Stereoselective Halo-Succinimide Facilitated α-Halogenations of Substituted α-Trialkylsilyl-β-Substituted-α,β-Unsaturated Esters

Article abstract of DOI:10.1021/acs.joc.1c00876

The NXS (X = Cl, Br)-mediated halogenation of a series of (E)-α-trimethylsilyl-β-alkyl(aryl)-α,β-unsaturated esters in dimethylformamide (DMF) has furnished (Z)-β-substituted-α-halogenated-α,β-unsaturated ester products in moderate to high isolated yields (58-90%) with dr values of >20:1 coupled with the inversion of olefin stereochemistry. The reaction process was hypothesized to include an initial halonium cation intermediate, followed by regioselective ring opening with DMF. Subsequentanti-E2-type concomitant elimination allowed for the stereoselective formation of the product vinylic bromo-and chloroesters.

Full text of DOI:10.1021/acs.joc.1c00876

pubs.acs.org/joc
Article
Stereoselective Halo-Succinimide Facilitated α‑Halogenations of
Substituted α‑Trialkylsilyl-β-Substituted-α,β-Unsaturated Esters
Kristina C. Probasco and Michael P. Jennings*
Cite This: J. Org. Chem. 2021, 86, 8945−8954
Read Online
sı
*
Metrics & More
Article Recommendations
Supporting Information
ACCESS
ABSTRACT: The NXS (X = Cl, Br)-mediated halogenation of a series
of (E)-α-trimethylsilyl-β-alkyl(aryl)-α,β-unsaturated esters in dimethyl-
formamide (DMF) has furnished (Z)-β-substituted-α-halogenated-α,β-
unsaturated ester products in moderate to high isolated yields (58−90%)
with dr values of >20:1 coupled with the inversion of olefin
stereochemistry. The reaction process was hypothesized to include an
initial halonium cation intermediate, followed by regioselective ring
opening with DMF. Subsequent anti-E2-type concomitant elimination
allowed for the stereoselective formation of the product vinylic bromo-
and chloroesters.
INTRODUCTION
■
Facile stereoselective olefin formation remains an important
area of research because of the boundless potential for further
downstream synthetic operations.1 More specifically, new
methods for the rapid construction of stereodefined vinyl
halides (i.e., Cl, Br, and I) containing additional reactive
functional groups are enormously sought after owing to their
ability to function as electrophilic coupling partners in a
myriad of metal-catalyzed cross-couplings, mostly involving Pd
complexes.2 One approach to such compounds centers on a
halogenation/desilylation process that ultimately provides a
simple vinyl halide product with inverted stereochemistry
Figure 1. Diverse utility of α-trialkylsilyl-β-substituted-α,β-unsatu-
rated esters in synthetic applications.
relative to the organosilane starting material.3 Because of the
numerous advantages of organosilane reagents,4−9 the develop-
ment of methods that provide stereodefined vinylsilanes
remains as a noteworthy area of research.10
RESULTS AND DISCUSSION
■
Recent reports from our laboratory have described the
stereoselective synthesis of α-trialkylsilyl-β-alkyl(aryl)-α,β-
unsaturated esters and the subsequent utilization of said
compounds for target-based synthetic applications (i.e.,
stereoselective deconjugations, conjugated silyl ketene acetal
formations, tandem stereoselective deconjugation-stabilized
Peterson olefinations, and diastereoselective conjugate addi-
tions/protonations), as shown in Figure 1.11 Based on our
interest in novel organosilane reagents, we sought to
investigate α-ester-substituted vinylsilanes as general nucleo-
philic precursors to stereodefined α-halo-α,β-unsaturated
esters. Herein, we wish to divulge a regio-and diastereose-
lective halosuccinimide-mediated α-halogenation of α-trialkyl-
silyl-β-alkyl(aryl)-α,β-unsaturated esters, which, in turn, affords
tri-and tetrasubstituted stereodefined vinyl halide (Cl and Br)
products with high levels of dr and in modest to excellent
yields.
Synthesis of Stereodefined α-Trialkylsilyl-β-Alkyl-
(Aryl)-α,β-Unsaturated Esters. Before fully investigating
the electrophilic halogenation of α-trialkylsilyl-β-alkyl(aryl)-
α,β-unsaturated esters, there was a need to expand the
synthetic scope of the catalytic carbocupration/silyl group
migration of propiolate esters 3 and 4 to include new Grignard
coupling reagents. Thus, using the previous reports as a
guide,11a,12 we examined the catalytic carbocupration of esters
3 and 4 with 5 mol % of CuI•2LiCl in the presence of
Received: April 15, 2021
Published: June 23, 2021
https://doi.org/10.1021/acs.joc.1c00876
© 2021 American Chemical Society
J. Org. Chem. 2021, 86, 8945−8954
8945

The Journal of Organic Chemistry
pubs.acs.org/joc
Article
Table 1. Vicinal Functionalization of 3 and 4 via a Catalytic Carbocupration-Silicon Group Migration Sequence with Various
a b
,
Aliphatic and Aromatic Grignard Reagents and R3SiOTf
a
b
1
E/Z ratio determined by H NMR (360 or 500 MHz) from the crude reaction mixture. Yields are of the isolated, pure compounds.
Me3SiOTf and/or Et3SiOTf (3.3 equiv) and 1.2 equiv of alkyl
or aryl Grignard reagents.13 As described in Table 1, catalytic
carbocupration with all of the aromatic Grignard examples and
propiolates 3 or 4 in the presence of Me3-or Et3SiOTf afforded
products 1a−1e with consistently high yields ranging from
83−92% with dr values >20:1 strongly favoring the E
isomer.11a Likewise, catalytic carbocupration (5 mol %) of
ethyl propiolate 3 with aliphatic Grignard reagents and
Me3SiOTf provided the vinyl silane products 1f−1i in modest
to good isolated yields (60−82%). Similarly, the dr values of
the aliphatic product esters remained very high with a >20:1
ratio for the E isomer. As observed previously, the isolated
yields for aliphatic esters 1f−1i were consistently lower than
those of the aromatic products when utilizing 5 mol % catalyst
loading. However, the dr values for all the synthesized esters
1a−1i remained very high (>20:1), irrespective of the catalyst
loading. In order to improve the isolated yields for aliphatic
Grignard reagents, a higher catalyst loading can be utilized, and
it has been further described in a previous report.11a
newly formed alkenyl halides, we chose to investigate the
bromination of α-trialkylsilyl-β-alkyl(aryl)-α,β-unsaturated es-
ters 1a−1i, shown in Table 1, with the anticipation of being
afforded with stereodefined α-bromo-β-substituted acrylate
ester products.3 The initial examination focused on the N-
bromosuccinimide (NBS)-mediated halogenation of o-tolyl-
ester 1a in a variety of solvents at room temperature.
As described in Table 2, the bromination (2 equiv of NBS)
of 1a in non-Lewis-basic solvents such as toluene and CH2Cl2
(entries 1 and 2) did not proceed at room temperature, and
unfortunately, it furnished the product alkenyl bromide 2a in
very low yields of <15%, with the majority of the remaining
mass balance as the starting material ester 1a. Because of the
1
poor yields, the dr of 2a was not determined by H NMR.
However, by exchanging the reaction medium to the more
Lewis-basic solvents Et2O, tetrahydrofuran (THF), and
dimethoxyethane (DME), the bromination of 1a readily
progressed with 2 equiv of NBS and afforded ester 2a with
increasing isolated yields of 26, 53, and 75%, respectively, and
a dr of >20:1 strongly favored the Z-isomer in entries 3−5.
Much to our delight, the halogenation of 1a in DMF at room
temperature under the previous mentioned reaction conditions
(NBS, 2 equiv) afforded ester 2a in 90% isolated yield with a
dr of >20:1 for the Z-olefin. Interestingly, lowering or
NXS (X = Cl, Br)-Mediated Halogenation of Stereo-
defined α-Trialkylsilyl-β-Alkyl(Aryl)-α,β-Unsaturated Es-
ters. Inspired by the Tamao report on the halogenolysis of
simple vinyl silanes utilizing a variety of reagents (NBS, Br2,
and ICl) and the resultant stereochemical outcomes of the
8946
https://doi.org/10.1021/acs.joc.1c00876
J. Org. Chem. 2021, 86, 8945−8954

The Journal of Organic Chemistry
pubs.acs.org/joc
Article
increasing the equivalence of NBS exhibited a deleterious effect
on the overall yield of 2a while maintaining the high levels of
dr in entries 7 and 8.
Table 2. Initial Bromination of Vinyl Silane 1a with NBS in
Various Solvents
Based on the results from Table 2, a single key point merits
further discussion. Very similar to the Tamao report, a
significant solvent effect for the NBS-mediated bromination of
1a was observed. In our case, the halogenation of 1a did not
proceed in the non-Lewis-basic solvents toluene and CH2Cl2.
However, ethereal solvents (Et2O, THF, and DME) allowed
for the production of 2a, but the extent of product formation
was dependent on the level of Lewis basicity.14 For example,
the bromination of 1a with NBS in Et2O provided the product
2a, although with a low isolated yield of 26%, whereas more
Lewis-basic solvents THF and DME afforded ester 2a in 53
and 75% yields, respectively. Moreover, when the reaction was
conducted in DMF (the most Lewis-basic solvent studied in
Table 1), there was complete conversion of 1a into product 2a,
with an isolated yield of 90% Thus, solvent dependency
influenced the reaction rate and ultimately the isolated yield,
but not the final stereochemistry of product 2a (>20:1 in all
cases), as shown in entries 3−6. Surprisingly, the lack of
solvent dependence on the final stereochemistry of product 2a
(and others, vide infra) contrasted with Tamao’s observations
on less-complex vinyl silane substrates.3
ab
,
c
entry
NBS equiv
solvent
yield %
Z/E
1
2
3
4
5
6
7
8
2.0
2.0
2.0
2.0
2.0
2.0
1.0
4.0
CH2Cl2
toluene
Et2O
<15
<15
26
53
75
90
55
62
ND
ND
>20/1
>20/1
>20/1
>20/1
>20/1
>20/1
THF
DME
DMF
DMF
DMF
a
b
Purified, isolated yield of vinyl bromide. Remaining mass balance
was a combination of the starting material and unidentifiable
products. Z/E ratio determined by H NMR (360 or 500 MHz)
c
1
from the crude reaction mixture; ND = Not Determined.
a b
,
Table 3. NXS (X = Cl, Br) Facilitated Halogenations of a Variety of α-Trialkylsilyl-β-Aryl-α,β-Unsaturated Esters
a
b
1
Z/E ratio determined by H NMR (360 or 500 MHz) from the crude reaction mixture. Yields are of the isolated, pure compounds.
8947
https://doi.org/10.1021/acs.joc.1c00876
J. Org. Chem. 2021, 86, 8945−8954

The Journal of Organic Chemistry
pubs.acs.org/joc
Article
a b
,
Table 4. NXS (X = Cl, Br) Facilitated Halogenations of a Variety of α-Trialkylsilyl-β-Alkyl-α,β-Unsaturated Esters
a
b
1
Z/E ratio determined by H NMR (360 or 500 MHz) from the crude reaction mixture. Yields are of the isolated, pure compounds.
Building on the observations from Table 2, attention was
With the observations in Table 3 of complete olefin
inversion in products 2a−2c during the NBS-mediated
halogenation of the three α-trimethylsilyl-β-aryl-α,β-unsatu-
rated esters 1a-1c, we opted to investigate the geometrical
outcome of a potential tetrasubstituted vinyl bromide product
derived from the α-trimethylsilyl-β,β-aryl,alkyl-α,β-unsaturated
ester 1d. Hence, the treatment of 1d under the standard
bromination conditions (2 equiv of NBS in DMF) for esters
1a−1c furnished the tetrasubstituted vinylic bromide product
2d as a single isomer (>20:1) in 70% isolated yield. After a
close inspection of the 1D NOE (Table 3), it was determined
that the stereochemistry of the olefinic moiety of 2d was
indeed the E isomer. As a result, the olefinic stereochemistry of
2d was retained with respect to the starting material 1d. This
observation was surprising and stood in stark contrast to that
of the three previous examples of 1a−1c leading to 2a−2c
from an olefinic geometry perspective (Z versus E stereo-
chemistry), thus suggesting that a different mechanism was in
operation for the NBS-mediated halogenation of ester 1d
versus that of 1a−1c, vide infra.
paid toward examining the scope and limitations of the NXS
(X = Cl, Br)-mediated halogenations of a variety of α-
trialkylsilyl-β-aryl-α,β-unsaturated esters (1a−1e) utilizing
DMF as the reaction medium at room temperature. Thus,
the treatment of 1b under the standardized reaction conditions
from Table 2 (2 equiv NBS in DMF) afforded the α-bromo-
ester product 2b15 in 73% isolated yield, with a dr of >20:1
with the Z-olefin geometry, as delineated in Table 3.
Interestingly, the attempted bromination of the m-substituted
methoxy aryl ester (1c) did not furnish the expected
stereodefined α-bromo-β-substituted acrylate ester product.
However, the halogenation with NBS of ester 1c provided the
bis-brominated ester 2c, while maintaining the high level of dr
for the newly formed vinylic bromide (>20:1 for the Z-
product) in 61% yield. In addition, the electron-rich aromatic
ring of 1c was concomitantly brominated at the C4-position
(para to the methoxy directing group) during the reaction, as
noted in Table 3.16 Unfortunately, lowering the equivalents of
NBS did not afford the monosubstituted vinylic bromo-ester
product and resulted in a lower overall yield of 2c with most of
the starting material 1c remaining. The geometry of the olefin
and aromatic substitution pattern of 2c was elucidated by 1D
NOE (see Table 3). Surprisingly, the replacement of the Me3Si
(TMS) group of 1b for the Et3Si (TES) moiety (1e) led to an
inferior dr (3:1 versus 20:1 for the Z-geometry) but greater
yield of the newly formed vinylic bromide product 2b under
identical halogenation conditions. This result was suggestive
that a trivial disparity in the substate structure (TMS versus
TES) could have deleterious effects on the levels of dr for the
halogenated product 2b.
The final example of Table 3 investigated the chlorination of
1b with N-chlorosuccinimide (NCS) under similar conditions
to the bromination process with NBS. Thus, the reaction of 1b
with NCS (2 equiv) in DMF at 60 °C for 24 h afforded the
vinylic chloride ester 2e17 with a 1.8:1 dr (slightly enriched in
1
the E isomer, as determined by H NMR) and 89% isolated
yield. Unfortunately, the chlorination of 1b with NCS did not
proceed at room temperature. Frankly, we were quite surprised
by the lack of stereochemical control of the reaction process
leading the chloro-olefin product, considering the only
variation was the usage of NCS in place of NBS. Once
8948
https://doi.org/10.1021/acs.joc.1c00876
J. Org. Chem. 2021, 86, 8945−8954

The Journal of Organic Chemistry
pubs.acs.org/joc
Article
Figure 2. Proposed mechanism to account for the complete geometrical olefin inversion of aliphatic esters 1f−1i during NXS-mediated
halogenation in DMF.
Figure 3. Proposed mechanism to account for the stereochemical olefin retention of the tetrasubstituted ester 1d during NBS-mediated
halogenation in DMF.
again, this example underscores the notion that an alteration in
reaction conditions (reagent choice, reaction temperature, or
subtle differences in the substrate) can have a dramatic effect
on the outcome of the halo-olefin dr.
greater isolated yield (90 versus 67% for 2f) and identical dr
(>20:1 for the Z-isomer). The more sterically encumbered β-
isopropyl-and cyclohexylesters 1f and 1g selectively provided
the Z-olefin geometry of the newly formed vinyl bromides 2f
and 2g. We were interested in expanding the aliphatic reaction
scope by examining the stereochemical outcomes of NBS-
mediated halogenation of less-hindered α-trimethylsilyl-β-
alkyl-α,β-unsaturated esters. Accordingly, the bromination of
the β-benzyl substituted TMS ester 1h readily proceeded with
NBS in DMF at room temperature and afforded the bromo-
ester product 2h after the standard workup with an 82%
isolated yield and a >20:1 dr favoring the Z-olefin.
With the observations from Table 3 in hand, we sought to
expand the reaction scope of the NXS (X = Br or Cl)-mediated
halogenation to include α-trimethylsilyl-β-alkyl-α,β-unsatu-
rated esters. As delineated in Table 4, the standardized
reaction conditions (2 equiv of NXS and DMF) were
duplicated from Table 3 for all the substrates 1f−1i. Thus,
the bromination of the isopropyl-substituted vinyl trimethylsi-
lane ester 1f with NBS in DMF afforded the expected
halogenated product 2f18 in 67% isolated yield with a >20:1 dr
favoring the Z-olefin geometry, as determined by 1H NMR. In
addition, the treatment of the cyclohexyl variant 1g with NBS
also furnished the predicted brominated product 2g18 with a
Comparably, the treatment of the β-n-octyl TMS ester 1i
with NBS furnished the corresponding vinyl bromo-ester 2i in
58% yield, with a continued dr of >20:1 for the Z-isomer.
Similar to the aromatic esters 1a−1c shown in Table 3, the
8949
https://doi.org/10.1021/acs.joc.1c00876
J. Org. Chem. 2021, 86, 8945−8954

The Journal of Organic Chemistry
pubs.acs.org/joc
Article
aliphatic counterparts (1f−1i) underwent NBS-mediated
bromination in DMF at room temperature, allowing for the
stereoselective formation of vinylic bromide products 2f−2i
with complete inversion of the olefin geometry, as determined
unlikely because of the complete geometrical inversion of
olefin stereochemistry, and because typically, it is only in
operation when a much stronger base (i.e., tetra-n-
butylammonium fluoride, TBAF) is employed with respect
to the substituted α-TMS esters with an appropriate leaving
group resident at the β-carbon.
While we illustrated multiple examples of the complete
geometrical olefin inversion during the NBS-mediated
bromination of α-trimethylsilyl-β-alkyl(aryl)-α,β-unsaturated
esters (>20:1 dr) in Tables 234, the tetrasubstituted congener
1d afforded the vinylic bromo-ester product 2d with a
complete retention of the alkene geometry, as determined by
1D NOE.
1
by H NMR in modest to excellent yields.
The final two entries shown in Table 4 investigated the
chlorination of 1f and 1h with NCS under conditions similar
to those of the NBS bromination process. Hence, the reaction
of 1f with NCS (2 equiv) in DMF at 60 °C for 24 h provided
the product vinylic chloride ester 2j with a >20:1 dr (enriched
1
in the Z-isomer, as determined by H NMR of the crude
material) and an 82% isolated yield. Likewise, the benzyl
derivative 1h readily underwent chlorination in the presence of
NCS to afford the product halogenated ester 2k in 80%
isolated yield with a very similar >20:1 dr for the Z-olefin. We
were extremely pleased by the high level of stereochemical
control of the reaction process leading the chloro-olefin
products 2j and 2k during the NCS-mediated chlorination of
the precursor α-trimethylsilyl-β-alkyl-α,β-unsaturated esters 1k
and 1h. Two important observations merit a brief discussion.
The first is that the β-alkyl TMS esters afforded very high levels
of dr (>20:1), as opposed to the β-aryl counterpart from Table
3 (1.8:1 dr). This suggests that different mechanisms might be
in operation, depending upon the starting material during the
NCS halogenation. The second key point is that the NCS
reaction mirrors the NBS process with respect to the complete
geometrical olefin inversion of the alkene starting material α-
trimethylsilyl-β-alkyl-α,β-unsaturated esters, leading to the
newly formed β-alkyl-α-haloesters shown in Table 4.
As delineated in Figure 3, we envisioned an initial reaction
pathway similar to that shown in Figure 2 using the
bromonium cation intermediate E post-NBS addition to 1d.
An ensuing regioselective ring opening of the bromonium
cation E would have afforded the highly stabilized β-
trimethylsilyl-3o-benzylic carbocation intermediate in which
two possible rotamers (F and G) could undergo elimination of
the TMS moiety via an E1-type pathway.20 Based on the high
dr in favor of product 2d, it would seem sensible that rotamer
G would have been the preferred conformation prior to the β-
silyl elimination process. Similar to Figure 2, elimination from
rotamer F was a possibility, but we did not observe any of the
ensuant Z-haloester product from the crude reaction mixture
1
by H NMR.
Unfortunately, the chlorination of 1b with NCS in DMF
lacked stereochemical control and afforded the resultant ester
product with a 1.8:1 dr. We surmised that both rotamers
similar to C and D, shown in Figure 2, might very well be in
operation based on the low dr of product 2e and the higher
reaction temperature (60 °C versus room temperature).
However, one cannot discount the possibility of a β-silyl-
stabilized carbocation intermediate (akin to the one proposed
and shown in Figure 3), followed by nonstereoselective TMS
elimination.20 Irrespective of the mechanistic pathway, the
NCS-mediated chlorination of an α-trimethylsilyl-β-aryl-α,β-
unsaturated ester was nonstereoselective and accentuated the
notion that a slight alteration in reagents (NBS versus NCS)
and ultimately reaction intermediates (bromonium versus
chloronium cations) can have a considerable effect on the
outcome of the halo-olefin dr. In support of the previous
statement, Lee and Jung recently reported that an NXS [X = Br
(100 °C), I (room temperature)]-mediated halogenation in
MeCN of a Z-α-trimethylsilyl-β-phenyl-α,β-unsaturated amide
afforded the corresponding Z-α-bromo/iodo-α,β-unsaturated
amide with complete retention of configuration, whereas this
work provided most ester products with a complete inversion
of the olefin geometry.21
Based on the vinyl halide products obtained from the
halogenation of (E)-α-trimethylsilyl-β-alkyl(aryl)-α,β-unsatu-
rated esters 1a−1i, we envisioned two possible mechanisms
that would account for the observed high levels of dr (>20:1),
as highlighted in Figures 2 and 3. The β-aliphatic ester
examples (1f−1i) from Table 4 provided the halogenated (Br
and Cl) products 2f−2k with dr levels of >20:1 for the Z-olefin
geometry coupled with the complete olefin inversion in all
cases. A proposed mechanism is outlined in Figure 2, which is
constructed from the previously reported Tamao model.3
Using ester 1f as a representative example, it was deemed
that the NXS addition in DMF to the olefin moiety should
have produced the halonium ion intermediate A. An ensuing
SN2-type addition of DMF to the β-carbon of intermediate A
would have subsequently afforded intermediate B and set the
stage for the final elimination en route to the observed
halogenated products. Thus, intermediate B included two
possible rotamers (C and D), both of which could undergo the
elimination of the TMS moiety concomitantly with DMF via
1
an E2-type pathway. Based on the H NMR of the crude
reaction mixture, we detected only products 2f (X = Br) and
2h (X = Cl) with dr values of >20:1. These observations
strongly suggest that the anti-periplanar rotamer C was in
operation along the E2-elimination pathway, leading to the
final halogenated ester products. While elimination via the syn-
periplanar rotamer D was a possibility, we did not detect any of
the resultant E-haloester. Moreover, it appeared that the
bromination of aromatic esters 1a−1c followed the identical
(or very similar) elimination pathway (rotamer C) based on
the very high levels of dr and the overall inversion of the olefin
geometry of the halogenated products 2a−2c. In addition to
the proposed mechanism, as described Figure 2, one could
suggest an alternative mechanistic pathway by means of an
E1cB process.19 However, this elimination route seems
CONCLUSIONS
■
In conclusion, we have examined the NXS (X = Cl, Br)-
mediated halogenation of a series of α-trimethylsilyl-β-
alkyl(aryl)-α,β-unsaturated esters in DMF and observed the
β-substituted-α-halogenated-α,β-unsaturated ester products in
moderate to high isolated yields with dr values of >20:1
coupled with the inversion of olefin stereochemistry in most
instances. Based on the observed products, a mechanistic
model was suggested, which included an initial halonium
cation intermediate, followed by regioselective ring opening
with DMF via an SN2 reaction mechanism. An ensuing anti-E2-
type concomitant elimination of the TMS moiety and DMF
8950
https://doi.org/10.1021/acs.joc.1c00876
J. Org. Chem. 2021, 86, 8945−8954

The Journal of Organic Chemistry
pubs.acs.org/joc
Article
Ethyl-(E)-4-Methyl-2-(Trimethylsilyl)Pent-2-Enoate (1f). Yield:
0.702 g, 82%; flash column chromatography: 3% ethyl acetate in
hexanes. H NMR (360 MHz, CDCl3) δ 5.89 (d, J = 9.3 Hz, 1H),
allowed for the stereoselective formation of the product vinylic
bromo-and chloroesters. Future directions of investigation will
include further utilization of α-trimethylsilyl-β-alkyl(aryl)-α,β-
unsaturated esters in the methodological development and
target-driven natural product synthesis. Results from these
studies will be reported in due course.
1
4.18 (q, J = 7.1 Hz, 2H), 2.96−2.86 (m, 1H), 1.29 (t, J = 7.0 Hz, 3H),
1.00 (d, J = 6.6 Hz, 6H), 0.13 (s, 9H).11a
Ethyl (E)-3-Cyclohexyl-2-(Trimethylsilyl)Acrylate (1g). Yield: 0.46
g, 60%, light yellow oil; flash column chromatography: 3% ethyl
1
acetate in hexanes. H NMR (500 MHz, CDCl3) δ 5.93 (d, J = 9.3
Hz, 1H), 4.19 (q, J = 7.1 Hz, 2H), 2.66−2.60 (m, 1H), 1.71−1.64 (m,
5H), 1.30 (t, J = 7.1 Hz, 2H), 1.29−1.24 (m, 2H), 1.20−1.04 (m,
3H), 0.12 (s, 9H). 13C{1H} NMR (125 MHz, CDCl3) δ 170.6, 156.4,
133.8, 59.8, 40.3, 32.5, 25.9, 25.6, 14.4, −1.3. IR (NaCl): 2977, 2927,
1713, 1606, 1448, 1263, 1192, 855 cm−1. HRMS (EI-EBE Sector) m/
z: [M] + Calcd for C14H26O2Si 254.1696; found 254.1702. Rf = 0.50,
3% EtOAc in hexanes.
Ethyl-(E)-4-Phenyl-2-(Trimethylsilyl)but-2-Enoate (1h). Yield:
0.734 g, 70%; flash column chromatography: 3% ethyl acetate in
hexanes. 1H NMR (360 MHz, CDCl3) δ 7.35−7.22 (m, 5H), 6.30 (t,
J = 7.0 Hz, 1H), 4.27 (q, J = 7.0 Hz, 2H), 3.74 (d, J = 7.0 Hz, 2H),
1.35 (t, J = 7.2 Hz, 3H), 0.18 (s, 9H).11a
EXPERIMENTAL SECTION
■
All the reactions were performed under Ar in flame-dried glassware.
All starting materials, solvents, reagents, and catalysts were
commercially available and used without further purification, except
for NBS, which was recrystallized in H2O. NMR spectra were
1
recorded with either a 360 or 500 MHz Bruker spectrometer. H
spectra were obtained using CDCl3 as the solvent with chloroform
(CHCl3: δ = 7.26 ppm) as the internal standard. 13C spectra were
obtained using CDCl3 as the solvent with chloroform (CDCl3: δ =
77.0 ppm) as the internal standard. High-resolution mass spectra were
recorded on an electric-magnetic-electric (EBE) sector instrument
using electron ionization (EI) at 70 eV. Column chromatography was
performed using 60−200 μm silica gel. Analytical thin layer
chromatography was performed on silica-coated glass plates with
the F-254 indicator. Visualization was accomplished using ultraviolet
(UV) light (254 nm) and KMnO4.
General Experimental Procedure for the Formation of α-
Trialkylsilyl-β-Alkyl(Aryl)-α,β-Unsaturated Esters. CuI (0.029 g,
0.15 mmol) and LiCl (0.013 g, 0.30 mmol) were placed in a 100 mL
round-bottom flask (flame-dried under vacuum) under Ar. Dry THF
(20 mL) was added, and the mixture was stirred at room temperature
for a period of 0.5 h until complete dissolution was achieved. The
clear, light yellow homogeneous solution was cooled to −78 °C, and
ethyl propiolate (0.294 g, 3.0 mmol) was added, followed by
trimethylsilyl trifluoromethanesulfonate (TMSOTf) (3.3 equiv, 1.8
mL, 9.9 mmol). After 5 min at −78 °C, the aryl or alkyl Grignard
reagent (1.2 equiv, 3.6 mmol) was added dropwise via a syringe, and
the solution was stirred at −78 °C for 1 h and allowed to warm to
room temperature. The reaction was quenched with H2O, and the
product was extracted with Et2O (3 × 25 mL), and the combined
organic layers were washed with deionized H2O, followed by
saturated NH4Cl. The organic layer was separated, dried with
MgSO4, and concentrated in vacuo to provide the crude product,
which was then analyzed by 1H NMR spectroscopy to determine
diastereoselectivity. Column chromatography of the crude material
(3% ethyl acetate in hexanes) afforded pure vinyl silane products.
Ethyl (E)-3-(o-Tolyl)-2-(Trimethylsilyl)Acrylate (1a). Yield: 0.692 g,
Ethyl (E)-2-(Trimethylsilyl)Undec-2-Enoate (1i). Yield: 0.56 g,
65%, yellow oil; flash column chromatography: 3% ethyl acetate in
hexanes. 1H NMR (500 MHz, CDCl3) δ 6.15 (t, J = 7.3 Hz, 1H), 4.19
(q, J = 7.1 Hz, 2H), 2.37−2.33 (m, 2H), 1.48−1.38 (m, 2H), 1.31−
1.26 (m, 10H), 1.27 (t, J = 7.1 Hz, 3H), 0.88 (t, J = 6.9 Hz, 3H), 0.13
(s, 9H). 13C{1H} NMR (125 MHz, CDCl3) δ 170.6, 151.8, 135.9,
59.9, 31.9, 31.7, 29.4, 29.3, 29.2, 29.1, 22.7, 14.4, 14.1, −1.3. IR
(NaCl): 2956, 2925, 2871, 2855, 1715, 1464, 1247,1191, 1033, 840,
754. HRMS (EI-EBE Sector) m/z: [M] + Calcd for C16H32O2Si
284.2160; found 284.2172. Rf = 0.62, 4% EtOAc in hexanes.
General Experimental Procedure for the α-Halogenated-
α,β-Unsaturated Esters. In a room with the overhead and fume
hood lights turned off, NBS or NCS (0.80 mmol, 2.0 equiv) was
added to a (flame-dried under vacuum) round-bottom flask under Ar.
The flask was then covered in aluminum foil, and a solution of vinyl
silane (1a−1i) (0.40 mmol, 1.0 equiv) in anhydrous DMF (1.00 mL)
was added in one portion. The mixture was stirred at room
temperature (for NBS) or 60 °C (for NCS, oil bath) for a minimum
of 24 h, where it was then quenched with saturated Na2CO3 (1.00
mL), and the product was extracted with CH2Cl2 (3 × 10 mL). The
combined organic layers were washed with deionized H2O (3 × 10
mL). The organic layer was dried with MgSO4 and concentrated in
vacuo to yield the crude product. Column chromatography of the
crude material (3% Et2O in pentane) afforded the pure halogenated
products 2a−2k in yields ranging from 58 to 91%.
Ethyl (Z)-2-Bromo-3-(o-Tolyl)Acrylate (2a). Yield: 0.092 g, 90%,
1
1
88%; flash column chromatography: 3% ethyl acetate in hexanes. H
yellow oil. Flash column chromatography: 3% Et2O in hexanes. H
NMR (500 MHz, CDCl3) δ 7.22−7.08 (m, 4H), 7.03 (s, 1H), 4.08
(q, J = 7.2 Hz, 2H), 2.31 (s, 3H), 1.09 (t, J = 7.2 Hz, 3H), 0.25 (s,
9H).11a
NMR (500 MHz, CDCl3) δ 8.29 (s, 1H), 7.66 (d, J = 7.5 Hz, 1H),
7.31−7.22 (m, 4H), 4.35 (q, J = 7.1 Hz, 2H), 2.32 (s, 3H), 1.40 (t, J =
7.1 Hz, 3H). 13C{1H} NMR (125 MHz, CDCl3) δ 163.1, 140.6,
137.0, 133.7, 130.1, 129.4, 128.6, 125.6, 115.7, 62.8, 19.9, 14.2. IR
(NaCl): 1720, 1481, 1257, 865, 482 cm −1. HRMS (EI-EBE Sector)
m/z: [M] + Calcd for C12H13BrO2 268.0099; found 268.0105. Rf =
0.39, 3% Et2O in pentane.
Ethyl (E)-3-Phenyl-2-(Trimethylsilyl)Acrylate (1b). Yield: 0.684 g,
1
92%; flash column chromatography: 3% ethyl acetate in hexanes. H
NMR (500 MHz, CDCl3) δ 7.30−7.20 (m, 5H), 6.77 (s, 1H), 4.15
(q, J = 7.2 Hz, 2H), 1.16 (t, J = 7.2 Hz, 3H), 0.19 (s, 9H).11a
Ethyl-(E)-3-(3-Methoxyphenyl)-2-(Trimethylsilyl)Acrylate (1c).
Yield: 0.734 g, 88%; flash column chromatography: 3% ethyl acetate
Ethyl (Z)-2-Bromo-3-Phenylacrylate (2b). Yield: 0.074 g, 73%,
1
yellow oil. Flash column chromatography: 3% Et2O in hexanes. H
1
in hexanes. H NMR (500 MHz, CDCl3) δ 7.23 (t, J = 7.8 Hz, 1H),
NMR (500 MHz, CDCl3) δ 8.22 (s, 1H), 7.86−7.84 (m, 2H), 7.44−
7.42 (m, 3H), 4.36 (q, J = 7.1 Hz, 2H), 1.39 (t, J = 7.1 Hz, 3H).15
Ethyl (Z)-2-Bromo-3-(2-Bromo-3-Methoxyphenyl)Acrylate (2c).
Yield: 0.060 g, 61%, yellow solid. Flash column chromatography: 3%
6.93 (d, J = 8.3 Hz, 1H), 6.89 (s, 1H), 6.83 (dd, J = 8.3, 3.0 Hz, 1H),
6.78 (s, 1H), 4.21 (q, J = 7.2 Hz, 2H), 3.79 (s, 3H), 1.23 (t, J = 7.2
Hz, 3H), 0.24 (s, 9H).11a
Ethyl-(E)-3-Phenyl-2-(Trimethylsilyl)but-2-Enoate (1d). Yield:
0.668 g, 85%; flash column chromatography: 3% ethyl acetate in
hexanes. 1H NMR (500 MHz, CDCl3) δ 7.30−7.21 (m, 5H), 3.86 (q,
J = 7.2 Hz, 2H), 2.19 (s, 3H), 0.92 (t, J = 7.2 Hz, 3H), 0.28 (s,
9H).11a
1
Et2O in hexanes. H NMR (500 MHz, CDCl3) δ 8.27 (s, 1H), 7.50
(d, J = 8.8 Hz, 1H), 7.40 (d, J = 3.0 Hz, 1H), 6.83 (dd, J = 8.8, 3.0 Hz,
1H), 4.38 (q, J = 7.1 Hz, 2H), 3.82 (s, 3H), 1.40 (t, J = 7.1 Hz, 3H).
13C{1H} NMR (125 MHz, CDCl3) δ 162.8, 158.4, 140.4, 135.2,
133.6, 117.1, 116.7, 115.8, 114.8, 63.0, 55.6, 14.2. IR (NaCl): 1720,
1463, 1280, 1234, 908, 729. HRMS (EI-EBE Sector) m/z: [M] +
Calcd for C12H12Br2O3 361.9153; found 361.9164. Rf = 0.29, 3% Et2O
in pentane.
Ethyl-(E)-3-Phenyl-2-(Triethylsilyl)Acrylate (1e). Yield: 0.722 g,
1
83%; flash column chromatography: 3% ethyl acetate in hexanes. H
NMR (360 MHz, CDCl3) δ 7.35−7.26 (m, 5H), 6.79 (s, 1H), 4.18
(q, J = 7.2 Hz, 2H), 1.21 (t, J = 7.2 Hz, 3H), 1.01 (t, J = 7.6 Hz, 9H),
0.75 (q, J = 7.6 Hz, 6H).11a
Ethyl (E)-2-Bromo-3-Phenylbut-2-Enoate (2d). Yield: 0.075 g,
70%, clear oil. Flash column chromatography: 3% Et2O in hexanes. 1H
8951
https://doi.org/10.1021/acs.joc.1c00876
J. Org. Chem. 2021, 86, 8945−8954

The Journal of Organic Chemistry
pubs.acs.org/joc
Article
NMR (500 MHz, CDCl3) δ 7.33−7.31 (m, 3H), 7.19−7.17 (m, 2H),
3.95 (q, J = 7.1 Hz, 2H), 2.32 (s, 3H), 0.91 (t, J = 7.1 Hz, 3H).
13C{1H} NMR (125 MHz, CDCl3) δ 164.9, 147.0, 141.2, 128.3,
128.0, 126.8, 111.1, 61.7, 25.9, 13.4. IR (NaCl): 1288, 1277, 1042,
700. HRMS (EI-EBE Sector) m/z: [M] + Calcd for C12H13BrO2
268.0099; found 268.0090. Rf = 0.18, 3% Et2O in pentane.
Ethyl (Z) and (E)-2-Chloro-3-Phenylacrylate (2e). Yield: 0.040 g,
89%, yellow oil. Flash column chromatography: 3% Et2O in hexanes.
(Z)-product: 1H NMR (500 MHz, CDCl3) δ 7.91 (s, 1H), 7.63 (d, J
= 7.5, 1H), 7.44−7.39 (m, 4H), 4.36 (q, J = 7.1 Hz, 2H), 1.39 (t, J =
7.0 Hz, 3H); (E)-product: 1H NMR (500 MHz, CDCl3) δ 7.34−7.26
(m, 5H), 7.21 (s, 1H), 4.21 (q, J = 7.2, 2H), 1.18 (t, J = 7.1, Hz,
3H).17
ASSOCIATED CONTENT
* Supporting Information
The Supporting Information is available free of charge at
https://pubs.acs.org/doi/10.1021/acs.joc.1c00876.
■
sı
Full spectroscopic data for all new compounds (PDF)
AUTHOR INFORMATION
Corresponding Author
■
Michael P. Jennings − Department of Chemistry and
Biochemistry, The University of Alabama, Tuscaloosa,
Alabama 35487-0336, United States; orcid.org/0000-
0002-1069-6246; Email: jenningm@ua.edu
Ethyl (Z)-2-Bromo-4-Methylpent-2-Enoate (2f). Yield: 0.069 g,
67%, yellow oil. Flash column chromatography: 3% Et2O in hexanes.
1H NMR (500 MHz, CDCl3) δ 7.08 (d, J = 9.3 Hz, 1H), 4.27 (q, J =
7.1 Hz, 1H), 2.88−2.83 (m, 1H), 1.33 (t, J = 7.1 Hz, 2H), 1.09 (d, J =
6.7 Hz, 3H).18
Author
Kristina C. Probasco − Department of Chemistry and
Biochemistry, The University of Alabama, Tuscaloosa,
Alabama 35487-0336, United States
Ethyl (Z)-2-Bromo-3-Cyclohexylacrylate (2g). Yield: 0.083 g, 90%,
1
yellow oil. Flash column chromatography: 3% Et2O in hexanes. H
NMR (500 MHz, CDCl3) δ 7.10 (d, J = 9.2 Hz, 1H), 4.27 (q, J = 7.1
Hz, 1H), 2.60−2.54 (m, 1H), 1.76−1.67 (m, 5H), 1.34−1.32 (m,
2H), 1.33 (t, J = 7.1 Hz, 2H), 1.21−1.16 (m, 3H).18
Complete contact information is available at:
https://pubs.acs.org/10.1021/acs.joc.1c00876
Experimental Procedure for the Synthesis of 2h @ 2.5
Mmol. In a dark room, NBS (5.00 mmol, 0.890 g, 2.0 equiv) was
added to a (flame-dried under vacuum) round-bottom flask under Ar.
The flask was then covered in aluminum foil, and a solution of 1h
(2.50 mmol, 0.656 g, 1.0 equiv) in anhydrous DMF (10.00 mL) was
added in one portion. The mixture was stirred at room temperature
for 24 h, where it was then quenched with saturated Na2CO3 (10.00
mL), and the product was extracted with CH2Cl2 (3 × 30 mL). The
combined organic layers were washed with deionized H2O (3 × 30
mL). The organic layer was dried with MgSO4 and concentrated in
vacuo to yield the crude product. Column chromatography of the
crude material afforded the pure halogenated product 2h (0.551 g) in
82% yield as pale yellow oil. Ethyl (Z)-2-bromo-4-phenylbut-2-enoate
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
■
Support for this project was provided by the University of
Alabama. We would like to thank Ashton Mueller and
Cameron Lange for their respective contributions to this
project.
REFERENCES
■
(1) (a) Horner, L.; Hoffmann, H.; Wippel, H. G. Phosphororgani-
sche Verbindungen, XII. Phosphinoxyde als Olefinierungsreagenzien.
Chem. Ber. 1958, 91, 61−63. (b) Wadsworth, W. S.; Emmons, W. D.
The Utility of Phosphonate Carbanions in Olefin Synthesis. J. Am.
Chem. Soc. 1961, 83, 1733−1738. (c) Still, W. C.; Gennari, C. Direct
Synthesis of Z-unsaturated Esters. A Useful Modification of the
Horner-Emmons Olefination. Tetrahedron Lett. 1983, 24, 4405−4408.
For a review on stabilized Wittig reagents, see: (d) Maryanoff, B. E.;
Reitz, A. B. The Wittig Olefination Reaction and Modifications
Involving Phosphoryl-Stabilized Carbanions. Stereochemistry, Mech-
anism, and Selected Synthetic Aspects. Chem. Rev. 1989, 89, 863−
1
(2h); flash column chromatography: 3% Et2O in hexanes. H NMR
(500 MHz, CDCl3) δ 7.43 (t, J = 7.3 Hz, 1H), 7.34−7.31 (m, 2H),
7.27−7.23 (m, 3H), 4.28 (q, J = 7.1 Hz, 2H), 3.70 (d, J = 7.3 Hz,
2H), 1.32 (t, J = 7.1 Hz, 3H). 13C{1H} NMR (125 MHz, CDCl3) δ
162.4, 144.0, 137. 2, 128.8, 128.6, 126.9, 117.0, 62.5, 38.4, 14.1. IR
(NaCl): 2360, 2341, 1652, 1255, 992, 799. HRMS (EI-EBE Sector)
m/z: [M] + Calcd for C12H13BrO2 268.0099; found 268.0096. Rf =
0.42, 3% Et2O in pentane.
Ethyl (Z)-2-Bromoundec-2-Enoate (2i). Yield: 0.059 g, 58%,
1
yellow oil. Flash column chromatography: 3% Et2O in hexanes. H
́
927. (e) Blakemore, P. R.; Cole, W. J.; Kocienski, P. J.; Morley, A. A
NMR (500 MHz, CDCl3) δ 7.29 (t, J = 7.2 Hz, 1H), 4.28 (t, J = 7.1
Hz, 2H), 2.36−2.31 (m, 2H), 1.54−1.47 (m, 2H), 1.33 (t, J = 7.1 Hz,
3H), 1.35−1.28 (m, 10H), 0.88 (t, J = 6.8 Hz, 3H). 13C{1H} NMR
(125 MHz, CDCl3) δ 162.6, 146.3, 116.3, 62.3, 32.1, 31.8, 29.3, 29.3,
29.2, 27.5, 22.6, 14.2, 14.1. IR (NaCl): 2926, 1730, 1718, 1235.
HRMS (EI-EBE Sector) m/z: [M] + Calcd for C13H23BrO2 290.0881;
found 290.0882. Rf = 0.45, 3% Et2O in pentane.
Ethyl (Z)-2-Chloro-4-Methylpent-2-Enoate (2j). Yield: 0.068 g,
82%, yellow oil. Flash column chromatography: 3% Et2O in hexanes.
1H NMR (500 MHz, CDCl3) δ 6.88 (d, J = 9.4 Hz, 1H), 4.28 (q, J =
7.1 Hz, 2H), 2.94−2.86 (m, 1H), 1.34 (t, J = 7.1 Hz, 3H), 1.08 (d, J =
6.7 Hz, 6H). 13C{1H} NMR (125 MHz, CDCl3) δ 162.8, 148.3,
122.8, 62.2, 29.1, 21.1, 14.2. IR (NaCl): 1734, 1721, 1251, 1145,
1041, 754 cm −1. HRMS (EI-EBE Sector) m/z: [M] + Calcd for
C8H13ClO2 176.0604; found 176.0601. Rf = 0.40, 3% Et2O in pentane.
Ethyl (Z)-2-Chloro-4-Phenylbut-2-Enoate (2k). Yield: 0.052 g,
80%, yellow oil. Flash column chromatography: 3% Et2O in hexanes.
1H NMR (500 MHz, CDCl3) δ 7.34−7.27 (m, 2H), 7.26−7.20 (m,
3H), 7.22 (t, J = 7.4 Hz, 1H), 4.28 (q, J = 7.1 Hz, 2H), 3.71 (d, J = 7.4
Hz, 2H), 1.32 (t, J = 7.1 Hz, 3H). 13C{1H} NMR (125 MHz, CDCl3)
δ 162.4, 140.2, 137.4, 128.8, 128.6, 126.8, 125.2, 62.30, 35.6, 14.1. IR
(NaCl): 1730, 1268, 1043 cm −1. HRMS (EI-EBE Sector) m/z: [M]
+ Calcd for C12H13ClO2 224.0604; found 224.0605. Rf = 0.27, 3%
Et2O in pentane.
Stereoselective Synthesis of trans-1,2-Disubstituted Alkenes Based on
the Condensation of Aldehydes with Metallated 1-Phenyl-1H-
tetrazol-5-yl Sulfones. Synlett 1998, 26−28. (f) Blakemore, P. R.
The Modified Julia Olefination: Alkene Synthesis via the Con-
densation of Metallated Heteroarylalkylsulfones With Carbonyl
Compounds. J. Chem. Soc., Perkin Trans. 1 2002, 2563−2585. For
a leading review on Mo and W metathesis, see: (g) Schrock, R. R.;
Hoveyda, A. H. Molybdenum and Tungsten Imido Alkylidene
Complexes as Efficient Olefin-Metathesis Catalysts. Angew. Chem.,
Int. Ed. 2003, 42, 4592−4633. For a leading review on Ru metathesis,
see: (h) Vougioukalakis, G. C.; Grubbs, R. H. Ruthenium-Based
Heterocyclic Carbene-Coordinated Olefin Metathesis Catalysts.
Chem. Rev. 2010, 110, 1746−1787.
(2) Negishi, E.-I.; de Meijere, A (Eds.), Handbook of Organo-
palladium Chemistry for Organic Synthesis, 2 Vols., Wiley: New York,
2002.
(3) Tamao, K.; Akita, M.; Maeda, K.; Kumada, M. Silafunctional
Compounds in Organic Synthesis. 32. Stereoselective Halogenolysis
of Alkenylsilanes: Stereochemical Dependence on the Coordination
State of the Leaving Silyl Groups. J. Org. Chem. 1987, 52, 1100−1106.
(4) For a few reviews on the Hosomi-Sakurai reaction, see: (a) Lade,
J. J.; Pardeshi, S. D.; Vadagaonkar, K. S.; Murugan, K.; Chaskar, A. C.
The Remarkable Journey of Catalysts From Stoichiometric to
8952
https://doi.org/10.1021/acs.joc.1c00876
J. Org. Chem. 2021, 86, 8945−8954

The Journal of Organic Chemistry
pubs.acs.org/joc
Article
Catalytic Quantity for Allyltrimethylsilane Inspired Allylation of
Acetals, Ketals, Aldehydes and Ketones. RSC Adv. 2017, 7, 8011−
8033. (b) Hosomi, A.; Miura, K. Development of New Reagents
Containing Silicon and Related Metals and Application to Practical
Organic Syntheses. Bull. Chem. Soc. Jpn. 2004, 77, 835−851.
(c) Markó, I. E.; Mekhalfia, A.; Murphy, F.; Bayston, D. J.; Bailey,
M.; Janousek, Z.; Dolan, S. Multicomponent Cyclizations. Efficient
Methodologies for the Preparation of Complex Natural Products. Pure
Appl. Chem. 1997, 69, 565−570. For the initial disclosure paper, see:
(d) Hosomi, A.; Sakurai, H. Chemistry of Organosilicon Compounds.
89. Syntheses of γ,δ-Unsaturated Alcohols from Allylsilanes and
Carbonyl Compounds in the Presence of Titanium Tetrachloride.
Tetrahedron Lett. 1976, 17, 1295−1298.
(5) For a couple of reviews that focus solely on the Hiyama
coupling, see: (a) Teizeira, R. R.; Barbosa, L. C. A.; Pilo-Veloso, D.
Palladium Catalyzed Cross Coupling Reactions of Organosilicon
Compounds: Historical, Synthetic and Mechanistic Aspects. Quim.
Nova 2007, 41, 1704−1499. (b) Hiyama, T. How I Came Across the
Silicon-Based Cross-Coupling Reaction. J. Organomet. Chem. 2002,
653, 58−61. For recent reviews that include the Hiyama coupling,
see: (c) Grimaud, L.; Jutand, A. Role of Fluoride Ions in Palladium-
Catalyzed Cross-Coupling Reactions. Synthesis 2017, 49, 1182−1189.
(d) Yang, H.; Yang, X.; Tang, W. Transition-metal Catalyzed
Asymmetric Carbon-Carbon Cross-Coupling With Chiral Ligands.
Tetrahedron 2016, 72, 6143−6174. (e) Glorius, F. Asymmetric Cross-
Coupling of Non-Activated Secondary Alkyl Halides. Angew. Chem.,
Int. Ed. 2008, 47, 8347−8349.
(6) For a series of reviews, see: (a) Hosokawa, S. Recent
Development of Vinylogous Mukaiyama Aldol Reactions. Tetrahedron
Lett. 2018, 59, 77−88. (b) Gati, W.; Yamamoto, H. Second
Generation of Aldol Reaction. Acc. Chem. Res. 2016, 49, 1757−
1768. (c) Averill, D. J.; Allen, M. J. Tools for Studying Aqueous
Enantioselective Lanthanide-Catalyzed Mukaiyama Aldol Reactions.
Catal. Sci. Technol. 2014, 4, 4129−4137. (d) Kalesse, M.; Cordes, M.;
Symkenberg, G.; Lu, H.-H. The Vinylogous Mukaiyama Aldol
Reaction (VMAR) in Natural Product Synthesis. Nat. Prod. Rep.
2014, 31, 563−594. (e) Roiban, G.-D.; Ilie, A.; Reetz, M. T. The
Chelation-Controlled Mukaiyama Aldol Reaction of Chiral α- and β-
Alkoxy Aldehydes. Chem. Lett. 2014, 43, 2−10. (f) Sutar, R. L.; Joshi,
N. N. Base-Catalyzed Mukaiyama-Type Aldol Additions, A
Continued Quest for Stereoselectivity. Tetrahedron: Asymmetry
2013, 24, 1345−1363. (g) Beutner, G. L.; Denmark, S. E. Lewis
Base Catalysis of the Mukaiyama Directed Aldol Reaction: 40 Years of
Inspiration and Advances. Angew. Chem., Int. Ed. 2013, 52, 9086−
9096. (h) Kan, S. B. J.; Ng, K. K.-H.; Paterson, I. The Impact of the
Mukaiyama Aldol Reaction in Total Synthesis. Angew. Chem., Int. Ed.
2013, 52, 9097−9108. (i) Matsuo, J.-i.; Murakami, M. The
Mukaiyama Aldol Reaction: 40 Years of Continuous Development.
Angew. Chem., Int. Ed. 2013, 52, 9109−9118.
(7) For a recent review, see: (a) Taheri kal Koshvandi, A.; Heravi,
M. M. Applications of Danishefsky’s Dienes in Asymmetric Oxo-
Diels-Alder Reactions. Tetrahedron: Asymmetry 2017, 28, 1506−1556.
(b) Li, Y.; Hu, Y.; Zhang, S.; Sun, J.; Li, L.; Zha, Z.; Wang, Z. Copper-
Catalyzed Enantioselective Hetero-Diels-Alder Reaction of Danishef-
sky’s Diene with Glyoxals. J. Org. Chem. 2016, 81, 2993−2999.
(c) Takeda, Y.; Hisakuni, D.; Lin, C.-H.; Minakata, S. 2-
Halogenoimidazolium Salt Catalyzed Aza-Diels-Alder Reaction
Through Halogen-Bond Formation. Org. Lett. 2015, 17, 318−321.
(d) Zhao, B.; Loh, T.-P. Asymmetric Hetero-Diels-Alder Reaction of
Danishefsky’s Dienes with α-Carbonyl Esters Catalyzed by an
Indium(III)-PyBox Complex. Org. Lett. 2013, 15, 2914−2917.
(8) For some leading references, see: (a) Reynolds, T. E.; Scheidt, K.
A. Catalytic Enantioselective α-Acylvinyl Addition Reactions of
Silyloxyallenes. Angew. Chem., Int. Ed. 2007, 46, 7806−7809.
(b) Reynolds, T. E.; Stern, C. A.; Scheidt, K. A. N-Heterocyclic
Carbene-Initiated α-Acylvinyl Anion Reactivity: Additions of α-
Hydroxypropargylsilanes to Aldehydes. Org. Lett. 2007, 9, 2581−
2584. (c) Reynolds, T. E.; Bharadwaj, A. R.; Scheidt, K. A.
Stereoselective Lewis Acid-Catalyzed α-Acylvinyl Additions. J. Am.
Chem. Soc. 2006, 128, 15382−15383. (d) Crimmins, M. T.;
Nantermet, P. G. Addition of Zinc Homoenolates to Acetlyenic
Esters: A Formal [3+2] Cycloaddition. J. Org. Chem. 1990, 55, 4235−
4237.
(9) (a) Wu, J.; Zhu, K.-C.; Yuan, P.-W.; Panek, J. S. Bifunctional
Homoallylic Carbamates From Chiral Silane Additions to in situ
Generated N-acyl Iminium Ions. Org. Lett. 2012, 14, 3624−3627.
(b) Kim, D.; Lee, J. S.; Lozano, L.; Kong, S. B.; Han, H.
Enantioenriched Bifunctional Crotylsilanes for the Asymmetric
Synthesis of Orthogonally Protected 2-Methyl-1, 3-diols. Org. Lett.
2013, 15, 5142−5145. (c) Chai, G.; Zeng, R.; Fu, C.; Ma, S. Iron-
Catalyzed Diastereoselective Synthesis of α-(Methoxycarbonyl)
allylsilanes. Eur. J. Org. Chem. 2013, 148−154. (d) Chen, D.; Zhu,
D.-X.; Xu, M.-H. Rhodium(I)-Catalyzed Highly Enantioselective
Insertion of Carbenoid into Si−H: Efficient Access to Functional
Chiral Silanes. J. Am. Chem. Soc. 2016, 138, 1498−1501.
(10) (a) Fleming, I.; Dunogués, J.; Smithers, R. The Electrophilic
Substitution of Allylsilanes and Vinylsilanes. Org. React. 1989, 37, 57−
575. (b) Shimizu, K.; Takimoto, M.; Sato, Y.; Mori, M. Nickel-
Catalyzed Regioselective Synthesis of Tetrasubstituted Alkene Using
Alkylative Carboxylation of Disubstituted Alkyne. Org. Lett. 2005, 7,
195−197. (c) Sumida, Y.; Kato, T.; Yoshida, S.; Hosoya, T.
Palladium-Catalyzed Regio- and Stereoselective Hydrosilylation of
Electron-Deficient Alkynes. Org. Lett. 2012, 14, 1552−1555.
(d) Rooke, D. A.; Menard, Z. A.; Ferreira, E. M. An Analysis of the
Influences Dictating Regioselectivity in Platinum-Catalyzed Hydro-
silylations of Internal Alkynes. Tetrahedron Lett. 2014, 70, 4232−
4244.
(11) (a) Johnson, D. A.; Mueller Hendrix, A. J.; Jennings, M. P.
Diastereoselective Syntheses of (E)-α-Trialkylsilyl-α,β-Unsaturated
Esters, α-Silane Substituted Conjugated Silyl Ketene Acetals, and α,γ-
Substituted Allyl Silanes. J. Org. Chem. 2018, 83, 9914−9928.
(b) Johnson, D. A.; Jennings, M. P. Tandem Copper-Catalyzed
Conjugate Addition-Diastereoselective Protonation of (E)-α-Trialkyl-
silyl-β-Alkyl(Aryl)-α,β-Unsaturated Esters. Org. Lett. 2018, 20, 6099−
6103. (c) Probasco, M. S.; Johnson, D. A.; Jennings, M. P.
Stereoselective One-Pot Deconjugation, Aldol, and Stabilized
Peterson Olefination of α-Trialkylsilyl-β-Alkyl-α,β-Unsaturated Esters.
Org. Lett. 2019, 21, 1379−1383.
(12) Hendrix, A. J. M.; Jennings, M. P. Vicinal Functionalization of
Propiolate Esters via Catalytic Carbocupration: Stereoselective
Formation of Substituted Vinyl Silanes. Org. Lett. 2010, 12, 2750−
2753.
(13) Kharasch, M. S.; Tawney, P. O. Factors Determining the
Course and Mechanisms of Grignard Reactions. II. The Effect of
Metallic Compounds on the Reaction Between Isophorone and
Methylmagnesium Bromide. J. Am. Chem. Soc. 1941, 63, 2308−2316.
(14) Maria, P. C.; Gal, J. F. A Lewis Basicity Scale for
Nonprotogenic Solvents: Enthalpies of Complex Formation With
Boron Trifluoride in Dichloromethane. J. Phys. Chem. 1985, 89,
1296−1304.
(15) Ganesh, M.; Namboothiri, I. N. N. Stereospecific Approach to
α,β-disubstituted Nitroalkenes via Coupling of α-bromonitroalkenes
With Boronic Acids and Terminal Acetylenes. Tetrahedron 2007, 63,
11973−11983.
(16) Mitchell, R. H.; Lai, Y.-H.; Williams, R. V. N-Bromosuccini-
mide-dimethylformamide: A Mild, Selective Nuclear Monobromina-
tion Reagent for Reactive Aromatic Compounds. J. Org. Chem. 1979,
44, 4733−4735.
(17) Arthuis, M.; Lecup, A.; Roulland, E. Pd0-Catalyzed Carbon-
ylation of 1,1-Dichloro-1-alkenes, A New Selective Access to Z-α-
chloroacrylates. Chem. Commun. 2010, 46, 7810−7812.
(18) Olpp, T.; Brueckner, R. Stereoselective Preparation of (E)-α-
bromo Acrylates From Mixtures of Brominated Ando Phosphonates.
Synthesis 2004, 2135−2152.
(19) McLennan, D. J. The Carbanion Mechanism of Olefin-Forming
Elimination. Q. Rev., Chem. Soc. 1967, 21, 490−506.
8953
https://doi.org/10.1021/acs.joc.1c00876
J. Org. Chem. 2021, 86, 8945−8954

The Journal of Organic Chemistry
pubs.acs.org/joc
Article
(20) Lambert, J. B.; Wang, G. T.; Finzel, R. B.; Teramura, D. H.
Stabilization of Positive Charge By .Beta.-Silicon. J. Am. Chem. Soc.
1987, 109, 7838−7845.
(21) Lee, H.; Cho, S.; Lee, Y.; Jung, B. Stereoselective Formal
Hydroamidation of Si-Substituted Arylacetylenes with DIBAL-H and
Isocyanates: Synthesis of (E)- and (Z)-α-Silyl-α,β-unsaturated
Amides. J. Org. Chem. 2020, 85, 12024−12035.
8954
https://doi.org/10.1021/acs.joc.1c00876
J. Org. Chem. 2021, 86, 8945−8954