Enamine/butadienylborane cycloaddition in the frustrated Lewis pair regime

Article abstract of DOI:10.1039/c5ob01602a

The dienylborane 2a was prepared by regioselective alkyne hydroboration of the conjugated enyne 1a with Piers' borane [HB(C₆F₅)₂]. Its reaction with a series of acetophenone derived enamines 3 resulted in the formation of

Full text of DOI:10.1039/c5ob01602a

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Enamine/butadienylborane cycloaddition in the
frustrated Lewis pair regime†
Cite this: DOI: 10.1039/c5ob01602a
Guo-Qiang Chen,a Fatma Türkyilmaz,a Constantin G. Daniliuc,‡a
Christoph Bannwarth,§b Stefan Grimme,§b Gerald Kehra and Gerhard Erker*a
The dienylborane 2a was prepared by regioselective alkyne hydroboration of the conjugated enyne 1a
with Piers’ borane [HB(C6F5)2]. Its reaction with a series of acetophenone derived enamines 3 resulted in
the formation of the strong enamine β-carbon adduct with the borane Lewis acid (4). In contrast B–C
adduct formation between the dienylborane 2a and a series of much more bulky cyclohexanone derived
enamines (6) is rapidly reversible above ca. −30 °C and then leads to the formation of the [4 + 2]cyclo-
addition products 8. A DFT study revealed that this reaction is probably taking a stepwise route, proceed-
ing by means of enamine addition to the dienylborane terminus to generate a zwitterionic borata–alkene/
iminium ion intermediate that undergoes rapid subsequent ring closure. Heating of the products 8 led
to amidoborane elimination from the vicinal amino/borane pair at the product framework to give the
respective hexahydronaphthalene product 10. Subsequent treatment with TEMPO (2 equiv.) resulted in
selective oxidation of the unsaturated ring to give the respective tetrahydronaphthalene derivative 12.
Received 31st July 2015,
Accepted 19th August 2015
DOI: 10.1039/c5ob01602a
www.rsc.org/obc
ence of suitable trapping agents, such as dihydrogen.4 In some
examples we had observed effective H–H splitting directly
Introduction
Hydroboration of enamines with HB(C6F5)2 has provided a taking place from the enamine/HB(C6F5)2 adduct. This was
viable pathway for synthesizing vicinal N/B frustrated Lewis thought to take place by means of an “invisible” intermediate
pairs (N/B FLPs).1 Some of them have been used for small FLP which was actually never directly observed along the reac-
molecule binding and/or activation. Most notably this tion pathway. Scheme 1 shows a typical example.4,5
regarded the heterolytic splitting of dihydrogen to give the
We have now found that enamines may show a related be-
respective ammonium/hydrido-borate zwitterions, some of havior towards strongly electrophilic dienylboranes. In some
which provided a suitable basis for the development of active cases they just form stable adducts; in other cases this adduct
metal-free hydrogenation catalysts.2 However, the use of the formation is reversible, which opens up an interesting route to
enamine/HB(C6F5)2 entry was not completely unproblematic achieve a formal [4 + 2]cycloaddition reaction. On this account
since these systems tend to show a few side reactions. At the we report about some typical examples and discuss both the
stage of the actual N/B FLP, hydride abstraction from C–H uncommon reaction mechanism of this six-membered ring
units at the α-position to the amine by the adjacent borane
represented the most serious interference via typical FLP reac-
tivity,1,3 but complications could also arise at the very begin-
ning of the reaction sequence. The enamine β-carbon atom is
a nucleophile and, consequently, in many cases adduct for-
mation took place with the electrophilic borane. Fortunately,
this turned out to become reversible in some cases in the pres-
aOrganisch-Chemisches Institut, Universität Münster, Corrensstraβe 40,
48149 Münster, Germany. E-mail: erker@uni-muenster.de
bMulliken Center for Theoretical Chemistry, Institut für Physikalische und
Theoretische Chemie, Universität Bonn, Beringstraβe 4, 53115 Bonn, Germany
†Electronic supplementary information (ESI) available: Details of the DFT calcu-
lations and experimental details. CCDC 1411182–1411189. For ESI and crystallo-
graphic data in CIF or other electronic format see DOI: 10.1039/c5ob01602a
‡X-ray single crystal structure analyses.
§Computational chemistry.
Scheme 1
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formation and the synthetically significant follow-up reactions
of the resulting frameworks that contain vicinal amine/borane
pairs of complementary functional groups.
Results and discussion
Enamine/dienylborane adduct formation
We generated the starting materials dienylboranes 2a,b by
HB(C6F5)2 hydroboration of the conjugated enynes 3-methyl-
butenyne (1a) and 1-ethynylcyclohexene (1b).6,7 The reactions
were complete after 3 h at r.t. The hydroboration took place
selectively at the terminal carbon–carbon triple bonds of these
substrates and left the CvC double bond untouched.
Fig. 1 Molecular structure of the adduct 4a (thermal ellipsoids are
shown with 30% probability). Selected bond lengths (Å) and angles (°):
C1–N11, 1.304(3); C1–C2, 1.473(3); C2–B1, 1.697(3); C3–C4, 1.328(3);
C4–C5, 1.474(5); C5–C6, 1.335(6); N11–C1–C21, 120.1(2); N11–C1–C2,
124.3(2); C1–C2–B1, 114.2(1); B1–C3–C4, 128.7(2); C3–C4–C5, 126.3(4);
N11–C1–C2–B1, −104.2(2); C21–C1–C2–B1, 74.9(2); B1–C3–C4–C5,
−179.1(6).
We then treated the in situ generated conjugated dienyl
bis(pentafluorophenyl)borane 2a with the enamines 3a,b. The
reaction of 2a and the enamine 3a (see Scheme 2) was com-
plete within 1 h at r.t. in dichloromethane and the workup
gave the product 4a as a colorless solid in 81% yield. The X-ray
crystal structure analysis revealed that we had isolated the
Lewis acid/base adduct.8 The enamine had served as a carbon
nucleophile and was added to the electrophilic boron atom.
This resulted in a zwitterionic product containing an iminium
ion having the –B(dienyl)(C6F5)2 group at the β-carbon atom
(see Fig. 1). In solution the iminium/borate betaine shows a
typical borate 11B NMR signal and a characteristic iminium
13C NMR resonance (see Table 1). It shows three 19F NMR
signals of the B(C6F5)2 moiety with a small Δδ19Fm,p chemical
shift separation as it is usually found for such a C6F5 substi-
tuent containing borate moiety.9
The reaction of the enamine 3b with the dienylborane 2a
proceeded analogously to give the C–B adduct 4b as a colorless
solid in 70% yield. It shows typical NMR features similar to
those of compound 4a (see Table 1).
The enamine 3a was also exposed to the dienylborane 2b
(in situ generated). Again we observed rapid Lewis base and
Lewis acid addition product formation under our typical reac-
Table 1 Selected NMR features of the iminium/borate adducts 4 and 5a
4ab
NC5H10
4bc
NEt2
5d
NC5H10
NR2
δ
δ
11B
−10.9
−11.4
−11.1
13C:
C1
C2
194.9
41.8
196.4
41.3
194.4
41.4
C3
C4
C5
C6
143.7
135.6
144.5
112.7
142.8
135.1
144.3
112.6
138.3
135.8
137.4
125.9
δ1H:
3-H
4-H
3J(3H,4H)
6-H
6.50
5.73
17.7
4.80/4.66
6.46
5.74
17.6
4.80/4.66
6.32
5.54
17.4
5.40
a Chemical shift in ppm (δ scale). b In CD2Cl2 at 273 K. c In CD2Cl2 at
263 K. d In CD2Cl2 at 253 K.
tion conditions (r.t. dichloromethane, 1 h). The workup gave
the product 5 in ca. 80% yield (see Table 1 for selected NMR
data; additional data of compounds 4a,b and 5 are provided in
the ESI†).
Formation of cycloaddition products
Since it appeared that the enamines 3a,b were too basic and
strongly favored nucleophilic attack at the electrophilic boron
Lewis acid side of the dienylboranes 2a,b we used considerably
more bulky enamines pyrrolidino-, piperidino- and morpho-
linocyclohexene (6a–c) for reaction with the dienylborane
system 2a.10
We first investigated the reaction of the dienylborane 2a
with pyrrolidinocyclohexene. The dienylborane was generated
Scheme 2
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in situ by hydroboration of the enyne 1a with Piers’ borane its nucleophilic β-carbon atom. The product 7a contains an exo-
[HB(C6F5)2] in CD2Cl2 as usual and then the enamine (1 molar cyclic iminium ion moiety at the central six-membered ring and
equiv.) was added at −80 °C. Reaction control by 11B NMR the borate substituent at its α-position [θ N1–C7–C6–B1 96.4(2)].
spectroscopy revealed that the Lewis acid/Lewis base adduct The intact conjugated dienyl unit is attached to the boron atom.
7a was formed instantaneously. The mixture was slowly The alkenylborane subunit is E-configured and the dienyl
warmed up with 11B NMR control. The adduct turned out to be moiety is found in a planar s-trans conformation.
stable up to ca. −30 °C, but at −20 °C and above it rearranged
Since we had seen in the in situ NMR-experiment that in
rapidly and completely to a new species, which later was this case the adduct formation was apparently reversible and
positively identified as the cycloaddition product 8a (see the compounds eventually reacted to give the product 8a we
Scheme 3).
performed the reaction between 6a and 2a under conditions of
We were able to characterize the adduct 7a by X-ray diffrac- thermodynamic control.
tion (see Fig. 2). For this purpose we performed the reaction of
The in situ generated dienylborane 2a reacted with the
the enamine 6a with the dienylborane 2a in dichloromethane enamine 6a in dichloromethane solution at r.t. Workup after
at low temperature (−45 °C). A layer of pentane was carefully 1 h reaction time gave the product 8a in 76% yield. It was
added on top and the mixture was left at −45 °C for several characterized by spectroscopy and X-ray diffraction. Single crys-
days to give single crystals suitable for X-ray crystal structure tals for the X-ray crystal structure analysis were obtained from
analysis of compound 7a. It showed that even the bulky dichloromethane/pentane by the diffusion method. The struc-
enamine 6a had added to the Lewis acidic boron center through ture features the newly formed bicyclo[4.4.0]decene framework
with a CvC double bond between carbon atoms C3 and C4
(see Table 2 and Fig. 3). Carbon atom C4 also bears the methyl
Table 2 Selected structural parameters of the cycloaddition products 8a
8a
NC4H8
8b
NC5H10
8c
NC4H8O
NR2
B1–N1
C1–N1
B1–C2
C1–C2
1.687(2)
1.589(2)
1.640(2)
1.541(2)
1.329(3)
90.2(1)
84.2(1)
86.9(1)
90.9(1)
1.733(5)
1.588(4)
1.643(5)
1.525(5)
1.329(5)
91.6(3)
83.1(2)
86.2(2)
92.0(2)
1.758(3)
1.586(3)
1.641(3)
1.532(3)
1.318(3)
92.1(1)
82.5(1)
86.0(1)
92.1(1)
22.0(1)
C3–C4
C1–C2–B1
C2–B1–N1
B1–N1–C1
N1–C1–C2
B1–C2–C1–N1
B1–C2–C1–C6
Scheme 3
−21.8(1)
91.7(1)
−21.2(3)
94.4(3)
−93.4(2)
a Bond lengths in Å and bond angles in deg.
Fig. 2 A view of the molecular structure of the enamine/dienylborane
adduct 7a (thermal ellipsoids are shown with 50% probability). Selected
bond lengths (Å) and angles (°): N1–C7, 1.295(2); C6–C7, 1.478(2); B1–
C6, 1.715(2); B1–C1, 1.616(2); C1–C2, 1.335(2); C2–C3, 1.472(2); C3–C4,
1.337(3); N1–C7–C6, 121.7(1); C1–B1–C6, 106.3(1); C1–C2–C3, 126.4(2);
B1–C6–C7–N1, 96.4(2); C1–C2–C3–C4, −174.8(2).
Fig. 3 A view of the molecular structure of the cycloaddition product
8a (thermal ellipsoids are shown with 50% probability).
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substituent. There is a vicinal pair of pyrrolidino and B(C6F5)2
substituents attached at the bridgehead carbon atom C1 and
the adjacent carbon center C2. The boron Lewis acid and the
amine Lewis base make a rather strong contact.1 This pair of
substituents is found to be cis-attached at the bicyclic carbon
framework.
In solution compound 8a features a 11B NMR resonance in
the typical tetracoordinated borate range (see Table 3).9 There
is a single set of 1H and 13C NMR signals. The pairs of the
methylene hydrogens at the ring carbon atoms C5, C7–C10
and also of the pyrrolidino-CH2 groups are all pairwise diastereo-
topic. Due to the chirality of the compound the pair of C6F5
substituents at the tetracoordinated boron center is diastereo-
topic. There is hindered rotation around the B-C6F5 vectors at
low temperature and we monitored a total of 10 19F NMR
signals of the compound 8a in d2-dichloromethane below
263 K.11
Fig. 4 Molecular structure of the cycloadduct 8b (thermal ellipsoids
are shown with 30% probability).
The reaction of piperidinocyclohexene 6b with the dienyl-
borane 2a was performed analogously. It gave the cyclo-
addition product 8b after workup in 64% yield. The product
was characterized by C,H-elemental analysis, X-ray diffraction
and variable temperature NMR spectroscopy. It shows similar
structural features of the framework as derivative 8a. However,
the more bulky piperidino substituent has a considerably
weaker N1⋯B1 amine/borane interaction (see Table 2). The
piperidino substituent is found in the usual chair confor-
mation. At the tetracoordinated ammonium center in com-
pound 8b it is the borane moiety that in the solid state
structure is orientated axially and the carbon substituent (C1)
is arranged equatorially (see Fig. 4).
we observe a decoalescence phenomenon that eventually leads
to the observation of a second isomer (8b′). Each of the
isomers then gave rise to the observation of 10 19F NMR reso-
nances. At 213 K in CD2Cl2 the isomer ratio was ca. 2 : 1.
We assume that we have observed slowing down of the
conformational piperidine chair interconversion on the
19F NMR time scale, which gives rise to the observation of
one isomer having the boron atom attached axially at the
ammonium nitrogen (as it was found in the crystal), whereas
the other isomer has the boron atom equatorially attached (see
Scheme 4, for further details see the ESI†).
The reaction of morpholinocyclohexene (6c) with the dienyl-
borane 2a took a similar course. In this case the product 8c
was isolated in 83% yield. The X-ray crystal structure ana-
lysis again showed a conformational arrangement at the
ammonium nitrogen center that shows the N–B vector orien-
tated axially. In solution we again detected a pair of confor-
mational isomers at low temperature (193 K) in a ratio of
In solution compound 8b shows the typical NMR features.
Due to the molecular chirality the C6F5 groups at the tetra-
valent borate are diastereotopic and give rise to a pair of p-C6F5
19F NMR signals. Lowering the temperature resulted in the
observation of several decoalescence processes. First of all we
see that the rotation around the B-C6F5 vectors becomes hin-
dered and eventually “frozen” in the 19F NMR time scale. Then
Table 3 Selected NMR spectroscopic features of the cycloaddition products 8a
8ab
Pyrrolidino
8bc
Piperidino
8cd
Morpholino
R2N
δ
δ
11B
3.2
2.7 [2.7]
2.2 [2.2]
13C:
C1
C2
C3
C4
75.5
36.8
122.1
126.5
22.8
32.8
75.9 [78.2]
34.3 [25.8]
121.0 [124.8]
126.1 [125.7]
22.4 [24.1]
31.0 [38.0]
75.8 [79.1]
33.7 [25.4]
120.2 [125.0]
126.1 [125.1]
22.2 [23.8]
30.4 [38.7]
CH3
C6
δ1H:
2-H
3-H
5-H
6-H
2.72
5.45
2.09/1.62
2.48
5.0, 5.9
2.89 [2.91]
5.30 [5.38]
2.08/1.50 [2.45/1.61]
2.31 [2.22]
7.1, 6.6, 5.4, 4.7 [6.5, 4.9, 4.6, 4.0]
2.88 [2.94]
5.28 [5.39]
2.06/1.51 [2.08/1.66]
2.27 [2.33]
7.5, 7.1, 5.7, 5.0 [6.7, 5.3, 4.7, 4.2]
19
Δδ
F
mp
a Chemical shift in ppm (δ scale). b In CD2Cl2 at 299 K. c In CD2Cl2 at 213 K; major [minor] isomer. d In CD2Cl2 at 193 K; major [minor] isomer.
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Scheme 4
Scheme 5
ca. 5 : 1, each of them showing a total of 10 19F NMR signals
due to hindered rotation around the B-C6F5 vectors (for details
see the ESI†).
tional with the large def2-QZVP basis set and the atom-pair-
wise D3(BJ) dispersion correction.17–19 A modified rigid-rotor
harmonic-oscillator treatment was used to account for
rotational–vibrational contributions to the free energy using
harmonic frequencies from
a corrected minimal basis
DFT (Density Functional Theory) analysis of the dienylborane/
enamine cycloaddition reaction
Hartree–Fock method (HF-3c),18,21–23 while solvation contri-
butions were included by means of the COSMO-RS(2012)
approach.24,25
There are two principal mechanistic alternatives to be taken
into account for the dienylborane 2a plus enamine conver-
sions to the cycloaddition products 8. This could be a con-
certed [4 + 2]cycloaddition reaction. In this case it would
correspond to a Diels–Alder reaction with inverse electron
demand since the enamines 6 are certainly quite electron rich
dienophiles.12 Then the question remains whether the attach-
ment of the single (C6F5)2B substituent at the diene terminus
would make this component electron poor enough to bring
the overall reaction into a reaction rate regime as it was experi-
mentally observed.
Our results are shown in Fig. 5. Our DFT results strongly
disfavour that this reaction proceeds via a concerted [4 + 2]cyclo-
addition since the resulting transition state is predicted to be
more than 50 kcal mol−1 in Gibbs free energy (ΔG‡) above the
reactants (for details see the ESI†). A two-step procedure is,
however, reasonable. The highest barrier was found for the first
step (i.e., the formation of the intermediate 9) and has a ΔG‡ of
about 15 kcal mol−1. The zwitterionic compound 9 is slightly
A stepwise reaction pathway would be an attractive alterna-
tive, because it had been observed (and recently quantified)
that boranes enable carbanion formation thermodynamically
and markedly favored at their α-position.13 The resulting α-boryl-
carbanions must rather be regarded as borata–alkenes due to
the substantial delocalization of the negative charge with the
adjacent borane Lewis acid.14–16 We had recently shown that
this stabilizing effect is especially pronounced for the
[(C6F5)2BvCHR]− borata–alkene situation.13 A recent DFT
study has shown that (C6F5)2B-CH3 is as CH acidic as cyclopenta-
diene (pKa ≈ 18 in DMSO solution). Therefore, addition of
the enamine to the terminal dienylborane position giving the
zwitterionic intermediate 9 must be considered as an alterna-
tive to the concerted [4 + 2]cycloaddition reaction. Subsequent
nucleophilic attack of the borata–alkene carbon atom at the
adjacent iminium ion functionality of the intermediate 9
would directly lead to the observed product 8 (see Scheme 5).
We were able to distinguish and decide between these
alternatives by a computational analysis of the system 2a + 6c
→ 8c employing dispersion-corrected DFT methods.17–22 For
Fig. 5 Energy diagram for the conversion of the dienylborane 2a and
the enamine 6c to the product 8c. The values given are computed Gibbs
free energies (ΔG/ΔG‡) in kcal mol−1 (for details see the ESI†). Electronic
single-point energies, we used the PW6B95 hybrid meta func- energies are obtained at the PW6B95-D3(BJ)/def2-QZVP level.
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higher in free energy compared with the separate reactants 2a
and 6c (ΔG ∼ 6 kcal mol−1). The second addition proceeds
with a small barrier of about 4 kcal mol−1 (w.r.t. the zwitterion
9) and the respective transition state is roughly 10 kcal mol−1
higher in free energy than the initial reactants. A significant
difference between both reaction pathways is the existence/
absence of the B–N Lewis adduct. It is present in the geometry
of the concerted transition state, thus weakening the electron-
withdrawing effect of the borane as well as the electron-
donating effect of the amine. In the two-step mechanism no
Lewis adduct is formed until the very end and therefore, the
formation of the zwitterionic intermediate 9 (see Scheme 5) is
not hindered.
In this case we have also calculated the relative energy (ΔG)
of the enamine/borane (C/B) adduct 7c. It is energetically
roughly as stable as the separate species 2a and 6c (ΔG ∼
+1 kcal) at room temperature. This means that it is slightly
more stable than the alleged intermediate 9 but much less
as compared to the final product 8c. The relative stability
computed here for compounds 7c, 8c and intermediate 9
is therefore in qualitative agreement with the experimental
observation made for the homologues 7a and 8a.
Fig. 6 Molecular structure of the amidoborane elimination product 11c
(thermal ellipsoids are shown with 15% probability). Selected bond
lengths (Å) and angles (°) from molecule A: B1–N1, 1.369(8); N1–C4,
1.464(1); N1–C1, 1.482(2); B1–N1–C1, 123.7(1); B1–N1–C4, 126.4(1);
B1–N1–C1–C2, 123.1(1); C11–B1–N1–C4, 179.2(1); C21–B1–N1–C1,
174.8(1).
Subsequent reactions
Although the N⋯B contact in compound 8c seems to be rather
loose, the system shows a tendency towards R2N-B(C6F5)2 elim-
ination.26,27 On a preparative scale this was cleanly achieved by
maintaining the cycloaddition product 8c in toluene solution
at 120 °C for 3 h. Workup involving filtration through silica
eventually gave the bicyclic cyclohexadiene derivative 10 as a
colorless oil in 82% yield (Scheme 6). The compound shows
13C NMR signals of the conjugated diene subunit at δ 138.9
(C1), 117.4 (C2), 118.6 (C3) and 132.7 (C4), respectively, with
the corresponding 1H NMR resonances at δ 5.47 and 5.46
(each m, each 1H, 3,2-H). The 1H NMR resonances of the
bridgehead C6-H unit occurs at δ 2.29 (13C: 36.7). Compound
10 shows a methyl 1H NMR resonance at δ 1.71 (for further
details see the ESI†). The amidoborane elimination product
11c was also isolated and it was characterized by X-ray diffrac-
tion (see Fig. 6).
Scheme 7
The bicyclic conjugated 1,3-diene system 10 was converted
to the aromatic methyl tetrahydroindenyl derivative 12.
Heating of the starting material 10 with two molar equivalents
of TEMPO28–30 for 4 days at 95 °C in benzene solution resulted
in a slow conversion to the arene derivative 12 by means of a
sequential hydrogen atom abstraction reaction by the persist-
ent nitroxyl radical with formation of the diamagnetic reaction
product TEMPOH (see Scheme 7).
The pyrrolidino and piperidino substituted cycloaddition
products 8a and 8b underwent the analogous reaction under
comparable conditions. We isolated the product 10 in these
cases as colorless oils in 54% and 79% yields, respectively (for
details see the ESI†).
Compound 12 was isolated in 51% yield. It shows three sep-
1
arate H NMR signals of the hydrogen atoms at the aromatic
nucleus [δ1H: 6.91, 6.88, and 6.79; 13C: δ 129.3, 126.6, 130.0].
The 1H NMR signal of the 3-CH3 group occurs at δ 2.16 (for
further details see the ESI†).
Conclusions
The reaction between the dienylboranes 2 and enamines seems
to be sensitive to steric bulk of the reagents. The dienylboranes
2 can apparently serve as strong boron Lewis acids as well
as carbon electrophiles. The enamines used in this study all
behaved as typical carbon nucleophiles or carbon Lewis bases,
respectively. The sterically non-encumbered acetophenone
Scheme 6
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based enamines 3 all formed strong boron–carbon Lewis borata–alkene/phosphonium product 14, which was isolated
acid/base adducts. So far we have not found any indication of and structurally characterized by X-ray diffraction.15,16 It seems
their transformation to cycloaddition products under equili- that this reaction as well as the recently reported uncatalyzed
brium conditions.
hydrophosphination of the dienylborane 2a to give the fru-
The more bulky cyclohexanone derived enamines 6 behave strated Lewis pair 16 represent a situation quite similar to the
differently. The reaction between pyrrolidinocyclohexene 6a here proposed nucleophilic enamine addition reaction to the
and the dienylborane 2a was shown to actually give the B–C dienylborane terminus (see Schemes 5 and 8).13,33,34
Lewis acid/base adduct at low temperature, but this is a weak
In a way the borata–alkenes themselves resemble enolate
adduct that rapidly dissociates upon warming. This seems to anions as they add to carbonyl groups and analogues and may
be a typical situation under frustrated Lewis pair control, subsequently proceed on to a condensation step (see the for-
namely weak reversible Lewis acid/base contact formation fol- mation of 11).35 Since the borata–alkenes contain one carbon
lowed by another reaction pathway under equilibrium con- atom less than the enolate anions their reactions eventually
ditions.31,32 Consequently, at temperatures above −30 °C we lead to “Umpolungs”-products, such as the formally 1,6-di-
have observed the formal [4 + 2]cycloaddition product for- substituted amino/boryl substituted products 8. But as already
mation between 6a and 2a to give compound 8a for this pointed out we do not want to drive this notion too far since
specific example.
the products 10 eventually could not be structurally distin-
The formation of the products 8 from the dienylboranes 2 guished from normal Diels–Alder products, were it not for the
and the enamines 6 can formally be regarded as [4 + 2]cyclo- very high calculated activation barrier of the concerted dienyl-
addition products. The result of our DFT study is not crucial borane plus enamine [4 + 2]cycloaddition reaction.
for the synthetic outcome of the reaction, but is essential for
The products 8 each feature a vicinal pair of enamine/
understanding its mechanistic course. It points out that in borane substituents at the newly formed framework. In the
this case the concerted Diels–Alder reaction is characterized by examples looked at in our study this led to a favorable R2N-B-
a very high activation barrier, despite the actually favorable (C6F5)2 elimination reaction upon heating to give the respect-
fact that the diene/ene orientation is prefixed by the prevailing ive hexahydronaphthalene derivatives 10 that contain a newly
B–N contact. But it might actually be that the electronic formed conjugated diene unit inside the framework. Sub-
consequences of that contact may have rendered the overall sequent treatment with TEMPO as a hydrogen atom abstract-
energetic situation rather unfavorable by converting an ing oxidant selectively converted 10 to the aromatic
energetically unfavorable Diels–Alder situation of inverse elec- tetrahydronaphthalene derivative 12. This sequence indicates
tron demand into an equally unfavorable Diels–Alder situation that the dienylborane plus enamine cycloadduct forming reac-
of usual electron demand but with only weakly inductively tion may have some synthetic relevance, and it will be useful
interacting substituents at both the diene and the dienophile.5 to explore the scope and application potential of this reaction
It may actually be that the preferred favorable B–N contact in some detail.
makes the electronics of the [4 + 2]cycloaddition transition
state unfavorable [ΔG‡calc ≥ 50 kcal mol−1].23,24
On the other hand the favored stepwise pathway according
to the DFT study might be substantially profiting from the
Experimental section
For general information and details of the characterization of
the compounds, see the ESI.†
high electronic stabilization of the resulting borata–alkene
functional group.13 We had previously shown that the addition
of the internal phosphane nucleophile to the adjacent dienyl-
borane in 13 (see Scheme 8) yields a stable zwitterionic
Preparation of compound 4a
A solution of the enyne 1a (21.0 mg, 0.32 mmol, 1 eq.) in
dichloromethane (1 mL) was added to a stirred suspension of
bis(pentafluorophenyl)borane (110 mg, 0.32 mmol, 1 eq.) and
dichloromethane (1 mL). After stirring the reaction mixture for
3 h at room temperature, a solution of the enamine 3a
(59.0 mg, 0.32 mmol, 1 eq.) in dichloromethane (1 mL) was
added to the yellow suspension. Before removal of the volatiles
in vacuo, the reaction mixture was stirred for 1 h at room temp-
erature. Then the obtained residue was washed with n-pentane
(2 × 1 mL) twice. Drying of the obtained solid in vacuo gave
compound 4a as a colorless powder (154 mg, 0.26 mmol,
81%). Crystals suitable for X-ray crystal structure analysis were
obtained at room temperature from a solution of compound
4a in dichloromethane covered with n-pentane. Anal. Calc. for
C30H24BF10N: C, 60.12; H, 4.04, N, 2.34. Found: C, 60.35;
H, 4.26; N, 2.23.
Scheme 8
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Preparation of compound 4b
Preparation of compound 8c
Following the procedure described for the generation of com- Following the procedure described for the generation of com-
pound 4a, the enamine 3b (78.0 mg, 0.44 mmol) in dichloro- pound 8b, compound 2a [0.36 mmol, in situ prepared by the
methane (1 mL) reacted with compound 2a [0.44 mmol, in situ reaction of bis(pentafluorophenyl)borane (123 mg) with the
prepared by the reaction of bis(pentafluorophenyl)borane enyne 1a (24.0 mg)], reacted with morpholinocyclohexene
(153 mg) with the enyne 1a (29.0 mg)]. Compound 4b was iso- (59.0 mg, 0.36 mmol) in dichloromethane (1 mL) to give color-
lated as a colorless powder (128 mg, 70%). Crystals suitable for less crystals of compound 8c (171 mg, 83%) which were suit-
X-ray crystal structure analysis were obtained from a solution able for X-ray crystal structure analysis. Anal. Calc. for
of compound 4b in dichloromethane at room temperature. C27H24BF10NO: C, 55.98; H, 4.18; N, 2.24. Found: C, 55.28;
Anal. Calc. for C29H24BF10N: C, 59.31; H, 4.12; N, 2.38. Found: H, 4.01; N, 2.35.
C, 58.92; H, 3.75; N; 2.33.
Generation of compound 10
Preparation of compound 5
For example: after heating a solution of compound 8b
(320 mg, 0.55 mmol, 1 eq.) in toluene (2 mL) at 120 °C for 3 h,
the reaction mixture was filtered twice through a column
(SiO2). Removal of the volatiles of the filtrate in vacuo gave
compound 10 as a colourless oil (65 mg, 0.44 mmol, 79%).
Following the procedure described for the generation of com-
pound 4a, the enamine 3a (54.0 mg, 0.29 mmol) in dichloro-
methane (1 mL) reacted with compound 2a [0.44 mmol, in situ
prepared by the reaction of bis(pentafluorophenyl)borane
(100 mg) with enyne 1b (31.0 mg)]. Compound 5 was isolated
Preparation of compound 12
as
a colorless powder (116 mg, 81%). Anal. Calc. for
A solution of compound 10 (205 mg, 1.38 mmol, 1 eq.) in
benzene-d6 (0.5 mL) was added to a solution of TEMPO
(432 mg, 2.77 mmol, 1 eq.) in benzene-d6 (1 mL). The reaction-
mixture was stirred for 4 days at 95 °C. After filtration (four
times) through a short silica column all volatiles were removed
in vacuo to give compound 12 as a yellow oil (103 mg,
0.70 mmol, 51%).
C33H28BF10N: C, 61.99; H, 4.41; N, 1.69. Found: C, 60.6;
H, 4.21; N, 1.69.
Preparation of compound 8a
The enyne 1a (33.0 mg, 0.5 mmol) and bis(pentafluorophenyl)-
borane (173 mg, 0.5 mmol) were dissolved in dichloromethane
(5 mL). The solution was stirred at r.t. for 3 h. Then the pyrroli-
dinocyclohexene 6a (75.6 mg, 0.5 mmol) was added and the
reaction mixture was stirred at r.t. for 1 h. After removal of the
volatiles in vacuo, pentane (2 mL) was added. The solid of the
resulting suspension was collected and washed with pentane
(2 × 1 mL) to give compound 8a in 76% yield (214 mg,
0.38 mmol). Crystals suitable for X-ray crystal structure analy-
sis were obtained by slow diffusion of pentane to a solution of
compound 8a in dichloromethane at −35 °C. Anal. Calc. for
C27H24BF10N: C 57.57; H 4.29; N 2.49. Found: C, 56.98; H, 3.93;
N, 2.72.
Acknowledgements
Financial support from the European Research Council (ERC)
and the Deutsche Forschungsgemeinschaft (DFG) is gratefully
acknowledged.
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