Diastereoselective and Enantiospecific Synthesis of 1,3-Diamines via 2-Azaallyl Anion Benzylic Ring-Opening of Aziridines

Article abstract of DOI:10.1021/acs.orglett.7b01886

The 1,3-diamine motif appears in numerous complex molecules, yet there are few methods for the stereoselective construction of this moiety. Herein, we demonstrate a stereocontrolled synthesis of 1,3-diamines, which bear up to three contiguous stereogenic centers, through benzylic ring-opening of aziridines with 2-azaallyl anion nucleophiles. Reactions proceed efficiently (yield up to 95%), diastereoselectively (dr up to >20:1), site selectively, and enantiospecifically to deliver products with differentiated amino groups.

Full text of DOI:10.1021/acs.orglett.7b01886

Letter
pubs.acs.org/OrgLett
Diastereoselective and Enantiospecific Synthesis of 1,3-Diamines via
2‑Azaallyl Anion Benzylic Ring-Opening of Aziridines
Kangnan Li,† Alexandria E. Weber,† Luke Tseng, and Steven J. Malcolmson*
Department of Chemistry, Duke University, Durham, North Carolina 27708, United States
S
* Supporting Information
ABSTRACT: The 1,3-diamine motif appears in numerous complex
molecules, yet there are few methods for the stereoselective
construction of this moiety. Herein, we demonstrate a stereocontrolled
synthesis of 1,3-diamines, which bear up to three contiguous
stereogenic centers, through benzylic ring-opening of aziridines with
2-azaallyl anion nucleophiles. Reactions proceed efficiently (yield up to
95%), diastereoselectively (dr up to >20:1), site selectively, and
enantiospecifically to deliver products with differentiated amino groups.
umerous natural products and pharmaceutical agents
contain multiple stereogenic centers bearing a nitrogen
favoring the syn-diastereomer (Scheme 1). In most cases, bond
formation occurs exclusively between the least hindered position
of the nucleophile and the benzylic carbon of the aziridine. All
transformations occur with >98% enantiospecificity (es).9,10
Additionally, 1,3-diamine products with three contiguous
stereogenic centers are generated from trans-disubstituted
aziridines. 2,2-Disubstituted tosylaziridines, unlike epoxides,8
undergo reaction at the fully substituted position11 and also with
complete inversion of stereochemistry to afford 1,3-diamines
bearing a quaternary stereogenic center.
We commenced by exploring the addition of phenyl-
substituted 1a to tosylaziridine 3a (Table 1). Our investigations
indicate that the diphenylketimine activating group of 1a is
crucial for obtaining the desired site isomer of product 4a and
that the tosyl group of the aziridine is essential for reactivity at
−78 °C (at which maximum diastereoselectivity is achieved).12
Although the base identity has little effect at higher temper-
ature,12 the role of the cation on reaction efficiency and
stereoselectivity at −78 °C is profound. The reaction is inefficient
with a Li cation (55% conv, dr = 6.0:1) (Table 1, entry 1), unlike
in reactions with epoxides where it is essential,8 and though the K
salt delivers 84% conversion to 4a, it is less stereoselective (5.0:1
dr) (Table 1, entry 3). The nucleophile generated with
NaHMDS (Table 1, entry 2), however, leads to 76% conversion
(68% yield) to 4a, which is generated as an 8.0:1 mixture of
diastereomers, each as a single enantiomer (es >98%). Increasing
to 2 equiv of nucleophile (Table 1, entry 4) improves conversion
to product (95% yield, dr = 8.0:1, es >98%). The reaction is
completely site selective under all conditions, with C−C bond
formation occurring solely between the less substituted position
of the anion and the aziridine’s benzylic carbon.13 In all cases, syn-
4a is the major diastereomer.14
N
atom; however, there are few approaches that directly and
stereoselectively generate a 1,3-diamine via C−C bond
formation.1−5 The majority of methods have relied on
Mannich-type reactions of enamides2b,e or nitrile enolate
equivalents,2f−j which require subsequent reduction of the
products’ imine or nitrile to generate the diamine. Alternatively,
an N-substituted carbanion might be added to a two-carbon N-
electrophile; largely this has involved reactions with nitro-
alkenes2a or cyanide addition to an aziridine,2c,d which also
necessitate reduction to obtain the 1,3-diamine. Conversely,
Murai has shown that doubly deprotonated thioamides may be
added to tosylaziridines to afford 1,3-diamine scaffolds directly
(Scheme 1, five examples, dr up to 4:1).3b
2-Azaallyl anions have emerged as potent nucleophiles for
accessing chiral amines.6,7 We have recently disclosed 2-azaallyl
anion additions to epoxides to prepare 1,3-amino alcohols.8 In
this work, we report that terminal aryl-substituted tosylaziridines
react efficiently with azaallyl anions, directly delivering products
with a 1,3-diamine framework in up to 95% yield and >20:1 dr,
Scheme 1. Synthesis of 1,3-Diamines by Stereoselective
Additions to Aziridines
The tautomeric aldimine 2a also efficiently undergoes
deprotonation with NaHMDS under the optimized conditions
Received: June 21, 2017
© XXXX American Chemical Society
A
DOI: 10.1021/acs.orglett.7b01886
Org. Lett. XXXX, XXX, XXX−XXX

Organic Letters
Letter
a
substitution undergo diastereoselective reaction with aziridine 3a
(dr = 6.0−9.5:1) (Table 2, entries 1−3 and 7−11). Reactions
with ortho-substituted aryl-containing nucleophiles are efficient
but less selective (Table 2, entries 4, 12, and 13). Hetero-
aromatic-substituted azaallyl anions (Table 2, entries 5, 6 and
14,15) are also competent reaction partners with the thiophenyl
nucleophile leading to the highest stereoselectivity (dr = 9.0:1).
Contrastingly, reaction with the furyl-substituted nucleophile
requires warming to −45 °C,15 generating 4f in 4.0:1 dr. In all
cases, azaallyl anion attack upon aziridine 3a generates a single
product with the exception of the para-methoxyphenyl-
containing azaallyl anion (entry 2).12
Table 1. Azaallyl Anion Counterion Effects
d
conv
b
yield
c
4a dr
es
e
entry imine
base
(%)
(%)
syn/anti
(%)
1
2
3
4
5
1a
1a
1a
1a
2a
LiHMDS
NaHMDS
KHMDS
NaHMDS
NaHMDS
55
76
nd
68
nd
95
90
6.0:1
8.0:1
5.0:1
8.0:1
8.5:1
nd
Azaallyl anions with vinyl and alkynyl substituents effectively
participate in reactions with aziridines (Scheme 2), delivering
>98
nd
84
f
f
>98
>98
>98
>98
Scheme 2. Vinyl- and Alkynyl-Substituted Azaallyl Anion
a−d
a
Additions
Reactions run with 0.1 mmol 3a. See the Supporting Information for
b
experimental details. Based on consumption of 3a as determined by
500 MHz 1H NMR spectroscopy of the unpurified mixture in
c
comparison with an internal standard. Isolated yield of purified
product as a mixture of diastereomers. Determined by 500 MHz H
NMR spectroscopy of the unpurified mixture. Determined by HPLC
analysis of purified products. 2.0 equiv of imine with 3.0 equiv of
d
1
e
f
NaHMDS; nd = not determined.
for ketimine 1a to generate the same resonance-stabilized 2-
azallyl anion. As expected, C−C bond formation with aziridine
3a is just as efficient and stereoselective (dr = 8.5:1, es >98%),
and diamine 4a is isolated in 90% yield (Table 1, entry 5).
Diphenylketimines 1b−g and benzhydrylaldimines 2b−j serve
as azaallyl anion precursors for preparing 1,3-diamines (Table 2).
Additions of aryl-substituted nucleophiles with para- or meta-
a−d
e
See Table 2. Isolated as the terminal alkyne from the Me3Si-
alkyne upon K2CO3/MeOH workup. See the Supporting Information.
a
Table 2. Aryl Group Variation within Azaallyl Anions
allylic and propargylic amines that provide handles for further
functionalization. In these cases, low temperature deprotonation
in the presence of the electrophile avoids nucleophile
decomposition and affords diamines 4q−s in 62−94% yield
(dr = 2.5−3.0:1, es >98%) with 80−90% site selectivity.
Several aryl-substituted terminal aziridines 3b−f efficiently
participate in reactions with azaallyl anions to afford diamine
products 4t−x in 5.5 to >20:1 dr and 61−91% yield (Table 3).
Electron-withdrawing groups in the arene’s para-position are
well-tolerated (Table 3, entry 1). An electron-donating para-
methyl affords diamine 4u in 61% yield (dr = 5.5:1) (Table 3,
b
c
d
entry imine
4, Ar
temp (°C) yield (%)
dr
es (%)
1
2
3
4
5
6
7
8
9
1b
1c
1d
1e
1f
4-BrC6H4
4-OMeC6H4
3-CF3C6H4
2-ClC6H4
2-furyl
−78
−78
−78
−60
−45
−78
−60
−78
−78
−78
−78
−78
−45
−60
−60
73
9.5:1
8.0:1
7.5:1
1.5:1
4.0:1
9.0:1
6.0:1
6.5:1
7.5:1
7.5:1
7.5:1
4.0:1
4.0:1
6.0:1
5.5:1
>98
>98
>98
>98
>98
>98
>98
>98
>98
>98
>98
>98
>98
>98
>98
e
93
89
91
87
82
72
69
78
73
83
92
91
74
79
1g
2b
2c
2d
2e
2f
2-thiophenyl
4-CNC6H4
4-FC6H4
Table 3. Addition of Azaallyl Anions to Aryl-Substituted
a
f
Aziridines
3-OMeC6H4
3-BrC6H4
3-PhC6H4
2-MeC6H4
2,6-Cl2C6H3
4-pyridyl
10
11
12
13
14
15
g
h
i
2g
2h
2i
b
c
d
entry
1
aziridine
4, Ar
yield (%)
dr
es (%)
j
2j
3-pyridyl
3b
3c
3d
3e
3f
4t, 4-CF3C6H4
4u, 4-MeC6H4
4v, 3-MeC6H4
4w, 2-MeC6H4
4x, 2-ClC6H4
88
61
80
91
78
5.5:1
5.5:1
8.0:1
>20:1
>20:1
>98
>98
>98
>98
>98
e
a
b
2
Reactions run with 0.1 mmol 3a. Isolated yield of purified product as
c
a mixture of diastereomers. Determined by 500 MHz 1H NMR
3
4
5
d
spectroscopy of the unpurified mixture. Determined by HPLC
analysis of purified products. Contains ca. 12% of an inseparable site
isomer. Reaction for 5 h. Deprotonation for 2 h. 0.8 mmol scale.
e
f
g
h
i
j
a−d
e
Reaction for 10 h. Reaction for 6 h.
See Table 2. Reaction at −60 °C.
B
DOI: 10.1021/acs.orglett.7b01886
Org. Lett. XXXX, XXX, XXX−XXX

Organic Letters
Letter
entry 2); however, the more donating para-methoxy substituent
leads only to aziridine decomposition under the reaction
conditions. Both meta- and ortho-substituted aziridine aryl
groups are amenable to azaallyl anion additions, as well
(diamines 4w,x) (Table 3, entries 3−5). All transformations
proceed with >98% enantiospecificity. As the aromatic
substituent is moved from the para- to the ortho-position,
stereoselectivity steadily improves with ortho groups leading to
>20:1 dr.
both diastereomers of 8 are obtained in the same enantiopurity as
aziridine 7 (es >98%), suggesting an SN2-like process.11
An advantage of this method is the differentiation of the two
masked amines within the products, with the benzophenone
imine serving as a double protecting group for one N atom while
the sulfonamide allows for monofunctionalization of the other
(Scheme 5). Hydrolysis of the imine within 4a, prepared on a
Scheme 5. Diversification of the Differentiated Amines within
1,3-Diamines 6a−c, bearing three contiguous stereogenic
centers, are generated when 1,2-disubstituted aziridines 5a−c
undergo ring-opening with the anion of ketimine 1a (Scheme 3).
the 1,3-Diamine Products
Scheme 3. Azaallyl Anion Additions to 1,2-Disubstituted
a-d
Aziridines
a-d
e
f
See Table 2. Reaction performed at −45 °C. Obtained using 2.0
equiv of NaHMDS in 95.5:4.5 er from 5c of equal enantiopurity.
Triphenylpropyldiamine 6a, whose symmetry is broken only by
the differentiated N groups, is obtained as a single enantiomer
with good diastereoselectivity and yield via azaallyl anion
addition (90%, dr = 10.0:1). Diamine 6b, with a smaller Me
group, is generated in 95% yield but with a diminished 3.0:1 dr.
The more sensitive nature of aziridine 5c requires that no excess
base be added to avoid partial aziridine elimination to the
unsaturated α-aminoester. Under these optimal conditions, α,γ-
diaminoester 6c is formed in 41% yield and 10.0:1 dr. The
product is obtained with >98% es, thereby indicating that it arises
via direct anion attack upon the aziridine and not through
conjugate addition to the unsaturated aminoester byproduct.
We have also examined azaallyl anion addition to 2,2-
disubstituted aziridine 7 (Scheme 4). Despite the added steric
gram-scale,12 proceeds under mildly acidic conditions to reveal
the nucleophilic primary amine within 9 (73%, dr >20:1 after a
single recrystallization) (Scheme 5, eq 1).16 Subsequent Ti-
mediated removal of the N-tosyl group17 delivers diamine 10
(66%, dr = 16.5:1) (Scheme 5, eq 2).
Conversely, the sulfonamide within the protected diamine
may be functionalized while retaining the imine, leading to
heterocyclic compounds via intramolecular C−N bond for-
mations. For example, the sulfonamide in 4x takes part in
Buchwald−Hartwig coupling to furnish dihydroindoline 11
(Scheme 5, eq 3).9g,18 Additionally, the terminal alkyne of 4s
undergoes Au-catalyzed cyclization of the sulfonamide to deliver
3-aminopyrrolidine 12 (Scheme 5, eq 4).19
Scheme 4. Enantiospecific Synthesis of a Stereogenic
Quaternary Carbon Center by Azaallyl Anion Addition
Aziridine 7
2-Azaallyl anions are useful building blocks for constructing
chiral amines through C−C bond formation. In this study, we
demonstrate that aziridines efficiently react with azaallyl anions
to prepare 1,3-diamines. Aryl-substituted terminal aziridines are
attacked at their benzylic position in a diastereoselective and
enantiospecific manner to deliver enantioenriched 1,3-diamines
that contain vicinal stereogenic centers. 1,2-Disubstituted
aziridines similarly undergo benzylic ring-opening to afford
diamine products with three contiguous stereogenic centers. A
2,2-disubstituted aziridine reacts enantiospecificially at the
sterically congested benzylic center, affording a 1,3-diamine
with a quaternary stereogenic center. The differentially protected
amines within the products facilitate downstream synthesis.
congestion at the benzylic site, nucleophilic attack exclusively
takes place there to deliver quaternary carbon-containing
diamine 8 in 92% yield, opposite site selectivity to that observed
with analogous epoxides.8 Diastereoselectivity in the trans-
formation is low and was not improved upon cooling; however,
C
DOI: 10.1021/acs.orglett.7b01886
Org. Lett. XXXX, XXX, XXX−XXX

Organic Letters
Letter
5, 2383. (d) Zhu, Y.; Buchwald, S. L. J. Am. Chem. Soc. 2014, 136, 4500.
(e) Li, M.; Berritt, S.; Walsh, P. J. Org. Lett. 2014, 16, 4312.
(f) Matsumoto, M.; Harada, M.; Yamashita, Y.; Kobayashi, S. Chem.
ASSOCIATED CONTENT
* Supporting Information
The Supporting Information is available free of charge on the
ACS Publications website at DOI: 10.1021/acs.orglett.7b01886.
■
S
Commun. 2014, 50, 13041. (g) Fernan
S. P. Chem. Sci. 2015, 6, 4973. (h) Wu, Y.; Hu, L.; Li, Z.; Deng, L. Nature
2015, 523, 445. (i) Li, M.; Yucel, B.; Jimenez, J.; Rotella, M.; Fu, Y.;
Walsh, P. J. Adv. Synth. Catal. 2016, 358, 1910. (j) Li, M.; Gonzalez-
́
dez-Salas, J. A.; Marelli, E.; Nolan,
́
X-ray data for rds504 (CIF)
Experimental procedures, analytical data for new com-
pounds, spectral data (PDF)
́
Esguevillas, M.; Berritt, S.; Yang, X.; Bellomo, A.; Walsh, P. J. Angew.
Chem., Int. Ed. 2016, 55, 2825. (k) Chen, P.; Yue, Z.; Zhang, J.; Lv, X.;
Wang, L.; Zhang, J. Angew. Chem., Int. Ed. 2016, 55, 13316. (l) Liu, J.;
Cao, C.-G.; Sun, H.-B.; Zhang, X.; Niu, D. J. Am. Chem. Soc. 2016, 138,
13103. (m) Guo, C.-X.; Zhang, W.-Z.; Zhou, H.; Zhang, N.; Lu, X.-B.
Chem. - Eur. J. 2016, 22, 17156. (n) Li, M.; Gutierrez, O.; Berritt, S.;
AUTHOR INFORMATION
■
Corresponding Author
*E-mail: steven.malcolmson@duke.edu.
ORCID
Pascual-Escudero, A.; Yesi̧ lcimen, A.; Yang, X.; Adrio, J.; Huang, G.;
Nakamaru-Ogiso, E.; Kozlowski, M. C.; Walsh, P. J. Nat. Chem. 2017,
DOI: 10.1038/nchem.2760.
Steven J. Malcolmson: 0000-0003-3229-0949
Author Contributions
†K.L. and A.E.W. contributed equally.
(7) For select examples of decarboxylative generation of azaallyl
anions, see: (a) Burger, E. C.; Tunge, J. A. J. Am. Chem. Soc. 2006, 128,
10002. (b) Yeagley, A. A.; Chruma, J. J. Org. Lett. 2007, 9, 2879.
(c) Fields, W. H.; Chruma, J. J. Org. Lett. 2010, 12, 316. (d) Liu, X.; Gao,
A.; Ding, L.; Xu, J.; Zhao, B. Org. Lett. 2014, 16, 2118. (e) Qian, X.; Ji, P.;
He, C.; Zirimwabagabo, J.-O.; Archibald, M. M.; Yeagley, A. A.; Chruma,
J. J. Org. Lett. 2014, 16, 5228. (f) Tang, S.; Park, J. Y.; Yeagley, A. A.;
Sabat, M.; Chruma, J. J. Org. Lett. 2015, 17, 2042.
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
■
(8) Daniel, P. E.; Weber, A. E.; Malcolmson, S. J. Org. Lett. 2017, 19,
3490.
This work was generously supported by the ACS Petroleum
Research Fund (56575-DNI1) and Duke University. K.L. thanks
Duke for Kathleen Zielik and Burroughs-Wellcome fellowships.
We thank Jason Luo for experimental assistance and Dr. Roger
Sommer (NC State) for X-ray crystallographic analysis.
(9) For enantiospecific ring-opening of terminal aryl-substituted
aziridines with carbon nucleophiles, see: (a) Ghorai, M. K.; Tiwari, D. P.
J. Org. Chem. 2010, 75, 6173. (b) Ghorai, M. K.; Nanaji, Y.; Yadav, A. K.
Org. Lett. 2011, 13, 4256. (c) Sayyad, M.; Mal, A.; Wani, I. A.; Ghorai, M.
K. J. Org. Chem. 2016, 81, 6424. For a kinetic resolution involving this
class of aziridines, see: (d) Chai, Z.; Zhu, Y.-M.; Yang, P.-J.; Wang, S.;
Wang, S.; Liu, Z.; Yang, G. J. Am. Chem. Soc. 2015, 137, 10088. For
enantiospecific transition-metal-mediated reactions of this class of
aziridines, see: (e) Calet, S.; Urso, F.; Alper, H. J. Am. Chem. Soc. 1989,
111, 931. (f) Piotti, M. E.; Alper, H. J. Am. Chem. Soc. 1996, 118, 111.
(g) Takeda, Y.; Ikeda, Y.; Kuroda, A.; Tanaka, S.; Minakata, S. J. Am.
Chem. Soc. 2014, 136, 8544.
REFERENCES
■
(1) For a review, see: Ji, X.; Huang, H. Org. Biomol. Chem. 2016, 14,
10557.
(2) For C−C bond-forming reactions that indirectly form 1,3-
diamines, see: (a) Johnson, T. A.; Jang, D. O.; Slafer, B. W.; Curtis, M.
D.; Beak, P. J. Am. Chem. Soc. 2002, 124, 11689. (b) Matsubara, R.;
Nakamura, Y.; Kobayashi, S. Angew. Chem., Int. Ed. 2004, 43, 1679.
(c) Fujimori, I.; Mita, T.; Maki, K.; Shiro, M.; Sato, A.; Furusho, S.;
Kanai, M.; Shibasaki, M. J. Am. Chem. Soc. 2006, 128, 16438. (d) Wu, B.;
Gallucci, J. C.; Parquette, J. R.; RajanBabu, T. V. Angew. Chem., Int. Ed.
2009, 48, 1126. (e) Terada, M.; Machioka, K.; Sorimachi, K. Angew.
Chem., Int. Ed. 2009, 48, 2553. (f) Yin, L.; Kanai, M.; Shibasaki, M. J. Am.
Chem. Soc. 2009, 131, 9610. (g) Zhao, J.; Liu, X.; Luo, W.; Xie, M.; Lin,
L.; Feng, X. Angew. Chem., Int. Ed. 2013, 52, 3473. (h) Hyodo, K.;
Kondo, M.; Funahashi, Y.; Nakamura, S. Chem. - Eur. J. 2013, 19, 4128.
(i) Lin, S.; Kawato, Y.; Kumagai, N.; Shibasaki, M. Angew. Chem., Int. Ed.
2015, 54, 5183. (j) Kondo, M.; Nishi, T.; Hatanaka, T.; Funahashi, Y.;
Nakamura, S. Angew. Chem., Int. Ed. 2015, 54, 8198.
(3) For C−C bond-forming reactions with N-substituted nucleophiles
that directly afford a 1,3-diamine framework, see: (a) Blyumin, E. V.;
Gallon, H. J.; Yudin, A. K. Org. Lett. 2007, 9, 4677. (b) Shibahara, F.;
Kobayashi, S-i.; Maruyama, T.; Murai, T. Chem. - Eur. J. 2013, 19, 304.
(c) Yoshimura, T.; Kinoshita, T.; Yoshioka, H.; Kawabata, T. Org. Lett.
2013, 15, 864.
(4) For C−N bond-forming reactions, see: (a) Trost, B. M.; Malhotra,
S.; Olson, D. E.; Maruniak, A.; Du Bois, J. J. Am. Chem. Soc. 2009, 131,
4190. (b) Kurokawa, T.; Kim, M.; Du Bois, J. Angew. Chem., Int. Ed.
2009, 48, 2777. (c) Lu, H.; Jiang, H.; Wojtas, L.; Zhang, X. P. Angew.
Chem., Int. Ed. 2010, 49, 10192.
(10) For a stereospecific glycine ester Schiff base alkylation, see: Lou,
S.; McKenna, G. M.; Tymonko, S. A.; Ramirez, A.; Benkovics, T.;
Conlon, D. A.; Gonzal
(11) (a) Forbeck, E. M.; Evans, C. D.; Gilleran, J. A.; Li, P.; Joullie,
M. J. Am. Chem. Soc. 2007, 129, 14463. (b) Kelley, B. T.; Joullie, M. M.
́
ez-Bobes, F. Org. Lett. 2015, 17, 5000.
́
M.
́
Tetrahedron: Asymmetry 2013, 24, 1233. (c) Ohmatsu, K.; Ando, Y.;
Ooi, T. J. Am. Chem. Soc. 2013, 135, 18706. (d) Kelley, B. T.; Carroll, P.;
Joullie, M. M. J. Org. Chem. 2014, 79, 5121.
́
(12) See the Supporting Information for details.
(13) Alkyl-substituted aziridines undergo terminal ring-opening but
deliver diamines with low diastereoselectivity (dr < 2.0:1).
(14) Identity of the major stereoisomer was determined by single-
crystal X-ray diffraction of imine hydrolysis product 9 (Scheme 5). All
other stereochemical assignments are made by inference.
(15) Several azaallyl anions are unreactive with 3a at −78 °C; however,
at either −60 or −45 °C, those reactions proceed to >98% conversion to
the 1,3-diamine within 3−10 h.
(16) Hydrolysis may be carried out directly in the workup of the
nucleophilic addition. See the Supporting Information for details.
(17) (a) Shohji, N.; Kawaji, T.; Okamoto, S. Org. Lett. 2011, 13, 2626.
(b) Huang, C.-Y.; Doyle, A. G. J. Am. Chem. Soc. 2012, 134, 9541.
(18) (a) Panteleev, J.; Zhang, L.; Lautens, M. Angew. Chem., Int. Ed.
2011, 50, 9089. (b) Ghorai, M. K.; Nanaji, Y. J. Org. Chem. 2013, 78,
3867.
(5) For reactions with simultaneous C−C and C−N bond formations,
see: (a) Kano, T.; Hashimoto, T.; Maruoka, K. J. Am. Chem. Soc. 2006,
128, 2174. (b) Sibi, M. P.; Stanley, L. M.; Soeta, T. Org. Lett. 2007, 9,
1553. (c) Rueping, M.; Maji, M. S.; Kucu̧ k, H. B.; Atodiresei, I. Angew.
Chem., Int. Ed. 2012, 51, 12864. (d) Hashimoto, T.; Takiguchi, Y.;
Maruoka, K. J. Am. Chem. Soc. 2013, 135, 11473.
(19) For a related cyclization, see: Ritter, S.; Horino, Y.; Lex, J.;
Schmalz, H.-G. Synlett 2006, 2006, 3309.
̈
̈
(6) (a) Ding, C. Z. Tetrahedron Lett. 1996, 37, 945. (b) Chen, Y.-J.;
Seki, K.; Yamashita, Y.; Kobayashi, S. J. Am. Chem. Soc. 2010, 132, 3244.
(c) Li, M.; Yucel, B.; Adrio, J.; Bellomo, A.; Walsh, P. J. Chem. Sci. 2014,
̈
D
DOI: 10.1021/acs.orglett.7b01886
Org. Lett. XXXX, XXX, XXX−XXX