Conversion of cyclic vinyl sulfones to transposed vinyl phosphonates

Article abstract of DOI:10.1021/ja072890p

Functionalized cyclic vinyl sulfones were directly converted to the "polarity reversed" vinyl phosphonates through an efficient one pot procedure. Ozonolysis of these vinyl sulfones and vinyl phosphonates furnish complementary sets of termini-differentiat

Full text of DOI:10.1021/ja072890p

Published on Web 08/16/2007
Conversion of Cyclic Vinyl Sulfones to Transposed Vinyl
Phosphonates
Mohammad N. Noshi, Ahmad El-awa, Eduardo Torres, and Philip L. Fuchs*
Contribution from the Department of Chemistry, Purdue UniVersity, 560 OVal DriVe,
West Lafayette, Indiana 47907
Received May 14, 2007; E-mail: pfuchs@purdue.edu
Abstract: Functionalized cyclic vinyl sulfones were directly converted to the “polarity reversed” vinyl
phosphonates through an efficient one pot procedure. Ozonolysis of these vinyl sulfones and vinyl
phosphonates furnish complementary sets of termini-differentiated ester-aldehydes. This strategy has been
applied for preparation of segments needed for the synthesis of Aplyronine A. The scope and limitations
of this transformation were defined.
Introduction
The synthesis of biologically significant compounds that
incorporate polypropionate sequences has been the focal point
1
for numerous research groups. The challenge of preparing
enantiopure polypropionates has prompted the Fuchs group to
explore cross-conjugated six- and seven-membered cyclic dienyl
sulfones as precursors of termini-differentiated acyclic arrays
2
bearing multiple stereocenters (Figure 1). This strategy exploits
the binary nature of organic synthesis to evolve a collection of
synthetic intermediates appropriate for the preparation of a large
number of targets.
Pursuant to synthesis of aplyronine A 12, vinyl sulfone 10
smoothly underwent ozonolysis to give the aldehyde ester 11
in excellent yield. Synthesis of 10 starts with known allylic
3
Figure 1. Termini differentiated acyclic arrays from dienyl sulfones.
alcohol 8, which was selectively epoxidized to yield the syn
4
epoxide 8a in 85% yield and 19:1 diastereoselectivity. Nu-
This conversion required treating vinyl sulfone 10 with 10
equiv of KCN, 10% 18-crown-6 in t-BuOH at reflux for 8 h to
give vinyl nitrile 13 in a 60-70% yield. The conditions of this
conversion and the toxicity of KCN/18-crown-6 prompted us
to pursue a milder and safer procedure. Consequently, phos-
phorus nucleophiles were considered as an alternative to cyanide.
Initial trials involved mixing the substrate vinyl sulfone
cleophilic opening of the epoxide 8a using sodium thiophenox-
ide occurs through the chairlike transition state giving diol 9 as
a single regioisomer in 92% yield.
Protection of the diol as the bismethyl ether was followed
by oxidation of the sulfide to the sulfone 9b and elimination of
the OMe group to yield vinyl sulfone 10 in 78% overall yield
(Scheme 1). However, difficulties encountered with the initial
with 3.1 equiv of diethyphosphite and 3.2 equiv of LiHMDS at
coupling strategy required preparation of the “reversed” alde-
hyde-ester fragment 14. While one can conceive a multistep
sequence that would accomplish the task from 11, it appeared
that reversing the polarity of the trisubstituted double bond in
vinyl sulfone 10 would more efficiently effect the desired
6
-78 °C for 28 h (Table 1).
This procedure necessitated use of HMPA to enable any
conversion to the target vinyl phosphonate. The requirement
for carcinogenic HMPA combined with the protracted reaction
times signaled the need for further optimization. Early attempts
involved using KHMDS in the absence of HMPA. Preparation
of the phosphite anion before mixing with the substrate was
appealing based upon the known sensitivity of vinyl sulfones
5
conversion. Initially the Taber reaction was employed to convert
vinyl sulfone 10 to vinyl nitrile 13 (Scheme 2).
(
1) (a) Kigoshi, H.; Ojika, M.; Ishigaki, T.; Suenaga, K.; MuTou, T.; Sakakura,
A.; Ogawa, T.; Yamada, K. J. Am. Chem. Soc. 1994, 116, 7443. (b)
Paterson, I.; Cowden, C. J.; Woodrow, M. D. Tetrahedron Lett. 1998, 39,
7
toward a strong base. Nevertheless, an in situ procedure is
6
037. (c) Paterson, I.; Woodrow, M. D.; Cowden, C. J. Tetrahedron Lett.
998, 39, 6041. (d) Paterson, I.; Blakey, S. B.; Cowden, C. J. Tetrahedron
equally effective if excess base added is avoided. A typical
procedure involves mixing 1.3 equiv of diethyl phosphite with
1
Lett. 2002, 43, 6005. (e) Calter, M. A.; Guo, X. Tetrahedron 2002, 58,
7
093. (f) Calter, M. A.; Zhou, J. G. Tetrahedron Lett. 2004, 45, 4847.
(2) Synthesis via vinyl sulfones 93; Chiral carbon catalog 15.
(3) Goering, H. L.; Kantner, S. S. J. Org. Chem. 1981, 46, 2144.
(4) The minor isomer was easily separable by flash column chromatography.
(5) Taber, D. F.; Saleh, S. A. J. Org. Chem. 1981, 46, 4817.
(6) Torres, E. Ph.D. Thesis, Purdue University, 2003.
(7) Hirata, T.; Sasada, Y.; Ohtani, T.; Aasada, T.; Kinoshita, H.; Senda, H.;
Inomata, K. Bull. Chem. Soc. Jpn. 1992, 65, 75.
11242
9
J. AM. CHEM. SOC. 2007, 129, 11242-11247
10.1021/ja072890p CCC: $37.00 © 2007 American Chemical Society

Cyclic Vinyl Sulfones to Transposed Vinyl Phosphonates
A R T I C L E S
Table 1. Substrates Used for Vinyl Phosphonate Formation
Scheme 1. Synthesis of Aplyronine A C16-C20 Segmenta
a
Conditions: (a) m-CPBA, DCM, rt, h, 85%, dr )19:1; (b) PhSH, NaH,
THF, rt, h, 92%; (c) NaH, MeI, THF, rt, 2 h; (d) m-CPBA, DCM, rt, 1 h;
(e) NaH, THF, rt, h, 78% (three steps); (f) (i) O3, CH2Cl2/MeOH (4:1),
NaHCO3, -78 °C; (ii) Ph3P (1.2 equiv), rt, 2 h, 90% over two steps.
Scheme 2. Conversion of Vinyl Sulfone 10 to Fragment 14a
Scheme 3. Early Trials to Transpose Vinyl Sulfone 10 to Vinyl
Phosphonate 21a
a
Conditions: (a) [KHMDS (1.2 equiv)/diethylphosphite (1.3 equiv)],
THF, rt, 60 s, 98% (1.5:1 respectively).
Scheme 4. Ozonolysis of Vinyl Phosphonate 22a
a
Conditions: (a) KCN (10 equiv), tBuOH, reflux, 8 h, 60-70%; (b)
O3, CH2Cl2/MeOH (4:1), NaHCO3, -78 °C then Ph3P, rt, 2 h.
1
.2 equiv of KHMDS in THF at room temperature for 15 min
followed by rapid addition of the solid vinyl sulfone. Within
0 s after addition the reaction color changes from a faint yellow
a
Conditions: (a) O3, CH2Cl2/MeOH (4:1), NaHCO3, -78 °C; (b) Ph3P
3
(1.2 equiv), rt, 2 h, 78% over two steps.
solution to a deep canary yellow one. After an additional 30 s,
a heavy white precipitate of potassium phenylsulfinate begins
forming. This reaction generated two products in an essentially
quantitative yield. The first product was the desired vinyl
phosphonate 21 and the second was the addition product 22 in
a 1.5:1 ratio, respectively (Scheme 3).
This result suggested that the presence of moisture was
decreasing the yield of vinyl phosphonate 21. Consequently, a
series of reactions were executed with thoroughly dried sub-
strates, reagents, and solvents. Gratifyingly, the reaction gave
vinyl phosphonate 21 in near quantitative yield with 22 observed
in only trace amounts. The conversion was clean, fast, and
higher yielding than that by the KCN procedure. Finally,
ozonolysis of vinyl phosphonate 21 in CH2Cl2/MeOH (4:1)
delivered aldehyde-ester fragment 14 in an 89% overall yield
(Scheme 4). It is worth mentioning that this aldehyde was quite
troublesome to handle. First, it was quite volatile, which resulted
J. AM. CHEM. SOC.
9
VOL. 129, NO. 36, 2007 11243

A R T I C L E S
Noshi et al.
Scheme 5. Proposed Mechanism for Vinyl Sulfone to Vinyl
Phosphonate End-for-End Redox Transposition
Figure 2. Effect of excess base on vinyl phosphonate 21.
product was the addition product 22 with only a trace of the
vinyl phosphonate 21. The typically formed potassium phenyl-
sulfinate precipitate was not observed. An experiment employing
40 mol % KHMDS with excess diethylphosphite probed whether
the first step in the reaction is catalytic in the base. Again, the
major isolated product was 22 (87%) proving that anion 22a is
quenched by diethylphosphite to regenerate the phosphite anion.
In this experiment 21 was isolated in 10% yield.
Effect of Excess Base
Like vinyl sulfones, vinyl phosphonate 21 is also sensitive
to strong bases. Reactions conducted at low concentration never
went to completion, while adding excess KHMDS to convert
residual 22 into 21 resulted in deprotonation of 21 at the allylic
position with concomitant 1,4-elimination of the methoxy group,
affording the dienyl phosphonate 23 in 79% yield (Figure 2).
Inadvertent use of excess base can result from impure
diethylphosphite. The deleterious effect of excess base is not
limited to vinyl phosphonate 21. Vinyl phosphonates, like vinyl
sulfones, undergo base-induced rearrangements to their allylic
in loss of mass upon vacuum drying. Second, it was very prone
to air oxidation giving the acid.8
Mechanistic Insights
1
1
As shown in Scheme 5, KHMDS deprotonates diethyl
phosphite in THF to give HMDS and a homogeneous yellow
solution of potassium phosphite. The latter is known to undergo
phosphite-phosphonate tautomerism favoring the nucleophilic
counterparts.
Counterion Effect
9
The effect of the counterion is especially interesting. As
mentioned previously, 1.3 equiv of the anion are needed to effect
complete conversion using KHMDS as a base. In comparison,
following the same protocol with NaHMDS in THF resulted in
a slower reaction rate with only about 50% conversion over
the same time interval along with ∼50% recovered starting
material. The slow rate using NaHMDS suggested the use of
an additional equivalent of NaOP(OEt)2 anion to complete the
reaction. Indeed, when 2.3 equiv of base was used with 2.4
equiv of diethylphosphite, the reaction was completed much
more rapidly. While the 1 equiV KHMDS reaction takes
approximately 60 s to complete, the 2 equiV NaHMDS reaction
requires 10-20 min at equivalent molarity. This is presumably
phosphorus atom. The phosphite anion attacks vinyl sulfone
1
0 in a conjugate addition fashion to give the deep canary yellow
1
0
anion 22a. Having an estimated pKa close to that of HMDS,
22a deprotonates HMDS to produce 22 and KHMDS. The
regenerated KHMDS deprotonates the phosphonate moiety to
furnish anion 22b. Anion 22b is perfectly set for an E1cb
elimination of potassium phenylsulfinate to afford the desired
vinyl phosphonate 21. This is the stage when the reaction starts
forming a heavy yellowish white suspension.
Effect of Moisture
One can conclude from the proposed mechanism that any
proton source in the reaction more acidic than HMDS will
prematurely quench the anion 22a and prevent regeneration of
KHMDS. Old bottles of KHMDS contain unknown levels of
KOH and HMDS due to adventitious hydrolysis. Using such
aged reagents results in using less KHMDS than required,
thereby increasing the relative stoichiometry of diethylphosphite.
+
due to the stronger nucleophilicity of the K cation compared
+
to the Na cation (during the initial step) combined with the
+
better overlap of K empty 3s orbitals with the sulfone oxygens
+
than that of Na 2s orbitals (during the final step). Also, it was
assumed that potassium sulfinate is less soluble in THF than
sodium sulfinate leading to a faster rate of precipitation due to
a smaller Ksp. This is based on the fact that commercially
available KHMDS in THF has a maximum strength of 0.91 M
compared to 2.0 M in the case of NaHMDS in THF. Another
difference is that the deep canary yellow color observable in
the KHMDS reaction evident of the 22a anion formation is not
obvious in the case of NaHMDS. Despite these differences, the
reaction yields were comparable in both cases. In stark contrast,
Effect of Excess Diethylphosphite
Excess diethyl phosphite has the same effect of moisture. The
anion 22a is likely capable of deprotonating diethylphosphite
to produce 22 and regenerate the phosphonate anion. To test
this hypothesis, an experiment where only 1 equiv of KHMDS
and 2 equiv of diethylphosphite was executed. The major
(
8) The half-life of 14 is roughly 30 min at ambient temperature while neat.
However, it is very stable in an oxygen-free solution.
(9) Maffei, M.; Buono, G. Tetrahedron 2003, 59, 8821.
(
10) Westerhausen, M. Coord. Chem. ReV. 1998, 176, 157.
(11) Kiddle, J. J.; Babler, J. H. J. Org. Chem. 1993, 58, 3572.
11244 J. AM. CHEM. SOC.
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Cyclic Vinyl Sulfones to Transposed Vinyl Phosphonates
A R T I C L E S
Scheme 6. Proof of the Reversibility of the First Step in the Vinyl
Sulfone to Vinyl Phosphonate Transposition
26 required 2 h. Substituted vinyl sulfone 10 underwent smooth
conversion to the vinyl phosphonate. However, unwanted
elimination of the methoxy group leads to dienyl phosphonate
23 if excess base is present. Vinyl sulfone 26 proved to be quite
resistant to the transformation due to hindrance of both faces
of the substrate. The reaction showed no conversion for 12 h
after which the starting material underwent slow decomposition.
The phosphonate anion adds regiospecifically to epoxide 31 in
a 1,4-addition fashion to afford the addition product in 85%
yield. It is worth mentioning that the regio- and stereoselective
phosphite addition to 31 could also be catalytic in the base.
Employing 8 mol % KHMDS in THF resulted in roughly the
same yield of the sole product. Vinyl sulfones 32-35 test
protecting group compatibility with this conversion. These
substrates have two substituents trans to each other and close
to the sulfone moiety presumably reflecting the somewhat longer
reaction times (∼30-50 min). Nevertheless, the conversion was
clean with no side products being observed. Substrates 3214 and
3
3, bearing acyl functionality, undergo the reaction without
difficulty to give the corresponding vinyl phosphonates in 63-
2% and 83% yield, respectively. Hydroxy vinyl sulfones 27
8
in the absence of HMPA, using even 3 equiv of LiHMDS
resulted in the starting material being completely recovered after
and 28 (entries 10 and 11, respectively) bearing unprotected
alcohol groups proved to be quite challenging substrates.
Nevertheless, the desired vinyl phosphonates were detected via
NMR as minor products while the major products were the
elimination products/caged phosphonates (depending on the
position of -OH on the substrate). This is presumably because
the initially formed alpha-sulfonyl anion is immediately quenched
by the free hydroxyl group (Table 2, entry 28), thus preventing
advancement to the vinyl phosphonate. The thus formed
24 h.
Effect of Reaction Concentration
Initial runs were performed at 0.1 M or 0.2 M concentrations.
It was observed that 0.1 M reactions consistently have 10-
2
0% of the starting material remaining. On the other hand,
reactions at 0.2 M or higher result in almost complete consump-
tion of the starting material.
1
5
O-anion then attacks the phosphonate moiety to afford the
This begged the question of whether the first step in the
mechanism was reversible. To explore this possibility, purified
adduct 22 was treated with 0.9 equiv of NaHMDS in THF at
room temperature. Vinyl sulfone 10 was regenerated along with
the formation of vinyl phosphonate 21 in almost a 1:1 ratio
upon rapid quenching of the reaction (Scheme 6). This confirms
that the first step is reversible and that both the sulfone and the
phosphonate moieties are competent as leaving groups. How-
ever, the final sulfonate elimination is irreversible, consistent
with the reported pKa values for diethylphosphite and benze-
nesulfinic acid; 1312 and 2.1 respectively. Since the initial
addition/elimination of phosphonate is reversible while the final
elimination of sulfonate is irreversible, 0.2 M reactions perform
better than 0.1 M ones due to increased local concentrations of
starting materials. Also, this concentration effect explains why
1
6
caged product 28a (see Supporting Information). In contrast,
vinyl sulfone 27 gave the transposed product 27b after elimina-
tion of the -OH group. This is presumably because the initially
formed alpha-sulfonyl anion suffers immediate E1cb elimination
of the -OH group and gives a new vinyl sulfone. In the basic
medium, this vinyl sulfone is rearranged to an allyl sulfone that
is transposed to 27b (see Supporting Information). To overcome
the free hydroxyl limitation, it was appealing to transiently
protect the -OH with a labile protecting group which would
be cleaved during the postreaction workup. The first strategy
attempted protecting the alcohol function as the monoanions
13
27a and 28b using a sodium, potassium, or lithium base at -78
°C. This was followed by the cannulation of the phosphite anion
at -78 °C and then warming to room temperature. Initial trials
utilized NaHMDS and KHMDS as bases. To our surprise, even
using 1 equiv of either base resulted in complete and immediate
decomposition of the vinyl sulfones. Next, LiHMDS was
employed with hopes that the oxidolithium intermediate might
be more stable. Indeed, treating the free hydroxyl vinyl sulfone
28 with 1 equiv of LiHMDS resulted in a stable LiO moiety
and no decomposition was observed. Unfortunately, however,
cannulation of the potassium salt of diethylphosphite anion to
the reaction again yielded the elimination product 28c as the
sole product.
2
.3 equiv of the phosphite anion are needed in the case of
NaHMDS since it is a weaker nucleophile than KHMDS
however, the NaOP(OEt)2 nucleophilicity is somewhat com-
(
pensated by the reaction concentration).
Reaction Scope and Limitation
Table 2 shows the data for using NaHMDS as a base. Vinyl
sulfones 24, 25, and 18 underwent the transposition smoothly
to the corresponding vinyl phosphonates in excellent yields
while the addition products were detected only in trace amounts
(
Table 2, entries 1-3). While transposition of five- and seven-
14) 1H NMR of vinyl sulfone 32 shows the acetate methyl at δ 1.57 ppm, an
(
interesting deviation from the expected value around δ 2.5 ppm.
15) X-ray structure of caged product 28a suggests that the O-anion is formed
through an intermolecular proton transfer rather than an anticipated
intramolecular proton transfer (see Supporting Information for suggested
mechanism).
membered substrates was complete in 10-20 min, vinyl sulfone
(
(
12) Guthrie, J. P. Can. J. Chem. 1979, 57, 236.
(
13) Burkhard, R. K.; Sellers, D. E.; DeCou, F.; Lambert, J. L. J. Org. Chem.
1
959, 24, 767.
(16) Structure confirmed by X-ray crystallography (see Supporting Information).
J. AM. CHEM. SOC. VOL. 129, NO. 36, 2007 11245
9

A R T I C L E S
Table 2. Substrates Used for Vinyl Phosphonate Formation Using NaHMDS or KO Bu as a Base
Noshi et al.
a
t
b
The next option involved transient protection of the alcohol
as an -OTMS group to be deprotected during the workup stage.
Therefore, the protection method requires the medium to be
silylating agent in the presence of an ammonium salt catalyst.17
This was accomplished by heating the vinyl sulfone at THF
reflux with 0.5 equiv of HMDS and catalytic ammonium sulfate
“
proton-free” by literally “evaporating” the -OH problematic
(
17) Montero, J. L.; Toiron, C.; Clave, J. L.; Imbach, J. L. Recl. TraV. Chim.
protons. The only applicable method was using HMDS as a
Pays-Bas 1988, 107, 570.
11246 J. AM. CHEM. SOC.
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Cyclic Vinyl Sulfones to Transposed Vinyl Phosphonates
A R T I C L E S
for 12 h resulting in clean and complete protection of the free
added in one portion under positive dry N
2
pressure. Stirring is resumed
for 1-30 min or until a heavy yellowish white precipitate is observed.
The reaction is monitored by TLC (60% ethyl acetate/hexanes, PAA
stain) for completion. Ether (10 mL) and brine solution (35 mL) are
-
OH as -OTMS (vinyl sulfones 29 and 30). After checking
the reaction pH to make sure the medium is neutral, the
diethylphosphite anion was cannulated into the reaction flask
at 25 °C. To our disappointment, we retrieved a mixture of
products among which were free hydroxyl vinyl sulfone, free
hydroxyl addition product, and free hydroxyl vinyl phosphonate.
This suggested that the phosphonate anion attacks the -OTMS
resulting in its deprotection. Fortunately, protection of the free
OH as OTES or OTBS (Table 2, entries 34 and 35) enables
added followed by a few drops of DI-H
for 10 min. The organic layer is separated and dried over anhydrous
Na SO for 30 min and then filtered. Evaporation under reduced
2
O, and the mixture is stirred
2
4
pressure affords crude vinyl phosphonate 21. Purification by column
chromatography (60% ethyl acetate/hexanes) yields pure vinyl phos-
phonate 21 as a light yellow oil (1.8 g, 93%).
18
Alternative in Situ Procedure Using KHMDS
smooth conversion to the desired vinyl phosphonate. It is worth
mentioning that a successful conversion of 34 and 35 to their
vinyl phosphonates could be achieved successfully using KO -
Solvents, starting materials, and reagents must be thoroughly dried
for a successful reaction. A flame-dried three-neck 25 mL flask is
charged with solid vinyl sulfone 10 (266 mg, 1 mmol), diethylphosphite
t
Bu in THF utilizing an in situ procedure. Finally, stereotriad
vinyl sulfone 36 was successfully converted to the desired vinyl
(0.17 mL, 1.3 mmol), and then with freshly distilled dry THF (4.5 mL)
t
at ambient temperature. The mixture is stirred for 1 min, then 0.91 M
KHMDS in THF (1.3 mL, 1.2 mmol) is added dropwise via syringe,
and stirring is continued for 30 min or until a heavy yellowish white
precipitate is observed. The reaction is monitored, worked up, and
isolated as before to afford pure vinyl phosphonate 21 as a light yellow
oil (228 mg, 87%).
phosphonate using either KO Bu or KHMDS to afford 36a in
6
0% and 78% yield, respectively.
Conclusion
This paper reports a new one-pot vinyl sulfone to vinyl
phosphonate transposition. Since ozonolysis of vinyl sulfones
afford termini-differentiated fragments ready for coupling,
ozonolysis of the corresponding vinyl phosphonates beautifully
elaborates the complementary “reversed” aldehyde-ester frag-
ments. This methodology is fast, run at ambient temperature,
high yielding, and tolerant of many functional groups. Many
substrates smoothly underwent this conversion, and this meth-
odology has been successfully applied to the synthesis of
Aplyronine A, which will be published separately.
t
Alternative in Situ Procedure Using KO Bu
A flame-dried three-neck 50 mL flask is charged with solid vinyl
sulfone 34 (50 mg, 0.2 mmol), diethylphosphite (40 µL, 0.3 mmol),
and then with freshly distilled dry THF (1 mL) at ambient temperature.
t
The mixture is stirred for 1 min at 0 °C, then 2 M KO Bu in THF
(0.14 mL, 0.28 mmol) is added dropwise via syringe, and stirring is
continued for 30 min or until a heavy yellowish white precipitate is
observed. The reaction is monitored, worked up, and isolated as before
to yield pure vinyl phosphonate 21 as a light yellow oil (38 mg, 78%).
General Experimental Procedure Using NaHMDS
Acknowledgment. We thank Dr. Douglas Lantrip for intel-
lectual and technical support. We acknowledge Arlene Rothwell
and Karl Wood for providing the MS data. Xavier Mollat du
Jourdin graciously provided the sample of substrate 36 used in
this study.
Solvents, starting materials, and reagents must be thoroughly dried
for a successful reaction. A flame-dried three-neck 100 mL flask is
charged with diethylphosphite (2.3 mL, 17.25 mmol) and then with
freshly distilled dry THF (27 mL) at ambient temperature. The mixture
is stirred for 1 min, then 2 M NaHMDS in THF (8.25 mL, 16.5 mmol)
is added dropwise via syringe, and stirring is continued for 30 min.
Supporting Information Available: Experimental procedures,
1
9
Stirring is stopped, and dry solid vinyl sulfone 10 (2 g, 7.5 mmol) is
1
spectroscopic and analytical data for new compounds, H and
1
3
C NMR spectra of key compounds. This material is available
5
(
18) The Taber reaction is known to successfully convert substrates with free
hydroxyl functionalities to their corresponding vinyl nitriles.
19) Cannulation of the dissolved vinyl sulfone in dry THF was equally effective
and more appealing for large-scale reactions.
free of charge via the Internet at http://pubs.acs.org.
(
JA072890P
J. AM. CHEM. SOC.
9
VOL. 129, NO. 36, 2007 11247