Understanding the mechanism of transition metal-free: Anti addition to alkynes: The selenoboration case

Article abstract of DOI:10.1039/c7cy02295f

The stereoselective anti-addition of selenoboranes to α,β-acetylenic esters and amides was achieved in a transition metal-free context using catalytic amounts of PCy₃. The reaction provides anti-3,4-selenoboration with concomitant delivery of α-vinyl selenides by protodeboronation with MeOH. Interestingly, in the absence of phosphine the selenoboration switches towards the formation of β-vinyl selenides. Theoretical calculations rationalize the regio- and stereoselectivity of the reaction by discovering a new mechanism for the anti-3,4-selenoboration. While the selenoborane is activated via the "push-pull" effect of B, the phosphine interacts with the β position of the alkynoate switching the polarity of the triple bond and favoring 1,3-selenoboration which provides the α-addition of the selenyl group. Then, the autocatalytic action of a second selenoborane reagent, which coordinates to the phosphorus ylide intermediate, determines the stereoselectivity and completes the catalytic process. Finally, the comparison of selenoborane reagents with diboranes and silaboranes, which have exhibited analogous reactivity, shows that the selenium moiety has a larger nucleophilic character favoring the performance of the reaction under mild conditions.

Full text of DOI:10.1039/c7cy02295f

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Understanding the mechanism of transition metal-free anti
addition to alkynes: the selenoboration case
Diego García-López,a Marc G. Civit,a Christopher M. Vogels,b Josep M. Ricart,a Stephen A.
Westcott,b Elena Fernández,*,a and Jorge J. Carbó*,a
Received 00th January 20xx,
Accepted 00th January 20xx
DOI: 10.1039/x0xx00000x
The stereoselective anti-addition of selenoboranes to α,β-acetylenic esters and amides was achieved in a transition metal-
free context using catalytic amounts of PCy3. The reaction provides the anti-3,4-selenoboration with concomitant delivery
of α-vinyl selenides by protodebonation with MeOH. Interestingly, in the absence of phosphine the selenoboration
switches towards the formation of β-vinyl selenides. Theoretical calculations rationalize the regio- and stereoselectivity of
the reaction by discovering a new mechanism for the anti-3,4-selenoboration. While the selenoborane is activated via
“push-pull” effects of B, the phosphine interacts with the β position of the alkynoate switching the polarity of the triple
bond and favoring the 1,3-selenoboration which produces the α-addition of selenyl group. Then, the autocatalytic action
www.rsc.org/
of
a second selenoborane reagent, which coordinates to the phosphorus ylide intermediate, determines the
stereoselectivity and completes the catalytic process. Finally, the comparision of selenoborane reagents with diboranes
and silaboranes, which had exhibited analogous reactivity, shows that selenium moiety has a larger nucleophilic character
favoring the performance of the reaction under mild conditions.
alkynylboration7,8 of the triple bond through the
intramolecular reaction of an alkoxide and selective delivery of
the nucleophilic boryl unit (Scheme 1a). DFT calculations
Introduction
The reactivity of diboron reagents and B-interelement systems
with organic molecules has become an important source of
selective functionalization.1 The addition of these reagents to
C-C triple bonds provides an attractive method for the regio-
and stereoselective synthesis of functionalized alkenes via the
formation of C-B and C-interelement bonds. Much effort has
been devoted to transition metal catalysis, which generally
generate1,2-cis-addition products selectively.2 However, some
outstanding examples of stereoselective trans-hydroboration
of terminal and internal alkynes were achieved by copper3 and
ruthenium4 catalysts, respectively. Also, Miyaura et al.
developed the hydroboration of terminal alkynes by Rh and Ir
complexes leading selectively to Z-alkenyl boranes5 via gem-
addition of B-H bond through a vinylidene intermediate.6
proposed a mechanism involving deprotonation of propargylic
alcohols by nBuLi, coordination of the resulting alkoxide to
activate the B-X bond, stereoselective migration of the boron
or allynyl group and the Li to form the anti-alkenyllithium
intermediate, and final intramolecuar capture of the boron.7,8
Santos et al. reported the substrate-assisted anti-diboration of
alkynamides using strong bases which deprotonates the amide
group (Scheme 1b),9a and then the procedure was extended to
silaboration.9b The DFT-derived mechanism indicates that the
generated alkoxide activates the diboron reagent
intramolecularly resulting in
α-addition of one boron, similar
to that found for propargyl alcohols, and then a rapid carbon-
carbon bond rotation leads to the thermodynamically favored
anti product.9a Alternatively, Sawamura et al. have achieved
the anti-selective carboboration,10 silaboration, and
diboration11 of alkynoates using catalytic amounts of PBu3
(Scheme 1c). The proposed mechanism involves the rotation of
an enolate double bond as the key step for selectivity-
determining, although in this case, it was not supported by
computational studies.10 The comparison of Sawamura’s
reactions with those of Uchiyama and Santos suggests that in
the absence of acidic protons alkynoates can be activated by
basic phosphines instead of Brønsted bases to produce the
alkoxy group, which in turns activates the boron reagent.
In recent years several transition metal-free approaches have
appeared to yield anti addition products using special
substrates or introducing directing groups (Scheme 1).1
Uchiyama et al. utilized propargyl alcohol substrates to provide
access to the selective anti-diboration7 and anti-
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Scheme 1. Stereoselective transition metal-free anti addition of diboron and B-
Scheme 3. Syn- and anti-hydroselenation towards β-vinyl selenides.
interelements reagents to activated alkynes.
Among the potential applications of B-interelement additions
to alkynes, processes for the selective synthesis of vinyl
selenides, which are important biological scaffolds, are
Results and Discussion
The previously determined mechanism for the 1,4-
selenoboration of ynones is illustrated in Scheme 4.18 The
activation of the boron atom with the oxygen of the carbonyl
challenging targets.12 The
β-vinyl selenides can be obtained
from α,β-acetylenic esters and ynones by means of rhodium-
catalyzed syn-hydroselenation to generate principally β-E-vinyl
group in the substrate leading to intermediate
nucleophilic attack of the –SePh moiety on the
A
, enhances the
carbon of the
selenides (Scheme 2a)13 or via anti-addition of organoselenols,
formed in situ from the corresponding diselenides and Zn in
β
triple bond yielding the 1,4 selenoborated allene intermediate
which undergoes protonolysis with methanol. Here, we
initially analyzed from the computational point of view
whether this process can be extended to β−acetylenic ester
acidic media, to provide the β-Z-vinyl selenides (Scheme
B
2b).14,15 Alternatively, phenylselenoborane16 can efficiently be
added to alkenes,17 in a transition-metal-free context, taking
advantage of the “push-pull” effect of B in the B-interelement
reagent. In a previous work, we proved that stereodefined Z-
alkenylselenides can be directly formed through the Lewis acid
interaction of the carbonyl unit from ynones and the Bpin
moiety on PhSe-Bpin, throughout 1,4-selenoborated
intermediates.18
α,
1-(4-methylphenyl)-3-phenyl-2-propyn-1-one, although the
ester functional group is expected to be less efficient than the
ketone in activating the B-Se bond through the “push-pull”
effect. To evaluate the feasibility of the reaction before
attempting it experimentally, we compared the potential free-
energy profile for the α,β−acetylenic ester with that previously
reported for α,β-acetylenic ketones at the same
computational level18 (R = OMe vs. Tol in Scheme 4). In the
initial activation of the boron atom with the oxygen of the
Herein we aim to understand the mechamism of the transition
metal-free addition of boron-interelement systems to
alkynoates catalyzed by phosphines. To this end we extend our
carbonyl group leading to intermediate
A, the free-energy
experimental selenoboration work to electron-deficient α,β
acetylenic esters adding catalytic amounts of phosphine as in
Sawamura’s reports.11 We came across a stereodivergent
-
barrier and the relative energy of are slightly higher (~2
A
kcal·mol-1) for the ester (R = OMe) than for the ketone (R =
Tol). Nevertheless, the lesser activation ability of the ester
group is mainly manifested on the nucleophilic attack of the –
synthesis of β-vinyl selenides and α-vinyl selenides, depending
on the mode of activation of the phenylselenoborane (Scheme
3). Eventually, experimental observations were used to
perform detailed DFT study of the reaction mechanism,
including the understanding of the role of the heteroelement
nature.
SePh moiety on the
1,4- selenoborated intermediate
barrier increases by 5.6 kcal·mol-1. Finally, the computed free-
β
carbon of the triple bond yielding the
B
, for which the energy
energy barrier for the protonolysis of intermediate B inverts
the trend, lowering by 10 kcal·mol-1. Thus, although the overall
computed free-energy barrier is somewhat higher (27.5
kcal·mol-1, from the reactants to the transition state TSA B) for
-
the
α,β−acetylenic ester, the value is still feasible for a
reaction occurring at the working temperature, 50 oC; and
therefore, there is enough theoretical support to carry out this
reaction experimentally.
Scheme 2. Regioselective transition metal-free synthesis of α− and β-seleniated α,β-
unsatuarted esters.
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Table 1. . β-Selenation of α,β-acetylenic esters, via 1,4-selenoboration.a
R = OMe
(R= Tol)
O
O
O
O
+
B
PhSe
B
Bpin
Ph
Se
PhSe
O
-
O
O
PhSe-Bpin
50ºC, 16h
O
+
Ph
OR
O
Se
OR
R
OR
exclusive Z-isomer
R'
R'
MeOH
Ph
R
no metal
no base
R'
Ph
0.0
(0.0)
+11.9
(+9.1)
no additives
Entry
Substrate
Product
NMR yield
(%)b
IY (%)c
A
ꢀG = 12.5
(10.1)
ꢀG = 15.6
O
1
(10.1)
O
1
82
74
O
B
O
O
MeO
O
B
O
R
+
H
MeO
2
3
Se
O
O
PhSe
SePh
H
O
G
= 1.4
(11.1)
ꢀ
90
89
79
78
Ph
R
Z-9
Ph
-0.3
(-17.4)
B
Scheme 4. Comparative relative free-energies and barriers (kcal·mol-1) for reaction
mechanism of β-selenated α,β-unsaturated ester and ketone (in parenthesis, values
taken from ref. 18.
4
5
The energetic profile for the
β-selenation of α,β-acetylenic
esters prompted us to carry out the expected reactivity with
representative substrates that combines aryl and alkyl groups
75
88
72
69
in the β-position, as well as sterically differentiated esters
groups. Table 1 shows the moderate to high conversions
observed for all the substrates tested, and in particular for
o
methyl-2-nonenoato (Z-9) (Table 1, entry 2), working at 50 C.
Lower temperatures provided only small amount of desired
products. The aryl or alkyl nature of the acetyl substituent did
not influence significantly the 1,4-selenoboration followed by
6
7
O
N
89
75
76
68
protonolysis towards the β-selenated α,β-unsaturated esters.
6
O
Substrates with electron-withdrawing p-substituents, such as
CF3 in ethyl (Z)-2-(phenylselanyl)-3-(4,4,5,5-tetramethyl-1,3,2-
dioxaborolan-2-yl)-3-(4-(trifluoromethyl)phenyl)acrylate only
converted 16%. The exclusive formation of the Z-isomer was
confirmed by spectroscopic data and the full characterization
of product Z-8 by X-ray diffraction (Figure 1), and contrast with
the Z/E mixture observed in the
ketones.18
β
-selenation of α,β-acetylenic
(a) Reaction conditions: α,β-acetylenic esters or amides (0.2 mmol), PhSe-Bpin
(1.1 eq), MeOH (0.15 mL), at 50 oC for 16h; (b) yields were determined by 1H NMR
analysis of the crude reaction mixture with naphthalene as an internal standard,
which was added after the reaction; (c) IY= isolated yield.
We extended the study to the
β-selenation of α,β-acetylenic
amides 3-(4-methoxyphenyl)-N,N-dimethylpropiolamide
and 3-(4-methoxyphenyl)-1-(pyrrolidin-1-yl)prop-2-yn-1-one
), and in both cases the conversion was comparable (Table 1,
entries 6 and 7) to the -selenation of α,β-acetylenic esters,
(6)
(
7
In the next step, we introduced catalytic amounts of
phosphine in order to switch the selenoboration of alkynoates
β
proving the generality of the method despite the functional
and towards the formation of
α-vinyl selenides with anti
group.
stereoselectivity, as Sawamura et al.11 observed for the
diboration or silaboration of α,β-acetylenic esters with PBu3. In
our hands, the addition of 10 mol% of PBu3 or PPh3 did not
convert substrate
1 into any selenated or borylated product,
o
working at 50 C with 1.1 equiv. of PhSe-Bpin (Table 2, entries
1,2). However, the use of PCy3 provided the formation of 61%
(NMR yield) of a new product identified as the corresponding
anti-3,4-addition product (Table 2, entry 3). We observed the
same yield working at rt, for 8h, or variable amount of PhSe-
Bpin reagent, therefore the optimized reaction conditions
Fig. 1. X-ray diffraction structure of product (Z)-3-phenyl-3-(phenylselanyl)acrylate (Z-8)
and confirming the Z-isomerism.
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included only 1.1 equiv of PhSe-Bpin reagent and 15 mol% oC, delivering compounds 19
Journal Name
-
22 in moderate values (Scheme
phosphine (Table 2, entries 3-6). Although the reaction works 5), representing the first attempt to obtain those high valued
efficiently under neat conditions, the addition of 0.15 mL of products.20 Similarly, we conducted the same selenoboration
THF was required to solubilize the Se-B reagent (Table 2, to alkynamides
6 and 7, and although the anti-3,4-
entries 7-9).
selenoborated products 23 and 24 were quantitatively
determined by NMR yield, their isolation was not successfully
accomplished.
Table 2. Optimization of reactivity between of α,β-acetylenic esters, via 1,4-
selenoboration.a
In order to understand the mechanism of the anti-addition to
alkynoates using catalytic amounts of phosphines and the
switch-like behavior of selenoboration, we carried out a
systematic DFT study. We initially explored a catalytic cycle
where the phosphine acts as a catalyst, based on previous
mechanisms proposed by Sawamura et al.10,11 for anti-
selective carboboration, silaboration and diboration (Scheme
6). The phosphine catalyst initiates the reaction by conjugative
addition to the alkynoate with the assistance of the Lewis
acidic boron, which activates the carbonyl group, yielding the
Entry
PR3 (mol%)
PhSe-Bpin
1.1 eq
1.1 eq
1.1 eq
1.1 eq
1.1 eq
1.1 eq
1.1 eq
1.5 eq
2.0 eq
T(ºC)
50 ºC
50 ºC
50 ºC
50 ºC
rt
t(h) / Sol
NMR yield
(%)b
1
2
3
4
5
6
7
8
9
PBu3
(10mol%)
16h
neat
/
/
/
-
zwitterionic allenolate intermediate
C. Then, the terminal
PPh3
(10mol%)
16h
neat
-
selenyl undergoes migration to form the ylide intermediate
D
,
in which the enolate double bond has to rotate (D’) to allow
PCy3
(10mol%)
16h
neat
61
60
62
62
63
63
65
the attack of ylidic carbon to the boron atom and to reach the
anti-stereochemistry. Finally, from the cyclic borate E, the B-O
PCy3
(10mol%)
8h / neat
8h / neat
8h / neat
8h / THF
8h / THF
8h / THF
bond cleavages and the phosphine eliminates to yield the
product.
PCy3
(10mol%)
PCy3
(15mol%)
rt
PCy3 (15 mol%)
PhSe-Bpin
O
B
O
O
O
O
K2CO3 (2M)
70ºC, 2h
OR(NR2
)
R'
OR
R'
OR(NR2)
PCy3
(15mol%)
rt
R'
THF(0.16 ml),
rt, 16h
Se
Ph
Se
Ph
11B NMR ( : 27-28 ppm)
PCy3
(15mol%)
rt
O
O
O
O
B
O
O
B
O
O
O
PCy3
(15mol%)
rt
Se
O
Se
Se
O
19
[22%]
16
60% [5%]
15
63%
(a) Reaction conditions: 1 (0.2 mmol), PhSe-Bpin (1.1 equiv), neat or THF (0.15
mL); (b) yields were determined by 1H NMR analysis of the crude reaction mixture
with naphthalene as an internal standard, which was added after the reaction.
O
O
Se
20
O
O
O
O
O
B
O
B
O
Product 15 was not able to be isolated as pure product from
33% [21%]
O
O
the reaction media, however, the transformation of substrates
Se
Se
O
O
O
3
,
4
, and
addition products 16
(Scheme 5). The addition of the Bpin moiety at the
of the substrate is confirmed by NMR data (11B NMR
5
into the corresponding anti-3,4-selenoborated
17 and 18 allowed their isolation
-position
: 27-29
17
18
66% [31%]
O
79% [23%]
,
Se
O
β
21
δ
22% [13%]
O
O
O
O
B
O
ppm). Two interesting points have to be addressed at this
moment: a) while the addition of PhSe-Bpin takes place at
room temperature, the addition of B2pin2 and PhMe2Si-Bpin
requires up to 80 oC; b) while the addition of PhSe-Bpin
involves PCy3 as additive, the addition of B2pin2 and PhMe2Si-
Bpin requires the most basic phosphine PBu3. Any attempt to
perform the 3,4-addition of PhSe-Bpin, B2pin2 and PhMe2Si-
Bpin to α,β-acetylenic ketones proved unsuccessful. The
products derived from the anti-3,4-selenoboration were
B
O
O
N
N
O
Se
Se
O
O
Se
O
22
40% [31%]
24
85%
23
81%
Scheme 5. α-Selenation of α,β-acetylenic esters and amides via anti-3,4-
selenoboration. Reaction conditions: α,β-acetylenic esters or amides (0.2 mmol), PhSe-
Bpin (1.1 eq), PCy3 (15 mol%), THF (0.15 mL), rt for 16h. For compound 15, reaction
time was 8h. Yields were determined by 1H NMR analysis of the crude reaction mixture
with naphthalene as an internal standard, which was added after the reaction. Isolated
yield in brackets.
further transformed into the corresponding α-hydroselenated
compounds, via protodeboronation process with K2CO319 at 70
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selenoboration. According to the calculations by Santos et al.,9
the stereoselectivity of the transition-metal-free anti-
diboration of alkynamides is due to a rapid carbon-carbon
bond rotation process (Figure 2b), which is thermodynamically
favored. However, in that case the use of strong base
deprotonates the original amide group generating an
intermediate in which the rotating carbon-carbon bond has
single bond character (dC-C = 1.491 Å) instead of the double
bond character in the corresponding intermediate
D (dC-C =
1.342 Å). Alternatively, Zhang et al.24 characterized
computationally the mechanism of anti selective
hydroboration of alkyne catalyzed by Ru complexes, showing
that the formation of
a
stable metallacyclopropene
intermediate, after hydrogen migration to the alkyne explains,
the selectivity (Figure 2c). Such an intermediate is not possible
in our metal-free context. Thus, we propose
a novel
mechanism, in which the selenoborane auto-catalyzes the
reaction.
(a)
O
B
O
B
O
O
Ph
O
O
C
MeO
Ph
MeO
Ph
Scheme 6. Hypothetic mechanism for anti-3,4-addition of PhSe-Bpin to α,β-acetylenic
ester adapted from the proposal for anti-selective carboboration, silaboration and
C
Ph
C
C
diboration (ref. 10 and 11). Relative free-energies and barriers in kcal·mol-1
.
Si
Si
C
C
PMe3
PMe3
Sawamura
(c)
We have computed the free-energy profile for the α-addition
of PhSe-Bpin to the -acetylenic ester 1-methyl-3-phenyl-2-
α,β
(b)
O
B
propyn-1-one catalyzed by PMe3 as model phosphine
assuming a Sawamura-type mechanism. The main energy
values are depicted in Scheme 6, and the details are provided
in the Supporting Information (Figure S1). According to our
calculations, the overall free-energy barrier for the formation
O
B
O
O
Ru
O
MeN
C
C
Bdan
C
C
H
Et
C
Et
Ph
of intermediate (
associated to the entropic cost of the two consecutive
additions to the alkynoate. In the intermediate the
phosphine addition changes the polarity of the triple bond
making -position the most electrophilic, while boron
C
) is about 26.5 kcal·mol-1, which is mainly
Zhang / Chung / Wu
Santos
C
,
Fig. 2. Comparison of key stereodetermining intermediates of different mechanistic
proposals for anti selective addition of borane compounds to alkynes.
α
coordination to the carbonyl oxygen activates selenium
nucleophilicity via a “push-pull” effect.21,22 As a result, the
migration of the selenyl to produce D is computed to be a fast
process with a low barrier, 4.1 kcal·mol-1. The formation of
ylide intermediate
D is thermodynamically favored, the
structure laying 1.2 kcal·mol-1 below reactants. Then, in order
to yield the observed stereoisomer, the bond between the
carbonylic- and the
computed free-energy barrier for rotation is as high as 48.8
kcal·mol-1. The
species has the typical structure of α-
α
-carbon should rotate 180o. However, the
D
stabilized phosphonium ylides,23 in which the P-C bond is still
covalent but has a significant polar interaction and its ylidic
substituent preserves the double bond character. Thus, the
Sawamura-type mechanism is less likely for selenoboration
due to the kinetic hindrance associated with carbon-carbon
bond rotation.
Alternatively, there are two novel mechanistic proposals in the
recent literature for related anti selective additions of boron
compounds to alkynes. Nevertheless after close examination,
none of them can be used to explain the results of
Scheme 7. Novel mechanistic proposal for anti-3,4-addition of PhSe-Bpin to α,β-
acetylenic ester implying autocatalysis of one of the selenoborane substrate.
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The new mechanism is schematically presented in Scheme 7, As shown in Figure 3, the coordination of the second PhSe-
while Figures 3 and 4 show the free-energy profile and the key Bpin molecule to the ylidic carbon of D yielding intermediate F
intermediates and transition states, respectively. The first part is somewhat endergonic (+6.6 kcal·mol-1) and it has moderate
of the mechanism is analogous to Sawamura’s proposal. Then, free-energy barrier, 20.2 kcal·mol-1. Analogous to the first
once the intermediate
be completed in three new steps: (1) the ylidic carbon of
acts as Lewis base and coordinates a second selenoborane and it promotes the selenyl 1,4-migration to the electrophic
molecule to yield intermediate , (2) the terminal selenyl carboxylic carbon resulting in intermediate and the
stereoselectively form concomitant release of the phosphine. Thus, the migration of
, and (3) the 1,2-elimination of PhSe-Bpin the activated selenyl group has an accessible free energy
D
is formed, the catalytic process could selenyl migration, the boron coordination enhances the
D
nucleophilic character of –SePh moiety via a “push-pull” effect
F
G
undergoes
1,4-migration
to
intermediate
G
occurs at the carboxylic group to yield the final product and barrier (20.6 kcal·mol-1 from
F to TSF-G). This step is exergonic
11.7 kcal·mol-1
regenerate PhSe-Bpin species.
by 17.1 kcal·mol-1, laying the intermediate
below reactants.
G
O
B
O
O
MeO
O
B
C
Ph
O
O
Se
Ph
C
Se
O
C
O
Ph
B
MeO
Se
O
C
B
Ph
O
PMe3
Ph
O
C
Se
PMe3
Ph
O
O
B
C
C
C
PMe3
Se
O
MeO
Ph
C
O
O
B
O
Ph
OMe
O
C
C
C
TSF-G
Ph
Ph
O
PMe3
Se
C
TSC
26.5
MeO
B
Ph
Se
26.0
TS1P
Se
C
O
PMe3
Ph
1P
21.1
C
C
C
TSD-F
19.0
25.5
C
O
MeO
Ph
B
Ph
O
TSC-D
15.9
O
PMe3
C
C
C
TSG
C
MeO
Ph
11.1
11.8
+
F
O
B
Se Ph
O
O
5.4
O
Ph
B
O
B
Se
D
O
PMe3
O
O
C
0.0 PMe3
C
C
C
-1.2
MeO
MeO
Ph
O
+
O
B
C
C
C
Ph
Ph
O
C
Ph
O
O
Se
MeO
Se
MeO
Ph
G
C
C
B
Ph
-11.7
Ph
C
O
Se
PMe3
O
C
B
O
-16.8
OMe
C
PMe3
O
O
O
B
C
Se
+
MeO
O
C
O
Ph
Se
B
Se Ph
C
C
PMe3
+
Ph
O
Ph
PhSe
C
O
+
B
Ph
O
O
B
Se Ph
O
Fig. 3. Free-energy profile (kcal·mol-1) for the anti-3,4-addition of PhSe-Bpin to α,β-acetylenic ester via autocatalysis of selenoborane.
More interestingly, the overall reaction leads to the anti- A detailed description of all the possible conformational and
addition of selenyl and boryl moieties to the triple bond of the enantiomeric isomers is provided in Figure S2 of the
substrate (see Figure 4). The steroselectivity can be explained Supporting Information. As illustrated by Figure 5, to reach the
by analyzing the conformations of the species involved in the
F
transition state for the selenyl migration, TSF-G, the PhSe-Bpin
→
G
transformation (see Figure 5). Note that several moiety coordinated to the ylidic carbon and the carboxylic
conformational and enantiomeric paths can be considered. group need to be syn to each other, forcing the initially added
However, for simplicity of our analysis, we have only discussed selenyl moiety (green colored) and the subsequent added
the conformational isomers connecting directly with the boryl moiety (orange colored) to be anti to each other. Thus,
lowest-energy path, which progresses through structure TSF-G
.
although coordination of PhSe-Bpin through transition state
6 | J. Name., 2012, 00, 1-3
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TSD-F can yield different conformers of
F
species, only those
with syn carboxyl-PhSeBpin arrangement would be reactive,
and consequently, the formation of products with cis
arrangement of selenyl and boryl moieties is not possible
(Figure 5, down). Finally, intermediate
G undergoes 1,2-
elimination of a PhSe-Bpin, which is built from the fragments
of two different molecules of PhSe-Bpin yielding the anti 3,4-
selenoborated product.
The computed free-energy profile of the overall mechanism in
Figure
4 indicates that the rate-determining process
corresponds to the coordination of the second PhSe-Bpin
molecule to the ylidic carbon and subsequent 1,3-mitration of
the selenyl moiety to the carboxylic carbon (D + PhSe-Bpin →
TSF-G) with an overall computed free energy barrier about 27
kcal·mol-1. In the mechanism, the phosphine might play a dual
role. First, it coordinates to the
alkynoate inverting the polarity of the triple bond and
directing the selenyl addition to the -carbon of the alkyne.
β-acetylenic carbon of the
α
Second, it generates a nucleophilic ylide which is able to
coordinate a second PhSe-Bpin molecule through the Lewis
acidic boron atom. Interestingly, the PhSe-Bpin acts as
autocatalyst allowing the overall anti addition of selenyl and
boryl units, and regenerating from the fragments of two
different PhSe-Bpin species.
Fig. 4. Molecular structures and main geometric parameters (Å) of the intermediates
and transition states for the novel mechanism of anti-3,4-addition of PhSe-Bpin to α,β-
acetylenic ester.
Ph
Experimentally, while the addition of PhSe-Bpin takes place at
room temperature, the addition of B2pin2 and PhMe2Si-Bpin
requires up to 80 oC. Thus, it would be interesting to
rationalize the higher reactivity of selenoborane reagent and
to related this to its stereoelectronic properties. Recently, we
identified electronic and steric descriptors of trivalent boron
compounds which can be qualitatively and quantitatively
related to their nucleophilic reactivity.25 Similarly, here we
compare those descriptors in activated B-interelement
compounds using the methoxy group as a model of the Lewis
base: MeO-→Bpin-X (X = -SePh, -Bpin and -SiMe3). Replacing
the interelement fragment from Bpin and SiMe to SePh, its
negative charge (q[X]), measured as the sum of all the natural
bond order (NBO) atomic charges, increases significantly from
.00 and -.12 to -.56 a.u. Likewise, the interelement p/s
Ph
Bpin
O
Se
C
Se 1,3-migration
G = 20.6
MeO
pinB
TSF-G: ꢀ
PhSe
PMe3
F
5.4
PMe3
Ph
Bpin
O
NO reaction
Se
Bpin
C
MeO
Ph
SePh
3.7
Fig. 5. Schematic representation of the stereoselectivity-determining step yielding anti
isomer. Relative free-energies and barrier in kcal·mol-1
.
Finally, we carried out kinetic simulations in order to compare
the mechanistic proposal (Fig. 3) with the experimental results,
taking into account the differences in concentration of the
catalyst, the reagents and the solvent. Supporting Information
provides details on the simulation, in which rate constants
emerged from DFT free-energy results via Transition State
population ratio of atomic orbital in the B-X
σ bond increases
(from 2.1 and 1.1 for X = SePh and Bpin to 5.3 for X = SePh),
which could indicate that the more p character the more
reactive is the fragment as a nucleophile. On the other hand,
we did not appreciate significant differences in the measure of
the steric bulkiness of the molecular environment using the
distance-weighted volume (VW) parameter.26 Thus, both
electronic descriptors, q[B] and p/s, indicate that selenoborane
activated via a “push-pull” effect has an enhanced nucleophilic
character. This might favor key reaction steps such as the
migration of the selenyl moiety explaining why the reaction
can take place at room temperature.
Theory. The initially estimated yield for
α-selenoborated
product at room temperature after 8 h is very low (< 1%),
indicating that computed barriers are too high. Besides the
strong dependence of rate constants on computed energy
values, one possible reason could be the limitations of
phosphine modelling. In fact if we replace the model PMe3
phosphine by the experimental PCy3, the free-energy barrier
for the first step (TS1P) reduces by 3 kcal·mol-1. Applying this
correction factor for all the steps involving phosphine, the
estimated yield of becomes 50% in 8 h, in good agreement
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with the experimental one for the formation of 15 (63%, Bpin species allows to perform the reaction under mild
Scheme 5).
conditions.
Additionally, we performed an experimental kinetic analysis of
Experimental
the selenoboration of
1 following the reaction by NMR
spectroscopy (Figures S1 and S2). NMR conditions with larger
amount of THF solvent containing some quantity of water
Synthesis of alkynoates. An oven-dried Schlenk equipped with a
magnetic stir bar was charged with 2 mmol of the appropriate alkyne
o
and dissolved in 3 mL of THF. At -78 C, 1.05 eq. of nBuLi (1.6 M) were
(~0.021%) resulted in the formation of
product Z-8 that used water as protonation source. The overall
free-energy barrier for the -vinyl selenide 15 is somewhat
lower (27.2 or 24.2 kcal·mol-1 for corrected and non-corrected
values) than for
-vinyl selenide Z-8 (27.5 kcal·mol-1). However,
at the early stages of the reaction, in which concentration of
reactants is high, the formation of -isomer is faster because
the -isomer formation is slowed down by the low
β-selenoboration
added dropwise. After stirring for 30 min, 1 eq. of the chloroformate
or carbamoyl chloride was added drop wise. After 8 h stirring the
reaction was allowed to rise to room temperature and let it react
overnight. The reaction was quenched with 2mL of saturated Na2S2O4
and extracted 3 times with 5mL of DCM. All the organic layers were
collected and dry over MgSO4 and evaporated to dryness. The crude
α
β
β
1
residue was analysed by H NMR. Then the products were purified by
α
concentration of the phosphine catalyst. The kinetic simulation
at NMR conditions derived from the energy values of the
proposed mechanisms reproduces the main experimental
silica gel flash chromatography.
Synthesis of α,β-acetylenic amides. An oven-dried Schlenck equipped
with a magnetic stir bar was charged with 2 mmol of the appropriate
o
alkyne and dissolved in 3 mL of THF. At -78 C, 1.05 eq. of nBuLi (1.6
features including the sigmoidal profile of α-selenated product
15 (see Figure S3 and S4). Thus, we can conclude that the
kinetic simulations further support the proposed mechanism,
and that the nature of the solvent is important to determine
the selectivity of the reaction.
M) were added dropwise. After stirring for 30 min, 1 eq. of carbamoyl
chloride was added drop wise. After 8 h stirring the reaction was
allowed to rise to room temperature and let it react overnight. The
reaction was quenched with 2mL of saturated Na2S2O4 and extracted 3
times with 5mL of DCM. All the organic layers were collected and dry
over MgSO4 and evaporated to dryness. The crude residue was
analysed by 1H NMR. Then the products were purified by silica gel flash
Conclusions
We have shown that the regio- and the stereoselectivity of the chromatography.
addition of selenoboranes to -acetylenic esters and amides Spectral data of ethyl 3-(4-methoxyphenyl)propiolate (3). Flash
can be controlled through the activation mode of the column chromatography yielded (367.6 mg, 90 %) as a colourless oil.
substrates in the absence of transition metal complexes. The 1H NMR (CDCl3, 400 MHz) δ 7.53 – 7.49 (m, 2H), 6.87 – 6.84 (m, 2H),
non-catalyzed reaction provides access to
-vinyl selenides 4.26 (q, J = 7.1 Hz, 2H), 3.80 (s, 3H), 1.32 (t, J = 7.1 Hz, 3H). 13C {1H}
α,β
3
β
though 1,4-selenoboration promoted by the “push-pull” effect NMR (CDCl3, 100 MHz) δ 161.5, 154.4, 135.0, 114.3, 111.4, 86.9, 80.2,
of B by the ester group. The addition of catalytic amounts of 62.0, 55.4, 14.2. HRMS (ESI) for C12H13O3 [M+H]+: calculated: 205.0865,
PCy3 phosphine switches the reaction to the anti-3,4- found: 205.0862. Characterization data matches literature.27
selenoboration with delivery of
α
-vinyl selenides by Spectral data of propyl 3-(4-methoxyphenyl)propiolate (4). Flash
protodeboronation with MeOH. Computational studies column chromatography yielded
4
(388.5 mg, 89 %) as a yellowish oil.
discovered a novel mechanism (Scheme 7) which differs from 1H NMR (CDCl3, 400 MHz) δ 7.55 – 7.51 (m, 2H), 6.89 – 6.85 (m, 2H),
previous mechanistic proposals for analogous anti-selective 4.17 (t, J = 6.8 Hz, 2H), 3.82 (s, 3H), 1.77 – 1.68 (m, 2H), 0.98 (t, J = 7.4
carboboration, silaboration and diboration (Scheme 6). The Hz, 3H). 13C {1H} NMR (CDCl3, 100 MHz) δ 161.5, 154.6, 135.0, 114.3,
phosphine addition to the
the regioselectivity favoring the 1,3-selenoboration and the [M+H]+: calculated: 219.1021, found: 219.1018.
production of -selenated phosphorus-ylide intermediate. Spectral data of isopropyl 3-(4-methoxyphenyl)propiolate (5). Flash
Then, the autocatalytic action of a second PhSe-Bpin substrate column chromatography yielded
(379.8 mg, 87 %) as a white solid. 1H
β position of the alkynoate modifies 111.4, 87.0, 80.2, 67.6, 55.5, 22.0, 10.5. HRMS (ESI) for C13H15O3
α
5
determines the stereoselectivity and completes the anti-3,4- NMR (CDCl3, 400 MHz) δ 7.56 – 7.52 (m, 2H), 6.89 – 6.86 (m, 2H), 5.15
1
selenoboration reaction. Thus, the ylidic carbon coordinates a (hept, J = 6.3 Hz, H), 3.83 (s, 3H), 1.33 (d, J = 6.3 Hz, 6H). 13C {1H} NMR
second selenoborane molecule, which is activated via “push- (CDCl3, 100 MHz) δ 161.5, 154.1, 135.0, 114.4, 111.6, 86.6, 80.6, 69.9,
pull” effect to produce the 1,4-migration of the selenyl moiety 55.5, 21.9. HRMS (ESI) for C13H15O3 [M+H]+: calculated: 219.1021,
to electrophilic carboxylic carbon. The conformational found: 219.1017.
arrangement of the reacting selenyl and carboxyl groups Spectral data of 3-(4-methoxyphenyl)-N,N-dimethylpropiolamide (6).
imposes the resulting anti-stereoselectivity of the boryl and Flash column chromatography yielded
6 (281.1 mg, 92 %) as a
1
the selenyl groups. Finally, the 1,2-elimination of PhSe-Bpin colourless oil. H NMR (CDCl3, 400 MHz) δ 7.54 – 7.43 (m, 2H), 6.93 –
occurs at the carboxylic group to yield the final product and to 6.80 (m, 2H), 3.83 (s, 3H), 3.28 (s, 3H), 3.02 (s, 3H). 13C {1H} NMR
regenerate PhSe-Bpin. The proposed mechanism is further (CDCl3, 100 MHz) δ 161.0, 155.1, 134.2, 114.3, 112.6, 90.8, 81.0, 77.2,
supported by kinetic modelling using DFT free-energy values to 55.5, 38.6, 34.3. HRMS (ESI) for C12H14NO2 [M+H]+: calculated:
obtain rate constants. The larger nucleophilic character of the 204.1025, found: 204.1023.
SePh moiety compared to those in related B2pin2 and PhMe2Si- Spectral data of 3-(4-methoxyphenyl)-1-(pyrrolidin-1-yl)prop-2-yn-1-
one (7). Flash column chromatography yielded
7 (330.3 mg, 96 %) as a
8 | J. Name., 2012, 00, 1-3
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1
colourless oil. H NMR (CDCl3, 400 MHz) δ 7.52 – 7.45 (m, 2H), 6.90 – MHz)
1
7.26 – 7.20 (m, 2H), 7.09 – 6.95 (m, 5H), 6.60 (s, H), 6.58 –
δ
6.84 (m, 2H), 3.83 (s, 3H), 3.76 – 3.68 (m, 2H), 3.56 – 3.49 (m, 2H), 2.02 6.54 (m, 2H), 3.68 (s, 3H), 3.08 (brs, 6H). 13C {1H} NMR (CDCl3, 100
– 1.90 (m, 4H).13C {1H} NMR (CDCl3, 100 MHz) δ 161.0, 152.7, 134.3, MHz)
167.1, 159.3, 156.1, 135.9, 132.6, 130.8, 130.2, 128.3, 127.4,
114.3, 112.7, 89.3, 82.1, 77.2, 55.5, 48.3, 45.5, 25.6, 24.9. HRMS (ESI) 117.1, 113.0, 55.3, 24.9. HRMS (ESI) for C18H20NO2Se [M+H]+:
for C14H15NNaO2 [M+Na]+: calculated: 252.1000, found: 252.1001.
calculated: 362.0659, found: 362.0651.
δ
General Procedure for β-selenation of α,β-acetylenic esters and Spectral data of Z)-3-(4-methoxyphenyl)-3-(phenylselanyl)-1-
amides. In the glove-box, an oven-dried resealable vial equipped with (pyrrolidin-1-yl)prop-2-en-1-one (Z-14). Flash column chromatography
Z-14
a magnetic stir bar was charged with 0.2 mmol of the alkynoate or yielded
ynamide compound. Then, the vial was charged with 1.1 eq. of pinB- MHz)
(49.2 mg, 69 %) as a colourless oil. 1H NMR (CDCl3, 400
δ
7.25 – 7.20 (m, 2H), 7.08 – 7.03 (m, 1H), 7.01 – 6.93 (m, 4H),
o
SePh solved in 0.15mL of dry MeOH. After 16 h at 50 C the reaction 6.58 – 6.52 (m, 2H), 6.45 (s, 1H), 3.67 (s, 3H), 3.55 (brs, 4H), 1.93 (brs,
was evaporated to dryness. The crude residue was analysed by GC-MS 4H). 13C {1H} NMR (CDCl3, 100 MHz)
165.3, 159.2, 156.9, 136.2,
and 1H NMR using naphthalene as an internal standard. Then the 132.6, 130.9, 130.2, 128.3, 127.5, 117.6, 112.9, 77.2, 55.3, 46.4 (brs),
δ
products were purified by silica gel flash chromatography.
25.7 (brs). HRMS (ESI) for C20H22NO2Se [M+H]+: calculated: 388.0816,
Spectral data of ethyl (Z)-3-phenyl-3-(phenylselanyl)acrylate (Z-8)
.
found: 388.0811.
Flash column chromatography yielded Z-8 (49.0 mg, 74 %) as a General Procedure for the insertion of pinB-SeR into α,β-acetylenic
yellowish solid.1H NMR (CDCl3, 400 MHz) δ 7.25 – 7.20 (m, 2H), 7.11 – esters and amides. In the glove-box, an oven-dried resealable vial
1
6.96 (m, 8H), 6.32 (s, H), 4.30 (q, J = 7.1 Hz, 2H), 1.35 (t, J = 7.1 Hz, equipped with a magnetic stir bar was charged with 0.2 mmol of the
3H). 13C {1H} NMR (CDCl3, 100 MHz) δ 166.9, 161.4, 139.2, 136.4, 129.3, alkynoate
128.7, 128.5, 128.1, 128.0, 127.6, 117.1, 60.7, 14.5. HRMS (ESI) for tricyclohexylphosphine in 0.15ml of dry THF was added. After stirring
C17H17O2Se [M+H]+: calculated: 333.0394, found: 333.0391.
in the glove-box for 5 min the vial was charged with 1.1 eq. of pinB-
or
ynamide
compound.
Then,
15mol%
of
Spectral data of methyl (Z)-3-(phenylselanyl)non-2-enoate (Z-9). Flash SePh. After 16 h at room temperature the reaction was evaporated to
1
column chromatography yielded Z-9 (51.4 mg, 79 %) as a yellowish oil. dryness. The crude residue was analysed by GC-MS and H NMR using
1
1H NMR (CDCl3, 400 MHz) δ 7.69 – 7.65 (m, 2H), 7.43 – 7.38 (m, H), naphthalene as an internal standard. Then the products were purified
1
7.36 – 7.32 (m, 2H), 6.16 (s, H), 3.76 (s, 3H), 2.17 – 2.13 (m, 2H), 1.34 by silica gel flash chromatography.
– 1.26 (m, 2H), 1.17 – 1.10 (m, 2H), 1.05 – 0.97 (m, 4H), 0.79 (t, J = 7.3 Spectral data of ethyl (Z)-3-(4-methoxyphenyl)-2-(phenylselanyl)-3-
Hz, 3H).13C {1H} NMR (CDCl3, 100 MHz) δ 167.7, 164.4, 137.7, 129.3, (4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)acrylate (16)
129.2, 127.6, 113.2, 51.5, 37.9, 31.4, 29.8, 28.5, 22.5, 14.1. column chromatography yielded 16 (4.9 mg, 5 %) as a yellowish oil. H
Spectral data of ethyl (Z)-3-(4-methoxyphenyl)-3- NMR (CDCl3, 400 MHz) 7.29 – 7.35 (m, 3H), 7.19 – 7.16 (m, 3H), 6.92
(phenylselanyl)acrylate (Z-10). Flash column chromatography yielded – 6.88 (m, 2H), 4.01 (q, J = 7.2 Hz, 2H), 3.82 (s, 3H), 1.29 (s, 12H), 0.94
.
Flash
1
δ
1
Z-10 (52.0 mg, 72 %) as a yellowish oil. H NMR (CDCl3, 400 MHz)
1
δ
(t, J = 7.1 Hz, 3H). 13C {1H} NMR (CDCl3, 100 MHz)
7.24 – 7.21 (m, 2H), 7.11 – 7.07 (m, H), 7.04 – 6.95 (m, 4H), 6.58 – 134.5, 132.9, 131.6, 131.0, 129.9, 129.0, 127.2, 113.5, 83.9, 62.8, 55.4,
δ 169.4, 159.8,
1
6.54 (m, 2H), 6.30 (s, H), 4.28 (q, J = 7.1 Hz, 2H), 3.68 (s, 3H), 1.34 (t, J 25.0, 13.7. 11B NMR (128.3 MHz, CDCl3)
= 7.1 Hz, 3H). 13C {1H} NMR (CDCl3, 100 MHz) 166.9, 161.0, 159.6, C24H30BO5Se [M+H]+: calculated: 489.1352, found: 489.1358.
136.1, 131.8, 130.2, 129.7, 128.5, 127.9, 116.7, 113.0, 60.6, 55.3, 14.5. Spectral data of propyl (Z)-3-(4-methoxyphenyl)-2-(phenylselanyl)-3-
HRMS (ESI) for C18H19O3Se [M+H]+: calculated: 363.0499, found: (4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)acrylate (17)
Flash
column chromatography yielded 17 (23.1 mg, 23 %) as a yellowish oil.
(Z)-3-(4-methoxyphenyl)-3- 1H NMR (CDCl3, 400 MHz)
7.40 – 7.33 (m, 3H), 7.17 – 7.14 (m, 3H),
δ 28.3. HRMS (ESI) for
δ
.
363.0495.
Spectral
data
of
propyl
δ
(phenylselanyl)acrylate (Z-11). Flash column chromatography yielded 6.91 – 6.88 (m, 2H), 3.93 (t, J = 6.7 Hz, 2H), 3.82 (s, 3H), 1.41 – 1.32 (m,
1
Z-11 (54.0 mg, 72 %) as a yellowish oil. H NMR (CDCl3, 400 MHz)
7.24 – 7.22 (m, 2H), 7.11 – 7.07 (m, 1H), 7.03 – 6.95 (m, 4H), 6.57 – MHz)
6.54 (m, 2H), 6.31 (s, 1H), 4.19 (t, J = 6.7 Hz, 2H), 3.68 (s, 3H), 1.78 – (bs), 127.0, 113.4, 83.8, 68.6, 55.3, 25.0, 21.6, 10.3. 11B NMR (128.3
1.69 (m, 2H), 0.99 (t, J = 7.4 Hz, 3H).13C {1H} NMR (CDCl3, 100 MHz) 27.9. HRMS (ESI) for C50H62B2NaO10Se2 [2M+Na]+:
MHz, CDCl3)
δ
2H), 1.29 (s, 12H), 0.70 (t, J = 7.4 Hz, 3H). 13C {1H} NMR (CDCl3, 100
169.9, 159.8, 134.3, 132.3, 131.5, 131.2, 129.9, 129.0, 128.3
δ
δ
δ
167.0, 160.9, 159.5, 136.1, 131.7, 130.2, 129.7, 128.5, 127.8, 116.7, calculated: 1027.2757, found: 1027.2789.
113.0, 66.2, 55.3, 22.2, 10.6. HRMS (ESI) for C19H21O3Se [M+H]+: Spectral data of isopropyl (Z)-3-(4-methoxyphenyl)-2-(phenylselanyl)-
calculated: 377.0656, found: 377.0651.
Spectral data of isopropyl
3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)acrylate (18)
.
Flash
(Z)-3-(4-methoxyphenyl)-3- column chromatography yielded 18 (31.1 mg, 31 %) as a yellowish oil.
(phenylselanyl)acrylate (Z12). Flash column chromatography yielded 1H NMR (CDCl3, 400 MHz)
δ 7.41 – 7.36 (m, 3H), 7.18 – 7.15 (m, 3H),
1
Z-12 (51.8 mg, 69 %) as a yellowish oil. H NMR (CDCl3, 400 MHz)
1
6.92 – 6.89 (m, 2H), 4.85 (hept, J = 6.3 Hz, H), 3.82 (s, 3H), 1.29 (s,
δ
1
7.23 – 7.21 (m, 2H), 7.11 – 7.07 (m, H), 7.03 – 6.95 (m, 4H), 6.57 – 12H), 0.95 (d, J = 6.3 Hz, 6H). 13C {1H} NMR (CDCl3, 100 MHz)
δ 169.6,
1
6.53 (m, 2H), 6.27 (s, 1H), 5.17 (hept, J = 6.2 Hz, H), 3.67 (s, 3H), 1.32 159.9, 132.6, 131.5, 131.4, 130.0, 129.0, 128.3, 127.1, 113.4, 83.6,
(d, J = 6.3 Hz, 6H). 13C {1H} NMR (CDCl3, 100 MHz)
159.5, 136.1, 131.8, 130.2, 129.7, 128.5, 127.8, 117.2, 113.0, 67.9, for C25H31BNaO5Se [M+Na]+: calculated: 525.1327, found: 525.1332.
55.3, 22.2. HRMS (ESI) for C19H21O3Se [M+H]+: calculated: 377.0656, Spectral
data of (Z)-3-(4-methoxyphenyl)-N,N-dimethyl-2-
δ δ 27.8. HRMS (ESI)
166.5, 160.6, 71.3, 55.3, 25.0, 21.3. 11B NMR (128.3 MHz, CDCl3)
found: 377.0648.
Spectral data
(phenylselanyl)acrylamide (Z13)
(phenylselanyl)-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-
1
of
(Z)-3-(4-methoxyphenyl)-N,N-dimethyl-3- yl)acrylamide (23). No Isolated Product 23. H NMR (CDCl3, 400 MHz)
.
Flash column chromatography
δ
7.25 – 7.21 (m, 2H), 7.19 – 7.13 (m, 2H), 7.09 – 6.98 (m, 3H), 6.63 –
1
yielded Z-13 (54.8 mg, 76 %) as a colourless oil. H NMR (CDCl3, 400
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6.57 (m, 2H), 3.69 (s, 3H), 3.09 (brs, 6H), 1.06 (s, 13H).11B NMR (128.3 functional30 and a standard 6–311G(d,p) basis set.31 Full geometry
MHz, CDCl3) 27.3. optimizations were performed without constraints. The nature of the
Spectral data of (Z)-3-phenyl-2-(phenylselanyl)-1-(pyrrolidin-1-yl)-3- stationary points encountered was characterized either as minima or
(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)prop-2-en-1-one (24) transition states by means of harmonic vibrational frequency analysis.
7.24 – 7.19 (m, The zero-point, thermal, and entropy corrections were evaluated to
2H), 7.14 – 7.09 (m, 2H), 7.08 – 6.95 (m, 3H), 6.60 – 6.54 (m, 2H), 3.68 compute Gibbs Free energies (T=298 K, p=1 bar). The selected method
(s, 3H), 3.56 (brs, 4H), 1.92 (brs, 4H), 1.04 (s, 12H). is analogous to that reported in ref. 18 and it allows a straightforward
General Procedure for one pot -selenation of alkynoates. In the comparison of the results. The kinetic simulation was carried out with
δ
.
1
No Isolated Product 24. H NMR (CDCl3, 400 MHz)
δ
α
glove-box, an oven-dried resealable vial equipped with a magnetic stir the Acuchem software32 and all rate constants were calculated using
bar was charged with 0.2 mmol of the alkynoate or ynamide Eyring approximation and Transition State Theory.
compound. Then, 15 mol% of tricyclohexylphosphine in 0.15ml of dry
THF was added. After stirring in the glove-box for 5 min the vial was
Conflicts of interest
charged with 1.1 eq. of pinB-SePh . After 16 h at room temperature
the reaction was evaporated to dryness. The crude residue was solved
There are no conflicts to declare.
in 2 mL of THF and 0.2 mL of K2CO3 (2 M) water solution was added
dropwise. The reaction was heated to reflux for 2 h. Then the reaction
was extracted with DCM and filtered through a pad of Celite and
Acknowledgements
MgSO4. The solvent was removed and the residue was analysed by GC-
The present research was supported by the Spanish Ministerio
1
MS and H NMR using naphthalene as an internal standard. Then the
de Economia y Competitividad (MINECO) through projects
products were purified by silica gel flash chromatography.
CTQ2016-80328-P (EF) and CTQ2014-52774-P (JJC), by NSERC
Spectral data of ethyl (Z)-3-phenyl-2-(phenylselanyl)acrylate (19)
.
(SAW), and by the Generalitat de Catalunya though project
2014SGR199 (JJC).
Flash column chromatography yielded 19 (14.6 mg, 22 %) as a
1
1
yellowish oil. H NMR (CDCl3, 400 MHz)
2H), 7.42 – 7.37 (m, 5H), 7.22 – 7.19 (m, 3H), 4.07 (q, J = 7.1 Hz, 2H),
1.04 (t, J = 7.1 Hz, 3H). 13C {1H} NMR (CDCl3, 100 MHz)
166.8, 145.0,
δ 8.15 (s, H), 7.66 – 7.64 (m,
δ
Notes and references
138.4, 135.3, 134.4, 131.9, 130.4, 129.2, 128.3, 127.2, 124.5, 62.0,
13.9. HRMS (ESI) for C17H17O2Se [M+H]+: calculated: 333.0394, found:
333.0392.
1
For recent reviews in boron chemistry and its synthetic
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Spectral
(phenylselanyl)acrylate (20). Flash column chromatography yielded 20
(15.2 mg, 21 %) as a yellowish oil. 1H NMR (CDCl3, 400 MHz)
8.17 (s,
data
of
ethyl
(Z)-3-(4-methoxyphenyl)-2-
δ
2
3
H. Yoshida, ACS Catal. 2016, 6, 1799.
1H), 7.75 – 7.72 (m, 2H), 7.40 – 7.37 (m, 2H), 7.22 – 7.18 (m, 3H), 6.93 –
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6.90 (m, 2H), 4.08 (q, J = 7.1 Hz, 2H), 3.83 (s, 3H), 1.06 (t, J = 7.1 Hz,
3H). 13C {1H} NMR (CDCl3, 100 MHz)
δ 167.0, 161.0, 145.8, 132.7,
4
5
6
131.3, 129.8, 129.2, 127.7, 127.0, 113.8, 70.7, 61.9, 55.5, 14.0. HRMS
(ESI) for C18H19O3Se [M+H]+: calculated: 363.0499, found: 363.0507.
Spectral
data
of
propyl
(Z)-3-(4-methoxyphenyl)-2-
(phenylselanyl)acrylate (21). Flash column chromatography yielded 21
1
(9.7 mg, 13 %) as a yellowish oil. H NMR (CDCl3, 400 MHz)
δ 8.20 (s,
7
8
Y. Nagashima, K. Hirano, R. Takita, M. Uchiyama, J. Am.
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1H), 7.77 – 7.73 (m, 2H), 7.39 – 7.36 (m, 2H), 7.22 – 7.18 (m, 3H), 6.93
– 6.89 (m, 2H), 4.00 (t, J = 6.7 Hz, 2H), 3.83 (s, 3H), 1.53 – 1.44 (m, 2H),
0.81 (t, J = 7.4 Hz, 3H).13C {1H} NMR (CDCl3, 100 MHz)
δ 167.1, 161.0,
146.2, 136.0, 132.7, 131.0, 129.2, 127.7, 126.8, 120.4, 113.8, 67.6,
55.5, 21.9, 10.5. HRMS (ESI) for C19H21O3Se [M+H]+: calculated:
377.0656, found: 377.0651.
9
Spectral
(phenylselanyl)acrylate (22). Flash column chromatography yielded 22
(23.3 mg, 31 %) as a yellowish oil. 1H NMR (CDCl3, 400 MHz)
8.15 (s,
data
of
isopropyl
(Z)-3-(4-methoxyphenyl)-2-
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δ
1H), 7.73 – 7.70 (m, 2H), 7.40 – 7.37 (m, 2H), 7.23 – 7.17 (m, 3H), 6.94 –
6.90 (m, 2H), 4.91 (hept, J = 6.2 Hz, 1H), 3.84 (s, 3H), 1.04 (d, J = 6.3 Hz,
6H). 13C {1H} NMR (CDCl3, 100 MHz)
δ 166.5, 160.9, 145.3, 132.6,
131.4, 130.2, 129.2, 127.8, 126.9, 121.4, 113.8, 69.5, 55.5, 21.5. HRMS
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Computational details. Geometry optimizations and transition state
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10 | J. Name., 2012, 00, 1-3
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