Hydroaminoalkylation of Allenes

Article abstract of DOI:10.1055/s-0037-1611790

The first examples of early-transition-metal-catalyzed hydroaminoalkylation reactions of allenes are reported. Initial studies performed with secondary aminoallenes led to the identification of a suitable titanium catalyst and revealed that under the reaction conditions, the initially formed hydroaminoalkylation products undergo an unexpected titanium-catalyzed rearrangement to form the thermodynamically more stable allylamines. The assumption that this rearrangement involves a reactive allylic cation intermediate provides a simple explanation of the fact that no successful early-transition-metal-catalyzed hydroaminoalkylations of allenes have previously been reported. As a result of the generation of the corresponding cation, the titanium-catalyzed intermolecular hydroaminoalkylation of propa-1,2-diene unexpectedly gives an aminocyclopentane product formed by incorporation of two equivalents of propa-1,2-diene.

Full text of DOI:10.1055/s-0037-1611790

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J. Bielefeld et al.
Letter
Synlett
Hydroaminoalkylation of Allenes
Jens Bielefeld
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Steffen Mannhaupt
Marc Schmidtmann
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Sven Doye*
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Institut für Chemie, Universität Oldenburg,
Carl-von-Ossietzky-Straße 9-11, 26111 Oldenburg,
Germany
doye@uni-oldenburg.de
Received: 27.11.2018
Accepted after revision: 24.03.2019
Published online: 10.04.2019
To provide a first proof of principle for the assumption
that, in principle, allenes might be suitable substrates for
hydroaminoalkylation reactions, we chose aminoallene 1 as
a substrate (Scheme 1) and we achieved a successful intra-
molecular hydroaminoalkylation. For this purpose, we
screened a variety of titanium-based catalysts (Figure 1)5a–f
that have already been successfully applied in hydroamino-
alkylation reactions of alkenes, 1,3-dienes, and styrenes. In
this context, it must be noted that we expected the forma-
tion of 2-vinylcyclopentane-1-amine 2, the cyclohex-2-en-
1-amine 3, and the 2-methylenecyclohexane-1-amine 4
(Scheme 1) as the hydroaminoalkylation products, because
DOI: 10.1055/s-0037-1611790; Art ID: st-2018-b0773-l
Abstract The first examples of early-transition-metal-catalyzed hy-
droaminoalkylation reactions of allenes are reported. Initial studies per-
formed with secondary aminoallenes led to the identification of a suit-
able titanium catalyst and revealed that under the reaction conditions,
the initially formed hydroaminoalkylation products undergo an unex-
pected titanium-catalyzed rearrangement to form the thermodynami-
cally more stable allylamines. The assumption that this rearrangement
involves a reactive allylic cation intermediate provides a simple explana-
tion of the fact that no successful early-transition-metal-catalyzed hy-
droaminoalkylations of allenes have previously been reported. As a re-
sult of the generation of the corresponding cation, the titanium-
catalyzed intermolecular hydroaminoalkylation of propa-1,2-diene un-
expectedly gives an aminocyclopentane product formed by incorpora-
tion of two equivalents of propa-1,2-diene.
C
C
Ti-catalyst
N-H and
C-H activation
[Ti]
Key words allenes, amines, C–H activation, homogeneous catalysis,
titanium, hydroaminoalkylation
titana-
aziridine
NH
N
p-Tol
p-Tol
1
insertion
Transition metal-catalyzed hydroaminoalkylation reac-
tions of alkenes with secondary or tertiary amines,1 which
involve C–H bond activation at the -carbon atom of the
amine,2 have attracted a great deal of attention during the
past decade. Whereas the use of group 3 metal catalysts3 is
limited to reactions of tertiary amines, late-transition-met-
al catalysts4 usually require the presence of a directing
group on the nitrogen atom of the amine. On the other
hand, the optimization of group 45 and group 56 metal-
based catalyst systems has resulted in significant progress
with regard to the scope of the alkene and amine, as well as
the activity of the catalyst. However, corresponding reac-
tions of other unsaturated substrates such as allenes or
alkynes have not been reported. This is regrettable because,
in particular, the conversion of allenes into allyl- or homo-
allylamines would offer simple possibilities for further
functionalization of the remaining C–C double bond.
3
2
1
N
[Ti]
N
[Ti]
p-Tol
p-Tol
protonolysis
at C-3
protonolysis
at C-1
NH
NH
NH
p-Tol
p-Tol
p-Tol
2
3
4
Scheme 1 Possible pathways for the titanium-catalyzed intramolecular
hydroaminoalkylation of aminoallene 1
© Georg Thieme Verlag Stuttgart · New York — Synlett 2019, 30, A–E

B
J. Bielefeld et al.
Letter
Synlett
corresponding cyclization reactions of aminoalkenes are
known to take place by a 5-exo-trig or a 6-exo-trig path-
way.5a,7
agreement with the ratios of 4 and 5 determined by GC
analysis of the crude reaction mixtures after 2.5 hours (4/5
= 91:9) and 24 hours (4/5 = 23:77). The products 4 and 5
could easily be identified by NMR analysis. For example, the
presence of the exomethylene group of 4 was strongly sup-
ported by two singlet signals in the 1H NMR spectrum
( = 4.77 and 4.84 ppm) and a corresponding signal for an
olefinic CH2 group in the 13C NMR spectrum ( = 106.7
ppm). In addition, the C–H group at position  to the N-
From a mechanistic point of view, the key intermediate
for the reaction is expected to be a titanaaziridine (Scheme
1),2 which should be capable of inserting one of the two C–
C double bonds of the allene moiety into its Ti–C bond. In-
sertion of the internal double bond should then deliver a
five-membered ring-containing vinyltitanium species,
which should finally give the 2-vinylcyclopentane-1-amine
2 after protonolysis. On the other hand, insertion of the ter-
minal double bond should result in a six-membered ring-
containing an allyltitanium intermediate. In this case, pro-
tonolysis of the allyltitanium species might take place in
the 1- or 3-position8 and, as a consequence, formation of
the two six-membered cyclic products 3 and 4 should occur.
During a catalyst screening, performed with Ti(NMe2)4,
Ti(NEt2)4, Ind2TiMe2 (Ind = η5-indenyl), the aminopyridina-
to titanium complexes I–III, and the formamidinato com-
plex IV (Figure 1) at temperatures between 100 °C and 170
°C, we first found that IV, originally a polymerization cata-
lyst synthesized by Eisen and co-workers,9 was the only ac-
tive catalyst for the conversion of 1 into a hydroaminoal-
kylation product.
1
atom of 4 is consistent with a H NMR signal at  = 3.71
ppm (dd) with an integral of one proton and a 13C NMR sig-
nal for a C–H group at  = 57.1 ppm. In contrast, the 1H NMR
and 13C NMR spectra of 5 showed signals for a CH2 group
adjacent to the N atom ( = 3.50 ppm, s, 2 H;  = 51.0 ppm,
CH2), and only one olefinic C–H group ( = 5.58–5.60 ppm,
m, 1 H;  = 122.9 ppm, CH).11
Table 1 Intramolecular Hydroaminoalkylation of Aminoallene 1 at 160
°C in the Presence of Catalyst IVa
C
10 mol% IV
+
p-cymene
160 °C
2.5 or 24 h
NH
NH
NH
p-Tol
p-Tol
p-Tol
1
4
5
Ti(NMe2)4
Entry
Time (h)
Ratiob 4/5
Yieldc (%) of 4 Yieldc (%) of 5
Ph
Ph
N
N
N
N
N
1
2
2.5
24
91:9d
50
4
5
H
2
2
Ti(NEt2)4
Ti(NMe2)2
Ti(NMe2)2
23:77d
35
Ind2TiMe2
I
II
a Reaction conditions: aminoallene (1, 0.5 mmol), IV (0.05 mmol, 10
mol%), p-cymene (15 mL), 160 °C.
b Determined by GC analysis before chromatography.
c Isolated yield.
iPr iPr
Ph
Ph
Ph
Ph
d According to GC analysis, the conversion of substrate 1 was close to quan-
titative. This strongly suggests that significant decomposition of the allene
and/or the products occurs under the reaction conditions.
Ph
N
N
N
Ph
N
N
H
iPr
iPr
Ti(NMe2)3
Ti(NMe2)3
III
IV
With sufficient quantities of 4 in hand, we were also
able to confirm its exomethylene-group-containing struc-
ture by single-crystal X-ray analysis (Figure 2).12
Figure 1 Titanium catalysts investigated for the intramolecular hy-
droaminoalkylation of aminoallene 1 (Ind = η5-indenyl)
However, instead of the expected formation of a mix-
ture of 2, 3, and 4, we surprisingly obtained the 2-methy-
lenecyclohexane-1-amine 4 and the allylic amine 5 (Table
1) in ratios that depended on the reaction conditions. After
a comprehensive optimization study (6–10 mol% IV, [1]=
0.025–0.625 mol/L in benzene, toluene, or p-cymene, reac-
tion time: 2–24 h), it was finally possible to isolate the hy-
droaminoalkylation product 4 in 50% yield from a reaction
mixture that had been stirred for 2.5 h at 160 °C in p-cy-
mene with a catalyst loading of 10 mol% of IV (Table 1, en-
try 1).10 Whereas in this case the allylamine side product 5
was obtained in only 5% yield, a corresponding experiment
involving heating to 160 °C for 24 h gave 5 in 35% yield and
4 in only 4% yield (entry 2). Both results were in good
Figure 2 Single-crystal X-ray structure of 4;12 ellipsoid representation
at the 50% probability level. Selected bond lengths [Å] and angles [°]:
C1–C2 = 1.5185(8), C2–C3 = 1.5059(8), C2–C4 = 1.3337(8), C1–C2–C3 =
113.61(5), C1–C2–C4 = 123.57(6), C3–C2–C4 = 122.76(6).
© Georg Thieme Verlag Stuttgart · New York — Synlett 2019, 30, A–E

C
J. Bielefeld et al.
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Because the dependency of the product ratio on the re-
action time suggests a rearrangement of the initially
formed hydroaminoalkylation product 4 (the disubstituted
exocyclic alkene) into the thermodynamically more stable
allylamine 5 (a trisubstituted endocyclic alkene) under the
reaction conditions, we investigated the conversion of 4
into 5 (Scheme 2). For this purpose, we initially heated a
solution of 4 in p-cymene to 160 °C for six hours in the ab-
sence of the titanium catalyst to rule out the possibility of a
simple thermal rearrangement. Because, in this case, the
formation of 5 could not be detected by GC analysis, the ex-
periment was repeated in the presence of 7 mol% of catalyst
IV and, not surprisingly, after six hours the product ratio
4/5 was found to be 14:86. With this result in hand, we then
conducted a final experiment on a preparative scale (10
mol% IV, 24 h), from which allylamine 5 was isolated in 63%
yield. From a mechanistic point of view, it seems to be rea-
sonable that the rearrangement of 4 to 5 involves the gener-
ation of an allylic cation intermediate in a process that is
initiated by the presence of the Lewis acidic titanium cata-
lyst (Scheme 2). This might also explain why no successful
hydroaminoalkylations of allenes have been previously re-
ported; the expected products can generally be converted
into reactive allylic cations and, correspondingly, a strong
likelihood of unwanted side reactions is to be expected in
these cases. In this context, it is worth mentioning that, to
the best of our knowledge, the corresponding Lewis acid-
catalyzed rearrangement of allylamines have not been pre-
viously reported.13 The fact that we were unable to identify
suitable reaction conditions for the hydroaminoalkylation
of aminoallene 1 to give the expected product 4 selectively
provides a clear indication that the rearrangement of 4 to 5
occurs at the temperatures that are required for the hy-
droaminoalkylation of 1 in the presence of catalyst IV. Con-
sequently, future research needs to focus on the identifica-
tion of more-active hydroaminoalkylation catalysts that are
active at lower temperatures, thereby avoiding the isomeri-
zation side reaction.
The assumption that the hydroaminoalkylation prod-
ucts obtainable from allenes are generally labile under the
reaction conditions was subsequently confirmed by two
cyclization experiments performed with the 1-aminoocta-
6,7-diene 6 at 160 °C in the presence of 10 mol% of IV (Table
2). During these experiments, we found again that after a
relatively short reaction time of two hours, the desired hy-
droaminoalkylation product 7 was the major product of the
reaction (Table 2, entry 1) whereas the rearranged allyl-
amine 8 dominated after 16 hours (entry 2). From a prepar-
ative point of view, the well-established fact that formation
of seven-membered rings is difficult to achieve can be re-
garded as a simple explanation for the isolation of 7 and 8 in
poor yields of only 5 and 10%, respectively. In addition, it
should also be mentioned that separation of 7 and 8 was
only possible on an analytical scale for characterization
purposes.11 Interestingly, traces of 8-(p-tolylamino)octan-
2-one were also isolated from the reaction mixtures, sug-
gesting that an unexpected intramolecular allene hydroam-
ination14 with the secondary amine15 moiety, initially lead-
ing to the formation of a moisture-sensitive eight-mem-
bered cyclic enamine, takes place as a side reaction.
Table 2 Intramolecular Hydroaminoalkylation of Aminoallene 6a
10 mol% IV
C
+
p-cymene
160 °C
2 or 16 h
NH
NH
NH
p-Tol
p-Tol
p-Tol
6
7
8
+ traces of
NH
O
p-Tol
Entry
Time (h)
Ratiob 7/8
Yieldc (%) of 7 + 8
1
2
2
74:26d
13:87d
5
16
10
a Reaction conditions: aminoallene (6, 0.5 mmol), IV (0.05 mmol, 10
mol%), p-cymene (15 mL), 160 °C.
10 mol% IV
p-cymene
b Determined by GC analysis before chromatography.
c Isolated yield.
d According to GC analysis, conversion of substrate 6 is close to quantita-
tive. This strongly suggests that significant decomposition of the allene
and/or the products occurs under the reaction conditions.
NH
NH
160 °C, 24 h
p-Tol
p-Tol
4
5
63%
+ [Ti]
– [Ti]
In contrast to the 1-aminoocta-6,7-diene 6, the 1-amino-
hexa-4,5-diene 9 (Scheme 3) was expected to undergo
smooth intramolecular hydroaminoalkylation to form the
relatively unstrained 2-methylenecyclopentane-1-amine
10 as the product. However, surprisingly, a reaction per-
formed with 9 at 160 °C in the presence of 10 mol% of IV
selectively delivered a 62% isolated yield of the six-mem-
bered-ring-containing enamine 11 (Scheme 3) as a result of
an unexpected intramolecular allene hydroamination. In
this context, it must be mentioned that hydroamination re-
p-Tol NH
+
[Ti]
no conversion in the absence of IV
Scheme 2 Rearrangement of the hydroaminoalkylation product 4 and
a possible mechanistic pathway
© Georg Thieme Verlag Stuttgart · New York — Synlett 2019, 30, A–E

D
J. Bielefeld et al.
Letter
Synlett
actions of unsaturated substrates with secondary amines
catalyzed by neutral group 4 metal complexes have rarely
been reported.15
In summary, we have presented the first examples of
early-transition-metal-catalyzed hydroaminoalkylation re-
actions of allenes. The studies performed with secondary
aminoallenes revealed that, under the reaction conditions,
the initially formed products undergo an unexpected rear-
rangement to the thermodynamically more stable allyl-
amine products. The assumption that this rearrangement
involves the generation of a reactive allylic cation interme-
diate, which can generally initiate unwanted side reactions,
might serve as a simple explanation for the fact that no suc-
cessful early-transition-metal-catalyzed hydroaminoal-
kylations of allenes have previously been reported in the
literature. As a result of the formation of a corresponding
cation, the first successful intermolecular hydroaminoal-
kylation of propa-1,2-diene finally resulted in the isolation
of an unexpected aminocyclopentane derivative formed by
incorporation of two equivalents of propa-1,2-diene.
C
10 mol% IV
p-cymene
160 °C, 2 h
NH
NH
p-Tol
p-Tol
10
9
10 mol% IV
N
p-cymene
160 °C, 2 h
p-Tol
11 62%
Scheme 3 Unexpected intramolecular hydroamination of aminoallene 9
Finally, we then applied the reaction conditions that
successfully facilitated the intramolecular allene hydroami-
noalkylation to an intermolecular reaction between N-
methylaniline (12) and propa-1,2-diene (Scheme 4), used
as a solution in toluene.16 Obviously, in this case, the initial
hydroaminoalkylation product 14 immediately undergoes
the previously discussed formation of an allylic cation that
reacts with a second equivalent of propa-1,2-diene to give
the interesting aminocyclopentane 13 as the final product
of the reaction. In this context, it is worth mentioning that
the low yield of only 17% obtained in this preliminary study
is not caused by insufficient catalytic activity, since a 100%
conversion of 12 was observed by GC analysis under the ap-
plied reaction conditions. The major problem was the for-
mation of an abundance of side products that were ob-
served by GC analysis, but could not be identified.
Funding Information
Funding Information: Deutsche Forschungsgemeinschaft, (Grant/
Award Number: 'DO 601/9-1')
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Acknowledgment
We thank the Deutsche Forschungsgemeinschaft (DO 601/9-1) for fi-
nancial support of our research, and Prof. Dr. Rüdiger Beckhaus for
helpful discussions.
Supporting Information
Supporting information for this article is available online at
https://doi.org/10.1055/s-0037-1611790.
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References and Notes
C
+
toluene
160 °C, 6 h
N
H
H2C
N
H
(1) For selected reviews on the hydroaminoalkylation of alkenes,
see: (a) Chong, E.; Garcia, P.; Schafer, L. L. Synthesis 2014, 46,
2884. (b) Hannedouche, J.; Schulz, E. Organometallics 2018, 37,
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12543.
5 equiv
12
13 17%
+ PhNH[Ti] – [Ti]
(2) Manßen, M.; Lauterbach, N.; Dörfler, J.; Schmidtmann, M.; Saak,
W.; Doye, S.; Beckhaus, R. Angew. Chem. Int. Ed. 2015, 54, 4383.
(3) For group-3-metal-catalyzed hydroaminoalkylation reactions
of alkenes with tertiary amines, see: (a) Nako, A. E.; Oyamada,
J.; Nishiura, M.; Hou, Z. Chem. Sci. 2016, 7, 6429. (b) Liu, F.; Luo,
G.; Hou, Z.; Luo, Y. Organometallics 2017, 36, 1557. (c) Gao, H.;
Su, J.; Xu, P.; Xu, X. Org. Chem. Front. 2018, 5, 59.
N
H
14
+ [Ti] – PhNH[Ti]
(4) For selected examples of late-transition-metal-catalyzed
hydroaminoalkylation reactions of alkenes, see: (a) Tran, A. T.;
Yu, J.-Q. Angew. Chem. Int. Ed. 2017, 56, 10530. (b) Spettel, M.;
Pollice, R.; Schnürch, M. Org. Lett. 2017, 19, 4287. (c) Thullen, S.
M.; Rovis, T. J. Am. Chem. Soc. 2017, 139, 15504. (d) Lahm, G.;
Opatz, T. Org. Lett. 2014, 16, 4201. (e) Schinkel, M.; Wang, L.;
Bielefeld, K.; Ackermann, L. Org. Lett. 2014, 16, 1876. (f) Kulago,
A. A.; Van Steijvoort, B. F.; Mitchell, E. A.; Meerpoel, L.; Maes, B.
U. W. Adv. Synth. Catal. 2014, 356, 1610.
CH2
C
H2C
Scheme 4 Intermolecular hydroaminoalkylation of propa-1,2-diene
with N-methylaniline (12), and a mechanistic explanation for the forma-
tion of product 13
© Georg Thieme Verlag Stuttgart · New York — Synlett 2019, 30, A–E

E
J. Bielefeld et al.
Letter
Synlett
(5) For selected examples of group 4 metal catalysts for hydroami-
noalkylation reactions, see: (a) Kubiak, R.; Prochnow, I.; Doye, S.
Angew. Chem. Int. Ed. 2009, 48, 1153. (b) Kubiak, R.; Prochnow,
I.; Doye, S. Angew. Chem. Int. Ed. 2010, 49, 2626. (c) Dörfler, J.;
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D.; Doye, S. Dalton Trans. 2015, 44, 12149. (g) Chong, E.; Schafer,
L. L. Org. Lett. 2013, 15, 6002.
(6) For selected examples of group 5 metal catalysts for hydroami-
noalkylation reactions, see: (a) Clerici, M. G.; Maspero, F. Syn-
thesis 1980, 305. (b) Nugent, W. A.; Ovenall, D. W.; Holmes, S. J.
Organometallics 1983, 2, 161. (c) Herzon, S. B.; Hartwig, J. F.
J. Am. Chem. Soc. 2007, 129, 6690. (d) Eisenberger, P.; Ayinla, R.
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L. Angew. Chem. Int. Ed. 2013, 52, 9144. (g) Chong, E.; Brandt, J.
W.; Schafer, L. L. J. Am. Chem. Soc. 2014, 136, 10898. (h) Brandt,
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(7) For examples of titanium-catalyzed intramolecular hydroami-
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2009, 1, 162. (b) Prochnow, I.; Zark, P.; Müller, T.; Doye, S.
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Shimon, L. J. W.; Eisen, M. S. Organometallics 2013, 32, 6337.
(10) 4-Methyl-N-(2-methylenecyclohexyl)aniline (4)
ylmethyl)-4-methylaniline [5; yield: 5 mg (0.02 mmol, 5%)] as a
yellow oil. Crystals of 4 were obtained by slow evaporation of a
solution in hexane.
4
Colorless liquid [yield: 50 mg (0.25 mmol, 50%)]; mp: = 59 °C. IR
(ATR) -1 3410, 2936, 2854, 1612, 1519, 1441, 1398, 1315, 1302,
1259, 1180, 1156, 1140, 1123, 1108, 1086, 908, 804 cm−1 1H
.
NMR (500 MHz, CDCl3):  = 1.38-1.46 (m, 2 H), 1.55–1.63 (m,
1 H), 1.79 (dq, J = 16.9, 4.0 Hz, 1 H), 1.88 (dq, J = 16.9, 4.1 Hz,
1 H), 2.03–2.13 (m, 2 H), 2.25 (s, 3 H), 2.44 (dt, J = 13.3, 3.8 Hz,
1 H), 3.71 (dd, J = 10.3, 4.3 Hz, 1 H), 3.75 (br. s, 1 H), 4.77 (s, 1 H),
4.84 (s, 1 H), 6.54 (d, J = 8.3 Hz, 2 H), 6.98 (d, J = 8.1 Hz, 2 H). 13
C
NMR (125 MHz, CDCl3, DEPT):  = 20.5 (CH3), 25.4 (CH2), 28.4
(CH2), 34.5 (CH2), 35.7 (CH2), 57.1 (CH), 106.7 (CH2), 113.6 (CH),
126.5 (C), 129.7 (CH), 145.3 (C), 149.6 (C). MS (EI, 70 eV): m/z
(%) = 201 (100) [M]+, 172 (15), 133 (15), 107 (61), 91 (11). HRMS
(EI, 70 eV): m/z [M+] calcd. for C14H19N: 201.1512; found:
201.1511.
(11) For details, see the Supporting Information.
(12) CCDC 1871667 contains the supplementary crystallographic
data for compound 4. These data can be obtained free of charge
from The Cambridge Crystallographic Data Centre via
www.ccdc.cam.ac.uk/data_request/cif.
(13) Allylamines have been used as substrates for nickel-catalyzed
cross-coupling reactions that involve cationic -allyl metal
intermediates, see: Trost, B. M.; Spagnol, M. D. J. Chem. Soc.,
Perkin Trans. 1 1995, 2083.
(14) For selected examples of titanium-catalyzed allene hydroami-
nation with primary amines, see: (a) Johnson, J. S.; Bergman, R.
G. J. Am. Chem. Soc. 2001, 123, 2923. (b) Ackermann, L.;
Bergman, R. G. Org. Lett. 2002, 4, 1475.
(15) For selected examples of hydroamination reactions with sec-
ondary amines achieved with neutral group 4 metal catalysts,
see: (a) Stubbert, B. D.; Marks, T. J. J. Am. Chem. Soc. 2007, 129,
6149. (b) Majumder, S.; Odom, A. L. Organometallics 2008, 27,
1174. (c) Müller, C.; Saak, W.; Doye, S. Eur. J. Org. Chem. 2008,
2731. (d) Leitch, D. C.; Payne, P. R.; Dunbar, C. R.; Schafer, L. L.
J. Am. Chem. Soc. 2009, 131, 18246. (e) Mukherjee, A.;
Nembenna, S.; Sen, T. K.; Pillai Sarish, S.; Ghorai, P. K.; Ott, H.;
Stalke, D.; Mandal, S. K.; Roesky, H. W. Angew. Chem. Int. Ed.
2011, 50, 3968. (f) Leitch, D. C.; Platel, R. H.; Schafer, L. L. J. Am.
Chem. Soc. 2011, 133, 15453.
In a glovebox under N2, amine 1 (101 mg, 0.5 mmol) and cata-
lyst IV (27 mg, 0.05 mmol, 10 mol%) were dissolved in p-
cymene (15 mL) in a 25 mL ampoule equipped with magnetic
stirrer bar. The ampoule was then sealed and heated at 160 °C
for 2.5 h. The product was purified by chromatography [silica
gel (250 g, length = 1 m, diam. = 20 mm), PE–Et2O (20:1, Rf =
0.36)] to give 4 as a colorless liquid [yield: 50 mg (0.25 mmol,
50%)], together with the byproduct N-(cyclohex-1-en-1-
(16) Cabezas, J. A.; Poveda, R. R.; Brenes, J. A. Synthesis 2018, 50,
3307.
© Georg Thieme Verlag Stuttgart · New York — Synlett 2019, 30, A–E