Palladium-Catalyzed Reactions of Allylic Boronic Esters with Nucleophiles: Novel Umpolung Reactivity

Article abstract of DOI:10.1055/s-0034-1380869

Oxidative palladium-catalyzed reaction conditions have been developed to allow for regioselective and stereoselective coupling of allylic boronic esters with a range of carbon-, oxygen-, and nitrogen-based nucleophiles. Studies into the mechanism of the r

Full text of DOI:10.1055/s-0034-1380869

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© Georg Thieme Verlag Stuttgart · New York
2015, 26, 1567–1572
letter
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P. J. Unsworth et al.
Letter
Synlett
Palladium-Catalyzed Reactions of Allylic Boronic Esters with
Nucleophiles: Novel Umpolung Reactivity
Phillip J. Unsworth
Lorenz E. Löffler
Adam Noble
NuH
Pd2(dba)3
R
R
R
Nu
PdII
Ar3P
[O]
Bpin
Varinder K. Aggarwal*
E/Z >95:5
transmetalation: RETENTION
linear to branched >95:5
School of Chemistry, University of Bristol, Cantock’s
Close, Bristol, BS8 1TS, UK
v.aggarwal@bristol.ac.uk
Ts
NuH =
EWG
EWG
RCO2H
N
H
CO2Me
Dedicated to Professor K. Peter C. Vollhardt with deep
appreciation, where science and art combine
Received: 23.03.2015
Accepted after revision: 07.05.2015
Published online: 20.05.2015
ters, it would also expand the scope of allylation reactions
through a novel methodology that is complementary to the
well-known Tsuji–Trost reaction8 and allylic C–H activation
protocols.9
DOI: 10.1055/s-0034-1380869; Art ID: st-2015-b0205-l
Abstract Oxidative palladium-catalyzed reaction conditions have
been developed to allow for regioselective and stereoselective coupling
of allylic boronic esters with a range of carbon-, oxygen-, and nitrogen-
based nucleophiles. Studies into the mechanism of the reaction have
shown that the key transmetalation step occurs with retention of ste-
reochemistry, since overall inversion is observed.
In support of our mechanistic hypothesis, we recently
reported a palladium-catalyzed procedure to achieve a for-
mal 1,3-rearrangement of a branched allylic boronic ester
to the linear isomer (Scheme 1, b).10 It was proposed that an
intermediate π-allyl palladium complex 2 was captured by
a nucleophilic source of boron [Na2HPO4/B2(pin)2].11 Crucial
Key words palladium, boronic ester, umpolung, allylation, oxidative
coupling
(a) proposed mechanism of oxidative coupling of allylic boronic esters:
R
Boronic esters are highly versatile intermediates that
undergo a wide variety of useful chemical transforma-
tions.1 In addition, their air and moisture stability, ease of
preparation, and low toxicity has further contributed to the
popularity of these important reagents. For example, allylic
boronic esters have been widely utilized in allylation reac-
tions of aldehydes2 and ketones3 as well as palladium-cata-
lyzed cross-couplings with aryl halides4 and allylic carbon-
ates.5 A key feature in all of these reactions is that the allylic
boronic ester acts as a nucleophile. We believed that it
might be possible to reverse this normal mode of reactivity
through the use of palladium(II) catalysis, thereby render-
ing the allylic boronic ester, an electrophilic allylating re-
agent, that would react with nucleophiles instead of elec-
trophiles. As shown in Scheme 1 (a), we reasoned that con-
version of the allylic boronic ester 1 into the π-allyl
palladium complex 2 could be achieved by transmetalation
with a suitable palladium(II) catalyst.6,7 This would then re-
act with a nucleophile in a Tsuji–Trost-type reaction giving
the allylated product 3 and palladium(0). Oxidation of pal-
ladium(0) to palladium(II) with an appropriate oxidant
would then complete the catalytic cycle. Not only would
such a protocol increase the synthetic utility of boronic es-
Bpin
1
PdIIX2
oxidation
coordination
[O]
PdIIX2
Pd0
R
Bpin
R
Nu
3
X
PdII
transmetalation
Bpin
nucleophilic
addition
R
X
2
NuH
(b) previous work on formal 1,3-rearrangement of allylic boronic esters:
Pd(OAc)2
R
B2(pin)2
PdII
X
R
Bpin
R
Bpin
Na2HPO4
CuCl2, THF
50–84%
>95:5 E/Z
2
1
Scheme 1 Proposed strategy for oxidative coupling of allylic boronic
esters
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P. J. Unsworth et al.
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to the success of this reaction was the addition of an oxi-
dant (CuCl2) to re-oxidize palladium(0) to palladium(II). If
such a process did indeed occur via an intermediate π-allyl
palladium complex then it should be possible to intercept it
with other nucleophiles. Herein we describe our success in
achieving a palladium-catalyzed coupling of allylic boronic
esters with a range of different carbon-, oxygen-, and nitro-
gen-based nucleophiles, thus demonstrating a novel um-
polung reactivity of this important class of reagents.
One of the key challenges in developing our proposed
methodology was to find a suitable oxidant that would be
capable of oxidizing palladium(0) to palladium(II) while
also being compatible with both the allylic boronic ester
and the nucleophile. Quinones have been successfully ap-
plied as oxidants in palladium(II)-catalyzed formation of
π-allyl intermediates by allylic C–H activation of terminal
olefins.9 Furthermore, the resulting π-allyl palladium
complexes have been demonstrated to react with a range of
nucleophiles. Based on this precedent we initially tested
p-benzoquinone (BQ) and 2,6-dimethylbenzoquinone
(DMBQ) as potential oxidants. Since some reports of allylic
C–H activation of terminal olefins have used Ph3P to sup-
press the formation of palladium black,9d we decided to in-
clude phosphine ligands in our initial investigations.
the absence of an oxidant to complete the palladium cata-
lytic cycle only traces of product were observed with large
amounts of 4 remaining. Low conversions were also ob-
served when BQ was used as the oxidant (Table 1, entries 2
and 3). Complete consumption of 4 was observed with
DMBQ as the oxidant, however, in the presence of NaOMe
only trace amounts of the desired product were obtained
(Table 1, entry 4). Pleasingly, it was found that in the ab-
sence of any added base the desired product was formed in
30% yield, importantly as a single regioisomer and a single
E-olefin isomer (Table 1, entry 5). Further evaluation of the
reaction conditions showed tri-2-furylphosphine to be a
superior ligand (Table 1, entry 6) and that an improved
yield could be obtained when using Pd2(dba)3
(dba = dibenzylideneacetone) in place of Pd(OAc)2 (Table 1,
entry 7).12 In the absence of ligand none of the desired
product was formed, instead, the major product was the di-
ene derived from β-hydrogen elimination of the π-allyl in-
termediate (Table 1, entry 8).13 Closer inspection of the
crude reaction mixtures from entries 5–7 revealed that a
small amount of β-hydrogen elimination (ca. 10–20%) also
occurred in the presence of phosphine ligands. However,
this undesired reaction pathway was completely sup-
pressed in the case of the nonbenzylic substrate 5 (Table 1,
entry 9). Furthermore, when using substrate 5 the loading
of palladium could be reduced to just 1 mol% without loss
in reaction efficiency.
We began by investigating the coupling of allylic boron-
ic ester 4 with dimethyl malonate. Encouragingly, treat-
ment of 4 and dimethyl malonate with Pd(OAc)2 in the
presence of Ph3P and a base (NaOMe), to aid transmetala-
tion of the boronic ester, resulted in the formation of the
desired product (Table 1, entry 1). However, as expected, in
With the optimized conditions in hand we proceeded to
examine the scope of the reaction (Scheme 2). It was found
that, in addition to malonates, 1,3-diketones and α-nitro-
Table 1 Reaction Optimization
MeO
O
O
O
O
Pd source (5 mol% Pd)
ligand (10 mol%)
R
O
O
+
R
OMe
Bpin
(1.0 equiv)
MeO
OMe
oxidant (1.3 equiv)
base (1.3 equiv)
DMF, r.t., 16 h
(1.3 equiv)
E/Z > 95:5
linear to branched > 95:5
4: R = CH(Me)Ph
5: R = Cy
O
BQ
O
DMBQ
Entry
Substrate
Pd Source
Oxidant
Base
Ligand
Yield (%)a
1
2
3
4
5
6
7
8
9c
4
4
4
4
4
4
4
4
5
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd2(dba)3
Pd2(dba)3
Pd2(dba)3
none
BQ
NaOMe
NaOMe
none
Ph3P
Ph3P
Ph3P
Ph3P
Ph3P
<10
<10
<10
<10
30
BQ
DMBQ
DMBQ
DMBQ
DMBQ
DMBQ
DMBQ
NaOMe
none
none
(2-furyl)3P
(2-furyl)3P
none
51
none
60 (53b)
0
none
none
(2-furyl)3P
70b
a Yields determined by 1H NMR spectroscopy using 1,3,5-trimethoxybenzene as internal standard.
b Isolated yield.
c Reaction conditons: 1 mol% Pd, 2 mol% ligand.
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ketones were competent nucleophiles in this allylation re-
action. Pleasingly, all products were formed in good yield,
with excellent regioselectivity for the linear product and as
a single E-olefin isomer.
We next looked at applying our conditions to nitrogen-
based nucleophiles, for which we chose the acidic N-tosyl-
carbamate nucleophile 6 (pKa = ca. 3.7).14 Unfortunately, ap-
plication of 6 to our standard reaction conditions led to the
formation of only trace amounts of product. However, in
the presence of 5 mol% EtN(i-Pr)2 the allylic amine prod-
ucts were obtained in good yields and, again, as single ste-
reoisomers and regioisomers (Scheme 4).
NuH (1.3 equiv)
9h
Pd2(dba)3 (0.5 mol%)
R
R
Nu
(2-furyl)3P (2 mol%)
DMF, r.t., 16 h
DMBQ (1.3 equiv)
Bpin
E/Z >95:5
linear to branched >95:5
(1.0 equiv)
Ts
6 (1.3 equiv)
N
H
CO2Me
MeO
O
Ph
O
Ts
N
Pd2(dba)3 (0.5 mol%)
R
R
OMe
Ph
Ph
CO2Me
Ph
Ph
(2-furyl)3P (2 mol%)
DMF, r.t., 48 h
DMBQ (1.3 equiv)
EtN(i-Pr)2 (5 mol%)
Bpin
(1.0 equiv)
53%a
MeO
63%a
Me
E/Z >95:5
linear to branched >95:5
O
O
O
O
OMe
O
Ts
Ts
70%
70%
O
N
N
Ph
CO2Me
CO2Me
NO2
81%
Scheme 4 Nitrogen-based nucleophiles
57%
Ph
74%
O
Scheme 2 Carbon-based nucleophiles. a Formed using 2.5 mol%
Pd2(dba)3 and 10 mol% phosphine.
When considering our proposed mechanism for this al-
lylation reaction (Scheme 1, a), we realized that while the
reactivity of π-allyl palladium complexes 2 has been well
studied, their generation from allylic boronic esters has not
been reported.15 Therefore, we wished to study the mecha-
nism of this transmetalation process (Scheme 5). The trans-
metalation of allyl metal reagents (e.g., allyl boronates4c,g
and silanes16) with palladium(II) complexes has been
demonstrated to proceed via an SE′ mechanism, in which
the palladium(II) can approach either syn or anti to the
metal center (Scheme 5, a). For example, Hiyama et al.
demonstrated that in the cross-coupling of allyl silanes
with aryl triflates, depending on the reaction conditions,
the transmetalation step could proceed via either syn or
anti SE′ mechanisms.16a In order to determine which of
these two possible transmetalation mechanisms is opera-
tive we used cyclohexenyl boronic ester 7 to study the ste-
reochemistry of our allylation reaction (Scheme 5, b). Sub-
stituted cyclohexenyl acetates have been used extensively
to probe the mechanism of Tsuji–Trost reactions17 and re-
lated processes involving π-allyl palladium intermediates.18
In particular, comparison of the relative stereochemistry of
the substrate and product is used to determine whether the
allylation reaction proceeds with overall retention or inver-
sion of stereochemistry. These substituted cyclohexenyl
substrates have been used to show that reactions of π-allyl
palladium complexes of type 8 (see Scheme 5, b) with soft
nucleophiles proceed with inversion of configuration,17b
whereas those with hard nucleophiles proceed with reten-
tion.18 As dimethyl malonate is a soft nucleophile it will re-
act with π-allyl palladium complex 8 with inversion of con-
We were also able to expand the scope of this reaction
to oxygen-based nucleophiles (Scheme 3). With no further
optimization of the reaction conditions, simply replacing
the malonate with a carboxylic acid resulted in high yields
of allylic ester products with excellent E selectivities. While
those derived from boronic ester 4 were formed exclusively
as the linear regioisomer, the reaction of boronic ester 5
with benzoic acid resulted in an 87:13 mixture of linear
and branched isomers, respectively. The origin of this re-
duction in selectivity for the linear regioisomer upon
switching from boronic ester 4 to 5 is currently unclear.
NuH (1.3 equiv)
Pd2(dba)3 (0.5 mol%)
R
R
Nu
(2-furyl)3P (2 mol%)
DMF, r.t., 16 h
DMBQ (1.3 equiv)
Bpin
E/Z >95:5
linear to branched >95:5
(1.0 equiv)
OAc
Ph
O
Ph
Ph
82%
92%
O
O
Ph
O
82%
(linear to branched = 87:13)
Scheme 3 Oxygen-based nucleophiles
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(a) possible stereochemical outcomes for transmetalation of allyl metal reagents
PdII
PdII
anti SE′
syn SE′
H
H
R
H
H
R
H
H
R
H
H
R
INVERSION
RETENTION
PdII
M
M
PdII
(b) determination of the stereochemistry of the transmetalation step
O
O
(3 equiv)
OMe
MeO
O
O
Pd2(dba)3 (0.5 mol%)
MeO
CO2Me
(2-furyl)3P (2 mol%)
DMF, r.t., 16 h
DMBQ (1.3 equiv)
pinB
trans/cis 83:17
co-ordination
CO2Me
9
OMe
49%
7
trans/cis 19:81
nucleophilic addition
INVERSION
R
O
transmetalation
RETENTION
RO PdII
pinB
PdIIOR
8
CO2Me
10
ROBpin
CO2Me
Scheme 5 Mechanistic study
figuration,17b therefore, the relative stereochemistry of the
product of the reaction of boronic ester 7 will reveal the
stereochemistry of the transmetalation step.
products with very high E selectivity. This process offers a
new way to access synthetically useful π-allyl intermediates
that is complementary to both the Tsuji–Trost reaction and
allylic C–H activation methodologies.
The known allylic boronic ester 719 was prepared as an
83:17 mixture of trans/cis diastereoisomers and coupled
with dimethyl malonate under our standard conditions
(Scheme 5, b). The allylation product 9 was formed in a
19:81 mixture of trans/cis diastereoisomers showing that
overall inversion had occurred. We can therefore conclude
that the transmetalation must be occurring syn to the bo-
ronic ester, generating π-allyl intermediate 8 with retention
of configuration, followed by inversion of configuration af-
ter nucleophilic addition of dimethyl malonate. It is pro-
posed that the transmetalation occurs via intermediate 10
containing a B–O–Pd linkage which directs the transmeta-
lation onto the same face as the boronic ester. This is con-
sistent with Suzuki–Miyaura couplings of allylic boronic es-
ters,4g and related reactions with allyl siloxanes,16c which
have been shown to occur through a syn SE′ transmetalation
process.
Acknowledgment
We thank EPSRC (EP/I038071/1) and the European Research Council
(FP7/2007-2013, ERC grant no. 246785) for financial support. P.J.U.
thanks the EPSRC-funded Bristol Chemical Synthesis Centre for Doc-
toral Training (EP/G036764/1). We thank Dr. Eddie Myers for valuable
discussions.
Supporting Information
Supporting information for this article is available online at
http://dx.doi.org/10.1055/s-0034-1380869.
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References and Notes
(1) Chinnusamy, T.; Feeney, K.; Watson, C. G.; Leonori, D.;
Aggarwal, V. K. In Comprehensive Organic Synthesis II; Vol. 7;
Knochel, P.; Molander, G. A., Eds.; Elsevier: Oxford, 2014, 692.
(2) For representative examples, see: (a) Hoffmann, R. W.; Zeiss, H.-
J. Angew. Chem., Int. Ed. Engl. 1979, 18, 306. (b) Brown, H. C.;
Jadhav, P. K. J. Am. Chem. Soc. 1983, 105, 2092. (c) Chen, J. L. Y.;
Scott, H. K.; Hesse, M. J.; Willis, C. L.; Aggarwal, V. K. J. Am. Chem.
Soc. 2013, 135, 5316. For a review, see: (d) Yus, M.; González-
Gómez, J. C.; Foubelo, F. Chem. Rev. 2013, 113, 5595.
In summary, we have developed a method for inverting
the normal mode of reactivity of allylic boronic esters from
nucleophiles to electrophiles. This has been achieved
through the application of oxidative palladium catalysis,
which now allows for the coupling of (normally nucleophil-
ic) allylic boronic esters with a range of carbon-, oxygen-,
and nitrogen-based nucleophiles.20 The process is highly re-
gioselective, giving exclusively the linear isomers of the
© Georg Thieme Verlag Stuttgart · New York — Synlett 2015, 26, 1567–1572

1571
P. J. Unsworth et al.
Letter
Synlett
(3) For representative examples, see: (a) Hoffmann, R. W.; Sander,
T. Chem. Ber. 1990, 123, 145. (b) Chen, J. L. Y.; Aggarwal, V. K.
Angew. Chem. Int. Ed. 2014, 53, 10992. For a review, see:
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OAc
Ph
11
Figure 1
(4) For examples of the coupling of allyltrifluoroborates, see:
(a) Yamamoto, Y.; Takada, S.; Miyaura, N. Chem. Lett. 2006, 35,
704. (b) Yamamoto, Y.; Takada, S.; Miyaura, N. Chem. Lett. 2006,
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Tachikawa, H. Organometallics 2008, 28, 152. For examples of
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V. J.; Wallner, O. A.; Szabó, K. J. J. Am. Chem. Soc. 2006, 128, 8150.
For examples of the coupling of allylic boronic esters, see:
(e) Gerbino, D. C.; Mandolesi, S. D.; Schmalz, H.; Podestá, J. C.
Eur. J. Org. Chem. 2009, 3964. (f) Glasspoole, B. W.; Ghozati, K.;
Moir, J. W.; Crudden, C. M. Chem. Commun. 2012, 48, 1230.
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Aggarwal, V. K.; Crudden, C. M. Chem. Eur. J. 2013, 19, 17698.
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2012, 134, 17470. (i) Yang, Y.; Buchwald, S. L. J. Am. Chem. Soc.
2013, 135, 10642.
O
O
(1.3 equiv)
OMe
MeO
Pd2(dba)3 (2.5 mol%)
DMBQ (1.3 equiv)
Ph
Ph
PdII
DMF, r.t., 16 h
Bpin
(1.0 equiv)
X
β-H elimination
Ph
12
(5) (a) Zhang, P.; Brozek, L. A.; Morken, J. P. J. Am. Chem. Soc. 2010,
132, 10686. (b) Zhang, P.; Le, H.; Kyne, R. E.; Morken, J. P. J. Am.
Chem. Soc. 2011, 133, 9716. (c) Brozek, L. A.; Ardolino, M. J.;
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(6) For related processes involving the formation of π-allyl palla-
dium complexes from allyl silanes, see: Macsári, K. J.; Szabó, K. J.
Tetrahedron Lett. 2000, 41, 1119.
Scheme 6
(14) Taylor, L. D.; MacDonald, R. J.; Rubin, L. E. J. Polym. Sci., Part A:
Polym. Chem. 1971, 9, 3059.
(15) In Suzuki–Miyaura reactions of allylic boronic esters the isom-
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slow with respect to reductive elimination, see ref. 4g.
(16) (a) Hatanaka, Y.; Goda, K.; Hiyama, T. Tetrahedron Lett. 1994, 35,
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(7) For related processes involving the formation of π-allyl palla-
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Shi, Z.-J. J. Am. Chem. Soc. 2008, 130, 12901. (b) Young, A. J.;
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White, M. C. J. Am. Chem. Soc. 2007, 129, 7274. (g) Reed, S. A.;
White, M. C. J. Am. Chem. Soc. 2008, 130, 3316. (h) Reed, S. A.;
Mazzotti, A. R.; White, M. C. J. Am. Chem. Soc. 2009, 131, 11701.
For representative examples with oxygen-based nucleophiles,
see: (i) Chen, M. S.; White, M. C. J. Am. Chem. Soc. 2004, 126,
1346. (j) Fraunhoffer, K. J.; Bachovchin, D. A.; White, M. C. Org.
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4730.
(18) (a) Matsushita, H.; Negishi, E. J. Chem. Soc., Chem. Commun.
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Chem. Soc. 1984, 106, 4833.
(19) Selander, N.; Paasch, J. R.; Szabó, K. J. J. Am. Chem. Soc. 2011, 133,
409.
(20) General Procedure
Allylic boronic ester (0.50 mmol), tris(dibenzylideneace-
tone)dipalladium(0) (0.50 mol%), tri(2-furyl) phosphine (2.0
mol%), and the nucleophile (1.3 equiv) were weighed into a dry
flask and placed under argon [for reactions with nitrogen nucle-
ophile 6, EtN(i-Pr)2 (5.0 mol%) was also added to the flask at this
stage]. A solution of 2,6-dimethylbenzoquinone (1.3 equiv) in
DMF (5.0 mL) was added in one portion, and the mixture was
stirred at r.t for 16 h, or until the reaction was complete as
determined by GC–MS analysis. 20% aq NaHSO3 (10 mL) was
added, and the mixture was stirred vigorously for 5 min. Et2O
(10 mL) was added, and the layers were separated. The aqueous
phase was extracted with Et2O (2 × 10 mL), and the combined
organic phases were washed with brine (10 mL), dried (MgSO4),
and concentrated in vacuo. Purification by flash column chro-
matography (pentane–EtOAc) yielded the allylation product.
Dimethyl (E)-2-(4-Phenylpent-2-en-1-yl)malonate
Yield 53%; E/Z >95:5; linear to branched >95:5; Rf = 0.25 (pen-
(10) Unsworth, P. J.; Leonori, D.; Aggarwal, V. K. Angew. Chem. Int.
Ed. 2014, 53, 9846.
(11) For other examples of borylations of π-allyl palladium com-
plexes with B2(pin)2, see: (a) Deng, H.-P.; Eriksson, L.; Szabó,
K. Chem. Commun. 2014, 50, 9207. (b) Tao, Z.-L.; Li, X.-H.;
Han, Z.-Y.; Gong, L.-Z. J. Am. Chem. Soc. 2015, 137, 4054.
(12) The desired product was accompanied by ca. 10% of acetate 11
when Pd(OAc)2 was used (Figure 1).
tane–EtOAc, 15:1); IR (neat): νmax = 2958, 1733 cm–1 1H NMR
.
(13) 1,4-Diene 12 was the major product in the absence of phos-
phine ligands (Scheme 6).
(400 MHz, CDCl3): δ = 1.29 (3 H, d, J = 7.0 Hz), 2.56–2.62 (2 H,
m), 3.39 (1 H, app p, J = 7.0 Hz), 3.41 (1 H, t, J = 7.6 Hz), 3.65 (3
H, s), 3.68 (3 H, s), 5.40 (1 H, dtd, J = 15.3, 7.0, 1.3 Hz), 5.68 (1 H,
© Georg Thieme Verlag Stuttgart · New York — Synlett 2015, 26, 1567–1572

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ddt, J = 15.3, 7.0, 1.3 Hz), 7.10–7.21 (3 H, m), 7.21–7.32 (2 H, m).
13C NMR (100 MHz, CDCl3): δ = 21.3, 32.0, 42.3, 52.0, 52.5, 52.5,
124.1, 126.2, 127.3, 128.5, 138.8, 145.8, 169.5. HRMS (ESI+): m/z
calcd for C16H21O4Na [M + Na+]: 299.1254; found: 299.1246.
(E)-4-Phenylpent-2-en-1-yl Benzoate
HRMS (ESI+): m/z calcd for C18H18O2Na [M + Na+]: 289.1199;
found: 289.1186.
Methyl (E)-(4-Phenylpent-2-en-1-yl)(tosyl)carbamate
Yield 81%; E/Z >95:5; linear to branched >95:5; Rf = 0.30 (pen-
tane–EtOAc, 6:1). IR (neat): νmax = 2961, 1732 cm–1 1H NMR
.
Yield 92%; E/Z >95:5; linear to branched >95:5; Rf = 0.30 (pen-
(400 MHz, CDCl3): δ = 1.38 (3 H, d, J = 7.0 Hz), 2.42 (3 H, s), 3.50
(1 H, app p, J = 6.8 Hz), 3.68 (3 H, s), 4.47 (2 H, app dt, J = 6.4, 1.2
Hz), 5.58 (1 H, dtd, J = 15.4, 6.4, 1.4 Hz), 5.98 (1 H, ddt, J = 15.4,
6.9, 1.2 Hz), 7.19–7.25 (5 H, m), 7.30–7.35 (2 H, m), 7.73–7.83 (2
H, m Hz). 13C NMR (100 MHz, CDCl3): δ = 21.2, 21.7, 42.1, 48.5,
53.8, 123.3, 126.3, 127.2, 128.6, 128.6, 129.3, 136.5, 140.1,
144.5, 145.3, 152.7. HRMS (ESI+): m/z calcd for C20H23O4NNaS
[M + Na+]: 396.1240; found: 396.12430.
tane–EtOAc, 30:1). IR (neat): νmax = 2966, 1715 cm–1 1H NMR
.
(400 MHz, CDCl3): δ = 1.40 (3 H, d, J = 7.1 Hz), 3.53 (1 H, qd,
J = 7.1, 6.6 Hz), 4.82 (2 H, m), 5.73 (1 H, dtd, J = 15.5, 6.2, 1.4 Hz),
6.05 (1 H, ddt, J = 15.5, 6.6, 1.3 Hz), 7.19–7.25 (3 H, m), 7.29–
7.35 (2 H, m), 7.41–7.46 (2 H, m), 7.54 (1 H, m), 8.05-8.09 (2 H,
m). 13C NMR (100 MHz, CDCl3): δ = 21.1, 42.1, 65.6, 123.0, 126.4,
127.3, 128.4, 128.6, 129.7, 130.5, 133.0, 140.4, 145.2, 166.5.
© Georg Thieme Verlag Stuttgart · New York — Synlett 2015, 26, 1567–1572