Metal-free borylative ring-opening of vinyl epoxides and aziridines

Article abstract of DOI:10.1039/c3ob41328d

A rational approach towards the borylative ring-opening of vinylepoxides and vinylaziridines, by the in situ formed MeO^-→bis(pinacolato) diboron adduct, has been developed. The enhanced nucleophilic character of the Bpin (sp²) moiety

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Metal-Free Borylative Ring-Opening of Vinyl Epoxides and Aziridines
Xavier Sanz,a,b Graham M. Lee,a,c Cristina Pubill-Ulldemolins,*a,b Amadeu Bonet,a Henrik Gulyás,a
Stephen A. Westcott,c Carles Bo,*b Elena Fernández*a
Received (in XXX, XXX) Xth XXXXXXXXX 20XX, Accepted Xth XXXXXXXXX 20XX
5
DOI: 10.1039/b000000x
A rational approach towards the borylative ring-opening of vinyl- epoxides and vinylaziridines, by the in
situ formed MeO-→bis(pinacolato) diboron adduct, has been developed. The enhanced nucleophilic
character of Bpin (sp2) moiety from the reagent favours the SN2’ conjugated B addition with the
concomitant aperture of the epoxide and aziridine rings. The reaction proceeds with total
10 chemoselectivity towards the polyfunctionalised (-OH, or -NHTs) allyl boronate. Theoretical calculations
have determined the transition states that come from the reaction of the vinylic substrates with the
activated MeO-→bis(pinacolato)diboron adduct, and a plausible mechanism for the organocatalytic
borylative ring opening reaction has been suggested.
45
Introduction
15 The activation of tetraalkoxydiboron reagents, to selectively
transfer the boryl moiety to unsaturated substrates, has always
been associated with the cleavage of the B-B bond by transition
metal complexes. But outstanding advances in the field have
emerged from the simple activation of (RO)2B-B(OR)2 via Lewis
20 acid-base interactions, achieving an organocatalytic chemo-,
regio- and enantioselective control on the C-B bond formation.1
During the last few years, selective metal-free -boration2 and
diboration3 of activated and unactivated alkenes, respectively,
have illustrated the potential of this new methodology, but still
25 many other applications of boron addition reactions remain
unexplored. It is known that the borylative ring opening of
vinylcyclopropanes,4,5 vinyl- epoxides6,7 and vinylaziridines,4,6
has exclusively been studied by activation of pinB-Bpin or
(HO)2B-B(OH)2 with Pd, Ni and Cu complexes (Scheme 1). In
30 these transformations the mechanism has not been well
established but certain features indicate that the activation of the
diboron reagent could take place via -bond metathesis. This
assumption is mostly supported by the fact that base is required8
to guarantee the efficiency of the ring opening allylic borylation.
35
Scheme 1. Metal mediated borylative ring-opening of vinyl
epoxides and aziridines
Results and discussion
Based on our previously developed protocols, 2b,c,f we decided to
launch a study on the catalytic synthesis of allyl boronates,
excluding the application of transition metals, aiming at
50
40 establishing
a
convenient organocatalytic methodology.
Specifically, we focused our efforts to study the transfer of a
nucleophilic boryl unit,9 from an in situ formed MeO–
→bis(pinacolato)diboron adduct,2c,10 to vinyl epoxides and vinyl
aziridines (Scheme 2).
55
Scheme 2. Metal-free approach towards borylative ring-opening
of vinyl epoxides and aziridines
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Organic & Biomolecular Chemistry
Page 2 of 7
Considering 3,4-epoxy-1-cyclohexene (1) as a model substrate,
the nucleophilic pinacolboryl unit can attack three electron
deficient reactive sites, that is the C3 and C4 carbons of the
epoxide ring and the C1 carbon of the C=C double bond. We have
experimentally observed (Scheme 3) that following mixing 1 and
the in situ generated MeO-→bis(pinacolato)diboron adduct in the
presence of 10 mol% of PCy3, the nucleophilic pinacolboryl unit
View Article Online
DOI: 10.1039/C3OB41328D
60
5
exclusively attacked at the double bond providing the 1,4- 65 Scheme 4. Copper mediated chemoselective nucleophilic Bpin
cyclohexenyl hydroxyboronate (2) via a SN2’ pathway, within 6h
attack on the epoxide functional group of 3,4-epoxy-1-
cyclohexene (1). X-Ray structure of 4-hydroxy-cyclohex-2-enyl-
phenyl-methanol (6)
10 at room temperature (Table 1, entry 1). NaOMe was determined
to be the most efficient base to assist the in situ MeO-
→bis(pinacolato)diboron adduct formation. The organoborane 2
could be isolated and fully characterized. One single diastereomer
Table 1. Organocatalytic borylative ring-opening of vinyl
was formed in the reaction which was identified as the trans 70 epoxides and vinyl aziridines with B2pin2.
15 isomer by (i) oxidizing the C-B bond with NaBO3 (Scheme 3a)
and (ii) reacting 2 with benzaldehyde (Scheme 3b). The
stereostructures of the corresponding 1,4-diol (3) and 1,3-diol (4)
were determined by 1H NMR spectroscopy. When the
organocatalytic borylative ring-opening of 1 was carried out in
20 the absence of PCy3, only moderate conversion was observed
(55%, 6h). The essential contribution of basic phosphines to
enhance the nucleophilic B addition has already been studied.11
Interestingly, in a comparative study carried out using CuCl to
activate the B2pin2 we found that the transition metal catalyzed
25 reaction afforded the 1,2-cyclohexenyl hydroxyboronate (5) via
SN2 addition (Scheme 4). That is, the presence of Cu(I) and base,
favoured the formation of Cu-Bpin,[1,9] and the nucleophilic Bpin
moeity attacked the epoxy group, while the C=C double bond
remained intact (Table 1, entry 2). In this particular case, the
30 product 5 could not be isolated and therefore its stereoselectivity
was not determined, but its reaction with benzaldehyde provided
the cis-4-hydroxy-cyclohex-2-enyl-phenyl-methanol (6). The X-
Ray structure of 6 confirmed the cis arrangement of the 1,4-
subtituents on the disubstituted cyclohexene (Scheme 4). The
35 different reactivity observed between the copper mediated
borylation and the metal-free approach could be understood by
the relative increase in nucleophilic character of the Bpin moiety
when attached to Cu than when bonded to the sp3 Bpin
counterpart.9d However, the unexpected finding about the
40 stereoselectivity on compound 5 is still under study.
Entry Substrate
Product
Base
T (ºC)
t
Conv. Isolated
(mmol)
(h) (%) Yield
(%)
1a
NaOMe
(0.06)
25
25
25
25
6
6
6
6
99
72
71
20
62
OH
2
NaOMe
(0.03)
Bpin
NaOtBu
(0.03)
Cs2CO3
(0.03)
Cs2CO3
(0.06)
2b
25
6
88
72c
NaOMe
(0.06)
3a
4a
50
50
20
20
99
90
66
68
NHTs
NaOMe
(0.06)
13
Bpin
[a] Standard conditions: substrate (0.3 mmol), diboron reagent:
B2pin2 = bis(pinacolato)diboron, (0.45 mmol), PCy3 (0.03 mmol),
MeOH (2.5 mmol), THF (3 mL). [b] substrate (0.3 mmol),
diboron reagent: B2pin2 (0.45 mmol), CuCl (0.015 mmol), MeOH
75 (2.5 mmol), THF (3 mL). [c] Isolated as 4-hydroxy-cyclohex-2-
enyl-phenyl-methanol (6).
45
50 Scheme 3. Organocatalytic borylative ring-opening of 1 and
reactivity of the allylboronate 2 with NaBO3 and benzaldehyde
To survey the scope of the organocatalytic borylative ring-
opening methodology, we next studied the reaction between the
80 adduct
MeO-→bis(pinacolato)diboron
and
2-methyl-2-
vinyloxirane (7). We found that, as in the case of the cyclic
epoxide 1, the C-B bond was formed via a bimolecular allylic
substitution (Table 1, entry 3). The relative position of the
functional groups was established by oxidation of 2-methyl-4-
85 pinacolboryl-butenol (8) to the corresponding 2-methyl-1,4-
55
2
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Organic & Biomolecular Chemistry
butendiol (9) (Scheme 5). By comparison with reported 1H NMR 55 In order to get deeper insight into the mechanism of the
data for the E isomer of 9,12 we determined that 8, was formed as
the E isomer.
organocatalytic borylative ring-opening of vinyl epoxides and
aziridines, we carried out a DFT basDedOI:s1t0u.d1y03V9ioe/nwC3AtOrhtBiec4le1mO3n2al8iinnDe
intermediates and transition state. As our group has previously
shown,[2c,f],[3] the crucial additives for activating B2pin2 are
5
60 Brönsted
base
and
MeOH
to
generate
MeO-
→bis(pinacolato)diboron adduct. Also in the present case, this
adduct is key starting point in the general mechanism for the
base/alcohol borylative ring-opening of epoxides and aziridines
as depicted in Figure 1, which shows the elementary steps of the
65 reaction between B2pin2 and 3,4-epoxy-1-cyclohexene (1) as a
model substrate. First, the methoxide ion, generated from MeOH
in the presence of base, forms a Lewis acid-base adduct with the
diboron reagent, the MeO-→bis(pinacolato)diboron adduct,
which we chose as the origin of energies. In the next step, a
70 transition state (TS1) was fully characterized and described as an
SN2’ reaction that involves a nucleophilic attack of the adduct sp2
boron moiety at the C1 carbon atom of the double bond, in a
concerted manner with the concomitant opening of the epoxide
ring. This interaction was identified as the overlap between the
75 strongly polarized B-B σ bond (HOMO) of the activated diboron
reagent and the antibonding π* orbital (LUMO) of the vinyl
epoxide (Figure 2).
Scheme 5. Oxidation of the allylboronate 8 with NaBO3
10
Acyclic and cyclic 2-vinyl aziridines have been synthetized in
this work in order to compare the influence of the different
heteroatoms in the borylative ring-opening via SN2’ pathway.
15 Following the methodolody established in the literature,13 we
prepared the 3,4-aziridine-1-cyclohexene (10), 2-methyl-2-
vinylaziridine (11) and 3-methyl-2-vinylaziridine (12), via the
Evans-type direct monoaziridination of cyclohexadiene and 2-
methyl butadiene using [N-(p-toluenesulfonyl) imino]iodinane
20 (PhI=NTs) and Cu(acac)2. When the adduct MeO-
→bis(pinacolato)diboron reacted with 10, exclusive formation of
1,4-cyclohexenyl tosylaminoboronate (13) was observed (Table
1, entry 4). The isolation of compound 13 and comparison with
reported NMR data for this polyfunctionalised compound,[6]
25 allowed to be characterized as the trans isomer. In agreement
with the organocatalytic borylative ring opening reaction of 1,
these reactions are stereoselective for the trans isomer, although
in the case of the cyclic aziridine longer reaction time and a slight
increase in temperature were required for complete conversion
30 (Table 1, entry 4). Oxidation of 13 towards 1,4-cyclohexenyl
tosylaminoalcohol (14) confirmed the trans isomer formation.
The substrates 2-methyl-2-vinylaziridine (11) and 3-methyl-2-
vinylaziridine (12), were prepared as a 2:1 mixture and the
borylative ring opening reaction proceeded with total conversion
35 towards a mixture of amino functionalized allyl boronate
compouds, which could be isolated via oxidation as a mixture of
2-methyl-1-tosylamino-4-butenol and 3-methyl-1-tosylamino-4-
butenol (1:0.7)6 (Scheme 6). The prevalence of the borylative
ring-opening via SN2’ pathway has also been demonstrated in
40 these acyclic vinyl aziridines. It has to be said that by product
formation was not observed and the isolated yields of the
products were only moderate due to the instability of the
functionalized allylic boronate compounds.
MeO H
Borated
Product
base
O
O
O
O
B
B
MeO-
MeOH
Reactant
-
-
O
O
OMe
B
O
B
I
O
B
80
O
0.0 (0.0)
O
-28.7 (-29.4)
O
TS
21.9 (35.7)
O
-
O
B
OMe
O
B
O
O
MeO
B
Substrate
O
O
O
85 Figure 1. Proposed reaction pathway for the borylative ring-
opening of vinyl epoxides and vinyl aziridines with B2pin2.
Electronic energy and Gibbs free energy (in parenthesis)
computed at the BP86 level relative to B2pin2·MeO- adduct plus
3,4-epoxy-1-cyclohexene as a model substrate. All values in
90 kcal·mol-1
step a
step b
45
OH
OH
TsN
TsN
Bpin
Bpin
NaBO3
H2O
TsHN
TsHN
B2pin2
15
+
11
TsHN
TsHN
+
+
NaOMe, PCy3
THF
16
12
MeOH
(15/16 = 1.4 /1)
Conv: 99%
(11/12 = 2 /1)
Conv: 100%
I.Y.: 40%
95
50 Scheme 6. Borylative ring opening of 11 and 12, followed by in
situ oxidation. Step a: Substrate (0.3 mmol), diboron reagent:
B2pin2 (bis(pinacolato)diboron), (0.45 mmol), NaOMe (0.6
mmol), PCy3 (0.03 mmol), MeOH (2.5 mmol), THF (3 mL), r.t.,
6h.
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Organic & Biomolecular Chemistry
Page 4 of 7
the bond distances of the new C2=C3 bonds as well as the bond
angles C3-C4-O/N in the TS1 (Table 2, entry 1 and 2), it is clear
55 that the structures of the TS1 in the case of DthOeI:e1p0o.x10id3e9s/Cre3sOeBm41b3le28D
Transition State
View Article Online
B2pin2·MeO-
more the features of reactants in free form than the intermediate I.
Contrarily, the structural features of TS1 for aziridines are closer
to those of the intermediates I, that is the C2=C3 bond distances
are shorter than in the case of epoxides and the C3-C4-N bond
60 angles are larger (Table 2, entries 3, 4 and 5). Epoxides have an
early TS1 while tosyl aziridines have a late TS1. This can be
understood taking into account that the developed charge on the
nitrogen due to the charge redistribution upon the nucleophilic
attack is stabilized by the tosyl group.
HOMO
5
Epoxide
LUMO
65 This stabilizating effect of the tosyl group is also reflected in the
energy values of the TS1, there is a clear trend: the TS’s for
aziridines are less energetically demanding than for epoxides
(Table 3, entries A, B, C, D and E. Note that both ΔE≠ and ΔG≠
values are aprox. 9-10 kcal.mol-1 lower for aziridines than for
70 epoxides). Thus, tosyl aziridines seem to be more reactive than
epoxides to undergo the SN2’ borylative ring-opening process.
10 Figure 2. An illustration of TS1 frontier orbitals HOMO (red-
blue) and LUMO (orange-cyan) for 1.
The structural features of the TS1 clearly reflect the cleavage of
the B-B bond (from 1.701 in free B2pin2, to 1.755 in B2pin2·MeO-
15 , to 2.096 in TS1 (Å)), and the formation of the new B-C1 bond
(1.988 Å). Also, according to the C-C bond distances, an allylic
type rearrangement can be observed, the C1-C2 bond distance
increases (from 1.344 in the substrate to 1.417 in TS1) while the
C2-C3 bond distance decreases (from 1.483 in the substrate to
20 1.438 in TS1), suggesting the formation of the new C2=C3 double
bond. Importantly, the C3-C4-O angle increases only slightly from
the substrate to the transition state (60.6 and 67.9 respectively).
Although this is indicative of concomitant aperture of the epoxide
ring, regarding this parameters the transition state is rather early.
25 Remarkably, the enhancement of electron density in the oxygen
atom (Voronoi charge in the substrate -0.24 to -0.36 in the TS)
corroborates that charge redistribution has taken place. The TS1
structure releases the “(pin)BOMe” byproduct and directly leads
to formation of an anionic intermediate I in which the epoxide
30 ring is completely open (C3-C4-O angle 110.6, Voronoi charge in
the oxygen atom -0.74). Further protonation of this I species in
the presence of the excess of MeOH provide the desired allyl
boronate product, and in this way methoxide ions are regenerated.
Table 2. Molecular structures for TS1 with the vinyl epoxides
and aziridines. Selected bond distances (d) are given in Å and
bond angle (a) in º.
75
TS-like-reactants
TS-like-product
Entry Substrate d(C2-C3) d(C3-O)
 (C3-C4-O/N)
TS1
I
1
2
3
1.438
1.418
1.399
1.624
1.865
2.118
67.9
110.6
112.1
113.7
80.9
91.1
The configuration of the final allylboronate product was
35 exclusively characterized as the trans isomer since the nucleopilic
attack of the sp2 boron moiety to C1 occurs in anti with regard to
the epoxide functional group. In addition to considering the
different conformations of this TS1 and possible stereoisomers of
the substrate (See SI for more details), we did also evaluate the
40 attack in syn that would lead to the cis product. However, the
TS1-syn was found to be more energetically demanding
(ΔΔE=+5.8; ΔΔG=+4.3 kcal.mol-1) than TS1-anti (see SI for
more details). These computational findings are in well
agreement with the experimental data, since with all the studied
45 substrates, the trans allylboronate product was the only one
formed. Note that both transition sates, TS1 and TS1-syn were
located and characterized for the other substrates (1, 7, 10, 11 and
12, see SI), being the syn attack the more energetically
demanding in all the cases. Although the nucleophilic attack in
50 anti is the energetically favoured for all the considered substrates,
we did found notable structural differences between the TS1 for
vinyl epoxides and the analogous tosyl aziridines. Considering
TsN
TsN
4
5
1.410
1.410
2.207
2.102
96.0
90.5
112.1
110.4
11
12
80
4
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Organic & Biomolecular Chemistry
Table 3. Relative electronic energy (kcal.mol-1) and Gibbs energy
Table 4. Computed pKa values for the intermediate species.
(kcal.mol-1) for the activation of the studied vinyl epoxides and
aziridines[a].
View Article Online
DOI: 10.1039/C3OB41328D
Entry
1
I
pKa
Entry Entry in Substrate
Table 1
E≠
Er
G≠
Gr
35.6
34.5
22.3
23.6
A
B
C
D
E
1
2
3
4
5
21.9
-28.7
35.7
-29.4
(20.4) (-30.8)
(34.2)
(-31.4)
2
3
4
17.3
-30.3
31.0
-31.5
(16.1) (-30.7)
(29.8)
(-31.9)
11.2
-56.5
26.7
-54.4
(11.6) (-61.0)
(27.1)
(-58.9)
TsN
TsN
8.9
-59.4
25.3
-56.2
(10.8) (-59.6)
(27.1)
(-56.4)
11
12
For all the studied substrates, we also determined the energy
barrier for the nucleophilic attack of the MeO-
→bis(pinacolato)diboron adduct to the epoxide and aziridine
40 group, this is at C3 instead of at C1. In all the cases, the attack that
would give rise to unobserved products present higher energy
barriers than mechanism delineated above (See SI). Thus, the
presented computational results also corroborate the prevalence
of the borylative ring-opening via SN2’ in absence of Cu catalyst.
10.2
-64.2
27.0
-61.7
(14.3) (-64.5)
(31.0)
(-62.0)
[a] Molecular geometries for all the species were optimized
using BP86 as a functional. Single point energies at the
metahybrid M06 level are in parenthesis. Additional calculations
in the Supporting Information.
5
Also, the resulting anionic I species with tosyl aziridines are
thermodynamically more stable than the corresponding epoxides
45
10 derived (Table 3, entries A, B, C, D and E,ΔEr and ΔGr values,
difference of aprox. 30 kcal.mol-1). Remarkably, independently of
the DFT functional used or considering dispersion effects with
the M06 functional, or even including solvent effects (see SI) the
general trend remains equal: vinyl tosylaziridines seem more
15 reactive, and their products are more stable, than the
corresponding epoxides. Comparing the studied vinyl epoxides,
the energy barrier for the TS1 of the acyclic 2-methyl-2-
vinyloxirane (7) is lower than for the cyclic (1) (Table 3, entry A
respect to B, ΔΔE=-4.1; ΔΔG=-4.7 kcal.mol-1 lower). Aziridines
20 follow the same trend (Table 3, entry C respect to D, ΔΔE=-2.3;
ΔΔG=-1.4 kcal.mol-1 lower), being lesser energetically
demanding than epoxides. This result can be rationalized by the
fact that terminal double bonds are more reactive than internal
ones. Note the high stability of the aziridines derived
25 intermediates, in which the negative charge is stabilised by the
tosyl group.
Conclusions
We have developed a metal-free borylative ring opening of vinyl
epoxides and vinyl aziridines. The sole addition of B2pin2 with a
base
and
MeOH
provided
in
situ
the
MeO-
50 →bis(pinacolato)diboron adduct. As a consequence of this Lewis
acid-base interaction, the sp2 Bpin moiety acquired an enhanced
nucleophilic character that allowed the attack at the conjugated
C=C of epoxides or aziridines, throughout a SN2’ pathway.
Further functionalization of the allylboronate products via
55 oxidation or reactivity with benzaldehyde allowed to confirm the
stereostructures. From a theoretical point of view, we proposed a
plausible mechanism for the metal-free borylation of cyclic and
non-cyclic vinyl epoxides and aziridines. The mechanism is in
accordance with our experimental results and helps to understand
60 the role of each reagent in the reaction
We also calculated the pKa values for the anionic intermediate
species, and values are collected in Table 4. As expected, vinyl-
alkoxides are more basic that the corresponding vinyl-amidures.
30 At the same level of theory, we evaluated11 the pKa of the strong
Verkade’s base (23.4), value that almost matched the
experimental value (26.8). Values in Table 4 suggest that both
vinyl-amidures and vinyl-alkoxides are as basic, or even more,
than Verkade’s base, so also able to deprotonate methanol.
Acknowledgements
Research supported by the Spanish Ministerio de Economia y
Competitividad (MINECO) through project CTQ2010-16226 and
65 CTQ2011-29054-C02-02, the Generalitat de Catalunya
(2009SGR-00462) and the ICIQ Foundation. We thank
AllyChem for the gift of bis(pinacolato)diboron. SAW thanks
NSERC. We thank ICIQ facilities for the XRay diffraction.
35
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Page 6 of 7
Experimental Section
(R.f.=0.49). The product could be isolated in 80.3 mg (71%
55 yield).
View Article Online
General procedures for the Organocatalytic Borylative Ring-
Opening of Vinyl Epoxides and Vinyl Aziridines with B2pin2.
DOI: 10.1039/C3OB41328D
The oxidation protocol: The allyl boronates obtained in the
above described procedure were converted into the corresponding
alcohols in the following manner. To the crude organoboron
product (cc. 0.3 mmol) in THF (3 mL), sodium perborate (90 mg,
Borylation of 3,4-epoxy-1-cyclohexene (1). Organocatalytic
method: The phosphine PCy3 (9.54 mg, 10 mol%), sodium
5
methoxide (33.4 mg, 0.6 mmol) and bis(pinacolato)diboron (114 60 0.9 mmol) and water (3 mL) were added. The reaction mixture
mg, 0.45mmol) were transferred into an oven-dried Schlenk tube
under argon. THF (3 mL) was added. The mixture was stirred for
10 minutes at room temperature to dissolve the phosphine and the
was stirred vigorously overnight at room temperature. The
reaction mixture was diluted with water and then extracted with
dichloromethane (3 x 20mL). The combined organic phase was
dried over MgSO4 and concentrated. Product 3 was purified by
10 borane reagent completely. The substrate (33 L, 0.3 mmol) and
MeOH (100 l, 2.5 mmol) were added, and the reaction mixture 65 flash chromatography using a silica gel column with ethyl acetate
was stirred at room temperature for 6 hours. An aliquot of 0.2 mL
as eluent (R.f.=0.70). The product could be isolated in 32.5 mg
(95% yield). Product 9 was purified by flash chromatography
using a silica gel column with ethyl acetate as eluent (R.f.=0.75).
The product could be isolated in 27.6 mg (90% yield).
was taken from the solution and gently concentrated on a rotary
1
evaporator at RT, and analyzed by H-NMR showing that one
15 single product was formed from the substrate. The obtained 4-
cyclohexenyl hydroxyboronate (2) was purified by flash
chromatography using a silica gel column previously deactivated
with triethylamine, and a mixture of petroleum ether and ethyl
acetate (10:3) as eluent (R.f.=0.35). The product could be isolated
20 in 41.7 mg (62% yield).
70 4.Allylation reaction of allyl boronates with benzaldehyde:
The allyl boronates 2 and 5 obtained in the organocatalytic and
copper mediated borylation, respectively, were derivatized with
benzaldehyde. To the crude organoboron product (cc. 0.3 mmol)
in THF (3 mL), benzaldehyde (100 L, 0.9 mmol) was added.
Borylation of 2-methyl-2-vinyloxirane (7): The phosphine PCy3 75 The reaction mixture was stirred vigorously overnight at room
(9.54 mg, 10 mol%), sodium methoxide (33.4 mg, 0.6 mmol) and
bis(pinacolato)diboron (114 mg, 0.45mmol) were transferred into
an oven-dried Schlenk tube under argon. THF (3 mL) was added.
25 The mixture was stirred for 10 minutes at room temperature to
temperature. Product 4 was purified by flash chromatography
using a silica gel column with ethyl acetate as eluent (R.f.=0.80).
The product could be isolated in 56.4 mg (92% yield). Product 6
was purified by flash chromatography using a silica gel column
dissolve the phosphine and the borane reagent completely. The 80 and a a mixture of petroleum ether and ethyl acetate (7:3) as
substrate (33 L, 0.3 mmol) and MeOH (100 l, 2.5 mmol) were
added, and the reaction mixture was stirred at 50ºC for 20 hours.
The reaction mixture was cooled to room temperature. An aliquot
30 of 0.2 mL was taken from the solution and gently concentrated on
a rotary evaporator at RT, and analyzed by 1H-NMR to probe that
one single product was formed from the substrate. The obtained
2-methyl-4-pinacolboryl-butenol (8) was purified by flash
chromatography using a silica gel column previously treated with
35 triethylamine, and a mixture of petroleum ether and ethyl acetate
(1:1) as eluent (R.f.=0.42). The product could be isolated in 42.0
mg (66% yield).
eluent (R.f.=0.49). The product could be isolated in 38.6 mg
(63% yield).
DFT studies: Molecular structures for all species were optimized
without constraints using DFT-based methods as implemented in
85 the Amsterdam Density Functional (ADF v2009.01)
package.[14,15] A triple-ξ plus polarization Slater basis set was
used on all atoms. Relativistic corrections were introduced by
scalar-relativistic zero-order regular approximation (ZORA).[16]
For geometry optimizations we used the local VWN correlation
90 potential[17] together with the Becke exchange and the Perdew
correlation[18-20] (BP86) generalized gradient (GGA) corrections.
Stationary points in the potential energy hypersurface were
characterized either as minima or transition states by means of
harmonic vibrational frequency calculations. Solvent effects were
Borylation of 3,4-aziridine-1-cyclohexene (10): The phosphine
PCy3 (9.54 mg, 10 mol%), sodium methoxide (33.4 mg, 0.6
40 mmol) and bis(pinacolato)diboron (114 mg, 0.45mmol) were
transferred into an oven-dried Schlenk tube under argon. THF (3 95 introduced by using the continuous solvent model COSMO.[21]
mL) was added. The mixture was stirred for 10 minutes at room
temperature to dissolve the phosphine and the borane reagent
completely. The substrate (0.3 mmol) and MeOH (100 l, 2.5
45 mmol) were added, and the reaction mixture was stirred at 50ºC
for 20 hours. The reaction mixture was cooled to room
temperature. An aliquot of 0.2 mL was taken from the solution
and gently concentrated on a rotary evaporator at RT, and
analyzed by 1H-NMR to probe that one single product was
50 formed from the substrate. The obtained 1,4-cyclohexenyl
tosylaminoboronate (13) was purified by flash chromatography
using a silica gel column previously traeted with triethylamine,
and a mixture of petroleum ether and ethyl acetate (7:3) as eluent
Single-point energy evaluations at the metahybrid M06[22] level
were performed self-consistently.
Notes and references
100 a Department de Química Física i Inorgànica
Univ. Rovira i Virgili, C/ Marcel.lí Domingo s/n, 43007 Tarragona (Spain)
Fax: (+) 34 977 559563
E-mail: mariaelena.fernandez@urv.cat ,
http://www.quimica.urv.cat/tecat/catalytic_organoborane_chemistry.php
105 bInstitute of Chemical Research of Catalonia (ICIQ). Avda. Països Catalans, 17.
43007 Tarragona (Spain)
cDepartment of Chemistry and Biochemistry, Mount Allison University, Canada
6
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DOI: 10.1039/C3OB41328D
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