Dearomatization of 3-Nitroindoles with Highly γ-Functionalized Allenoates in Formal (3+2) Cycloadditions

Article abstract of DOI:10.1002/chem.201903455

3-Nitroindoles are easily reacted with highly substituted γ-allenoates in the presence of a commercially available phosphine catalyst. For instance, allenoates derived from biomolecules such as amino and deoxycholic acids are combined for the first time w

Full text of DOI:10.1002/chem.201903455

DOI: 10.1002/chem.201903455
Communication
&
Cycloadducts
Dearomatization of 3-Nitroindoles with Highly g-Functionalized
Allenoates in Formal (3+2) Cycloadditions
Lꢀo Birbaum,[a] Laurent Gillard,[a] Hꢀlꢁne Gꢀrard,[b] Hassan Oulyadi,[a] Guillaume Vincent,[c]
Xavier Moreau,[d] Michael De Paolis,*[a] and Isabelle Chataigner*[a, b]
heimer nitronate is a key to push the reaction forward. An in-
Abstract: 3-Nitroindoles are easily reacted with highly
substituted g-allenoates in the presence of a commercially
tramolecular catching is likely to be particularly useful, since it
could facilitate the reaction of the transient species to gener-
available phosphine catalyst. For instance, allenoates de-
ate a dearomatized polycyclic compound, following a formal
rived from biomolecules such as amino and deoxycholic
cycloaddition process. Actually, concerted cycloadditions in-
acids are combined for the first time with 3-nitroindole.
volving electron-poor aromatics can be considered as the
upper limit of this type of reactivity.[3] Normal electron demand
The corresponding dearomatized (3+2) tricyclic cycload-
ducts are obtained as a-regioisomers exclusively. DFT
(4+2) cycloadditions involving nitroarenes and electron-rich
computations shed light on this multi-step reaction mech-
dienes have been described by us and others.[4] Nitroarenes
anism and on the selectivities observed in the sequence.
can also react in tandem (4+2)/(3+2) processes and in this
case the intermediate nitronate is trapped in a subsequent
(3+2) cycloaddition.[5] Concerted or formal (3+2) reactions on
In organic synthesis, electron-poor alkenes are essential build-
ing blocks, used as electrophiles in many chemical transforma-
tions. When the same alkene moiety is embedded in an aro-
matic ring, the resonance stabilization energy renders this
compound almost inert towards most neutral nucleophiles.
The possible interaction of an aromatic double bond bearing
an electron-withdrawing group with different nucleophilic spe-
cies is, however, of great synthetic interest, since this approach
leads to complex tridimensional structures from easily available
raw materials. Nucleophilic dearomatization reactions have
been developed for some time, mainly with polar organome-
tallic nucleophiles.[1] Regarding the electrophilic aromatic com-
pounds, nitro(hetero)arenes have been regularly used with dif-
ferent types of nucleophiles because of the highly electron-
withdrawing character of the nitro group.[2] In most cases, the
addition is reversible and trapping the intermediate Meisen-
nitro aromatic compounds have also been reported lately,
mainly on 3-nitroindoles. Those involve azomethine ylides,[6]
azomethine imines,[7] trimethylenemethanes,[8] vinyl-cyclopro-
panes,[9] -aziridines[10] or -epoxides[11] under palladium catalysis,
or isothiocyanato oxindoles and thiol derivatives[12] (Figure 1).
Figure 1. (3+2) Cycloadditions and annulations involving 3-nitroindole de-
rivatives.
[a] L. Birbaum, Dr. L. Gillard, Prof. H. Oulyadi, Dr. M. De Paolis,
Prof. I. Chataigner
UNIROUEN, INSA Rouen, CNRS
COBRA, Normandie Univ, 76000 Rouen (France)
E-mail: michael.depaolis@univ-rouen.fr
isabelle.chataigner@univ-rouen.fr
Very recently, Zhang, Lu, Shi, Bandini, and Ye independently
described the reactivity of 3-nitroindoles with buta-2,3-dieno-
ates in (3+2) dearomatizing annulation processes.[13] The ex-
pected cyclopentaindolines were elegantly obtained resorting
to chiral (or not) phosphine catalysis. Bandini reported these
reactions in the presence of g-alkyl allenoates (Figure 1).[13d]
These very recent publications prompted us to report our
own results directed toward the dearomatization of 3-nitroin-
doles in (3+2) annulations using allenoates bearing functional
groups in the g position.[14,15] Allenoates bearing alkene,
alkyne, silylether, and amine moieties were thus employed to
attain elaborated indolines or dihydrobenzofurans. Our own in-
vestigations started before these reactions were reported on 3-
nitroindoles. Thus, ignoring if the nitrated aromatic double
[b] Prof. H. Gꢀrard, Prof. I. Chataigner
CNRS, Laboratoire de Chimie Thꢀorique, LCT UMR7616
Sorbonne Universitꢀ, 75005 Paris (France)
[c] Dr. G. Vincent
Institut de Chimie Molꢀculaire et des Matꢀriaux d’Orsay (ICMMO)
Univ. Paris-Sud, Universitꢀ Paris-Saclay, CNRS UMR 8182
91405 Orsay cedex (France)
[d] Prof. X. Moreau
Institut Lavoisier Versailles, UMR CNRS 8180
Universitꢀ de Versailles-St-Quentin-en-Yvelines, Universitꢀ Paris Saclay
78035 Versailles cedex (France)
Supporting information and the ORCID identification number(s) for the
author(s) of this article can be found under:
https://doi.org/10.1002/chem.201903455.
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bond would behave as the electron-poor 2p component, we
reacted nitroindole 1a and ethyl 2,3-butadienoate (2a)
(2 equiv) in the presence of 20 mol% of the cheap and easily
accessible triphenylphosphine. This first test, run in toluene at
room temperature, led to a promising result since the expect-
ed indoline 3aa was formed within 48 h. The process regiose-
lectivity proved to be complete, and the a-isomer is the only
cycloadduct observed (62% conversion, 42% isolated yield). In-
creasing the reaction time did not lead to any improvement.
Optimization of the reaction conditions included adjustment
of the solvents and of the loading and nature of the catalyst
(see the Supporting Information (SI) for details). This did not
lead to better results. Only the use of a solvent mixture (tolu-
ene : CH2Cl2, 1:1), which better solubilizes both substrates and
intermediates, leads to slightly improved results. In 2007, Yu
showed that the addition of water to the reaction medium has
a positive impact on the reaction course, facilitating the [1,2]-
proton shift required after cyclization to release the cyclopen-
tenic adduct and the catalyst.[16] We thus added water to the
solvent mixture and were pleased to observe that it indeed
leads to a significant improvement, as the reaction is faster
and indoline 3aa is isolated in a 72% yield after 17 h
(Figure 2).[17]
The reactivity of 3-nitroindoles 1b–d was then explored, be-
ginning with a modulation of the nitrogen protecting/activat-
ing group (Figure 2). Interestingly the carbamate (N-Boc)
indole 1c is converted into indoline 3ca in 78% yield while
the other indoles are less efficient.[18] The N-Ts indole 1a,
which displays a similar reactivity, was preferred for the rest of
the study since its preparation is straightforward. Likewise,
changing the ester substitution on the allenoate has little
effect: using benzyl allenoate 2b affords the corresponding in-
doline 3ab in a similar yield.
We then turned our attention to allenoates bearing a g-sub-
stitution. Allenoate 2c, with a methyl group, is assembled with
nitroindole 1a into 3ac, obtained in a 60% overall yield (d.r.=
1:1). The methylated dipole is less reactive than its unsubstitut-
ed counterpart and a higher 458C reaction temperature is re-
quired in this case, in the presence of a more nucleophilic tri-
n-butylphosphine.
Figure 2. (3+2) Annulations involving 3-nitroindole derivatives. [a] Using
PPh3. [b]: Reaction performed at r.t. [c]: Conversion rate determined by
1H NMR on the crude reaction mixture. [d]: Overall isolated yield. [e]: Using
PnBu3. [f]: Reaction performed at 458C. [g]: Isolated as a diastereomeric mix-
ture. [h]: Only the trans major diastereomer is depicted in the figure. [i]: Re-
action performed at 608C. [j]: Reaction performed in the presence of an alle-
noate synthesized from a Mukaiyama salt intermediate (see SI), containing
an inert isomer. [k]: Reaction performed in non-degassed conditions. [l]: Dia-
stereomers were separated by reversed phase chromatography (HPLC).
So far, this type of cycloaddition has never been described
with more hindered allenoates. Pleasingly, involving the g-iPr
or g-Cy allenoates 2d and 2e at 458C leads to the formation
of the expected indolines 3ad and 3ae, isolated in 64 and
63% yields (3:2 and 3:1 d.r.), respectively. The major adducts
feature a trans relationship between the nitro and alkyl groups
as shown by NOESY experiments (see SI). A gram scale reaction
can be performed with the isopropyl substituted allenoate 2d
and furnishes 3ad in a 56% isolated yield, with only a slight
erosion on this scale. The unreacted starting indole (20%) can
be recovered (yield brsm : 70%).
as a silyloxy ether or NBoc protected amine. The dearomatiza-
tion occurs in good yields and similar diastereoselectivities,
3ah and 3ai being isolated in 68 and 70% yields, respectively
(2:1 d.r.). To a lesser extent, amino acid substituted allenoate
derived from glutamic acid 2j proves also reactive and fur-
nishes 3aj in a 28% yield. Interestingly, NOESY experiments
show that only the cycloadducts featuring a trans relationship
between the ring junction and the substituent brought by the
allenoate were formed (2:1 d.r.), and the cis isomers are not
observed here. The yield drop observed in this case was as-
signed to the lower stability of the diBoc protected allenoate.
To address this issue, the NMeBoc protected allenoate 2k was
The reaction was then extended to functionalized allenoates,
bearing alkynyl or alkenyl groups appendages ready for further
transformations.[19] At 608C, these cycloadditions led to indo-
lines 3af and 3ag isolated in 44[20] and 62% yield (3:2 and 3:1
d.r.), respectively. Hitherto unreported, the g-substituent of the
allenoate can also bear a chain possessing a heteroatom such
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considered and better conversion and yield are noted (respec-
tively 70 and 62%, 3:3 (trans):2:1 (cis) d.r.).[20] With this chiral
dipole, the facial selectivity leads to the formation of the ster-
eomers resulting from the attack of the dipole on both faces
of the nitroindole (see SI for assignment of the cis/trans stereo-
selectivity).
on the C2 atom (0.39/À0.58 vs. 0.31/À0.55 on C4). Since the
nitropyrrole largest LUMO coefficient is located on the C2
carbon atom, the a-regioisomer formation is rationalized by
simple FMO analysis (see SI).
The reaction pathways between nitropyrrole A and dipole
D1 were then examined computationally, considering four ap-
proaches for this cycloaddition step, namely the two leading
to the a- and g-regioisomer and two stereoarrangements in
both cases (equivalent to endo/exo approaches in a (4+2) cy-
cloaddition) (Table 1).
The allenoate derived from the deoxycholic acid 2l, combin-
ing a sterically hindered and unprotected biomolecule remains
reactive toward nitroindole 1a in the usual conditions, (95%
conversion, 2:2 (trans):1:1 (cis) d.r.) (see SI). All diastereomers
could be separated by HPLC in an overall 65% yield.
The reaction was next tried on a 3-nitrobenzofurannic deriv-
ative 4 and we were pleased to observe an efficient dearoma-
tive (3+2) annulation in the presence of 2a and PPh3
(Figure 3). Cycloadduct 5 was isolated in 67% yield.[21]
Table 1. DFT calculations on the formal (3+2) cycloaddition steps.
Figure 3. Formal (3+2) cycloaddition of 3-nitrobenzofuran 4 with allenoate
2a.
Entry
Approach
D
DG°
TSa[a,b,d]
DGr
E[a,b]
DG°
TSb[a,c,d]
DGr
F[a,c]
In these dearomative processes, all substituted allenoates
lead to the exclusive formation of the corresponding a-re-
gioisomers. This suggests that the potential pathways generat-
ing the a and g-regiosisomers are clearly differentiated. In con-
trast, the cis/trans diastereoselectivity of the formal cycloaddi-
tion is modestly controlled and competitive mechanisms for
the corresponding diastereomeric routes are expected (vide
infra for DFT calculations). At any rate, all these examples show
the great potential of this methodology, that remain efficient
with highly functionalized and hindered allenoates.
1
2
3
4
5
6
7
8
a
a’
g
D1
D1
D1
D1
D2-int
D2-ext
D2-int
D2-ext
D2-int
D2-ext
D2-int
D2-ext
11.6
12.4
13.9
14.0
12.6
17.0
15.7
20.1
18.1
23.3
19.8
22.6
À5.4
À5.1
À5.7
À5.4
À4.3
À2.4
À4.9
À1.5
À2.0
À0.3
0.3
13.2
10.9
9.6
2.2
1.1
3.3
1.0
7.4
10.7
5.1
7.9
7.5
9.4
4.9
9.2
g’
a
a
a’
a’
g
8.5
17.0
16.8
16.6
14.2
14.3
17.1
11.9
16.3
9
10
11
12
g
g’
g’
3.9
To get an insight into the reaction mechanism, DFT calcula-
tions were undertaken on a realistic model,[22] considering ni-
tropyrrole A in the presence of PMe3 (B), taken as phosphine
model, and the unsubstituted allenoate C1 (Figure 4, see SI for
details).
[a] Gibbs Free Energy differences relative to A and D (D1 or D2-int), in kcal
molÀ1. [b] TSa, adduct: transition state and zwitterionic adduct for the
first step (formation of CÀC bond a). [c] TSb, cycloadduct: transition state
and cycloadduct for the second step (formation of CÀC bond b). [d] Rate-
determining TS in bold.
Addition of the phosphine catalyst on C1 leads to the reac-
tive 1,3-dipole D1, whose most stable conformation expectedly
shows a favorable PÀO ester interaction (PÀO=2.97 ꢃ).[16b] This
associative step is highly activated (DG° =20.33 kcalmolÀ1),
and thermodynamically favored (DGr =À2.7 kcalmolÀ1). D1 fea-
tures a high energy HOMO, with largest coefficient and charge
Two-step mechanisms are computed in all cases, with the
formation of bonds a and b in two subsequent steps. The first
step leads to the formation of a zwitterionic Michael adduct,
which then cyclizes intramolecularly in a second step.
The first transition states appear to be relatively lower in
energy than expected for a dearomatizing process (between
11.6 and 14.0 kcalmolÀ1, Table 1, entries 1–4), and should thus
be representative of a relatively easy step, in accordance with
a dearomatization occurring at room temperature. In line with
the FMO and charge analyses, formation of the bond between
the two C2 carbon atoms of both the dipole and nitropyrrole,
associated to the a arrangement, is favored for this first step.
More surprising is the stability of the dearomatized Michael
adduct (between À5.1 and À5.7 kcalmolÀ1) and the relatively
Figure 4. Model substrates used in DFT calculations.
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high barriers for the second step (DG°(TSb) between 8.5 and
13.2 kcalmolÀ1, with respect to separated substrates, between
13.9 and 18.6 kcalmolÀ1 with respect to the Michael adduct,
see SI), which are unexpectedly high values for an intramolecu-
lar cyclization step. These figures suggest that, for the a ap-
proaches, the determining step is not the dearomatizing one
but rather the intramolecular cyclization.[23] Formation of the
a-cycloadduct appears to be favored over the g-one by only a
small energy difference (0.6 kcalmolÀ1, see SI). This is not in
line with the experimental data, which show that the a-re-
gioisomers are exclusively formed in all cases. In contrast, the
small difference between the a and a’ approaches reflects the
diastereoselectivity observed experimentally.
The prototropy step was next considered starting from the
unsubstituted cycloadduct Fa (Table 1). A direct proton trans-
fer appears to be energy demanding (DG° =41.9 kcalmolÀ1
,
Figure 6. Proposed mechanism with calculated DG values (DG° and DGr in
kcalmolÀ1 respective to separated (A+B+C+H20).
Figure 5).[24] This high value suggests that this intramolecular
the final cycloadduct probably drives the reaction to comple-
tion, by shifting all the possible equilibria, and explains the
whole sequence.
We then considered the same process in the presence of a
g-methyl substituted allenoate C2. The dipole generated by in-
teraction of C2 with phosphine B can lead to two isomeric di-
poles, depending on the position of the methyl group, namely
D2-int and D2-ext. D2-int is computationally more stable than D2-ext
,
by 7.7 kcalmolÀ1, probably due to unfavorable steric interac-
tions between the hydrogen atoms of PMe3 and Me in the
latter.
Since these interactions can vary a lot during the cycloaddi-
tion process, both dipole configurations were considered in
the calculations. Thus, combining the a/g approaches with the
diastereomeric arrangements a/a’ and g/g’ leads to the com-
putations of eight different pathways (Table 1, entries 5–12).[26]
In this case, the cis/trans diastereomers for both the a and g
isomers are possibly formed depending on the approach. The
same trends as before are observed and the following conclu-
sions can be drawn: i) the presence of the Me group signifi-
cantly increases the activation barriers, in line with the experi-
ence which shows that a higher reaction temperature is re-
quired with substituted allenoates ii) depending on the ap-
proach, the highest energy TS can either be the first or the
second one, iii) the computed values for a given TS or inter-
mediate are very sensitive to the approach (a/g/a’/g’/dipole
configuration) as Gibbs free energies span on a range of about
10.7 kcalmolÀ1 in each case; iv) despite these differences, no
clear-cut preference for one pathway can be drawn, as the rate
determining activation Gibbs Free Energies (first or the second
step depending on the arrangements) are all between 19.2
Figure 5. Different propotropy paths considered.
process is highly unlikely and that the presence of water mole-
cules (intentionally added or from the reaction mixture) favors
the process. Performing the prototropy in the presence of one
or two water molecules is much easier and favors the proton-
ation/deprotonation (see SI). The most favored computed path
involves a protonation from the side opposite to the one bear-
ing the proton to be abstracted, followed by a deprotonation
step involving an hydroxide anion (DG° =12.3 kcalmolÀ1,
DG° =9.6 kcalmolÀ1, respectively). Even if other combinations
of cycloadduct/water molecules can be considered, these re-
sults show unambiguously that the prototropy sequence is fa-
vored when water molecules are present in the reaction
medium. Here again, this is in line with the experimental data
that show that introduction of water to the medium acceler-
ates the whole process (Figure 6).[25]
and 24.6 kcalmolÀ1 [22]
In particular, the differences between
.
the approaches leading to the trans vs. cis diastereomers are
relatively small and this can explain the modest diastereomeric
ratios observed experimentally. Considering the regioselectivi-
ty, the a-isomers are controlled by the second step, whereas
the g ones are controlled by the first one, probably because
this step involves a more sterically demanding organization as-
The final step of the sequence involves the regeneration of
the phosphine catalyst and appears to be highly favorable
both from the kinetic and thermodynamic points of view
(DG° = +2.8 kcalmolÀ1, DGr =À18.5 kcalmolÀ1). The stability of
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In conclusion, we have shown that dearomatizing (3+2)
formal cycloadditions involving 3-nitroindoles are possible with
highly and diversely substituted g-allenoates. The functional-
ized a-cycloadducts are exclusively obtained, with cis/trans dia-
stereoselectivities up to 3:1. This latter result can be under-
stood on the basis of DFT calculations, which suggest that the
energy barriers of the diastereomeric approaches are not sig-
nificantly different. In contrast, DFT calculations do not explain
the exclusive formation of the a-regioisomers, but rather sug-
gest that both the a and g-pathways are not highly different
and, thus, small variations in the reaction conditions could
modify the preferred pathway toward the formation of the
complementary g-regioisomer. Expectedly, the dearomatizing
step is the determining one during the formation of the g-cy-
cloadducts, for steric and electronic reasons. Astonishingly,
however, this is not true for the formation of the a-regioiso-
mers, for which the determining step appears to be the subse-
quent intramolecular cyclization. Efforts directed toward the
development of g-regioselective pathways by modifying the
experimental conditions and substrates substitutions are cur-
rently under way.
Acknowledgements
Financial support from the Agence Nationale pour la Recher-
che (ANR-17-CE07-0050), Labex SynOrg (ANR-11-LABX-0029),
Rouen University, CNRS, INSA Rouen, and Rꢀgion Haute-Nor-
mandie (CRUNCh network) is acknowledged. CRIANN (Saint Eti-
enne du Rouvray, France) is also acknowledged for their gener-
ous allocation of computer time. We thank Dr. Arnaud Voituriez
for grateful discussions.
[14] For the seminal work and review on Lu (3+2) annulation reaction, see
for instance: a) C. Zhang, X. Lu, J. Org. Chem. 1995, 60, 2906–2908;
b) X. Lu, C. Zhang, Z. Xu, Acc. Chem. Res. 2001, 34, 535–544.
[15] For an example involving a nitroolefin, see: X.-Y. Guan, Y. Wei, M. Shi,
Org. Lett. 2010, 12, 5024–5027.
Conflict of interest
[16] a) Y. Xia, Y. Liang, Y. Chen, M. Wang, L. Jiao, F. Huang, S. Liu, Y. Li, Z.-X.
Yu, J. Am. Chem. Soc. 2007, 129, 3470–3471; b) Y. Liang, S. Liu, Y. Xia, Y.
Li, Z.-X. Yu, Chem. Eur. J. 2008, 14, 4361–4373.
The authors declare no conflict of interest.
[17] Even a smaller amount of water in the medium is sufficient (3.2 equiv
representing a drop).
Keywords: annulation · allenoate · dearomatization · density
functional calculation · nitrondole
[18] This surprising result, in which the Boc-protected indole appears to be
more reactive than the Ts-protected one is reminiscent of the work
published recently, see ref. [13], as well as some results we had report-
ed before, see: a) I. Chataigner, C. Panel, H. Gꢀrard, S. R. Piettre, Chem.
Commun. 2007, 3288.
[19] The allenoates are accessible from the corresponding carboxylic acids,
via the in situ generation of ketenes, using Mukaiyama salt. See: R. L.
Funk, P. M. Novak, M. M. Abelman, Tetrahedron Lett. 1988, 29, 1493–
1496. They were obtained as mixture with isomeric alkyne esters, which
proved inert in the reaction conditions. See the Supporting Informa-
tion.
[1] See for instance: F. Lꢄpez Ortiz, M. J. Iglesias, I. Fernꢅndez, C. M. Andffljar
Sꢅnchez, G. Ruiz Gꢄmez, Chem. Rev. 2007, 107, 1580–1691.
[2] See for instance: M. Ma˛kosza, Chem. Eur. J. 2014, 20, 5536–5545.
[3] These concerted processes have been shown to be highly asynchro-
nous in most cases. See for instance: N. Chopin, H. Gꢀrard, I. Chataigner,
S. R. Piettre, J. Org. Chem. 2009, 74, 1237–1246.
[4] For nitro-indoles, -pyrroles or -naphthalenes involved as dienophiles in
Diels–Alder cycloadditions, see for instance: a) E. Wenkert, P. D. R. Moel-
ler, S. R. Piettre, J. Am. Chem. Soc. 1988, 110, 7188–7194; b) T. L. S. Kish-
Chem. Eur. J. 2019, 25, 1 – 7
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[20] For this compound, several HPLC purifications were required to get the
pure separated diastereomers, leading to a decrease of the overall iso-
lated yield.
[24] The direct proton transfer was already reported to be high in energy.
See refs. [13d] and [16b], for instance.
[25] In the recently published papers, some reactions were performed in
the absence of water. In these cases, the more acidic dipeptidic cata-
lysts used can probably act as a proton transfer agent.
[26] These arrangements can explain the formation of trans/cis diastereo-
mers. Alternatively, rotation of the allylic chain on the zwitterion can
justify the formation of the two diastereomers. See ref. [13d], SI. These
rotations require a protonation/rotation/deprotonation sequence on
the zwitterion and the computed values (evaluated using the nudged
elastic band method) are in the same range as ours. They were not
computed in our case.
[27] Studies are underway to assess the impact of the calculation method
and of the selected models on the competition between the two
stages of these formal cycloaddition.
[21] This result contrasts with those reported by Zhang (ref. [13a]) in the
presence of the differently substituted 2-nitrobenzofuran, which proved
inert in the presence of an allenoate dipole precursor and required the
involvement of MBH carbonates. In contrast, the possible dearomative
(3+2) annulation on 2-nitrobenzofurans with allenoates has been re-
ported recently, see: a) J.-Q. Zhao, L. Yang, Y. You, Z.-H. Wang, K.-X. Xie,
X.-M. Zhang, X.-Y. Xu, W.-C. Yuan, Org. Biomol. Chem. 2019, 17, 5294–
5304; b) X.-H. Yang, J.-P. Li, D.-C. Wang, M.-S. Xie, G.-R. Qu, H.-M. Guo,
Chem. Commun. 2019, 55, 9144–9147.
[22] For calculation cost reasons, PMe3 was considered as a model phos-
phine (see for instance refs. [16] and [13d]), and 3-nitropyrrole was con-
sidered as a model of 3-nitroindole (see for instance ref. [18]). No no-
ticeable difference in the calculation conclusion was observed between
these two heterocycles.
Manuscript received: July 29, 2019
[23] Rate-determining TSs are determined relative to the starting adducts in
each case (A+D for the first step, Michael adduct E for the second).
See the Supporting Information.
Revised manuscript received: September 3, 2019
Accepted manuscript online: September 11, 2019
Version of record online: && &&, 0000
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Communication
COMMUNICATION
3-Nitroindoles and benzofurans are
easily reacted with substituted g-alle-
noates in the presence of a commercial-
ly available phosphine catalyst. For in-
stance highly functionalized allenoates
derived from biomolecules such as
amino or deoxycholic acids are com-
bined with 3-nitroindole to yield the
corresponding cyclopentaindolines.
&
Cycloadducts
L. Birbaum, L. Gillard, H. Gꢀrard,
H. Oulyadi, G. Vincent, X. Moreau,
M. De Paolis,* I. Chataigner*
&& – &&
Dearomatization of 3-Nitroindoles
with Highly g-Functionalized
Allenoates in Formal (3+2)
Cycloadditions
Chem. Eur. J. 2019, 25, 1 – 7
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These are not the final page numbers! ÞÞ