Face to face activation of a phenylselenium borane with α,β-unsaturated carbonyl substrates: Facile synthesis of C-Se bonds

Article abstract of DOI:10.1039/c4cc02098g

Activated olefins directly react with a phenylselenium borane, at room temperature, without any metal or organocatalytic assistance. Up to 10 examples of β-(phenylseleno) substituted ketones and aldehydes have been prepared and theoretical evidence for the mechanism opens up non-existing pathways to create C-heteroatom bonds as a general tool. This journal is the Partner Organisations 2014.

Full text of DOI:10.1039/c4cc02098g

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Face to face activation of a phenylselenium
borane with a,b-unsaturated carbonyl substrates:
facile synthesis of C–Se bonds†
Cite this: Chem. Commun., 2014,
50, 8420
Received 20th March 2014,
Accepted 3rd June 2014
Xavier Sanz,ab Christopher M. Vogels,c Andreas Decken,d Carles Bo,*b
Stephen A. Westcott*c and Elena Fernandez*a
´
DOI: 10.1039/c4cc02098g
www.rsc.org/chemcomm
Activated olefins directly react with a phenylselenium borane, at room the selenol PhSeH and one equivalent of the borane HBpin.4
temperature, without any metal or organocatalytic assistance. Up to Complete conversion of the starting materials to 1 was achieved
10 examples of b-(phenylseleno) substituted ketones and aldehydes have selectively using 0.02 mol% of RhCl(PPh3)3. Compound 1 was
been prepared and theoretical evidence for the mechanism opens up characterized using a number of physical methods including
non-existing pathways to create C–heteroatom bonds as a general tool. multinuclear NMR spectroscopy. A peak in the 11B NMR spectra of
1 at 33 ppm is consistent with a three-coordinate RBpin group.5,6
Recently, there has been considerable interest in the generation of The selenium boron species 1 was also characterized by a single
organoselenium compounds for their extensive applications in crystal X-ray diffraction study, and the molecular structure is shown
organic synthesis, materials science, ligands for transition metals in Fig. 1. The Se–B distance of 1.950(3) Å is somewhat shortened
and even as therapeutic agents.1 Of particular significance is the compared to that of previous carborane examples, which tend to be
synthesis of selenium substituted carbonyl compounds which are greater than 2.0 Å.3a–e Complete crystallographic details, including
well known to act as enone b-anion synthons.2 Routes to these bond distances and angles, are included in the ESI.†
remarkable compounds either suffer from low yields and/or harsh
Quaternization of one boron atom in species containing B–B and
reaction conditions utilizing the sensitive and malodorous selenols. B–E bonds (E = elements from group 14) facilitates the heterolytic
A study by Leonard and Livinghouse showed that novel monomeric cleavage of these stable bonds.5 The pull–push effect of diboranes,
selenium boron compounds, derived from dialkylboranes, could be silaboranes and aminoboranes when reacted with bases, by forming
used as a gentle and efficient alternative to the starting selenols.2c the corresponding Lewis acid–base adducts [Nu-B(OR)2–B(OR)2],6
8
Unfortunately, reactions with bulky a,b-unsaturated carbonyl com- [Nu-B(OR)2–SiMe2Ph]7 and [Nu-B(OR)2–NR2 ], facilitates the
0
pounds gave the corresponding organoselenium products in low release of a boryl, silyl or amine moiety with enhanced nucleophilic
yields, presumably due to the steric congestion arising from the character. However, their reactivity with olefins, even activated
bulky borane group. While selenium boron compounds derived olefins such as a,b-unsaturated carbonyl compounds, has
from carboranes are well known,3 the synthetic potential of these always required the assistance of bases, principally alkoxides
simple compounds has not yet been fully realised. As a result, we (ꢀOMe, ꢀOtBu) or N-heterocyclic carbenes, to activate the B–B,
decided to prepare the analogous compound from pinacolborane B–Si or B–N reagent. Now, we have found that the simple addition of
(HBpin, pin = 1,2-O2C2Me4) and examine its reactivity with a number a,b-unsaturated carbonyl compounds to the selenium boron species
of a,b-unsaturated carbonyl compounds.
PhSeBpin (1) selectively promotes the PhSe transfer (Scheme 1).
The selenium boron species PhSeBpin (1) was prepared by the
room temperature metal catalysed dehydrogenative borylation of
a
´
´
`
Department Quımica Fısica i Inorganica, University Rovira i Virgili,
C/Marcelꢁli Domingo, s/n, Tarragona, Spain. E-mail: mariaelena.fernandez@urv.cat
b
¨
Institute of Chemical Research of Catalonia (ICIQ), Avda. Paısos Catalans, 16,
43007 Tarragona, Spain. E-mail: cbo@iciq.cat
c Department of Chemistry and Biochemistry, Mount Allison University, Sackville,
Fig. 1 Ball and stick diagram of 1 with hydrogen atoms omitted for clarity.
Selected bond distances (Å): Se(1)–C(1) 1.923(3), Se(1)–B(1) 1.950(3), B(1)–
O(2) 1.349(4), B(1)–O(1) 1.349(3); selected bond angles (1): C(1)–Se(1)–B(1)
103.69(12), O(2)–B(1)–O(1) 115.2(2), O(2)–B(1)–Se(1) 118.3(2), O(1)–B(1)–
Se(1) 126.5(2), B(1)–O(1)–C(7) 105.9(2), B(1)–O(2)–C(8) 106.9(2).
NB, Canada. E-mail: swestcott@mta.ca
d Department of Chemistry, University of New Brunswick, Fredericton, NB, Canada
† Electronic supplementary information (ESI) available. CCDC 991941. For ESI
and crystallographic data in CIF or other electronic format see DOI: 10.1039/
c4cc02098g
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Table 1 Conjugate addition of the PhSe moiety to a,b-unsaturated
ketonesa
Conv.b I.Y.
Entry Substrate
1
Product
Solvent (%)
(%)
CHCl3
27
Scheme 1 Hypothetical reactivity of phenylselenium boranes with a,b-
unsaturated ketones and aldehydes.
2
Benzene 30
Remarkably, this direct addition does not require the presence
of a transition metal complex, base or even co-solvent, such as
MeOH, unlike other E-Bpin additions.
3
THF
THF
THF
THF
THF
THF
THF
THF
THF
THF
40
24
29
69
67
99
95
78
65
41
35
With the aim of activating 1 and selectively transferring the
PhSe moiety to electron deficient olefins, we first attempted
to find the optimal conditions for the conjugate addition of
4-phenyl-3-buten-2-one (2). When the reaction was carried out
in chloroform, benzene and THF as solvents, at room tempera-
ture, a low percentage of the b-(phenylseleno) substituted ketone
was observed (Table 1, entries 1–3). An excess of PhSeBpin reagent
(1.5 eq.) or higher reaction temperatures (60 1C) did not improve
the product formation.
4c
5d
6
49
60
54
49
70
31
39
The influence of other a,b-unsaturated ketones on the prepara-
tion of b-(phenylseleno) substituted ketones was next examined. As
shown in Table 1, the substrate trans-1-phenyl-2-buten-1-one (4)
was more efficiently converted into the corresponding product 5
(Table 1, entry 6) than the analogue 4-phenyl-3-buten-2-one (2)
(Table 1, entry 3) under the same reaction conditions. Substrates
with a Ph group bound to the CQO (4 and 6) were converted into
the 1,4-product with better conversion values (Table 1, entry 7).
More remarkably, the aliphatic ketones 1-penten-2-one (8) and
4-hexen-3-one (10), which contain an ethyl group bonded to the
carbonyl group, were quantitatively transformed into the corres-
ponding b-(phenylseleno) substituted ketones 9 and 11 with up
to 99% conversion (Table 1, entries 8 and 9). For the bulkiest
aliphatic ketones, 3-hepten-2-one (12) and 3-nonen-2-one (14),
the conversion diminished slightly (Table 1, entries 10 and 11),
probably as a consequence of the more hindered b-position.
Next, we turned our attention to explore the b-selenation of
a,b-unsaturated aldehydes. In the case of cinnamaldehyde (16),
the conjugate addition of PhSe was similar to the same reaction
on 4-phenyl-3-buten-2-one (2), indicating that the functional
groups ketone or aldehyde do not provide a significant difference
in the CQO interaction with Bpin (Table 1, entries 3 and 12).
When the substrate was the aliphatic aldehyde crotonaldehyde
(18), quantitative transformation into the desired product was
observed (99%, Table 1, entry 13), however the conjugate addition
of PhSe on trans-2-hexenal (20) (Table 1, entry 14) was diminished.
Unfortunately, when a,b-unsaturated esters were subjected to the
same reactivity, the corresponding b-(phenylseleno) substituted
esters were not formed.
7
8
9
10
11
12
13
THF
THF
99
53
68
50
14
a
Reaction conditions: substrate (0.10 mmol), PhSeBpin (1.1 eq.), THF
b
(2 mL), 25 1C, 16 h. Conversion calculated by NMR spectroscopy from
an average of two assays. PhSeBpin (1.5 eq.). T = 60 1C.
c
d
proposed reaction pathway (Gibbs free energy profile in the gas
In order to establish a rational understanding of the reac- phase) for the reaction of 1 with 3-penten-2-one, chosen as
tion outcome we carried out theoretical studies by means of the model substrate. In the first step, the carbonylic oxygen
DFT methods including dispersion effects (M06-2X, see ESI†) to interacts with the empty p orbital of the boron atom, in the
unravel the mechanism of this new reaction of PhSeBpin (1) same way as other nucleophiles (alkoxides, carbenes), thus
with a,b-unsaturated carbonyl compounds. Scheme 2 shows the increasing the nucleophilic character of the PhSe moiety.
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Fig. 2 Optimized structures of TS1, I1, TS2 1_2 and TS2 1_4 with the
selected geometric parameters in Å.
Scheme 2 Proposed reaction pathway for the reaction of PhSeBpin (1)
with 3-penten-2-one. All energies are in kcal molꢀ1
.
Indeed, the first intermediate is formed (I1, Se–B = 2.089 Å,
B–O = 1.619 Å, O–C2 = 1.244 Å) which lies 9.1 kcal molꢀ1 above
that of the reactants. Note that the electronic energy profile of
this intermediate is 5.8 kcal molꢀ1 more stable than the two
separated entities, and it is raised in free energy because of the loss
of translational entropy. All Gibbs free energy values provided in the
manuscript do not include any additional correction. We located a
transition state (TS1, Se–B = 2.039 Å, B–O = 1.899 Å, O–C2 = 1.234 Å)
for the formation of intermediate I1, which reflects the
activation of the Se–B bond, whereupon the bond distance was
computed to be Se–B (1.953 Å) in the free reagent. The next step is
the boron–selenium bond cleavage, which is concerted with respect
to the attack of the nucleophilic selenium on the electrophilic
substrate through a second transition state. Thus, selenium can
attack either the b position (TS2 1_4) or the carbonylic carbon (TS2
1_2). In TS2 1_4 it can be observed that the Se–B distance increases
(Se–B = 2.170 Å) while the B–O distance decreases (B–O = 1.551 Å).
The electronic rearrangement of the double bond can be observed
by the increase of the O–C2 bond (O–C2 = 1.281 Å) and the decrease
of the C2–C3 bond distances (DC2–C3 = ꢀ0.06 Å). In TS2 1_2 the
increase of the Se–B bond (Se–B = 2.223 Å) distance can be observed
as well as the decrease of the B–O (B–O = 1.539 Å) and increase of
the O–C2 bond (O–C2 = 1.282 Å). The optimized structures of TS1,
I1, TS2 1_2 and TS2 1_4 are shown in Fig. 2.
Fig. 3 Relative Gibbs free energies of the most relevant species in the
reaction of 3-penten-2-one with PinBSePh (1) and its S and O analogous.
same conditions. However, it is important to mention that in the
case of the oxygen analogues the pathway is clearly different than
the other two: no TS1 was located, and the reaction would occur in
only one step. Moreover, the activation energy in this case is much
higher than that for the Se and S species, and the reaction would
lead to a product that is even less stable than the reactants. Based
on these theoretical arguments, we expect that the reaction will
probably work for the S–B reagent derivative under the same
reaction conditions as observed with the selenium reagent, but it
will not work for an oxygen equivalent based reagent.
Indeed, these predictions have been confirmed experimentally
for the analogous thioboration reaction. The reagent PhSBpin (22)4
was added to 4-hexen-3-one (10) in THF as the solvent, at room
temperature, in the absence of any additive. After 16 h the PhS
moiety was directly and quantitatively transferred to the activated
olefins, to form the corresponding 5-phenylsulphanyl-hexan-3-one
(23) after work-up, as a result of the 1,4-addition reaction (Scheme 3).
The simplicity of the chemical operation confirms the theoretical
prediction, but also opens a useful methodology to generate orga-
nosulfur compounds in a facile and highly efficient way, which
contrasts with all the previous reports involving 1,4-addition of thiols
to a,b-unsaturated carbonyl compounds that require additional
catalysts or bases.10,11 Additional experimental studies are currently
underway, particularly with cyclic a,b-unsaturated carbonyl ketones,
the results of which will be disclosed in due course.
It is important to highlight that the 1,4-addition pathway is less
energetically demanding than the 1,2-addition, and also it leads to a
more stable intermediate I2 1_4 which, after protonation, becomes a
more stable b-selenated ketone (P 1_4). In all the cases studied
(Table 1) the corresponding seleno-alcohol P 1_2 was never experi-
mentally observed. Therefore, the 1,4-addition product P 1_4 is
obtained due to both kinetic and thermodynamic reasons.
At this point we decided to explore theoretically the reaction
of the same substrate, 3-penten-2-one, with the sulphur
(PinBSPh) and oxygen (PinBOPh) analogues of PinBSePh (1).
Fig. 3 plots graphically the relative Gibbs free energies of the
TS1, I1, TS2 1_4 and I2 1_4 structures for selenium, sulphur
and oxygen borane reagents.9 Note that the energies for PinB-
SePh and PinBSPh are very similar, almost identical, and this
would indicate that both reactions might take place under the
Scheme 3 Extrapolated reactivity of PhSBpin to a,b-unsaturated ketones
on the basis of theoretical prediction of direct 1,4-addition reaction.
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The direct reactivity between p-phenylselenium pinacolborane
(PhSeBpin) and a,b-unsaturated ketones or aldehydes opens a non-
existing pathway towards the selective synthesis of b-(phenylseleno)
substituted carbonyl compounds. The substrate scope of the
a,b-unsaturated ketones or aldehydes is wide and includes cyclic
and acyclic substrates.12 DFT studies propose a plausible mecha-
nism for the reaction and explain the high selectivity towards the
1,4-addition product. Moreover, predictions were made on the
reactivity of the sulphur and oxygen analogues. Eventually, an
example of the direct reaction between PhSBpin and 4-hexen-3-one
corroborates that selenium and sulphur follow the same pathway in
the facile 1,4-addition to a,b-unsaturated carbonyl compounds.
This research has been supported by the Spanish Ministerio de
Economia y Competitividad (MINECO-CTQ2010-16226, CTQ2011-
29054-C02-02), the Generalitat de Catalunya 2009SGR-00259, the
ICIQ Foundation, the Natural Sciences and Engineering Research
Council of Canada and Mount Allison University. X. Sanz thanks
URV-ICIQ for the grant.
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12 Under the same reaction conditions described in Table 1, the cyclic
a,b-unsaturated ketone 2-cyclopente-1-one and 2-cyclohexen-1-one
were transformed into the b-seleno adducts (65% and 93% conver-
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