Use of silver carbonate in the Wittig reaction

Article abstract of DOI:10.1021/jo401972a

An efficient synthesis of olefins by the coupling of stabilized, semistabilized, and nonstabilized phosphorus ylides with various carbonyl compounds in the presence of silver carbonate is reported. Wittig olefination of aromatic, heteroaromatic, and aliphatic aldehydes (yields >63%) and a ketone (yield 42%) are demonstrated. These reactions proceed overnight at room temperature, under weakly basic conditions, and as such extend the applicability of the Wittig reaction to base-sensitive reactants.

Full text of DOI:10.1021/jo401972a

Note
pubs.acs.org/joc
Use of Silver Carbonate in the Wittig Reaction
Lukas Jedinak,† LaToya Rush,† Mijoon Lee, Dusan Hesek, Jed F. Fisher, Bill Boggess, Bruce C. Noll,
and Shahriar Mobashery*
Department of Chemistry and Biochemistry, University of Notre Dame, Notre Dame, Indiana 46556, United States
S
* Supporting Information
ABSTRACT: An efficient synthesis of olefins by the coupling of stabilized, semistabilized, and nonstabilized phosphorus ylides
with various carbonyl compounds in the presence of silver carbonate is reported. Wittig olefination of aromatic, heteroaromatic,
and aliphatic aldehydes (yields >63%) and a ketone (yield 42%) are demonstrated. These reactions proceed overnight at room
temperature, under weakly basic conditions, and as such extend the applicability of the Wittig reaction to base-sensitive reactants.
he Wittig reaction is a standard methodology for the
synthesis of the alkene due to its specificity of bond
general method for the mild, room temperature olefination of
base-sensitive and α-epimerizable aldehydes is lacking.4
T
placement and its use of relatively mild conditions. The classic
method generates the requisite phosphorus ylide, using a base
of appropriate basicity, which then reacts with an aldehyde or
ketone to yield the corresponding alkene.1 Under the classical
conditions, the Wittig reaction has certain limitations with base-
sensitive compounds, such as self-condensation of the carbonyl,
disproportionation of the carbonyl via the Cannizzaro reaction,
and epimerization of adjacent stereocenters.2 Modifications to
the Wittig conditions to accommodate these limitations include
Masamune’s and Roush’s use of LiCl with DBU3 and the use by
Blasdel et al. of lithium 1,1,1,3,3,3-hexafluoroisopropoxide.4
Other bases that have been found effective5,6 include tertiary
amines,7,8 LiOH,9 KH,10 and KOSiMe3.11 Though Wittig and
Horner−Wadsworth−Emmons reactions using mild bases have
been described, most examples are limited to stabilized ylides or
to Horner−Wadsworth−Emmons phosphonates bearing an
electron-withdrawing group at the α-carbon, thus enabling
deprotonation of the phosphonium salt (or phosphonate) using
a weaker base.12−15 Attempts to form a nonstabilized ylide, by
alkylphosphonium halide deprotonation with a mild base, have
failed.16 The first Wittig olefination of nonstabilized ylide
promoted by weak carbonate base (K2CO3) was achieved in the
solid state under ball-milling conditions.17 In solution-phase
chemistry, potassium carbonate18 or sodium bicarbonate14,19
were used, but the reactions required elevated temperatures and
were conducted only with stabilized or semistabilized ylides.
The Wittig reaction was successfully applied to the synthesis of
unsaturated amino acids20,21 without loss of stereochemical
integrity, using K3PO4 as a strong base under phase-transfer
conditions at elevated temperature (90 °C).20 However, a
During the synthesis of meso-diaminopimelate (an amino
acid found in the cell wall of Gram-negative bacteria) we sought
a means to generate ylide 2a so as to enable a synthetic route
based on the Wittig reaction as the key synthetic connection
(Scheme 1). As both the ylide and the aldehyde counterparts
contain acidic α-carbons, this system had the potential for
erosion of stereochemical integrity in both reagents. As a
possible solution to this dilemma, we chose to evaluate silver
Scheme 1
Received: September 10, 2013
© XXXX American Chemical Society
A
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Note
carbonate (Ag2CO3) as the base. While Ag2CO3 has a
recognized ability to exert basicity in reactions that exploit its
halophilic character,22−24 to our knowledge this ability has not
been explored previously in the context of the Wittig reaction.
Our first efforts appeared unpromising. Treatment of a mixture
of phosphonium iodide 4 and aldehyde 1 with Ag2CO3 gave a
complex mixture. Nonetheless, a significant constituent of this
mixture was purified. Single-crystal X-ray analysis revealed its
structure as that shown as compound 5. We contemplated that
5 was formed from ylide 2b by intramolecular reaction with the
ester. Notwithstanding the failure to give the desired product
en route to meso-diaminopimelate, the reaction implicated
Ag2CO3 as a capable reagent for ylide formation.
essentially identical (46%) yield. The yield for the reaction of p-
chlorobenzaldehyde 6b with K2CO3 alone as the base was poor
(7%). Use of 2 equiv of Ag2CO3 and 2 equiv of the
phosphonium salt improved the yield from 50% to 72%,
without change in the dr of the product. These results
emphasize the halide affinity of the Ag(I) cation as a driving
force for ylide formation. Verkade et al.16 described an
analogous Wadsworth−Emmons−Horner reaction promoted
by a mild triaminophosphine base, but in their case p-
chlorobenzaldehyde 6b did not react with alkylphosphonate,
presumably because the weaker base was unable to deprotonate
less acidic alkylphosphonate. This outcome highlights the
ability of silver carbonate to deprotonate even a less acidic
alkylphosphonium halide under mild conditions.16
For another example of the use of Ag2CO3, we chose 2-
furaldehyde 6c as a commercially available, heterocyclic
aldehyde. Wittig reaction of 6c with 7b yielded olefin 8g in a
yield of 85%. The reaction was complete in 2 h and thus was a
much faster reaction compared to the reaction with compounds
6a and 6b. When 2-furylaldehyde 6c was coupled with
phosphonium salt 7a, compound 8f was obtained in 87% yield.
Ketones are less reactive in the Wittig olefination compared
to aldehydes. We chose cyclohexanone as a representative
ketone to couple with reagent 7a. As expected, the reaction was
sluggish and required heating (60 °C, overnight in acetonitrile).
Unsaturated ester 8h was obtained in 42% yield (entry 8). This
yield is less than the reported yields for this same reaction
(98%) using sodium methoxide as the base.25 On the other
hand, when cyclohexanone 6d was reacted with 7a using
K2CO3 as base, only trace quantities (less than 1% detected by
1H NMR) of the ester product 8h were formed. This result
emphasizes the beneficial effect of silver cation for the Wittig
reaction and demonstrates the profound effect of the silver ion
over the potassium ion.
This implication prompted the further exploration of silver
carbonate as a mild base for ylide formation (stabilized,
semistabilized, and nonstabilized ylides) for the Wittig reaction.
As outlined in the general Scheme 2, we generated the ylide by
Scheme 2
reaction of a triphenylphosphonium salt with Ag2CO3 in
acetonitrile. After 1 h, the resulting ylide was then treated with
an aldehyde, in expectation of alkene formation.
We used (carbomethoxymethyl)triphenylphosphonium
chloride 7a as the ylide precursor, Ag2CO3 in acetonitrile at
room temperature as the reaction conditions, and p-
anisaldehyde 6a as the carbonyl acceptor. We compared the
outcome of this reaction to one using commercial methyl
(triphenylphosphoranylidene)acetate without Ag2CO3. Both
reactions gave the desired product 8a. Encouraged by this
result, we set up several Wittig reactions using various
phosphonium halides, including aromatic 7b, heterocyclic 7c,
and aliphatic 7d examples (Table 1), in reaction with p-
anisaldehyde. Styrene derivatives 8a−d were obtained in 63−
97% yields. The poorest yield, seen for styrene 8d (entry 4), is
likely due to the poorer acidity of ethyl triphenylphosphonium
bromide 7d. The diastereoselectivity of the reaction leading to
8a and 8c strongly favored the E isomer, as expected for
stabilized ylides (7a and 7c).
The E/Z selectivity decreased for semistabilized and
nonstabilized ylides (7b and 7d) leading to 8b, 8d, and 8e,
respectively. It is remarkable that even the aliphatic
alkylphosphonium halides 7d could be deprotonated using
Ag2CO3 in acetonitrile at room temperature (entries 4 and 5)
to form the nonstabilized ylide under mild conditions. We
evaluated Ag2O and AgOAc as alternative sources of Ag(I) in
the reaction of aldehyde 6b with 7d. The yield of olefin 8e was
poorer (28% in the case of AgOAc and 68% in the case of
Ag2O).
Aldehyde 6e is an example of an aliphatic aldehyde as a
useful synthetic reagent. This aldehyde is derived from D-
aspartate and is a precursor to unsaturated amino acids.21 The
reaction of 6e with benzyltriphenylphosphonium chloride 7b
gave compound 8j in 60% yield. The yield was improved to
83% by using freshly prepared aldehyde 6e, as obtained by
DIBAL-H reduction of the corresponding methyl ester,21 prior
the Wittig reaction. The analogous reactions of 6e with the
Wittig reagents 7a and with 7c gave 8i (82% yield) and 8k
(97% yield), respectively. Moreover, olefins 8i, 8j, and 8k each
were obtained with high enantiomeric ratios (er >95:5 as
assessed by chiral support HPLC analysis, as shown in the
Supporting Information). No evidence for loss of stereo-
chemical integrity by the Ag2CO3 base was seen. Again, we
compared Ag2CO3 with other bases (entries 9 and 10). While
Wittig olefination using K2CO3 gave the product 8i in 69%
yield (82% with Ag2CO3), the reaction with the less acidic
phosphonium salt 7b gave a much poorer yield (8%). Using the
strong base t-BuOK for the olefination of the base-sensitive
aliphatic aldehyde 6e primarily caused self-reactions of the
starting aldehyde. The olefin product was detected in small
amounts in the crude mixture (yield of less than 1% as
Silver carbonate is an affordable (approximate cost of $1/
mmol) reagent for smaller scale reactions. We evaluated the
possibility that the combination of the inexpensive base K2CO3
with Ag2CO3 might mitigate reagent cost. Reaction of the
phosphonium salt 7d with 4-chlorobenzaldehyde 6b under the
standard reaction conditions (1 equiv Ag2CO3) gave alkene 8e
in 50% yield (Table 1, entry 5). Using a mixture of 0.5 equiv of
K2CO3 and 0.5 equiv of Ag2CO3 in this same reaction gave an
4
1
determined by H NMR, entry 9). Epimerizable aldehydes 6f
and 6g having an α-stereogenic carbon were condensed with
phosphonium salt 7a in THF at 0 °C yielding olefins 8l and 8m
in high yield and remarkably high E/Z ratio (>95% E isomer).
Both olefins 8l and 8m were obtained without observable
1
epimerization as determined by H NMR of the crude mixture
(entries 12 and 13). To explore potential of the reaction to be
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Table 1. Wittig Reactions of Phosphonium Salts 7a−d with Carbonyl Compounds 6a−g
a
b
c
1
Structures are of the major product. E:Z ratio was determined from H NMR spectra of the crude product. 2 equiv of Ag2CO3 and 2 equiv 7d
d
e
f
were used. 0.5 equiv of Ag2CO3 and 0.5 equiv of K2CO3 were used. K2CO3 was used instead of Ag2CO3. In the analogous example, aldehyde 6b
and diethyl ethylphosphonate gave no Wittig reaction when promoted by the weak base bicyclic triaminophosphine (ref 16) in THF. Reaction
g
h
i
mixture was heated at 60 °C. Enantiomeric ratio determined by chiral support HPLC analysis. t-BuOK was used instead of Ag2CO3.
j
k
Diastereoisomeric ratio determined by 1H NMR of crude sample. Reaction was performed in THF because of the poorer solubility of the carbonyl
l
compound in MeCN. Reaction was performed at 0 °C.
scale up, we conducted Wittig olefination of aldehyde 6e with
phosphonium salt 7a at 10-mmol scale. We obtained a
comparable result to the 1-mmol scale reaction (92% yield,
dr 95:5).
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Note
combined filtrate was concentrated under reduced pressure, and the
crude product was purified by chromatography on silica gel (6:1
hexanes/EtOAc) to yield compound 8a as a colorless oil (0.38 g,
97%). For NMR analysis, the E and Z isomers were separated by a
second chromatography. The 1H NMR spectrum of both isomers
Silver carbonate is a reagent with substantial promise for the
convenient (as an out of the bottle reagent added to reagent-
quality solvent) Wittig reaction of stabilized and semistabilized
ylides with base-sensitive aldehydes, and for the Wittig reaction
of nonstabilized ylides with enolizable aldehydes, with good to
excellent (63−97%) yields.
matched the reported values.14,27 E-8a: H NMR (500 MHz, CDCl3)
1
δ 3.77 (s, 3H), 3.80 (s, 3H), 6.29 (d, J = 16.0 Hz, 1H), 6.88 (d, J = 8.8
Hz, 2H), 7.44 (d, J = 8.8 Hz, 2H), 7.63 (d, J = 16.0 Hz, 1H). Z-8a: 1H
NMR (500 MHz, CDCl3) δ 3.73 (s, 3H), 3.83 (s, 3H), 5.84 (d, J =
12.6 Hz, 1H), 6.86 (d, J = 12.6 Hz, 1H), 6.88 (d, J = 9.0 Hz, 2H), 7.70
(d, J = 9.0 Hz, 2H).
EXPERIMENTAL SECTION
■
General Methods. All organic reagents were purchased from
commercial suppliers and used without further purification. Solvents
were HPLC grade (THF and acetonitrile used directly from the bottle,
without additional drying). Reactions were monitored by thin-layer
chromatography using UV light, or ninhydrin or phosphomolybdic
acid staining, for visualization. Flash chromatography was carried out
Methyl (2R)-3-(Bis(tert-butyloxycarbonyl)amino)-5-phenyl-
pent-4-enoate (8j). Compound 8j was prepared following the
representative procedure. Compound 8j was obtained on a 1 mmol
1
scale as a colorless oil (0.34 g, 83%) and by H NMR was a 1:1 E/Z
1
mixture: H NMR (500 MHz, CDCl3) δ 1.42 (s, 9H), 1.45 (s, 9H),
1
with 230−400 mesh silica gel 60. H, 13C, H,H−COSY, H,C-HSQC,
2.80−2.89 (m, 1H), 2.98−3.14 (m, 3H), 3.71 (s, 3H), 3.75 (s, 3H),
5.02−5.09 (m, 2H), 5.65 (ddd, J = 11.6, 8.8, 6.0 Hz, 1H, PhCHCH,
Z), 6.17 (ddd, J = 15.7, 9.0, 6.1 Hz, 1H, PhCHCH, E), 6.43 (d, J =
15.7 Hz, 1H, PhCHCH, E), 6.55 (d, J = 11.6 Hz, 1H, PhCHCH,
Z), 7.17−7.24 (m, 1H), 7.25−7.35 (m, 4H); 13C NMR (126 MHz,
CDCl3) δ 28.099, 28.08, 29.3, 33.9, 52.3, 52.4, 58.0, 58.2, 125.8, 126.3,
126.9, 127.3, 127.6, 128.3, 128.5, 128.9, 131.8, 133.2, 137.1, 137.4,
152.0, 152.1, 170.9, 171.0; MS (ESI-TOF) m/z [M + Na]+ calcd for
C22H31NNaO6 428.2044, found 428.2025; er >95:5 for both E/Z
isomers determined by chiral support HPLC analysis.
and H,C-HMBC NMR spectra were recorded on 300, 400, and 500
1
MHz spectrometers. H and 13C chemical shifts were referenced to
residual solvent. NMR assignments for new compounds were made on
the basis of H−H COSY, H−C HSQC, and H−C HMBC
correlations. High-resolution mass spectra were obtained via FAB or
ESI ionization with TOF detection or EI ionization with orthogonal
acceleration TOF detection. Chiral phase HPLC analyses were
performed on (S,S) Whelk-O1 (25 cm × 4.6 mm i.d.) using
hexanes/2-propanol or hexanes/2-propanol/diethylamine as the
mobile phase. Reactions were carried out at room temperature
under a nitrogen atmosphere and were run overnight (18 h) unless
otherwise noted.
Methyl (2R)-3-(Bis(tert-butyloxycarbonyl)amino)-5-(pyridin-
2-yl)pent-4-enoate (8k). Compound 8k was prepared following the
representative procedure, with the exception that triphenyl(pyridin-2-
ylmethyl)phosphonium chloride hydrochloride 7c was used as the
ylide precursor. The title compound was obtained on a 1 mmol scale
as a pale yellow oil (0.39 g, 97%) as a 6:1 E/Z mixture. The E and Z
isomers were subsequently separated for NMR analysis by a second
chromatography. E-8k: 1H NMR (500 MHz, CDCl3) δ 1.44 (s, 18H),
2.90 (dddd, J = 14.5, 9.8, 8.7, 1.0 Hz, 1H), 3.09 (dddd, J = 14.5, 6.4,
5.1, 1.2 Hz, 1H), 3.74 (s, 3H), 5.08 (dd, J = 9.8, 5.1 Hz, 1H), 6.57 (d, J
= 15.6 Hz, 1H), 6.70 (ddd, J = 15.6, 8.7, 6.4 Hz, 1H), 7.12 (dd, J = 6.9,
4.9 Hz, 1H), 7.29 (d, J = 7.8 Hz, 1H), 7.62 (ddd, J = 7.8, 6.9, 1.2 Hz,
1H), 8.52 (dd, J = 4.9, 1.2 Hz, 1H); 13C NMR (126 MHz, CDCl3) δ
27.9, 33.7, 52.2, 57.7, 83.2, 121.0, 121.9, 131.2, 132.6, 136.6, 148.9,
Reagents and Known Products. Aldehydes 6e,21 6f,4 and 6g4
were prepared according to the literature procedures. Silver carbonate
was purchased from commercial suppliers or was freshly prepared
from silver nitrate.26 Both reagents gave comparable results.
Compounds 8a,14,27 8b,28,29 8c,30 8d,31,32 8e,33 8f,34 8g,35,36 8h,25
8i,21 and 8l4 are known. Their NMR spectra were identical to the
referenced values. The synthesis of methyl 4-methoxycinnamate 8a is
given as representative example.
Phosphonium, 1-Methyl-1-[(3S)-3-[[(1,1-dimethylethoxy)-
carbonyl]amino]-4-oxo-4-[(4-methoxyphenyl)methoxy]butyl]-
1-diphenyl, Iodide (1:1) (4). Methyldiphenylphosphonium iodide
(4) was prepared by refluxing N-Boc-2-amino-4-iodobutanoate 4-
methoxyphenylmethyl ester and methyldiphenylphosphine in benzene.
4: 1H NMR (500 MHz, CDCl3) δ 1.36 (s, 9H), 2.15 (s, 2H), 2.76 (d, J
= 13.4 Hz, 3H), 3.29 (m, 2H), 3.75 (s, 3H), 4.37 (m, 1H), 5.08, 5.14
(AB, J = 12.0 Hz, 2H), 5.98 (d, J = 5.4 Hz, 1H), 6.81 (d, J = 8.6 Hz,
2H), 7.28 (d, J = 8.4 Hz, 2H), 7.58−7.90 (m, 11H); 13C NMR (126
MHz, CDCl3) δ 8.8 (d, J = 55.1 Hz), 19.9 (d, J = 53.5 Hz), 24.2, 28.3,
53.4, 55.4, 67.5, 114.0, 118.5 (d, J = 36.2 Hz), 119.2 (d, J = 36.2 Hz),
127.5, 130.4, 130.4, 130.5, 130.6, 132.5, 132.6, 135.0 (d, J = 3.3 Hz),
135.1 (d, J = 3.3 Hz), 155.8 (m), 159.8, 170.8; MS (ESI-TOF) m/z
[M + H]+ calcd for C30H38NO5P 523.2482, found 523.2502.
( )-4-[((1,1-Dimethylethoxy)carbonyl)amino]-3-oxo-1,1-di-
phenylphosphorinanium, 2-Ylide (5). An acetonitrile solution of 4
(0.71 g, 1.1 mmol) was stirred with Ag2CO3 (0.28 g, 1.0 mmol) for 1 h
at room temperature. The reaction mixture was filtered through a layer
of Celite. Evaporation of volatiles followed by column chromatography
gave 5 as a crystalline solid. The structure of 5 was determined by X-
ray crystallography (Supporting Information). 5: 1H NMR (500 MHz,
CDCl3) δ 1.42 (s, 9H), 1.83 (m, 1H), 2.53−2.71 (m, 2H), 2.75−2.92
(m, 1H), 3.68 (d, J = 12.0 Hz, 1H), 3.93 (d, J = 11.2 Hz, 1H), 6.22 (br
s, 1H), 7.48−7.70 (m, 10H); 13C NMR (126 MHz, CDCl3) δ 21.2 (d,
J = 55.1 Hz), 26.5, 28.6, 48.9 (d, J = 101.2 Hz), 54.7, 79.2, 129.3,
129.4, 129.5, 131.5 (m), 131.6, 131.9, 132.0, 132.9, 156.8, 185.4; MS
(ESI-TOF) m/z [M + H]+ calcd for C22H27NO3P 384.1723, found
384.1746.
1
151.9, 155.3, 170.6. Z-8k: H NMR (500 MHz, CDCl3) δ 1.42 (s,
9H), 1.43 (s, 9H), 3.35−3.40 (m, 2H), 3.73 (s, 3H), 5.18 (dd, J = 8.6,
6.6 Hz, 1H), 5.90 (ddd, J = 11.8, 7.8, 7.3 Hz, 1H), 6.57 (d, J = 11.8 Hz,
1H), 7.13 (dd, J = 7.1, 5.1 Hz, 1H), 7.28 (d, J = 6.9 Hz, 1H), 7.66
(ddd, J = 7.1, 6.9, 1.5 Hz, 1H), 8.60 (d, J = 4.4 Hz, 1H); 13C NMR
(126 MHz, CDCl3) δ 28.0, 29.7, 52.3, 58.3, 83.2, 121.5, 124.2, 130.8,
132.1, 136.3, 149.3, 152.1, 156.3, 171.2; MS (ESI-TOF) m/z [M +
H]+ calcd for C21H31N2O6 407.2177, found 407.2170; er >95:5
determined for E isomer by chiral support HPLC analysis.
Methyl (2E,4S)-4-[[(2S)-2-[[(1,1-Dimethylethoxy)carbonyl]-
amino]-1-oxo-3-phenylpropyl]amino]pent-2-enoate (8l). Com-
pound 8l was prepared from aldehyde 6f and Wittig reagent 7a
following the representative procedure, except THF was used as a
solvent and the reaction was performed at 0 °C for 18 h. A 1 mmol
scale reaction gave 8l (0.31 g, 82%) as a white powder. Its 1H and 13
C
NMR spectra matched the reported values:4 1H NMR (400 MHz,
CD3OD) δ 1.23 (d, J = 6.9 Hz, 3H), 1.39 (s, 9H), 2.86 (dd, J = 13.5,
8.1 Hz, 1H), 3.01 (dd, J = 13.5, 7.1 Hz, 1H), 3.72 (s, 3H), 4.24−4.30
(m, 1H), 4.52−4.59 (m, 1H), 5.68 (d, J = 15.7 Hz, 1H), 6.72 (dd, J =
15.7, 5.3 Hz, 1H), 7.19−7.29 (m, 5H); 13C NMR (126 MHz,
CD3OD) δ 19.9, 28.8, 39.7, 47.1, 52.2, 57.7, 80.8, 121.0, 128.0, 129.6,
1
130.6, 138.4, 150.4, 157.6, 168.5, 173.6; dr >95:5 determined by H
NMR.
Methyl (2E,4R)-4-[[(2S)-2-[[(1,1-Dimethylethoxy)carbonyl]-
amino]-1-oxo-3-phenylpropyl]amino]pent-2-enoate (8m).
Compound 8m was prepared from aldehyde 6g and Wittig reagent
7a following the representative procedure, except THF was used as a
solvent and the reaction was performed at 0 °C for 16 h. A 1 mmol
Methyl 4-Methoxycinnamate (8a). (Carbomethoxymethyl)-
triphenylphosphonium chloride (0.82 g, 2.2 mmol) was added to a
suspension of Ag2CO3 (0.55 g, 2.0 mmol) in acetonitrile (5 mL). After
1 h, p-anisaldehyde (0.27 g, 2.0 mmol) was added. The reaction
mixture was stirred overnight. The dark brown mixture was filtered
through a layer of Celite. The Celite pad was washed with EtOAc. The
1
scale reaction gave 8m (0.34 g, 90%) as a white powder: H NMR
(400 MHz, CD3OD) δ 1.09 (d, J = 7.1 Hz, 3H), 1.40 (s, 9H), 2.88
D
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Note
(dd, J = 13.4, 7.9 Hz, 1H), 2.99 (dd, J = 13.4, 7.2 Hz, 1H), 3.70 (s,
3H), 4.25 (dd, J = 7.9, 7.2 Hz, 1H), 4.45−4.54 (m, 1H), 5.94 (d, J =
15.7 Hz, 1H), 6.84 (dd, J = 15.7, 5.1 Hz, 1H), 7.19−7.30 (m, 5H); 13C
NMR (126 MHz, CD3OD) δ 19.6, 28.8, 39.4, 47.2, 52.2, 57.8, 80.8,
121.0, 127.9, 129.6, 130.6, 138.6, 150.4, 157.7, 168.6, 173.8; MS (ESI-
TOF) m/z [M + H]+ calcd for C20H29N2O5 377.2071, found
377.2065; [M + Na]+ calcd for C20H28N2NaO5 399.1890, found
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3768.
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1
399.1869; dr 95:5 determined by H NMR.
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ASSOCIATED CONTENT
■
6756−6760.
S
* Supporting Information
(19) McNulty, J.; McLeod, D. Chem.Eur. J. 2011, 17, 8794−8798.
MS data for 8a−m; chromatograms used to determine the
́ ́
(20) Remond, E.; Bayardon, J.; Ondel-Eymin, M.-J.; Juge, S. J. Org.
enantiomeric ratios for 8i−m; H and 13C NMR spectra for
1
Chem. 2012, 77, 7579−7587.
compounds 4, 5, and 8a−m; crystallographic information file
(CIF) for compound 5. This material is available free of charge
via the Internet at http://pubs.acs.org.
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AUTHOR INFORMATION
■
Corresponding Author
*Email: mobashery@nd.edu.
(24) Fackler, J. Sci. Synth. 2004, 3, 663−690.
(25) Kapferer, T.; Bruckner, R. Eur. J. Org. Chem. 2006, 2119−2133.
̈
Author Contributions
(26) Xu, Ch.; Liu, Y.; Huang, B.; Li, H.; Qin, X.; Zhang, X.; Dai, Y.
Appl. Surf. Sci. 2011, 257, 8732−8736.
†Both authors contributed equally to this work.
Notes
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(28) Mu, B.; Li, T.; Xu, W.; Zeng, G.; Lu, P.; Wu, Y. Tetrahedron
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The authors declare no competing financial interest.
(29) Aggarwal, V. K.; Fulton, J. R.; Sheldon, C. G.; Vicente, J. J. Am.
Chem. Soc. 2003, 125, 6034−6035.
ACKNOWLEDGMENTS
■
The work was supported by NIH Grant No. GM61629. L.J. was
supported by the Projects of Operational Program Research
and Development for Innovations from the Ministry of
Education and Sports of Czech Republic (CZ.1.07/2.4.00/
31.0130, CZ1.07/2.3.00/20.0009, and CZ.1.07/2.2.00/
28.0184). The Mass Spectrometry & Proteomics Facility of
the University of Notre Dame is supported by Grant No.
CHE0741793 from the NSF. High-resolution mass spectra
were obtained at the Department of Chemistry and
Biochemistry, University of Notre Dame. We thank a reviewer
for the suggestion that we evaluate the use of a mixed K2CO3/
Ag2CO3 base (Table 1, entry 5).
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