Catalytic Diastereoselective [5 + 2] Annulation of N-Acryloyl Indoles with Cyclic Sulfonyl Enamides: Facile Access to Isoeburnamonine

Article abstract of DOI:10.1021/acs.orglett.9b04556

ZnBr₂-catalyzed stereoselective [5 + 2] annulation of N-acryloyl indoles with cyclic sulfonyl enamides is reported, providing a concise and efficient synthesis of isoeburnamonine, which is the key intermediate for norvincamine. Both [2 + 2] and

Full text of DOI:10.1021/acs.orglett.9b04556

pubs.acs.org/OrgLett
Letter
Catalytic Diastereoselective [5 + 2] Annulation of N‑Acryloyl Indoles
with Cyclic Sulfonyl Enamides: Facile Access to Isoeburnamonine
Song Wei, Long Zheng, Sunewang R. Wang,* and Yong Tang*
Cite This: https://dx.doi.org/10.1021/acs.orglett.9b04556
Read Online
sı
*
Metrics & More
Article Recommendations
Supporting Information
ACCESS
ABSTRACT: ZnBr2-catalyzed stereoselective [5 + 2] annulation of
N-acryloyl indoles with cyclic sulfonyl enamides is reported,
providing a concise and efficient synthesis of isoeburnamonine,
which is the key intermediate for norvincamine. Both [2 + 2] and [4
+ 2] cycloadducts, depending on the ring size of the enamides, have
been shown to be the important intermediates for this [5 + 2]
annulation.
onor−acceptor (D−A) cyclobutanes have proven as
Dpowerful synthetic synthons for the rapid construction of
highly substituted (poly)cyclic compounds in recent years.1−4
Remarkably, [4 + 2] cycloaddition reactions of such cyclo-
butane synthons with substituted indoles have been well-
demonstrated in total synthesis of several bioactive indoline
alkaloids, such as ( )-aspidospermidine,5 ( )-11-demethoxy-
16-epi-myrtoidine,6 and ( )-akuammicine7 by us and others
(see Figure 1a). Recently, France and co-workers have
reported an elegant intramolecular ring-opening cyclization
of D−A cyclobutanes produced in situ from a variety of
alkenes such as aromatic alkenes and vinyl sulfides to access
azepino[1,2-a]indole cores.8,9 However, they found that
reactions with N-acyl enamides failed to deliver the aminated
azepino[1,2-a]indoles that are prevalent in the core structure
of bioactive indole alkaloids such as correantine B and
akagerine. Motivated by our success in Lewis-acid-catalyzed
stereoselective cyclizations of cyclic N-tosyl enamides (1) with
activated Michael acceptors,10 especially the [2 + 2] annulation
to give the D−A amino-cyclobutanes,10b we attempted to
prepare the troublesome aminated azepino[1,2-a]indoles by
the use of cyclic sulfonyl enamides. We report herein the
ZnBr2-catalyzed diastereoselective annulation of 1 with N-
acryloyl indoles 2 to the tetracyclic amino-azepino[1,2-
a]indoles 3 (see Figure 1b).11 More importantly, this method
provides concise access to isoeburnamonine (4),12 which is the
key intermediate in total synthesis of norvincamine reported by
the Winterfeldt group.13
Figure 1. Cyclizations with D−A cyclobutanes for natural indole
alkaloid synthesis.
Our study was commenced with the reaction between N-
tosyl enamide 1a (0.10 M, in DCM) and N-acryloyl indole 2a
(1.1 equiv) catalyzed by 10 mol % of ZnBr2 at 25 °C. To our
delight, a single azepino[1,2-a]indole diastereomer 3aa was
produced in 41% yield (Table 1, entry 1), the relative
configuration of which was unambiguously confirmed by
Received: December 19, 2019
https://dx.doi.org/10.1021/acs.orglett.9b04556
© XXXX American Chemical Society
Org. Lett. XXXX, XXX, XXX−XXX
A

Organic Letters
pubs.acs.org/OrgLett
Letter
a
Table 1. Optimization of Reaction Conditions
b
entry
catalyst
ZnBr2
ZnBr2
ZnCl2
FeCl3
Sc(OTf)3
Yb(OTf)3
In(OTf)3
Cu(ClO4)2·6H2O
Zn(ClO4)2·6H2O
ZnBr2
time (h)
yield (conversion) (%)
c
1
24
24
24
24
24
24
24
24
24
48
48
17
48
41 (100)
74 (92)
51 (86)
39 (87)
65 (91)
69 (90)
63 (88)
54 (99)
64 (83)
2
3
4
5
6
7
8
9
d
10
69 (100)
e
d
11
12
13
ZnBr2
ZnBr2
ZnBr2
81 (100)
e f
d
,
77 (100)
g
d
83 (100)
a
Reaction conditions: 1a (0.10 M, 1.0 equiv), 2a (1.1 equiv), catalyst
b
(10 mol %), and 4 Å MS (100.0 mg) in DCM (1.0 mL), 25 °C. The
conversion and the yield were determined by the H NMR spectrum
1
of the crude mixture with 1,1,2,2-tetrachloroethane (TTCE) as an
c
d
e
internal standard. Run without 4 Å MS. Isolated yield. Run with
f
g
0.24 M of 1a in DCM (1.0 mL). Run at 35 °C. Run with 0.24 M of
2a (1.0 equiv) and 1a (1.1 equiv) in DCM (1.0 mL).
single-crystal X-ray analysis.14 Note that the relative stereo-
chemical outcome between the ester group and the electron-
donating substituent in the alkene components was completely
reversed, when compared to those reported in the work of the
France group,8a possibly influenced by the cyclic structure.
Moreover, the addition of 4 Å MS improved the yield to 74%,
although the conversion of 1a was only 92% (Table 1, entry 2).
Other Lewis acids were then screened in the presence of 4 Å
MS. While Yb(OTf)3 showed an activity comparable to that of
zinc bromide, other frequently used Lewis acidic metal
chlorides, triflates, and perchlorate hydrates resulted in inferior
yields of 3aa with similar conversions (Table 1, entries 3−9).
Within an extended time, 1a was fully consumed; however, the
yield of 3aa changed slightly (Table 1, entry 10). A screening
of the concentration of 1a showed that the reaction performed
at a higher concentration gave 3aa in 81% isolated yield (Table
1, entry 11).14 Warming the reaction at 35 °C remarkably
accelerated the reaction, but a slight decrease in the yield was
observed (Table 1, entry 12). To our delight, 3aa was also
isolated in good yield when N-acryloyl indole 2a, which is the
more-complex C5 component, was used as the limiting reagent
(Table 1, entry 13). No other diastereomers were observed in
the reactions examined.
With the optimal reaction conditions in hand, the scope of
the [5 + 2] annulation with various N-tosyl enamides was
studied. As shown in Figure 2, N-tosylated 2,3-dihydropyrroles
with 4-alkyl substituents, such as methyl (1a), ethyl (1b), n-
propyl (1c), allyl (1d), and benzyl (1e), reacted smoothly with
2a at 25 °C, giving the corresponding azepino[1,2-a]indoles
(3aa−3ea) as the single diastereomer in good to excellent
yields. The allyl group in 3da could allow for further
elaboration. Interestingly, N-tosyl-2,3-dihydropyrrole (1f) was
also suitable for the [5 + 2] annulation, but 3fa was obtained in
Figure 2. Scope for the [5 + 2] annulation: Unless otherwise
specified, 1 (0.26 mmol), 2 (0.24 mmol), ZnBr2 (10 mol %), and 4 Å
MS (100.0 mg) in DCM (1.0 mL), 25 °C, 48 h. Isolated yield.
[Footnote a indicates conditions including In(OTf)3 (15 mol %) and
4 Å MS (30.0 mg).]
57% yield with a moderate diastereoselectivity, indicating the
important role of the 4-substituents in the cyclic N-sulfonyl
enamides for the excellent diastereomeric ratio (dr) selectivity.
Unfortunately, 4-arylated N-sulfonyl 2,3-dihydropyrroles were
unreactive, possibly because of the reduced reactivity of the
double bond caused by the conjugate effect of aryls. In
addition, this annulation was sensitive to the ring size of the
cyclic enamide. For example, the reaction with the six-
membered ring enamide 1g was much slower even warmed
at 35 °C. Moreover, like the acyclic sulfonyl enamides, the
reaction with the seven-membered ring enamide N-tosyl-6-
methyl-2,3,4,5-tetrahydro-1H-azepine produced a complicated
mixture.
A wide range of functional groups on the indole ring of N-
acryloyl indoles 2 were well-tolerated in the ZnBr2-catalyzed [5
+ 2] annulation (Figure 2). Specifically, 3-methylated
substrates 2 with halo (2b, 2e−2g, and 2j), methyl (2c and
2h), and methoxy (2d and 2i) substituents on the 4-, 5-, or 6-
positions of the indole ring reacted readily with 1a under the
optimal reaction conditions, diastereoselectively affording the
corresponding products (3ab−3aj) in yields up to 90%.
Moreover, the 3-methyl group in 2a could be replaced by ethyl
(2k) or the β-functionalized ethyl groups (2l−2n) without the
significant loss of the product yields. Interestingly, the 3-
unsubstituted indole 2o was less reactive and only 51% yield of
3ao was obtained. Given the promising further cyclization of
the tethered alkyl halides in 3am and 3an with the pyrrolidine
B
https://dx.doi.org/10.1021/acs.orglett.9b04556
Org. Lett. XXXX, XXX, XXX−XXX

Organic Letters
pubs.acs.org/OrgLett
Letter
ring after removal of the tosyl group, we became interested in
the application of this [5 + 2] annulation for the synthesis of
isoeburnamonine 4. Thus, the reaction of 1b and 2n was
attempted, which delightedly gave the desired product 3bn in
74% isolated yield under slightly harsher conditions. Notably,
the stronger Lewis acid In(OTf)3 was used for the reaction of
the less-reactive six-membered congener 1h with 2n, giving
3hn in 60% yield heated at 35 °C for 72 h. As shown by the X-
ray structure of 3hn,14 the displacement of the 3-methyl group
with the long-chain 3-alkyl substituents did not affect the
relative configuration of the products.
Scheme 2. ZnBr2-Catalyzed Formation and Ring Expansion
of D−A Cyclobutane Intermediates
The synthetic utility of this annulation was further illustrated
by a four-step synthesis of isoeburnamonine 4 in 31% overall
yield (Scheme 1).13 The synthesis started with ZnBr2-catalyzed
Scheme 1. Gram-Scale Reaction and a Concise Synthesis of
Isoeburnamonine 4
isolated pure compound 7ga partially transformed to the
azepino[1,2-a]indole product 3ga and the original N-acryloyl
indole 2a in yields of 41% and 16%, respectively (Scheme 3).
reaction of N-tosyl-4-ethyl-2,3-dihydropyrrole 1b with indole
2n on the gram scale, diastereoselectively affording 1.17 g of
3bn in 72% isolated yield. The compound 3bn was smoothly
decarboxylated by treatment with NaCl in wet DMSO at 130
°C, giving the product 5 in 85% isolated yield. After removal of
the N-tosyl group with Na/naphthalene, an intramolecular
cyclization finally furnished the target compound 4 in 50%
yield.
Scheme 3. Isolation of a Bicyclic N,O-Acetal Intermediate
In the first study on the [5 + 2] annulation reported by
France and co-workers,8a they have confirmed one of the
diastereomers of the 1,1,2-trisubstituted cyclobutanes from the
[2 + 2] cycloaddition as an important intermediate in the
reaction. Interestingly, from the reaction of 1b with 2n
catalyzed by ZnBr2 at 25 °C for 144 h, a single cis diastereomer
cis-6bn was isolated in 16% yield along with 57% yield of 3bn.
Moreover, its trans isomer trans-6bn, the molecular structure
of which was further confirmed by single-crystal X-ray
analysis,14 was obtained in 17% yield when cis-6bn was
subjected to catalytic ZnBr2 for further transformation to 3bn
(Scheme 2). Compared with the ring expansion experiment of
trans-6bn catalyzed by ZnBr2, the cyclobutane cis-6bn was
found to be more stable and more selective in the
transformation to 3bn (Scheme 2). Thus, in our reactions
with the cyclic sulfonyl enamides, the reactivity of these
cyclobutane intermediates toward the final azepino[1,2-a]-
indole products seems to be highly dependent on their
stereochemistry.
Thus, the unexpected hetero-[4 + 2] annulation product may
also serve as a key intermediate for the [5 + 2] annulation, very
likely depending on the ring size of the cyclic sulfonyl enamide.
Based on the above observations, a plausible mechanism via
1,4- zwitterionic intermediate I, which can also be regenerated
from the cyclobutane (6) or the bicyclic N,O-acetal (7)
intermediates that were produced, depending on the ring size
of sulfonyl enamides, was proposed in Scheme 4. The facile
reversibility of the ZnBr2-catalyzed [2 + 2] and [4 + 2]
cycloadditions between the two substrates provides a
continuous supply of intermediate I to overcome the entropic
activation barrier for the seven-membered ring formation in
the [5 + 2] annulation.15 Possibly due to the unfavored
conformation, intermediate I with the six-membered N-
heterocycle seems to be less reactive for the intramolecular
Friedel−Crafts-type alkylation to give the product 3. Thus, the
competing formation of N-acryloyl indole 2a from the [4 + 2]
In addition to 28% yield of the desired [5 + 2] cycloadduct
3ga, the bicyclic N,O-acetal 7ga was isolated in 33% yield from
the ZnBr2-promoted reaction of the six-membered ring
enamide 1g with 2a at 25 °C for 48 h. Surprisingly, upon
further exposure to 10 mol % of ZnBr2 at 25 °C for 48 h, the
C
https://dx.doi.org/10.1021/acs.orglett.9b04556
Org. Lett. XXXX, XXX, XXX−XXX

Organic Letters
pubs.acs.org/OrgLett
Letter
Shanghai Engineering Research Center of Molecular
Scheme 4. Proposed Mechanism for [5 + 2] Annulation
Therapeutics and New Drug Development, East China Normal
University, Shanghai 200241, China; orcid.org/0000-
0002-7099-2928; Email: rxwang@chem.ecnu.edu.cn
Yong Tang − State Key Laboratory of Organometallic
Chemistry, Shanghai Institute of Organic Chemistry, Chinese
Academy of Sciences, University of Chinese Academy of Sciences,
Shanghai 200032, China; Chang-Kung Chuang Institute, East
China Normal University, Shanghai 200241, China;
orcid.org/0000-0002-5435-9938; Email: tangy@sioc.ac.cn
Authors
Song Wei − State Key Laboratory of Organometallic Chemistry,
Shanghai Institute of Organic Chemistry, Chinese Academy of
Sciences, University of Chinese Academy of Sciences, Shanghai
200032, China
Long Zheng − State Key Laboratory of Organometallic
Chemistry, Shanghai Institute of Organic Chemistry, Chinese
Academy of Sciences, University of Chinese Academy of Sciences,
Shanghai 200032, China
Complete contact information is available at:
https://pubs.acs.org/10.1021/acs.orglett.9b04556
Notes
cycloadduct 7ga was observed (Scheme 3). Accordingly, the
1,4-zwitterionic intermediates generated from larger cyclic or
acyclic N-sulfonyl enamides may be more problematic in the
seven-membered ring formation, thus giving unfruitful results.
In summary, a catalytic stereoselective [5 + 2] annulation of
N-acryloyl indoles with cyclic sulfonyl enamides is described,
providing an efficient four-step synthesis of isoeburnamonine,
the key intermediate for natural product norvincamine, in 31%
overall yield. The use of both the N-sulfonyl protecting group
and the 5- or 6-membered cyclic structure of the enamides are
the key for the success of this [5 + 2] annulation reaction.
More interestingly, in addition to the known D−A cyclo-
butanes, the novel bicyclic N,O-acetals generated from hetero-
[4 + 2] cycloaddition, depending on the ring size of the
enamides, were also defined as the key intermediates for this [5
+ 2] annulation reaction for the first time.
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
■
This work was sponsored by the National Natural Science
Foundation of China (NSFC) (Nos. 21432011 and
21772224), the Strategic Priority Research Program of the
Chinese Academy of Sciences (No. XDB20000000), The
Science and Technology Commission of Shanghai Municipal-
ity (No. 17JC1401200), the NSFC/RGC Joint Research
Scheme (No. 21461162002) to Y.T. The authors also
acknowledge Key Research Program of Frontier Sciences,
CAS (No. QYZDY-SSW-SLH016), the Natural Science
Foundation of Shanghai (No. 17ZR1436900) and Pujiang
Program (No. 19PJ1402700) to S.R.W.
REFERENCES
■
(1) (a) Fu, N.-Y.; Chan, S.-H.; Wong, H. N. C. In The Chemistry of
Cyclobutanes; Rappoport, Z., Liebman, J. F., Eds.; Wiley: Chichester,
U.K., 2005; Vol. 1, p 357. (b) Reissig, H. U.; Zimmer, R. Thrilling
Strain! Donor−Acceptor-Substituted Cyclobutanes for the Synthesis
of (Hetero)cyclic Compounds. Angew. Chem., Int. Ed. 2015, 54, 5009.
(c) De, N.; Yoo, E. J. Recent Advances in the Catalytic Cycloaddition
of 1,n-Dipoles. ACS Catal. 2018, 8, 48.
ASSOCIATED CONTENT
* Supporting Information
■
sı
The Supporting Information is available free of charge at
https://pubs.acs.org/doi/10.1021/acs.orglett.9b04556.
Experimental procedures and characterization data
(PDF)
(2) (a) Hu, J.-L.; Wang, L.; Xu, H.; Xie, Z.; Tang, Y. Highly
Diastereoselective and Enantioselective Formal [4 + 3] Cycloaddition
of Donor−Acceptor Cyclobutanes with Nitrones. Org. Lett. 2015, 17,
2680. (b) Hu, J.-L.; Zhou, L.; Wang, L.; Xie, Z.; Tang, Y. Copper
Catalyzed Asymmetric [4 + 2] Annulations of D−A Cyclobutanes
with Aldehydes. Chin. J. Chem. 2018, 36, 47. (c) Kuang, X.-K.; Zhu, J.;
Zhou, L.; Wang, L.; Wang, S. R.; Tang, Y. Synergetic Tandem
Enantiomeric Enrichment in Catalytic Asymmetric Multi-Component
Reactions (AMCRs): Highly Enantioselective Construction of
Tetracyclic Indolines with Four Continuous Stereocenters. ACS
Catal. 2018, 8, 4991.
(3) (a) Parsons, A. T.; Johnson, J. S. Formal [4 + 2] Cycloaddition
of Donor−Acceptor Cyclobutanes and Aldehydes: Stereoselective
Access to Substituted Tetrahydropyrans. J. Am. Chem. Soc. 2009, 131,
14202. (b) Levens, A.; Ametovski, A.; Lupton, D. W. Enantioselective
[4 + 2] Annulation of Donor−Acceptor Cyclobutanes by N-
Heterocyclic Carbene Catalysis. Angew. Chem., Int. Ed. 2016, 55,
Accession Codes
CCDC 1968687−1968689 contain the supplementary crys-
tallographic data for this paper. These data can be obtained
free of charge via www.ccdc.cam.ac.uk/data_request/cif, or by
emailing data_request@ccdc.cam.ac.uk, or by contacting The
Cambridge Crystallographic Data Centre, 12 Union Road,
Cambridge CB2 1EZ, UK; fax: + 44 1223 336033.
AUTHOR INFORMATION
Corresponding Authors
■
Sunewang R. Wang − State Key Laboratory of Organometallic
Chemistry, Shanghai Institute of Organic Chemistry, Chinese
Academy of Sciences, University of Chinese Academy of Sciences,
Shanghai 200032, China; Chang-Kung Chuang Institute and
D
https://dx.doi.org/10.1021/acs.orglett.9b04556
Org. Lett. XXXX, XXX, XXX−XXX

Organic Letters
pubs.acs.org/OrgLett
Letter
16136. (c) Garve, L. K. B.; Kreft, A.; Jones, P. G.; Werz, D. B.
Synthesis of 2-Unsubstituted Pyrrolidines and Piperidines from
Donor−Acceptor Cyclopropanes and Cyclobutanes: 1,3,5-Triazinanes
as Surrogates for Formylimines. J. Org. Chem. 2017, 82, 9235.
(d) Kreft, A.; Ehlers, S.; Jones, P. G.; Werz, D. B. Ring-Opening
Reactions of Donor−Acceptor Cyclobutanes with Electron-Rich
Arenes, Thiols, and Selenols. Org. Lett. 2019, 21, 6315.
(4) (a) Moustafa, M. M. A. R.; Stevens, A. C.; Machin, B. P.;
Pagenkopf, B. L. Formal [4 + 2] Cycloaddition of Alkoxy-Substituted
Donor−Acceptor Cyclobutanes and Aldehydes Catalyzed by Yb-
(OTf)3. Org. Lett. 2010, 12, 4736. (b) Stevens, A. C.; Palmer, C.;
Pagenkopf, B. L. The Formal [4 + 3] Cycloaddition between Donor−
Acceptor Cyclobutanes and Nitrones. Org. Lett. 2011, 13, 1528.
(c) Vemula, N.; Stevens, A. C.; Schon, T. B.; Pagenkopf, B. L. The [4
+ 2] Cycloaddition of Donor−Acceptor Cyclobutanes and Nitro-
soarenes. Chem. Commun. 2014, 50, 1668.
(13) (a) Takayama, H.; Winterfeldt, E. Reactions with Indole
Derivatives, XLIX. The Stereoselective Total Synthesis of D-
̈
Norvincamine. Heterocycles 1984, 22, 1565. (b) Bolsing, E.;
Winterfeldt, E. Reactions of Indole Derivatives. XLVI. Stereoselective
Route to Isoeburnamonine. Chem. Ber. 1981, 114, 1932.
(14) Experimental procedures and characterization data are provided
in the Supporting Information.
(15) Byrne, L. A.; Gilheany, D. G. Simple Syntheses of Seven-
Membered Rings via an Entropy/Strain Reduction Strategy. Synlett
2004, 933.
(5) Kawano, M.; Kiuchi, T.; Negishi, S.; Tanaka, H.; Hoshikawa, T.;
Matsuo, J.; Ishibashi, H. Regioselective Inter- and Intramolecular
Formal [4 + 2] Cycloaddition of Cyclobutanones with Indoles and
Total Synthesis of ( )-Aspidospermidine. Angew. Chem., Int. Ed.
2013, 52, 906.
(6) Zhu, J.; Cheng, Y.-J.; Kuang, X.-K.; Wang, L.; Zheng, Z.-B.;
Tang, Y. Highly Efficient Formal [2 + 2 + 2] Strategy for the Rapid
Construction of Polycyclic Spiroindolines: A Concise Synthesis of 11-
Demethoxy-16-epi-myrtoidine. Angew. Chem., Int. Ed. 2016, 55, 9224.
(7) Feng, L.-W.; Ren, H.; Xiong, H.; Wang, P.; Wang, L.; Tang, Y.
Reaction of Donor-Acceptor Cyclobutanes with Indoles: A General
Protocol for the Formal Total Synthesis of ( )-Strychnine and the
Total Synthesis of ( )-Akuammicine. Angew. Chem., Int. Ed. 2017, 56,
3055.
(8) (a) Shenje, R.; Martin, M. C.; France, S. A Catalytic
Diastereoselective Formal [5 + 2] Cycloaddition Approach to
Azepino[1,2-a]indoles: Putative Donor−Acceptor Cyclobutanes as
Reactive Intermediates. Angew. Chem., Int. Ed. 2014, 53, 13907.
(b) Parker, A. N.; Martin, M. C.; Shenje, R.; France, S. Calcium-
Catalyzed Formal [5 + 2] Cycloadditions of Alkylidene β-Ketoesters
with Olefins: Chemodivergent Synthesis of Highly Functionalized
Cyclohepta[b]indole Derivatives. Org. Lett. 2019, 21, 7268.
(9) For a recent review on [5 + 2] cycloadditions and their synthetic
application, see: Gao, K.; Zhang, Y.-G.; Wang, Z.; Ding, H. Recent
Development on the [5 + 2] Cycloadditions and Their Application in
Natural Product Synthesis. Chem. Commun. 2019, 55, 1859.
(10) (a) Liu, Q.-J.; Wang, L.; Kang, Q.-K.; Zhang, X. P.; Tang, Y.
Cy-SaBOX/Copper(II)-Catalyzed Highly Diastereo- and Enantiose-
lective Synthesis of Bicyclic N,O Acetals. Angew. Chem., Int. Ed. 2016,
55, 9220. (b) Wei, S.; Yin, L.; Wang, S. R.; Tang, Y. Catalyst-
Controlled Chemoselective All-Alkene [2 + 2 + 2] and [2 + 2]
Cyclizations of Enamides with Electron-Deficient Alkenes. Org. Lett.
2019, 21, 1458.
(11) For examples on cyclizations with sulfonyl enamides, see:
(a) Feltenberger, J. B.; Hayashi, R.; Tang, Y.; Babiash, E. S. C.; Hsung,
R. P. Enamide-Benzyne-[2 + 2] Cycloaddition: Stereoselective
Tandem [2 + 2]-Pericyclic Ring-Opening-Intramolecular N-Tethered
[4 + 2] Cycloadditions. Org. Lett. 2009, 11, 3666. (b) Gigant, N.;
Gillaizeau, I. Construction of Nitrogen-Fused Tetrahydroquinolines
via a Domino Reaction. Org. Lett. 2012, 14, 4622. (c) Dohi, T.;
Toyoda, Y.; Nakae, T.; Koseki, D.; Kubo, H.; Kamitanaka, T.; Kita, Y.
Phenol and Aniline Oxidative Coupling with Alkenes by Using
Hypervalent Iodine Dimer for the Rapid Access to Dihydrobenzofur-
ans and Indolines. Heterocycles 2015, 90, 631. (d) Zhou, L.; Yu, S.-Y.;
Tang, Y.; Wang, L. Facile Stereoselective Approach to Diverse
Spiroheterocyclic Tetrahydropyrans: Concise Synthesis of (+)-Brous-
sonetine G and H. Angew. Chem., Int. Ed. 2019, 58, 15016.
(12) One epimer of eburnamonine has been previously named as
́
́
́
“isoeburnamine” as well. See: Novak, L.; Rohal, J.; Szantay, C.;
Czibula, L. Synthesis of Vinca Alkaloids and Related Compounds. VI.
Synthesis of Eburanamonine and Isoburnamonine. Heterocycles 1977,
6, 1149.
E
https://dx.doi.org/10.1021/acs.orglett.9b04556
Org. Lett. XXXX, XXX, XXX−XXX