomimetic and green nature. Intense
efforts over the last decade to investigate organocatalysis have
resulted in an eruption of selective and efficient strategies for the
synthesis of organic molecules.[1] Specifically in the field of
Lewis base catalysis,[2] N-heterocyclic carbenes (NHCs) facili-
tate a wide number of powerful bond-forming reactions.[3]
Inspired by the biological conversion of pyruvate into acetyl
Co-A by a thiamin cofactor, NHC catalysis utilizes the electron
lone pair of nitrogen-containing heterocycles (i.e., thiazolium,
imidazolium, and triazolium-derived carbenes) to promote
a variety of reactions including acyl anion chemistry,[4]
homoenolate[5] and enolate[6] equivalents, reductions,[3c] and
oxidations.[7] Carbene catalysis is well known for the 1,2-
addition of the carbene to a carbonyl group of a substrate,
affording an acyl anion or homoenolate equivalent (Scheme 1). A
less developed reactivity mode for these Lewis base catalysts is
the conjugate addition of an a,b-unsaturated carbonyl-
containing compound to generate a reactive enolate intermediate.
Both Fu and Ye have independently reported NHC-catalyzed
b-Umpolung-type and Morita–Baylis–Hillman (MBH)
reactions[8] of a,b-unsaturated carbonyl substrates.[9] The
Rauhut–Currier (RC) reaction[10] involves the nucleophile
catalyzed coupling of a reactive intermediate (enolate) gener-
ated from an activated alkene to a secondary Michael acceptor,
thereby forging a new C–C bond between the a-position of the
alkene and the b-position of the secondary electrophile. To the
best of our knowledge, there has been no report of a NHC-
catalyzed RC reaction. This conjugate addition mode is an
under-explored area for carbene catalysis and offers oppor-
tunities for reaction design and development beyond the
established manifold resulting from 1,2-addition of the NHC to a
carbonyl group (e.g., acyl anion and homoenolate equivalent
reactions). In this work, we report that NHCs are compatible
1,2-NHC Addition
␦Ϫ
␦Ϫ
ϩ
Umpolung via
1,2 CϭO addition
1,4-NHC Addition
ϩ
This work
carbene
catalysis
Scheme 1. 1,2 and 1,4-addition modes of N-heterocyclic carbene (NHC)
catalysis.
Ó CSIRO 2011
10.1071/CH11264
0004-9425/11/081158

RESEARCH FRONT
N-Heterocyclic Carbene-Promoted Rauhut–Currier Reactions
1159
Results and Discussion
Table 1. Optimization table and ORTEP of 2 (displayed at 50 %
probability).
We initially explored the compatibility of NHC-homoenolate
equivalents with vinyl sulfones to access cyclopentanones by a
formal [3þ2] annulation. However, the product isolated was
confirmed as the intermolecular RC product (the X-ray crys-
tallography data has been submitted to the Cambridge Crystal-
lographic Data Centre) not the desired homoenolate equivalent
addition product. This RC process represents a new mode of
NHC reactivity and a different type of carbene catalysis
compared with the benzoin/Umpolung modality. While intra-
molecular RC reactions have been reported by the groups of
Krische,[10b] Roush,[10c,d] Miller,[10e] and others,[10h] we have
been interested in Lewis base catalysis in general[13] and
developing new intermolecular versions of this reaction for
some time.[10g] After screening potential azolium salts as pre-
catalysts, we found that triazolium D was the only catalyst that
led to the formation of the RC products such as 2 (Table 1). The
product structure was confirmed by single crystal X-ray
diffraction. During reaction optimization, we focused on using
non-nucleophilic bases to avoid possible complications of
competitive base conjugate addition. Our best results were
obtained with sodium tert-butoxide as the base and dichloro-
methane as the solvent. The choice of solvent and amount
of base was important to avoid an unusual side product,
(phenylperoxy)(1,3,3-tris(phenylsulfonyl)propyl)sulfane, which
we observed in solvents such as THF and acetonitrile. This
compound has been reported previously in studies of 1,1-
bis(phenylsulfonyl)ethylene with enamine catalysis.[11d,i] The
use of two equivalents of the enal partner was determined to be
the ideal stoichiometry for this process. We found it odd that
even though excess of the aldehyde was used, there was no
evidence for the typical NHC-homoenolate chemistry present in
the reaction mixture (the excess aldehyde was recovered during
purification).
؉
Entry
Azolium
mol %
Base
Solventa
Yield 2 (%)b,c
1
2
A
B
C
D
E
F
20
20
20
20
20
20
20
20
20
20
tBTMG
tBTMG
tBTMG
tBTMG
tBTMG
tBTMG
NaOtBu
DBU
CH2CL2
CH2CL2
CH2CL2
CH2CL2
CH2CL2
CH2CL2
CH2CL2
CH2CL2
CH2CL2
CH2CL2
10
0
3
0
4
15
0
5
6
0
7
D
D
D
D
39
trace
0
8
9
Et3N
10
K2CO3
0
ꢀ0.25 M. bisolated yields. ꢀ20 mol % azolium, 20 mol % base at 258C
a
c
for 25 h
With optimized reaction conditions that provided the inter-
molecular RC product between the vinyl sulfone and a,b-
unsaturated aldehyde, we examined the scope of the reaction
with respect to the enal component (Table 2). Having an
electron withdrawing substituent on the aryl ring resulted in
the products in good to moderate yields, potentially because of
the increased electrophilicity of the b-position of the a,b-
unsaturated aldehyde. Reactions with enals with non-electron
withdrawing groups or groups that would block the b-position
provided lower yields. The other product generated was trans-
1,2-bis(phenylsulfonyl)ethylene and accounted for the mass
balance. Unfortunately, the substrate scope of this process is
currently limited and mixed sulfone/carbonyl group compounds
are not suitable substrates.
There are two main possible reaction pathways for the
generation of the RC product (Scheme 2). In pathway A
(NHC catalyzed), the NHC undergoes an initial conjugate
addition to the vinyl sulfone, forming intermediate anion I that
adds to cinnamaldehyde in a conjugate fashion. The resulting
enolate II then undergoes a 4-exo-tet cyclization to produce a
heavily substituted cyclobutane intermediate with concomitant
regeneration of the carbene catalyst. Subsequent deprotonation
of the a-position of the exocyclic aldehyde and elimination
provides RC product 2. The alternative route involves a more
complicated process (pathway B, NHC initiated). The NHC
performs a conjugate addition to the vinyl sulfone to produce a
sulfinate ion in situ. In previous reported studies, we have
observed a smooth rearrangement of 1,1-bis vinyl sulfones to
1,2-bis sulfones by a sulfinate ejection/re-addition process.[12]
The in situ sulfinate anion generated by NHC addition to the
vinyl sulfone acts as the nucleophilic catalyst which then
undergoes 1,4-addition to the enal, thereby forming enolate
VI. At this point, anion VI would add to the vinyl sulfone and
deprotonation resultsinthe RCproduct2. In support of pathway B,
we have added sodium sulfinate (1 equiv.) to a solution of
cinnamaldehyde and vinyl sulfone and observed the RC product

RESEARCH FRONT
1160
R. L. Atienza and K. A. Scheidt
Table 2. Enal substrate scope.
؉
Entry
Producta
Yield (%)b
1
2
3
4
5
6
7
39
2
3
4
5
6
55
61
56
49
64
7
8
58
8
9
9
98
41
49
10
11
10
˚
a ꢀ20 mol % D, 20 mol % base, 3 A MS, and 0.25 M at 408C. b – isolated yield

RESEARCH FRONT
N-Heterocyclic Carbene-Promoted Rauhut–Currier Reactions
1161
Pathway A: NHC-catalyzed
Me
Mes
N
N
2
N
Me
O
PhSO2
SO2Ph
Me
H
Ph
PhSO2
H
N
Regeneration
of NHC
Me
III
I
N
N
O
Mes
SO2Ph
H
Mes
N
Ph
N
R
R
N
II
Me
Me
R ϭ SO2Ph
Pathway B: NHC-initiated
PhSO2
PhSO2
SO2Ph
Me
Me
Mes
2
N
N
SO2Ph
H
N
N
Me
Me
O
N
N
1
Mes
Ph
SO2Ph
Regeneration
of NHC
VII
I
O
H
H
PhSO2
SO2Ph
Me
O
Ph
SO2Ph
PhSO2
SO2Ph
Me
B
N
H
H
VI
Me
N
N
N
Ph
Mes
SO2Ph
Me
N
N
V
IV
Mes
PhSO2
PhSO2
Regeneration
of NHC
H
SO2Ph
NHC
SO2Ph
VIII
Scheme 2. Possible reaction mechanisms
NHC
IX
with unidentified side products. However, the process did
require a full equivalent of sulfinate (not 20 mol-% as per the
normal reaction conditions) and does not rule out possible
conjugate additions of the carbene to the vinyl sulfone (or enal)
as depicted in pathway A.
Experimental
All reactions were carried out under a nitrogen atmosphere in
flame-dried glassware with magnetic stirring. Dichloromethane
was purified by passage through a bed of activated alumina.[14]
Reagents were purified before use unless otherwise stated fol-
lowing the guidelines of Perrin and Armarego.[15] Purification
of reaction products was carried out by flash chromatography
using EM Reagent silica gel 60 (230–400 mesh). Analytical
thin-layer chromatography (TLC) was performed on EM
Reagent 0.25 mm silica gel 60-F plates. Visualization of TLC
plates was accomplished with UV light. Infrared spectra were
recorded on a Perkin Elmer 1600 series FT-IR spectrometer.
1H NMR spectra were recorded on a Bruker A500 (500 MHz)
spectrometer and are reported in ppm using solvent as an
internal standard (CDCl3 at 7.26 ppm). Data are reported as
(ap ¼ apparent, s ¼ singlet, d ¼ doublet, t ¼ triplet, q ¼ quartet,
m ¼ multiplet, br ¼ broad; coupling constant(s) in Hz; integra-
tion. Proton-decoupled 13C NMR spectra were recorded on a
Conclusion
We have demonstrated that a triazolium-derived NHC promotes
the RC reaction between enals and vinyl sulfones. This process
is noteworthy since the majority of NHC Lewis base reactivity
comes from the addition to a carbonyl carbon, and not the
b position of an a,b-unsaturated substrate. These results add to
the growing list of and new reactivity modes for NHCs beyond
the well established acyl anion and homoenolate equivalent
strategies. Further development of this promising NHC reac-
tivity pattern with other atypical NHC electrophilic partners is
under investigation.

RESEARCH FRONT
1162
R. L. Atienza and K. A. Scheidt
Bruker A500 (125 MHz) spectrometer and are reported in ppm
using solvent as an internal standard (CDCl3 at 77.0 ppm). Mass
spectrometric data for the products were acquired on an Agilent
6210 LC-Tof High Resolution Mass Spectrometer, using an
Electro Spray Ionization source. Samples were introduced using
1 mL direct injection. The solvent used was 90 % MeOH/10 %
129.1, 78.8, 22.2. m/z HRMS (ESI) Calc. for C23H20ClO5S2þ
[M þ H]þ 475.0435. Found 475.0438.
(E)-2-(Naphthalen-2-ylmethylene)-4,
4-bis(phenylsulfonyl)butanal (4)
Prepared according to the general procedure with dichloro-
methane, yielding 48 mg (61 %) as a pale yellow solid (25 %
EtOAc/hexanes, RF ¼ 0.17). nmax (film)/cmꢀ1 3062, 2924, 2853,
1676, 1620, 1448, 1331, 1149, 1079. dH (500 MHz; CDCl3) 9.53
(s, 1H), 8.07 (s, 1H), 7.96 (dd, J 13.1, 5.9, 3H), 7.79 (d, J 8.4,
4H), 7.67–7.58 (m, 6H), 7.41–7.38 (m, 4H), 5.55 (t, J 6.8, 1H),
3.62 (d, J 6.8, 2H). dC (125 MHz; CDCl3) 194.9, 152.3, 137.5,
136.1, 134.5, 133.7, 133.1, 131.2, 130.0, 129.6, 128.94, 128.94,
127.92, 127.79, 127.1, 126.3, 79.1, 21.9 m/z HRMS (ESI) Calc.
for C27H23O5Sþ2 [M þ H]þ: 491.0981. Found 491.0983.
water/0.1 % formic acid flowing at 0.5 mL minꢀ1
.
General Procedure for Formation of RC Product
To a reaction vial containing a magnetic stirring bar was added
the corresponding 1,1-bis(phenylsulfonyl)ethylene (50 mg,
˚
0.16 mmol), enal (2 equiv.), flame-dried 3 A molecular sieves,
and dichloromethane (0.4 mL). A dichloromethane solution
(0.2 mL) containing the azolium salt (0.03 mmol) and base
(0.03 mmol) was then added, bringing the reaction solution to
0.25 M. The reaction was then heated to 408C for 24 h. The
unpurified reaction was filtered through a pad of silica, washing
with EtOAc and concentrated under vacuum. The material was
purified by column chromatography (silica, 25 % EtOAc/
hexanes), and after concentration of the appropriate fractions
afforded the product.
(E)-2-(4-Bromobenzylidene)-4,4-bis(phenylsulfonyl)
butanal (5)
Prepared according to the general procedure with dichloro-
methane, yielding 47 mg (56 %) as a yellow solid (25 % EtOAc/
hexanes, RF ¼ 0.14). nmax (film)/cmꢀ1 3067, 2923, 2852, 1677,
1628, 1448, 1330, 1149, 1079, 1009. dH (500 MHz, CDCl3) 9.43
(s, 1H), 7.80–7.78 (m, 4H), 7.68–7.60 (m, 5H), 7.49 (t, J 7.8,
4H), 7.38–7.34 (m, 2H), 5.52 (t, J 6.9, 1H), 3.41 (d, J 6.9, 2H).
dC (125 MHz, CDCl3) 194.8, 150.8, 137.5, 136.5, 134.7, 132.7,
132.4, 131.0, 129.5, 129.1, 124.7, 78.9, 22.1. m/z HRMS (ESI)
Calc. for C23H20BrO5Sþ2 [M þ H]þ: 518.9930. Found 518.9942.
(E)-2-Benzylidene-4,4-bis(phenylsulfonyl)butanal (2)
Prepared according to the general procedure with dichlor-
omethane, yielding 28 mg (39 %) as a white solid (25 % EtOAc/
hexanes, RF ¼ 0.18). nmax (film)/cmꢀ1 3065, 2957, 2849, 1665,
1625, 1447, 1313, 1146, 1079. dH (500 MHz, CDCl3)
9.22 (s, 1H), 7.58–7.57 (m, 4H), 7.42 (m, 2H), 7.26–7.04
(m, 10H), 5.36 (t, J 6.9, 1H), 3.25 (d, J 6.9, 2H). dC (125 MHz,
CDCl3) 195.0, 152.3, 137.6, 135.9, 134.6, 133.8, 130.2, 129.6,
129.19, 129.01, 78.9, 22.1. m/z HRMS (ESI) Calc. for
C23H21O5Sþ2 [M þ H]þ 441.0825. Found 441.0825.
(E)-2-(3-Chlorobenzylidene)-4,4-bis(phenylsulfonyl)
butanal (6)
Prepared according to the general procedure with dichloro-
methane, yielding 38 mg (49 %) as a yellow solid (25 % EtOAc/
hexanes, RF ¼ 0.17). nmax (film)/cmꢀ1 3068, 2925, 2855, 1679,
1629, 1448, 1331, 1150, 1079. dH (500 MHz, CDCl3) 9.47
(s, 1H), 7.84–7.82 (m, 5H), 7.69–7.66 (m, 2H), 7.52–7.36
(m, 8H), 5.59 (t, J 7.0, 1H), 3.43 (d, J 6.9, 2H). dC (125 MHz,
CDCl3) 194.7, 150.4, 137.5, 137.0, 135.5, 135.1, 134.7, 130.5,
130.1, 129.54, 129.36, 129.1, 127.4, 78.9, 22.3. m/z HRMS
(ESI) Calc. for C23H20ClO5Sþ2 [M þ H]þ: 475.0435. Found
475.0440.
A colourless tabular crystal of C23H20O5S2 having approxi-
mate dimensions of 0.52 ꢁ 0.29 ꢁ 0.12 mm3 was mounted using
oil (Infineum V8512) on a glass fiber. All measurements were
made on a Bruker APEX-II CCD Diffractometer with a CuK I S
source at a temperature of 250(2) K with a theta range for data
collection of 1.848 to 30.478. Cell constants and an orientation
matrix for data collection corresponded to a triclinic, space
˚
group P-1, with a 9.3104(5), b 10.4613(6), and c 11.7985(6) A,
a 89.825(3)8, b 70.317(2)8 and g 72.560(2)8. For Z ¼ 2 and
FW ¼ 440.51, the calculated density is 1.426 g cm3. The linear
absorption coefficient, m, for Mo Ka radiation is 0.293 mmꢀ1
.
(E)-4-(2-Formyl-4,4-bis(phenylsulfonyl)but-1-en-1-yl)
benzonitrile (7)
The maximum and minimum transmission factors were: 0.9662
and 0.8625, respectively. Of the 27 149 reflections collected,
6158 were unique (Rint 0.0668). The final cycle of full-matrix
least-squares refinement on F2 was based on 6158 reflections
and 271 variable parameters and converged with agreement
factors of R1 0.0496 and wR2 0.1468 and goodness-of-fit on
F2 ¼ 0.990. Further information is contained in the CIF file,
available from the Cambridge Crystallographic Data Centre,
CCDC 833171.
Prepared according to the general procedure with dichloro-
methane, yielding 49 mg (64 %) as a yellow solid (25 % EtOAc/
hexanes, RF ¼ 0.14). nmax (film)/cmꢀ1 3067, 2929, 2229, 1681,
1448, 1331, 1313, 1148, 1079. dH (500 MHz, CDCl3) 9.48
(s, 1H), 7.75 (t, J 8.8, 6H), 7.66–7.60 (m, 4H), 7.49–7.41
(m, 5H), 5.53 (t, J 7.1, 1H), 3.37 (d, J 7.1, 2H). dC (125 MHz,
CDCl3) 194.6, 149.4, 138.24, 138.20, 137.5, 134.8, 132.7,
129.9, 129.4, 129.1, 118.2, 113.4, 78.6, 22.5. m/z HRMS (ESI)
Calc. for C24H20NO5Sþ2 [M þ H]þ: 466.0777. Found 466.0736.
(E)-2-(4-Chlorobenzylidene)-4,4-bis(phenylsulfonyl)
butanal (3)
(E)-2-(Naphthalen-1-ylmethylene)-4,4-
bis(phenylsulfonyl)butanal (8)
Prepared according to the general procedure with dichloro-
methane, yielding 42 mg (55 %) as a white solid (25 % EtOAc/
hexanes, RF ¼ 0.18). nmax (film)/cmꢀ1 3067, 2924, 2853, 1677,
1628, 1448, 1330, 1150, 1090, 1080. dH (500 MHz, CDCl3) 9.44
(s, 1H), 7.81–7.79 (m, 4H), 7.66 (ap t, 2H), 7.51–7.36 (m, 9H),
5.54 (t, J 6.9, 1H), 3.42 (d, J 6.9, 2H). dC (125 MHz, CDCl3)
194.8, 150.8, 137.6, 136.4, 134.7, 132.2, 130.8, 129.52, 129.46,
Prepared according to the general procedure with dichloro-
methane, yielding 46 mg (58 %) as a yellow solid (25 % EtOAc/
hexanes, RF ¼ 0.21). nmax (film)/cmꢀ1 3063, 2925, 1679, 1627,
1448, 1331, 1151, 1079. dH (500 MHz, CDCl3) 9.75 (s, 1H),
8.11–7.99 (m, 5H), 7.71–7.48 (m, 8H), 7.33–7.29 (m, 5H),
5.56 (t, J 6.8, 1H), 3.42 (d, J 6.8, 2H). dC (125 MHz, CDCl3)

RESEARCH FRONT
N-Heterocyclic Carbene-Promoted Rauhut–Currier Reactions
1163
194.7, 150.5, 137.2, 134.5, 131.1, 130.7, 130.4, 129.6, 128.8,
127.4, 127.0, 126.9, 125.5, 124.2, 79.3, 22.3. m/z HRMS (ESI)
Calc. for C27H23O5Sþ2 [M þ H]þ: 491.0981. Found 491.0982.
at Northwestern University for assistance with compound characterization,
John Roberts (NU) for assistance with X-ray crystallography, and Daniel
Cohen (NU) for providing a,b-unsaturated aldehyde substrates.
(E)-2-(4-Nitrobenzylidene)-4,4-bis(phenylsulfonyl)
butanal (9)
References
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Prepared according to the general procedure with dichloro-
methane, yielding 77 mg (98 %) as a pale orange solid (25 %
EtOAc/hexanes, RF ¼ 0.12). nmax (film)/cmꢀ1 3070, 2926, 1682,
1572, 1448, 1341, 1313, 1150, 1079. dH (500 MHz, CDCl3) 9.56
(s, 1H), 8.29 (d, J 8.2, 2H), 7.91 (d, J 7.2, 2H), 7.79–7.48
(m, 11H), 5.57 (t, J 7.0, 1H), 3.20 (d, J 6.9, 2H). dC (125 MHz,
CDCl3) 194.7, 149.5, 138.0, 134.6, 134.3, 129.2, 125.5, 78.5,
22.6 m/z HRMS (ESI) Calc. for C17H16NO5Sþ [M þ H]þ:
486.0676. Found 486.0677.
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(E)-2-(4-Acetylbenzylidene)-4,4-bis(phenylsulfonyl)
butanal (10)
Prepared according to the general procedure with dichloro-
methane, yielding 32 mg (41 %) as a pale yellow solid (25 %
EtOAc/hexanes, RF ¼ 0.23). nmax (film)/cmꢀ1 3067, 2620, 2848,
1680, 1604, 1448, 1359, 1330, 1313, 1267, 1148, 1079. dH
(500 MHz, CDCl3) 9.46 (s, 1H), 8.02 (d, J 8.3, 1H), 7.77–7.75
(m, 4H), 7.64–7.57 (m, 6H), 7.46–7.41 (m, 4H), 5.52 (t, J 7.0,
1H), 3.42 (d, J 7.0, 2H), 2.64 (s, 3H). dC (125 MHz; CDCl3)
197.3, 194.8, 150.5, 138.2, 137.6, 134.7, 129.62, 129.46,
129.09, 128.95, 78.7, 26.9, 22.4. m/z HRMS (ESI) Calc. for
C25H23O6Sþ2 [M þ H]þ: 483.0931. Found 483.0924.
(Wiley-VCH: Weinheim).
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hexanes, RF ¼ 0.12). nmax (film)/cmꢀ1 3065, 2953, 2847, 1721,
1678, 1448, 1437, 1331, 1313, 1282, 1183, 1149, 1114, 1079.
dH (500 MHz, CDCl3) 9.48 (s, 1H), 8.12 (d, J 8.3, 1H), 7.80–7.78
(m, 4H), 7.66–7.63 (m, 3H), 7.55 (d, J 8.0, 2H), 7.49–7.44
(m, 5H), 5.54 (t, J 7.0, 1H), 3.98 (d, J 0.8, 2H), 3.43 (d, J 7.0, 3H).
dC (125 MHz, CDCl3) 194.7, 166.3, 150.6, 138.1, 137.52,
137.43, 134.7, 131.2, 130.2, 129.50, 129.37, 129.1, 78.8, 52.5,
22.3. m/z HRMS (ESI) Calc. for C25H23O7Sþ2 [M þ H]þ:
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Accessory Publication
Spectroscopic and X-ray crystallography data are available as an
accessory publication available on the Journal’s website. CCDC
833171 contains the supplementary crystallographic data for
this paper. These data can be obtained free of charge from The
Cambridge Crystallographic Data Centre via www.ccdc.cam.
ac.uk/data_request/cif.
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Acknowledgements
Support for this work was provided by the NIH (GM73072-01), an NIGMS
Research Supplement to Promote Diversity in Health-Related Research
(R.L.A.), and an NIGMS Ruth L. Kirschstein NRSA fellowship
(F31 GM96752). The authors thank S. Shafaie and C. L. Stern at
Integrated Molecular Structure Education and Research Center (IMSERC)

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