Stereoselective synthesis of 3-spiropiperidino indolenines via SN2-type ring opening of activated aziridines with 1H-indoles/Pd-catalyzed spirocyclization with propargyl carbonates

Article abstract of DOI:10.1039/c8cc04249g

3-Spiropiperidino indolenines have been synthesized via novel Lewis acid-catalyzed S_N2-type ring opening of activated aziridines with 1H-indoles followed by Pd-catalyzed dearomative spirocyclization with propargyl carbonates in up to 88% yields

Full text of DOI:10.1039/c8cc04249g

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ARTICLE
Stereoselective Synthesis of 3-Spiropiperidino Indolenines via SN2-
Type Ring Opening of Activated Aziridines with 1H-Indoles/Pd-
Catalyzed Spirocyclization with Propargyl Carbonates
Received 00th January 20xx,
Accepted 00th January 20xx
DOI: 10.1039/x0xx00000x
Sajan Pradhan, Chandan Kumar Shahi, Aditya Bhattacharyya, and Manas K. Ghorai*
3-Spiropiperidino indolenines have been synthesized via a novel
Lewis acid-catalyzed SN2-type ring opening of activated aziridines
with 1H-indoles followed by Pd-catalyzed dearomative
spirocyclization with propargyl carbonates in up to 88% yields. The
step and pot-economic transformation comprises sequential C–C,
C–N, and C–C bond forming steps generating two stereogenic
centers including an all-carbon quaternary stereocenter to furnish
the products in diastereomerically pure (dr >99:1) forms with
excellent enantiomeric excess (ee up to >99%). The synthetic
versatility of the strategy has been illustrated by converting the
synthesized products into spirocyclic indolenine 2-piperidinones,
dihydropiperidines, and 5-alkynylated piperidines.
Figure 1. Biologically active 3-spiropiperidino indolenines.
3-Spiropiperidino indolenine is a privileged heterocyclic scaffold
with exceptional pharmaceutical significance. It constitutes
structural cores of several naturally-occurring alkaloids with
valuable biological activities. Figure 1 shows a few such
reduction.10 Other noteworthy routes involve intramolecular
SNAr reactions,11 Ir-catalyzed allylic dearomatization of 2-
iodoindoles,12
Ag(I)-catalyzed
intramolecular
examples: I is a calcitonin gene-related peptide (CGRP) receptor
cycloisomerization of indolylcyclopropenes13 etc. However, the
few available methods for the synthesis of 3-spiropiperidino
indolenines8,12,13 suffer from limited substrate scope and
functionalizability of the products as well as poor
stereoselectivity.
antagonist for headache therapy,1 II and III are 11β-
hydroxysteroid dehydrogenase type-1 enzyme inhibitors useful
in the treatment and prophylaxis of obesity and diabetes,2 and
(+)-koumine (IV) is the main alkaloid of Gelsemium elegans
Benth. that is used as a folk medicine to treat migraines,
neuralgia, sciatica, cancer, and various types of sores.3
In recent years, activated aziridines and azetidines have
emerged as important building blocks in organic synthesis.14
Our longstanding involvement in exploring and exploiting the
area of Lewis acid (LA)-catalyzed SN2-type ring-opening
transformations of aziridines and azetidines has emanated
several expedient methodologies such as ring-opening
cyclization (ROC)15 and domino ring-opening cyclization
(DROC)16 to directly access various aza-heterocycles. In this
vein, we envisaged an effective and general stereoselective
synthetic route to 3-spiropiperidino indolenines via LA-
catalyzed ring opening of activated aziridines with 1H-indoles
followed by Pd-catalyzed dearomative spirocyclization with
propargyl carbonates. Herein, we report our preliminary results
as a communication.
Synthesis of spirocyclic indolenines4 can be achieved by
classical methodologies such as interruptive Fischer indolization
employing arylhydrazines and cycloalkanecarbldehydes5 or
acid-mediated intramolecular cyclization of the corresponding
arylhydrazones.6 However, the most recent approach includes
also spirocyclization of indoles with different electrophilic
components including alkylation,7 Pd/Ir/Ru-assisted addition to
π-allyl intermediates derived from allylic acetates or
carbonates,8 intramolecular Michael/Mannich cascade reaction
of indolyl methyl enones,9 spirocyclization of N-
arylisonicotinamides followed by hydrogenation and
To begin with, 2-phenyl-N-tosylaziridine (1a) was reacted with
2-phenyl-1H-indole (2a) in the presence of 10 mol % LiClO4 in
acetonitrile at 80 °C for 3 h15c and the corresponding ring-
opened product 3a was obtained as a single regioisomer in 92%
yield. 3a was subsequently treated with tert-butyl prop-2-yn-1-
a. Department of Chemistry, Indian Institute of Technology Kanpur, Kanpur 208016,
Uttar Pradesh, India.
E-mail: mkghorai@iitk.ac.in
Electronic Supplementary Information (ESI) available: Experimental procedures,
analytical data, NMR spectra, HPLC chromatograms, and crystallographic data (PDF)
X-ray data for compound 5f (CCDC 1813319) (CIF). See DOI: 10.1039/x0xx00000x
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yl carbonate (4a) in the presence of 10 mol % Pd(PPh3)4 and 20
mol % (±)-BINAP in DCE at 85 °C and to our delight the desired
3-spiropiperidino indolenine 5a was obtained with an exocyclic
olefinic moiety at the 2-position of the piperidine ring in 90%
yield in 2 h (Scheme 1).
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Scheme 1. Lewis acid-catalyzed SN2-type ring opening of 2-phenyl-N-tosylaziridine with
2-phenyl-1H-indole followed by Pd-catalyzed dearomative spirocyclization
We subsequently achieved the pot-economy by conducting
the ring opening of 1a with 2a in the presence of 10 mol % LiClO4
in CH3CN at 80 °C. Upon complete consumption of the starting
materials, 4a was added to the reaction mixture followed by the
addition of 10 mol % Pd(PPh3)4 and 20 mol % (±)-BINAP in DCE
and the temperature was elevated to 85 °C. The reaction
completed in 9 h and 5a was obtained in 51% overall yield
(Scheme 2).
Scheme 3. Synthesis of 5′-Aryl-Substituted 3-Spiropiperidino Indolenines from 2-
Arylaziridines
1a and 1c separately in two different experiments, and the
respective 3-spiropiperidino indolenines 5h and 5i were
obtained in enhanced yields. Chloro
(2d) and bromo
substituents (2e) at the 5-position of the 2-p-tolyl-1H-indoles
were well-accommodated in the strategy and the respective
products 5j and 5k were obtained in excellent yields. When 2-
methyl-1H-indole
chlorophenyl)-N-tosylaziridine (1g), the respective products 5l
and 5m formed in very high yields. Unsubstituted 1H-indole (2g
(2f) was reacted with 1a and 2-(3-
)
Scheme 2. One-pot synthesis of 3-spiropiperidino indolenine 5a
was also found to be a good candidate for the transformation
which produced the corresponding 3-spiropiperidino
indolenine 5n in 60% yield. Notably, the various halogen groups
The reaction conditions were optimized to obtain 5a in an
improved yield by screening several Pd catalysts, ligands, and
solvents.19 The best result was obtained with 10 mol %
Pd(PPh3)4 and 20 mol % 1,1'-bis(diphenylphosphino)ferrocene
(dppf) ligand in DMSO at 120 °C and in 5 min, 5a was obtained
in 86% yield. The approach was subsequently generalized by
employing a diverse range of 2-aryl-N-tosylaziridines under the
optimized reaction conditions. When 2-(4-chlorophenyl)-1-
tosylaziridine (1b) was reacted with 2a in the presence of 10 mol
% LiClO4 in acetonitrile at 80 °C for 3 h, the corresponding ring-
opened product formed which thereafter underwent
spirocyclization with 4a to produce 5b in 84% yield. Considering
the importance and usefulness of the fluorinated17 and
trifluoromethylated18 compounds in the pharmaceutical
industry, we synthesized 3-spiropiperidino indolenines bearing
various fluorine substituents. For this purpose, the 3-fluoro
variant of the 2-aryl-N-tosylaziridine 1c was treated with 2a and
4a under the optimized ROC conditions, and 5c formed in 88%
appended around the molecular framework of 5 could naturally
allow further synthetic elaborations to other biologically and
synthetically significant compounds as demonstrated later in
this paper. To study the electronic effect of the N-arylsulfonyl
group on the strategy, 1-((4-fluorophenyl)sulfonyl)-2-
phenylaziridine (1h) was exposed to the optimized reaction
conditions with 2a and 4a and 5o was obtained in 77% yield. On
the other hand, when 1i with a strong electron-donating mesityl
group attached with the N-sulfonyl group was reacted with 2a
and 4a, the corresponding product 5p formed in marginally
increased yield (79%). All the results are shown in Scheme 3.
To gain a mechanistic insight, reactions were studied with
phenyl- substituted propargyl carbonates. When ring opening
of 1a was carried out with 2a followed by spirocyclization with
tert-butyl (3-phenylprop-2-yn-1-yl) carbonate
(4b), the
corresponding 3′,5′-diphenyl-substituted 3-spiropiperidino
indolenine 5q was obtained as a single diastereomer in 56%
yield (>99:1 dr, Scheme 4). When the experiment was revisited
by employing 1a and 2a with the isomeric tert-butyl-(1-
phenylprop-2-yn-1-yl) carbonate (4c), the formation of the
same 5q was also observed as a single diastereomer, in slightly
enhanced yield (64%, >99:1 dr).19 The relative stereochemistry
of the two phenyl groups at the 3′ and 5′-positions of 5q was
found to be trans as determined by nuclear Overhauser effect
(NOE) experiments.19
yield. Next, 1-tosyl-2-(2-(trifluoromethyl)phenyl)aziridine (1d
)
was reacted with 2a and 4a to obtain 5d in 65% yield. To gauge
the generality of the methodology in terms of stereoelectronic
effect of the 2-aryl groups in the aziridine, 2-(naphthalen-2-yl)-
1-tosylaziridine (1e) was reacted with 2a and 5e formed in 70%
yield. We subsequently subjected various 2-ary-N-
tosylaziridines and 2-aryl/alkyl substituted NH-free indoles to
the optimized one-pot ROC conditions to further generalize the
strategy. Electron-rich 5-methyl-2-phenyl-1H-indole (2b) was
reacted with 1a and 5f formed in 80% yield within 15 min. The
transformation was successful with 2-(3-bromophenyl)-N-
tosylaziridine (1f) and 5g was obtained in comparable yield
(79%). Increase in the efficiency of the transformation was
noted when 2-(4-fluorophenyl)-1H-indole (2c) was reacted with
The synthetic significance of the strategy was further
demonstrated by the synthesis of enantioenriched 3-
spiropiperidino indolenines by reacting enantiopure activated
aziridine (R)-1a (>99% ee) with a range of substituted 2-
2 | J. Name., 2012, 00, 1-3
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Scheme 4. Diastereoselective Synthesis of 3-Spiropiperidino Indolenines from 2-Phenyl-
N-tosylaziridine and Substituted Propargyl Carbonates
aryl/alkyl-1H-indoles. While 2-phenyl and 2-methyl-1H-indoles
2a and 2f furnished the respective products (S)-5a and (S)-5l
with excellent enantiomeric excesses (99% ee), the substituted
2-aryl indoles 2b–d produced the corresponding products (S)-5f
Scheme 6. Lewis acid-catalyzed isomerization of 3-Spiropiperidino Indolenine to 3-
(98% ee), (S)-5h (98% ee), and (S)-5j (95% ee) with slightly
reduced optical purity (Scheme 5) which is probably due to the
partial racemization of the starting enantiopure aziridine via
ring-opening by indole followed by bond rotation and
cyclization back to the other enantiomer of the aziridine.
Another possibility: the ring-opening product may undergo
another SN2 attack by indole itself giving rise to the other
enantiomer of the ring-opening product. We do believe that
these two processes are responsible for reduced ee in these
cases depending on the nucleophilicity of different indoles.20
Spirodihydropyridino Indolenine.
co-ordinates with the nitrogen of the aziridine
sulfonyl oxygen) to generate a highly reactive intermediate
The indole nucleophile attacks the benzylic position of in an
SN2 fashion to generate that subsequently rearomatizes to
generate the corresponding ring-opened product . In the next
step, the propargyl carbonate and Pd(0) catalyst get involve in
a decarboxylative oxidative addition reaction to form the
cationic Pd-allenyl species . The in-situ generated tert-
butoxide anion deprotonates the N–H of the sulfonamide group
of leading to the anionic species . Next, the negatively
charged nitrogen of the sulfonamide group attacks the central
carbon of Pd-allene to form the Pd-carbenoid species that
subsequently undergo proton migration to form the
corresponding Pd-π-allyl species . Subsequent spirocyclization
from the indolyl-C3 center and reductive elimination generate
the desired 3-spiropiperidino indolenine and Pd(0) reenters
1 (or with the
A.
A
B
3
4
C
3
D
C
E
F
5
Scheme 5. Enantiospecific synthesis of 3-spiropiperidino indolenines from enantiopure
2-phenyl-N-tosylaziridine.
into the catalytic cycle. Now, the formation of 5q from the
reactions of aziridine 1a and 1H-indole 2a with the isomeric
phenyl-substituted propargyl carbonates 4b and 4c could only
be explained by the presence of a common intermediate F due
to its delocalized nature. The concomitant spirocyclization from
the indolyl-C3 center must take place at the more stable
We envisaged a novel strategy to convert the synthesized 3-
spiropiperidino
indolenines
into
the
isomeric
dihydropyridines21 by Lewis acid-catalyzed isomerization of the
exocyclic double bond. Therefore, when 5j was treated with 2.0
equiv of zinc(II) bromide in benzene at 80 °C for 1 h, the
benzylic position of the Pd-π-allyl species F. Formation of the cis
corresponding 3-spirodihydropyridino indolenine
6 formed in
diastereomer of 5q would result in severe steric congestion
between 2-Ph and 3′-Ph groups which is absent in the trans
diastereomer. Hence, both transformations exclusively favor
the formation of the trans diastereomer 5q (Scheme 7).
excellent yield (82%, Scheme 6a). We directed our subsequent
efforts to construct 3-spiropiperidino indoleninone framework
that could be useful as versatile synthetic precursors for other
privileged heterocycles22 from the synthesized 3-
spiropiperidino indolenines by the oxidative cleavage of the
exocyclic C=C bond. Accordingly, when 5a was treated with 5
mol % ruthenium(III) chloride and 6.0 equiv of sodium periodate
in a CH3CN, CCl4 and H2O solvent system (2:1:1) at room
temperature for 40 min,23 the corresponding 3-spiropiperidino
To conclude, we have developed
a highly valued
transformation for the synthesis of a wide range of 3-
spiropiperidino indolenines possessing an exocyclic olefinic
moiety at the 2-position of the piperidine ring via one-pot Lewis
acid catalyzed SN2-type ring opening of activated aziridines with
2-substituted
1H-indoles
followed
by
Pd-catalyzed
indoleninone
7 formed in 65% yield (Scheme 6b). We next
spirocyclization with propargyl carbonates. The high yields,
excellent diastereo- and enantiospecificity and the wide
substrate scope of the synthesized products underscore the
utility and efficiency of the transformation. We strongly believe
that the methodology will be useful in synthetic organic and
medicinal chemistry for the construction of such spirocyclic aza-
heterocycles of biological relevance.
attached a highly functionalizable ‘alkyne arm’24 to the
synthesized 3-spiropiperidino indolenines by subjecting 5k to
the classic Sonogashira coupling reaction conditions25 along
with phenyl acetylene (8) in the presence of 5 mol % CuI and 10
mol % Pd(PPh3)2Cl2 in 1:1 triethylamine and DMF solvent system
at 90 °C for 5 h. Gratifyingly, we observed the formation of the
corresponding coupling product 9 in 71% yield (Scheme 6c).
M.K.G. is grateful to IIT Kanpur, India and CSIR, India for
financial support. S.P. thanks CSIR, India for research fellowship.
On the basis of the experimental observations, a plausible
mechanism for the formation of 3-spiropiperidino indolenines
has been provided in Scheme 7. At first, the Lewis acid
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Scheme 7. Plausible mechanistic pathway for the synthesis of 3-spiropiperidino indolenines from activated aziridines via ring
opening with 1H-indoles followed by dearomatizing spirocyclization with propargyl carbonate.
13 P.-L. Zhu, Z. Zhang, X.-Y. Tang, I. Marek and M. Shi,
References
ChemCatChem 2015, 7, 595.
1
C. A. Stump, A. G. Quigley, C. R. Theberge and M. R. Wood,
PCT Int. Appl. (2010), WO 2010107605 A1 20100923.
(a) S. Peddi, M. V. Patel and J. J. Rohde, U.S. Pat. Appl. Publ.
(2010), US 20100267738 A1 20101021; (b) H. Nakashima, T.
Araki, T. Ogamino, Y. Kaneko, K. Abe, K. Shibuya and T. Ohgiya,
PCT Int. Appl. (2008), WO 2008142859 A1 20081127.
(a) Y.-K. Xu, L. Yang, S.-G. Liao, P. Cao, B. Wu, H.-B. Hu, J. Guo
and P. Zhang, J. Nat. Prod. 2015, 78, 1511; (b) C.-T. Liu, Q.-W.
Wang and C.-H. Wang, J. Am. Chem. Soc. 1981, 103, 4634; (c)
C. Rujjanawate, D. Kanjanapothi, A. Panthong, J.
Ethnopharmacol. 2003, 89, 91.
14 (a) M. K. Ghorai, A. Bhattacharyya, S. Das and N. Chauhan,
Top. Heterocycl. Chem. 2016, 41, 49 and references cited
therein; (b) M. Nonn, A. M. Remete, F. Fülöp and L. Kiss,
Tetrahedron 2017, 73, 5461; (c) N. Piens and M. D'Hooghe,
Eur. J. Org. Chem. 2017, 5943; (d) J.-J. Feng and J. Zhang, ACS
Catal. 2016, 6, 6651; (e) H. N. Rubin, K. Van Hecke, J. J. Mills,
J. Cockrell and J. B. Morgan, Org. Lett. 2017, 19, 4976; (f) S. C.
Schmid, I. A. Guzei and J. M. Schomaker, Angew. Chem., Int.
Ed. 2017, 56, 12229; (g) X. Li, J. Guo, L. Lin, H. Hu, F. Chang, X.
Liu and X. Feng, Adv. Synth. Catal. 2017, 359, 3532; (h) J.
Dolfen, K. Vervisch, N. De Kimpe and M. D'Hooghe Chem.—
Eur. J. 2016, 22, 4945.
15 (a) C. K. Shahi, S. Pradhan, A. Bhattacharyya, R. Kumar, M. K.
Ghorai, Eur. J. Org. Chem. 2017, 3487; (b) S. Pradhan, C. K.
Shahi, A. Bhattacharyya, N. Chauhan, M. K. Ghorai,
ChemistrySelect 2017, 2, 550; (c) S. Pradhan, C. K. Shahi, A.
Bhattacharyya, N. Chauhan, M. K. Ghorai, Org. Lett. 2017, 19,
3438; (d) C. K. Shahi, A. Bhattacharyya, Y. Nanaji, M. K. Ghorai,
J. Org. Chem. 2017, 82, 37.
2
3
4
5
(a) M. J. James, P. O'Brien, R. J. K. Taylor and W. P. Unsworth,
Chem.—Eur. J. 2016, 22, 2856; (b) R.-D. Gao, C. Liu, L.-X. Dai,
W. Zhang, and S.-L. You, Org. Lett. 2014, 16, 3919.
(a) K. G. Liu, J. R. Lo and A. J. Robichaud, Tetrahedron 2010
,
66, 573; (b) P. Golubev, O. Bakulina, D. Dar'in and M. Krasavin,
Eur. J. Org. Chem. 2016, 3969; (c) P. Golubev and M. Krasavin,
Eur. J. Org. Chem. 2017, 1740; (d) V. Estevez, L. Kloeters, N.
Kwietniewska, E. Vicente-Garcia, E. Ruijter and R. V. A. Orru,
Synlett 2017, 28, 376; (e) R. E. Lyle and L. Skarlos, Chem.
Commun. 1966, 644; (f) J. G. Rodríguez, Y. Benito and F.
Temprano, J. Heterocycl. Chem. 1985, 22, 1207; (g) Y.-D. Shao
and S.-K. Tian, Chem. Commun. 2012, 48, 4899.
16 (a) A. Bhattacharyya, C. K. Shahi, S. Pradhan, M. K. Ghorai,
Org. Lett. 2018, 20, 2925; (b) A. Bhattacharyya, C. V. Kavitha,
M. K. Ghorai, J. Org. Chem. 2016, 81, 6433; (c) I. A. Wani, M.
Sayyad, M. K. Ghorai, Chem. Commun. 2017, 53, 4386.
17 J. Wang, M. Sánchez-Roselló, J. L. Aceña, C. del Pozo, A. E.
Sorochinsky, S. Fustero, V. A. Soloshonok and H. Liu, Chem.
Rev. 2014, 114, 2432.
6
7
8
Y. Benito, L. Canoira, N. Martinez-Lopez, J. G. Rodriguez and F.
Temprano, J. Heterocycl. Chem. 1987, 24, 623.
J. W. Huffman, C. B. S. Rao and T. Kamiya, J. Org. Chem. 1967
32, 697.
(a) S. Sakai, E. Yamanaka, M. Kitajima, M. Yokota, N. Aimi, S.
Wongseripatana and D. Ponglux, Tetrahedron Lett. 1986, 27,
4585; (b) Q.-F. Wu, H. He, W.-B. Liu and S.-L. You, J. Am. Chem.
Soc. 2010, 132, 11418; (c) X. Zhang, W.-B. Liu, Q.-F. Wu and S.-
L. You, Org. Lett. 2013, 15, 3746; (d) A. E. Nibbs, T. D.
Montgomery, Y. Zhu and V. H. Rawal, J. Org. Chem. 2015, 80,
4928; (e) T. D. Montgomery, A. E. Nibbs, Y. Zhu and V. H.
Rawal, Org. Lett. 2014, 16, 3480.
,
18 C. Zhang, Org. Biomol. Chem. 2014, 12, 6580.
19 See the Supporting Information for details.
20 (a) M. K. Ghorai, D. P. Tiwari and N. Jain, J. Org. Chem. 2013
,
78, 7121; (b) P. Sykes, in A Guidebook in Mechanism in Organic
Chemistry, John Wiley and Sons, Inc., New York, 6th edn, 1985,
p. 89.
21 (a) M. Z. Wrona and G. Dryhurst, Bioorg. Chem. 1990, 18, 291;
(b) M. Z. Wrona and G. Dryhurst, Biochem. Pharmacol. 1991
,
41, 1145.
9
Q. Cai, C. Zheng, J.-W. Zhang and S.-L. You, Angew. Chem. Int.
Ed. 2011, 50, 8665.
22 Z. Zuo, W. Xie and D. Ma, J. Am. Chem. Soc. 2010, 132, 13226.
23 P. H. J. Carlsen, T. Katsuki, V. S. Martin and K. B. Sharpless, J.
Org. Chem. 1981, 46, 3936.
24 C. Balakrishnan, S. Natarajan and M. A. Neelakantan, RSC Adv.
2016, 6, 102482.
25 K. Sonogashira, J. Organomet. Chem. 2002, 653, 46.
10 G. Arnott, H. Brice, J. Clayden and E. Blaney, Org. Lett. 2008
,
10, 3089.
11 H. H. Ong, and M. N. Agnew, J. Heterocycl. Chem. 1981, 18,
815.
12 J. T. R. Liddon, A. K. Clarke, R. J. K. Taylor and W. P. Unsworth,
Org. Lett. 2016, 18, 6328.
This journal is © The Royal Society of Chemistry 20xx
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