Diastereoselective aminooxygenation and diamination of alkenes with amidines by hypervalent Iodine(III) reagents

Article abstract of DOI:10.1021/ol503000c

Diastereoselective anti-aminooxygenation and anti-diamination of alkenes with amidines were enabled by hypervalent iodine(III) reagents such as PhI(OCOR)₂ and PhI(NMs₂)₂, respectively. The present transformation offers diastereochemically pure dihydroimidazoles divergently from E- and Z-alkenes.

Full text of DOI:10.1021/ol503000c

Letter
pubs.acs.org/OrgLett
Diastereoselective Aminooxygenation and Diamination of Alkenes
with Amidines by Hypervalent Iodine(III) Reagents
Hui Chen, Atsushi Kaga, and Shunsuke Chiba*
Division of Chemistry and Biological Chemistry, School of Physical and Mathematical Sciences, Nanyang Technological University,
Singapore 637371, Singapore
S
* Supporting Information
ABSTRACT: Diastereoselective anti-aminooxygenation and anti-
diamination of alkenes with amidines were enabled by hypervalent
iodine(III) reagents such as PhI(OCOR)2 and PhI(NMs2)2,
respectively. The present transformation offers diastereochemically
pure dihydroimidazoles divergently from E- and Z-alkenes.
ifunctionalization of alkenes is one of the most powerful
tion followed by acetoxylation of the putative organocopper
Dprocesses for chemical manipulations in organic synthesis. intermediates (Scheme 2).5b,11 However, this aminoacetoxyla-
Represented by the Sharpless dihydroxylation1 and amino-
hydroxylation,2 a variety of strategies enabling stereo- and
Scheme 2. Cu-Catalyzed Aminooxygenation of Alkenes with
chemoselective difunctionalization of alkenes have been
exploited to construct diverse molecular complexity.3 Among
them, intramolecular amino-difunctionalization of alkene has
offered promising synthetic tactics for regio- and stereoselective
construction of nitrogen-containing heterocycles (azahetero-
cycles), which are omnipresent in potent pharmaceutical drugs.4
Within this arena, use of alkenyl amides/sulfonamides is the
mainstream of methodology development under various
oxidative reaction conditions (Scheme 1 for a typical example
with exo-cyclization).
Amidines (Previous Works)
tion strategy was amenable only to functionalization of the
terminal alkene, which limited the substrate scope and the
potential application. For example, the reaction of amidine 1a
having an internal E-alkenyl moiety under the optimized reaction
conditions [15 mol % of Cu(OAc)2-1,10-phen, 1.2 equiv of
PhI(OAc)2, and 1 equiv of K3PO4 in DMF at room temperature]
provided a complex mixture of unidentified compounds (Table
1, entry 1). Continuous investigation of the mixture could lead to
isolation of a very small amount of amino-acetoxylation product
2a (<10% yield) as a single diastereomer. The structure of 2a
could be secured by X-ray crystallographic analysis of the
corresponding deacetylated alcohol 3a (see Table 1, entry 7),12
showing that anti-aminooxygenation takes place during the
process. With the inherently electron-rich nature of amidines in
mind, we envisioned that the amidine moiety could be activated
(oxidized) only with hypervalent iodine(III) reagents under
metal-free reaction conditions.13,14 Indeed, it was found that the
reaction of 1a only with PhI(OAc)2 in the absence of Cu(OAc)2
could provide the same anti-aminoacetoxylation product 2a in
15% yield, along with a mixture of unidentified compounds
(Table 1, entry 2). Further screening of solvents for the
PhI(OAc)2-mediated reaction of amidine 1a revealed that choice
of the solvent noticeably affects the reaction efficiency (entries
3−6). Although the reactions in MeCN and toluene gave only
Scheme 1. Intramolecular Amino-Difunctionalization of
Alkenyl Amides for Azaheterocycle Synthesis
On the other hand, oxidative amino-difunctionalization of
alkene installed on amidine moieties exhibits distinct trends and
aspects in the synthesis of nitrogen-containing molecules, as (1)
the intrinsic electron-rich nature of amidines might result in
unique and unprecedented modes of the reaction processes for
alkene difunctionalization5 and (2) the azaheterocycle products,
cyclic amidines such as dihydroimidazoles, include 1,3-diamino
functionality and further reductive ring-opening of them would
offer the construction of highly functionalized amines.6 Herein,
we report diastereoselective anti-aminooxygenation7,8 and anti-
diamination9,10 of alkenes with amidines mediated by hyper-
valent iodine(III) reagents.
We have recently developed Cu-catalyzed PhI(OAc)2-
mediated aminooxygenation (aminoacetoxylation) of N-allyla-
midines for construction of 4-(acetoxymethyl)-4,5-dihydroimi-
dazoles, which proceeded presumably via alkene aminocupura-
Received: October 13, 2014
© XXXX American Chemical Society
A
dx.doi.org/10.1021/ol503000c | Org. Lett. XXXX, XXX, XXX−XXX

Organic Letters
Letter
a
a
Table 1. Optimization of the Reaction Conditions
Scheme 3. Aminooxygenation of Amidines 1
b
entry
R
solvent
DMF
time (h)
products
yield (%)
c
1
Me
Me
Me
Me
Me
Me
CF3
Ph
20
20
24
24
24
20
7
2a (R′ = Ac)
2a (R′ = Ac)
2a (R′ = Ac)
2a (R′ = Ac)
2a (R′ = Ac)
2a (R′ = Ac)
3a (R′ = H)
4a (R′ = Bz)
10
15
45
2
3
4
5
6
7
8
DMF
MeCN
d
toluene
CF3CH2OH
CH2Cl2
CH2Cl2
CH2Cl2
19 (32)
70
e
79
e
82
e
d
38
71 (11)
a
The reactions were carried out using 0.3 mmol of 1a in solvent (0.1
b
c
M) at room temperature. 1H NMR yields. The reaction was carried
out using Cu(OAc)2 (15 mol %), 1,10-phenanthroline (15 mol %),
d
PhI(OAc)2 (1.2 equiv), and K3PO4 (1 equiv). Recovery yield of 1a.
e
Isolated yields.
poor yields of 2a (entries 3 and 4), the reactions in
trifluoroethanol (CF3CH2OH) and dichloromethane (CH2Cl2)
enabled formation of 2a in good yields with full conversion of
amidine 1a (entries 5 and 6). The best result was obtained from
the reaction in CH2Cl2, affording 2a in 79% yield (entry 6). We
next investigated the effect of carboxylate ions in the hypervalent
iodine(III) reagents on the present alkene amino-oxygenation
event. More electron-deficient iodobenzene bis(trifluoroacetate)
[PhI(OCOCF3)2] accelerated the reaction with amidine 1a,
leading to full conversion within 7 h to give anti-amino-
hydroxylation product 3a in 82% yield (entry 7). In this process,
the initially installed trifluoroacetyl group was labile and thus
removed during the processes of aqueous workup and
purification through silica gel chromatography. On the other
hand, use of iodobenzene bis(benzoate) [PhI(OCOPh)2]
resulted in a slower reaction probably due to the steric hindrance
of PhI(OCOPh)2, forming benzoate 4a in 71% yield with
recovery of 1a in 11% yield even after running for 38 h (entry 8).
With these optimized reaction conditions in hand, the
substrate scope of amidines 1 for the present anti-amino-
oxygenation of alkene was then investigated using PhI(OAc)2
and PhI(OCOCF3)2 (Scheme 3). We first investigated
substituent compatibility of R1 and R2 on the amidine moiety
as well as R3 on the E-alkene part. By varying R1, the reactions
allowed installing electron-deficient benzene rings having
trifluoromethyl (for 1b) or 3,5-difluoro (for 1c) substituents to
provide the corresponding dihydroimidazoles in good yields,
while the reaction with amidine 1d bearing a 2-naphthyl group as
R1 resulted in moderate yields of aminooxygenation products 2d
and 3d. Replacement of R2 from phenyl to benzyl (for 1e) did
not affect the present anti-aminooxygenation, providing 2e and
3e in good yields. By installing allyl at R2 (for 1f), the reactions
provided 2f and 3f as sole products through anti-amino-
oxygenation of the 3-phenylallyl moiety, demonstrating
intriguing chemoselectivity of the present process. Investigation
of the substituent effect of R3 on the E-alkene revealed that 4-
chloro- (for 1g) and 4-methoxyphenyl (for 1h) groups could be
installed to afford 2g−h and 3g−h in good yields. Amidine 1i
having a 3-indolyl moiety as R3 also performed well, while
another diastereomer, syn-aminooxygenation product, was
generated as a minor component [6.1:1 with PhI(OAc)2; 4.9:1
with PhI(OCOCF3)2] (see the Supporting Information for
a
All of the reactions were conducted using 0.3 mmol of N-
allylamidines 1 in CH2Cl2 (3 mL) under a N2 atmosphere. See
Table S1 in the Supporting Information showing starting materials and
b
c
products of each entry. 1.5 equiv of PhI(OCOCF3)2 was used. 1.4
d
equiv of PhI(OAc)2 was used. 1.3 equiv of PhI(OAc)2 was used.
e
f
Complex mixtures of unidentified compounds were formed. 3m′: R
g
= COCF3. Alkene 1n contains a small amount of Z-isomer (E/Z =
21:1).
discussion about the generation of minor diastereomer).
Unfortunately, it was found that the present reaction did not
proceed with amidine 1j bearing a propyl group as R3.
We then became interested in the reactions of amidines 1k−m
with 3,3-disubstituted allyl moieties. It is worthy of note that in all
cases the aminooxygenation proceeded smoothly and selectively
to afford dihydroimidazoles 2k−m and 3k−m bearing a
quaternary carbon and a newly formed C−O bond. The reaction
of 1m with PhI(OCOCF3)2 provided trifluoroacetate 3m′ as a
B
dx.doi.org/10.1021/ol503000c | Org. Lett. XXXX, XXX, XXX−XXX

Organic Letters
Letter
major product along with hydrolyzed alcohol 3m only in 12%
yield.
Scheme 5. Diamination of Amidine 1a with PhI(NTs2)2 and
PhI(NMs2)2
a
Having obtained these promising results on the present
aminooxygenation, we next prepared amidines 1n and 1o having
E- and Z-alkenyl moieties, respectively. As expected, the present
anti-aminooxygenation led to the formation of 2n/3n and 2o/3o
from E- and Z-alkenes, respectively, in good yields, showing
diastereo-divergency of the process.
The reactions of amidine 1p having a methyl group as R5 at the
C2 allyl position could construct another quaternary carbon at
the C4 position of dihydroimidazoles 2p and 3p in
diastereoselective fashion. Similarly, the present strategy was
successfully applied for construction of spirocyclic dihydroimi-
dazoles 2q/3q and 2r/3r.
The effect of a methyl substituent installed at the C1 allylic
position (as R6) on the diastereoselectivity of the present
cyclization was also investigated. The reactions of 1s−u were
performed to construct three successive stereogenic centers in
good diastereoselectivity and chemical yields, in which the C−N
bond-forming cyclization occurs selectively from the opposite
side of the methyl group.
We next investigated the reactivity of N-butenylamidine 1v for
construction of the 6-membered ring (tetrahydropyrimidine). In
contrast to the above successful examples of anti-amino-
oxygenation observed for a series of N-allylamidines, the reaction
of 1v with either PhI(OAc)2 or PhI(OCOCF3)2 resulted in
formation of a complex mixture of unidentified compounds.
Installation of the dimethyl functionality at the allylic position
turned out to be crucial to achieve the desired anti-amino-
oxygenation. The reaction of amidine 1w with PhI(OAc)2
afforded tetrahydropyrimidine 2w in 52% yield as a single
diastereomer, while O-acetyl amidoxime 5w was also formed in
32% yield.
a
All the reactions were conducted using 0.3 mmol of N-allylamidines 1
b
in CH2Cl2 (3 mL) under a N2 atmosphere. The reaction was
conducted at room temperature, and 1a was recovered in 9% yield.
cyclohexenyl dihydroimidazole 8m in 70% yield (Scheme 6)
(see the Supporting Information for the proposed mechanism for
generation of alkene 8m).
Scheme 6. Reaction of Amidine 1m Using PhI(NMs2)2
On the basis of these observations, the present process
proceeded via stepwise sequence of syn-aziridination of
alkenes8e,f and nucleophilic ring-opening of aziridinium ions
with counter carboxylate ions, necessarily resulting in anti-
aminooxygenation of alkenes (Scheme 4).15
In summary, we have developed a method for diastereose-
lective anti-aminooxygenation and anti-diamination of N-
allylamidines that is mediated solely by hypervalent iodine(III)
reagents. We anticipate that this strategy is capable of supplying
various polyamine compounds useful for medicinal, materials,
and catalysis applications. Further investigation to elucidate the
detailed reaction mechanism and application of this strategy for
other types of amino-functionalization of alkenes is currently in
progress in our laboratory.
Scheme 4. Proposed Mechanistic Possibility
ASSOCIATED CONTENT
* Supporting Information
■
S
Experimental procedures and characterization of new com-
pounds. This material is available free of charge via the Internet at
http://pubs.acs.org.
It is worth noting that PhI(NTs2)2 and PhI(NMs2)2 were
capable of realizing diastereoselective anti-diamination of 1a,
affording 6a and 7a in good yields, respectively (Scheme 5). The
reaction with sterically less hindered PhI(NMs2)2 was smoother
than that with PhI(NTs2)2 at room temperature. The scope of
the anti-diamination reaction was then investigated. Amidines
having a disubstituted alkene (for 1c,g) provided the
corresponding products 6 and 7 in good to moderate yields.
Diamination of the (E)-2-methyl-3-allyl moiety proceeded well,
resulting in formation of the C4-quaternary carbon in
dihydroimidazole 7p. Diastereoselective construction of three
successive stereogenic centers was also achieved in the
diamination of amidine 1u. However, the reaction of 3,3-
disubstituted allylamidines such as 1m with PhI(NMs2)2 did not
form the expected diamination product 7m but provided
AUTHOR INFORMATION
Corresponding Author
■
*E-mail: shunsuke@ntu.edu.sg.
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
■
This work was supported by funding from Nanyang Techno-
logical University and Singapore Ministry of Education and
Singapore Ministry of Education (Academic Research Fund Tier
2: MOE2012-T2-1-014). We thank Dr. Yongxin Li and Dr.
Rakesh Ganguly (Division of Chemistry and Biological
C
dx.doi.org/10.1021/ol503000c | Org. Lett. XXXX, XXX, XXX−XXX

Organic Letters
Letter
Weerasekera, S. L. J. Am. Chem. Soc. 2010, 132, 1188. (g) Bowen, E. G.;
Wardrop, D. J. Org. Lett. 2010, 12, 5330. (h) Cochran, B. M.; Michael, F.
E. Org. Lett. 2008, 10, 5039. (i) Correa, A.; Tellitu, I.; Domínguez, E.;
SanMartin, R. J. Org. Chem. 2006, 71, 8316. (j) Serna, S.; Tellitu, I.;
Domínguez, E.; Moreno, I.; SanMartin, R. Tetrahedron 2004, 60, 6533.
(k) Serna, S.; Tellitu, I.; Domínguez, E.; Moreno, I.; SanMartin, R.
Tetrahedron Lett. 2003, 44, 3483. (l) Nicolaou, K. C.; Baran, P. S.;
Zhong, Y.-L.; Barluenga, S.; Hunt, K. W.; Kranich, R.; Vega, J. A. J. Am.
Chem. Soc. 2002, 124, 2233.
(9) For reports on azaheterocycle synthesis by diamination of alkenyl
amides catalyzed by transition metals, see: (a) Turnpenny, B. W.;
Chemler, S. R. Chem. Sci. 2014, 5, 1786. (b) Ingalls, E. L.; Sibblad, P. A.;
Kaminsky, W.; Michael, F. E. J. Am. Chem. Soc. 2013, 135, 8854.
Chemistry, School of Physical and Mathematical Sciences,
NTU) for assistance with X-ray crystallographic analysis.
REFERENCES
■
(1) For leading reviews, see: (a) Kolb, H. C.; VanNieuwenhze, M. S.;
Sharpless, K. B. Chem. Rev. 1994, 94, 2483. (b) Zaitsev, A. B.; Adolfsson,
H. Synthesis 2006, 1725. (c) Bolm, C.; Hildebrand, J. P.; Muniz, K.
̃
Catalytic Asymmetric Synthesis; Ojima, I., Ed.; Wiley-VCH: Weinheim,
2000; p 399.
(2) For leading reviews, see: (a) Muniz, K. Chem. Soc. Rev. 2004, 33,
̃
166. (b) Donohoe, T. J.; Callens, C. K. A.; Flores, A.; Lacy, A. R.; Rathi,
A. H. Chem.Eur. J. 2011, 17, 58. (c) Muniz, K. Comprehensive
̃
Chirality; Carreira, E. M., Yamamoto, H., Eds.; Elsevier: Amsterdam,
2012; Vol. 5, 9.183.
(c) Chav
́
ez, P.; Kirsch, J.; Streuff, J.; Muniz, K. J. Org. Chem. 2012, 77,
̃
1922. (d) Sibbald, P. A.; Rosewall, C. F.; Swartz, R. D.; Michael, F. E. J.
(3) For reviews, see: (a) Cheng, Y. A.; Yu, W. Z.; Yeung, Y.-Y. Org.
Biomol. Chem. 2014, 12, 2333. (b) Chemler, S. R.; Bovino, M. T. ACS
́
Am. Chem. Soc. 2009, 131, 15945. (e) Iglesias, A.; Per
Chem.Eur. J. 2009, 15, 10563. (f) Sibbald, P. A.; Michael, F. E. Org.
Lett. 2009, 11, 1147. (g) Muniz, K.; Hovelmann, C. H.; Streuff, J. J. Am.
́
ez, E. G.; Muniz, K.
̃
Catal. 2013, 3, 1076. (c) Muniz, K.; Martínez, C. J. Org. Chem. 2013, 78,
̃
̃
̈
2168. (d) Wu, W.; Jiang, H. Acc. Chem. Res. 2012, 45, 1736.
(e) Denmark, S. E.; Kuester, W. E.; Burk, M. T. Angew. Chem., Int. Ed.
2012, 51, 10938. (f) Donohoe, T. J.; Callens, C. K. A.; Lacy, A. R.;
Winter, C. Eur. J. Org. Chem. 2012, 655. (g) Schultz, D. M.; Wolfe, J. P.
Synthesis 2012, 44, 351. (h) De Jong, S.; Nosal, D. G.; Wardrop, D. J.
Tetrahedron 2012, 68, 4067. (i) McDonald, R. I.; Liu, G.; Stahl, S. S.
Chem. Rev. 2011, 111, 2981. (j) Wolfe, J. P. Synlett 2008, 2913.
(k) Jensen, K. H.; Sigman, M. S. Org. Biomol. Chem. 2008, 6, 4083.
(l) Chemler, S. R.; Fuller, P. H. Chem. Soc. Rev. 2007, 36, 1153.
Chem. Soc. 2008, 130, 763. (h) Muniz, K.; Hovelmann, C. H.; Campos-
̃
̈
Gom ez, J. M.; Streuff, J.; Nieger, M. Chem.
́
ez, E.; Barluenga, J.; Gonzal
Asian J. 2008, 3, 776. (i) Muniz, K. J. Am. Chem. Soc. 2007, 129, 14542.
́
̃
(j) Streuff, J.; Hovelmann, C. H.; Nieger, M.; Muniz, K. J. Am. Chem. Soc.
2005, 127, 14586.
̈
̃
(10) For reports on azaheterocycle synthesis by diamination of alkenyl
amides under transition-metal-free reaction conditions, see: (a) Hong,
K. B.; Johnston, J. N. Org. Lett. 2014, 16, 3804. (b) Chav
́
ez, P.; Kirsch, J.;
Hovelmann, C. H.; Streuff, J.; Martínez-Belmonte, M.; Escudero-Adan
́
,
̈
(m) Minatti, A.; Muniz, K. Chem. Soc. Rev. 2007, 36, 1142. (n) Li, G.;
̃
E. C.; Martin, E.; Muniz, K. Chem. Sci. 2012, 3, 2375. (c) Muller, C. H.;
̃
̈
Kotti, S. R. S. S.; Timmons, C. Eur. J. Org. Chem. 2007, 2745.
(4) For selected reviews on azaheterocycle synthesis, see: (a) Vo, C.-M.
T.; Bode, J. W. J. Org. Chem. 2014, 79, 2809. (b) Thomas, G. L.;
Johannes, C. W. Curr. Opin. Chem. Biol. 2011, 15, 516. (c) Tohme, R.;
Darwiche, N.; Gali-Muhtasib, H. Molecules 2011, 16, 9665. (d) Danda-
pani, S.; Marcaurelle, L. A. Curr. Opin. Chem. Biol. 2010, 14, 362.
(e) Welsch, M. E.; Snyder, S. A.; Stockwell, B. R. Curr. Opin. Chem. Biol.
2010, 14, 347. (f) Carey, J. S.; Laffan, D.; Thomson, C.; Williams, M. T.
Org. Biomol. Chem. 2006, 4, 2337.
Frohlich, R.; Daniliuc, C. G.; Hennecke, U. Org. Lett. 2012, 14, 5944.
̈
(d) Kim, H. J.; Cho, S. H.; Chang, S. Org. Lett. 2012, 14, 1424. (e) Kong,
A.; Blakey, S. B. Synthesis 2012, 44, 1190. (f) Li, H.; Widenhoefer, R. A.
Tetrahedron 2010, 66, 4827.
(11) For an account on our Cu-catalyzed aerobic molecular
transformation for synthesis of azaheterocycles, see: Chiba, S. Bull.
Chem. Soc. Jpn. 2013, 86, 1400.
(12) The structures of compounds 3a, 3i, 3n, 3o, 3s, and 6a were
determined by X-ray crystallographic analyses. See the Supporting
Information for more details. The structures of the other products were
speculated from these results.
(13) Long and Zhu independently reported hypervalent I(III)-
mediated sp2 aromatic C−H amination with amidines for synthesis of
benzimidazoles; see: (a) Lin, J.-P.; Zhang, F.-H.; Long, Y.-Q. Org. Lett.
2014, 16, 2822. (b) Huang, J.; He, Y.; Wang, Y.; Zhu, Q. Chem.Eur. J.
2012, 18, 13964.
(14) For reviews on application of hypervalent iodine reagents in
organic synthesis, see: (a) Samanta, R.; Matcha, K.; Antonchick, A. P.
Eur. J. Org. Chem. 2013, 5769. (b) Zhdankin, V. V. J. Org. Chem. 2011,
76, 1185. (c) Liang, H.; Ciufolini, M. A. Angew. Chem., Int. Ed. 2011, 50,
11849. (d) Duschek, A.; Kirsh, S. F. Angew. Chem., Int. Ed. 2011, 50,
1524. (e) Yusubov, M. S.; Maskaev, A. V.; Zhdankin, V. V. ARKIVOC
2011, i, 370. (f) Merritt, E. A.; Olofsson, B. Angew. Chem., Int. Ed. 2009,
48, 9052. (g) Uyanik, M.; Ishihara, K. Chem. Commun. 2009, 2086.
(h) Dohi, T.; Kita, Y. Chem. Commun. 2009, 2073. (i) Zhdankin, V. V.;
Stang, P. J. Chem. Rev. 2008, 108, 5299. (j) Ochiai, M.; Miyamoto, K.
Eur. J. Org. Chem. 2008, 4229. (k) Deprez, N. R.; Sanford, M. S. Inorg.
Chem. 2007, 46, 1924. (l) Ochiai, M. Chem. Rec. 2007, 7, 12. (m) Wirth,
T. Angew. Chem., Int. Ed. 2005, 44, 3656.
(5) For our recent reports on alkene difunctinoalization with amidines,
see: (a) Wang, Y.-F.; Zhu, X.; Chiba, S. J. Am. Chem. Soc. 2012, 134,
3679. (b) Sanjaya, S.; Chiba, S. Org. Lett. 2012, 14, 5342.
(6) We have demonstrated conversion of several dihydroimidazole
products to polyamines by the AlH3 reduction, see the Supporting
Information.
(7) For reports on azaheterocycle synthesis by aminooxygenation of
alkenyl amides catalyzed by transition metals, see: (a) Lu, D.-F.; Zhu, C.-
L.; Jia, Z.-X.; Xu, H. J. Am. Chem. Soc. 2014, 136, 13186. (b) Liu, G.-S.;
Zhang, Y.-Q.; Yuan, Y.-A.; Xu, H. J. Am. Chem. Soc. 2013, 135, 3343.
(c) Paderes, M. C.; Keister, J. B.; Chemler, S. R. J. Org. Chem. 2013, 78,
506. (d) Zhang, Y.-Q.; Yuan, Y.-A.; Liu, G.-S.; Xu, H. Org. Lett. 2013, 15,
3910. (e) Paderes, M. C.; Belding, L.; Fanovic, B.; Dudding, T.; Keister,
J. B.; Chemler, S. R. Chem.Eur. J. 2012, 18, 1711. (f) Karyakarte, S. D.;
Smith, T. P.; Chemler, S. R. J. Org. Chem. 2012, 77, 7755. (g) de Haro,
T.; Nevado, C. Angew. Chem., Int. Ed. 2011, 50, 906. (h) Paderes, M. C.;
Chemler, S. R. Eur. J. Org. Chem. 2011, 3679. (i) Mancheno, D. E.;
Thornton, A. R.; Stoll, A. H.; Kong, A.; Blakey, S. B. Org. Lett. 2010, 12,
4110. (j) Paderes, M. C.; Chemler, S. R. Org. Lett. 2009, 11, 1915.
(k) Sherman, E. S.; Chemler, S. R. Adv. Synth. Catal. 2009, 351, 467.
(l) Muniz, K.; Iglesias, A.; Fang, Y. Chem. Commun. 2009, 5591.
̃
(15) Detailed discussion on the proposed mechanism especially for
syn-aziridination was described in the Supporting Information.
(m) Fuller, P. H.; Kim, J.-W.; Chemler, S. R. J. Am. Chem. Soc. 2008, 130,
17638. (n) Xu, H.-C.; Moeller, K. D. J. Am. Chem. Soc. 2008, 130, 13542.
(o) Alexanian, E. J.; Lee, C.; Sorensen, E. J. J. Am. Chem. Soc. 2005, 127,
7690. (p) Noack, M.; Gottlich, R. Chem. Commun. 2002, 536.
̈
(8) For reports on azaheterocycle synthesis by aminooxygenation of
alkenyl amides under transition-metal-free reaction conditions, see:
(a) Farid, U.; Wirth, T. Angew. Chem., Int. Ed. 2012, 51, 3462.
(b) Moriyama, K.; Izumisawa, Y.; Togo, H. J. Org. Chem. 2012, 77, 9846.
(c) Wardrop, D. J.; Bowen, E. G. Org. Lett. 2011, 13, 2376. (d) Deng, Q.-
H.; Wang, J.-C.; Xu, Z.-J.; Zhou, C.-Y.; Che, C.-M. Synthesis 2011, 43,
2959. (e) Lovick, H. M.; Michael, F. E. J. Am. Chem. Soc. 2010, 132,
1249. (f) Wardrop, D. J.; Bowen, E. G.; Forslund, R. E.; Sussman, A. D.;
D
dx.doi.org/10.1021/ol503000c | Org. Lett. XXXX, XXX, XXX−XXX