Enantioselective synthesis and stereoselective ring opening of N-acylaziridines

Article abstract of DOI:10.1002/anie.201204224

Kinetic resolution of N-acylaziridines by nucleophilic ring opening was achieved with (R)-BINOL as the chiral modifier under boron-catalyzed conditions (see scheme; Ar=3,5-dinitrophenyl). The consumed enantiomer of aziridine can be further converted to an enantioenriched 1,2-chloroamide with recovery of (R)-BINOL. Copyright

Full text of DOI:10.1002/anie.201204224

Angewandte
Chemie
DOI: 10.1002/anie.201204224
Enantioselective Synthesis
Enantioselective Synthesis and Stereoselective Ring Opening of
N-Acylaziridines**
Jennifer Cockrell, Christopher Wilhelmsen, Heather Rubin, Allen Martin, and
Jeremy B. Morgan*
Enantiomerically pure aziridines are important synthetic
intermediates for the synthesis of biologically active mole-
cules.[1] The inherent ring strain and presence of stereogenic
carbons attached to nitrogen make the aziridine a linchpin
structure for the formation of enantioenriched 1,2-amino
alcohols, 1,2-diamines, 1,2-amino thiols, and remote secon-
dary amines.[2] Catalytic asymmetric aziridination has been
reported for N-sulfonyl,[3] N-acyloxy,[4] N-alkyl,[5] and N-
phosphoryl[6] aziridines with varying substrate scope; how-
ever, stereodefined N-acylaziridines cannot be directly pro-
duced in this manner. Enantioenriched N-acylaziridines can
be generated from existing functionalized chiral synthons.[7]
An alternative process for single enantiomer synthesis is
kinetic resolution[8] which is known for reproducible produc-
tion of enantiopure material, even on large scale. Despite the
synthetic utility of single enantiomer aziridines, their produc-
tion by kinetic resolution remains underdeveloped.[9] Moretti
et al. disclosed an enzyme-catalyzed resolution of N-acylazir-
idines with limited substrate scope.[9c] The successful develop-
ment of a versatile kinetic resolution for terminal epoxides,[10]
the oxygen-analogue of aziridines, revolutionized their pro-
duction as single enantiomers. Herein we report an opera-
tionally simple kinetic resolution of N-acylaziridines with
a broad substrate scope using non-racemic 1,1’-bi-2-naphthol
(BINOL, 4) as the resolution reagent. The BINOL-derived
byproduct (2) is further processed to recover BINOL and
produce an enantiomerically pure 1,2-chloroamide (3,
Scheme 1). The high synthetic utility of enantioenriched N-
acylaziridines is also demonstrated.
Scheme 1. Boron-catalyzed kinetic resolution of N-acylaziridines.
BIN=BINOL
choice of Lewis acid, desymmetrization[13] of meso-aziridines
by nucleophiles can be achieved.[14] Early examples by Oguni
et al.[15] employed zinc-tartrate reagents for the asymmetric
thiolysis of aziridines. More recently, Shibasaki et al. have
exploited the propensity for ring opening of N-acylaziridines
to develop desymmetrization reactions with carbon[16] and
nitrogen[17] nucleophiles. Antilla et al.[18] and Della Sala
et al.[19] have demonstrated that chiral phosphoric acids also
catalyze efficient desymmetrization reactions of meso-N-
acylaziridines. Hydrogen bonding catalysts have also been
developed for asymmetric chlorination[20] and thiolation[21] by
aziridine desymmetrization. RajanBabu et al. recently
reported the desymmetrization[22] and regiodivergent ring
opening[23] of N-acylaziridines with azide. Despite the wide
interest in asymmetric reactions of N-acylaziridines, their
production as single stereoisomers by non-enzymatic kinetic
resolution has not been disclosed.
N-Acylaziridines have a significant place in the develop-
ment of aziridine ring opening reactions. The twisted amides
are highly activated for nucleophilic addition at both the
carbonyl carbon and the aziridine carbon backbone.[2c] Lewis
acids[11] and Lewis bases[12] can promote the rearrangement of
N-acylaziridines to oxazolines; however, with the correct
N-Acylaziridines similar to 5 are known to undergo
rearrangement under Lewis acid conditions[11] to the corre-
sponding oxazoline (6), a process that could be engineered to
produce enantioenriched 5 and 6 by kinetic resolution
(Scheme 2). We hoped to extend our recent work with N-
acylaziridines[24] to develop an asymmetric method for their
[*] J. Cockrell, C. Wilhelmsen, H. Rubin, A. Martin, Prof. J. B. Morgan
Department of Chemistry and Biochemistry
University of North Carolina Wilmington
Dobo Hall, Wilmington, NC 28403 (USA)
E-mail: morganj@uncw.edu
[**] The authors are grateful to the Donors of the American Chemical
Society Petroleum Research Fund and UNCW for financial support.
The Bruker NMR instrument used for 2D NMR studies was
purchased with funds from the NSF (CHE-0821552). The HRMS
data was collected by using a Bruker MicrOTOF-Q II purchased with
funds from the NSF (CHE-1039784) and UNCW. We thank Jared
Arnette for preliminary studies.
Supporting information for this article is available on the WWW
under http://dx.doi.org/10.1002/anie.201204224.
Scheme 2. Observation of aziridine kinetic resolution. DNB=3,5-dini-
trobenzoyl; DNP=3,5-dinitrophenyl.
Angew. Chem. Int. Ed. 2012, 51, 1 – 5
ꢀ 2012 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
1
These are not the final page numbers!

.
Angewandte
Communications
production. During a screen of enantioenriched Lewis acid
complexes, a 3,5-dinitrobenzoyl(DNB)-protected aziridine
(5) underwent kinetic resolution in the presence of triphenyl
borate (B(OPh)3) and (R)-4.[25] Instead of the anticipated 3,5-
dinitrophenyl (DNP) oxazoline 6 or phenol addition,[26]
24 h at room temperature to reach 13% conversion. Disub-
stituted aziridines gave markedly different results depending
on substituent relationship. A trans-aziridine was poorly
selective (entry 9), while a cis-aziridine was resolved with
excellent selectivity (entry 10). Silyl ethers were tolerated
with synthetically useful s-factors (entries 8 and 11); however,
increased catalyst loading was required to produce efficient
conversion. Attempts to generate DNB-protected aziridines
containing tertiary or benzylic stereocenters were unsuccess-
ful.[29]
1
a BINOL-derived side product was identified by H NMR
spectroscopy. Therefore, we concluded that BINOL had
facilitated a kinetic resolution by functioning as a nucleophile.
Considering the low cost of non-racemic BINOL,[27] the
process in Scheme 2 appeared to have significant synthetic
importance, even if it may ultimately require 0.5 equiv of the
chiral nucleophile. Following brief optimization of reaction
conditions (see Supporting Information), a series of structur-
ally diverse DNB-protected aziridines were subjected to
kinetic resolution (Table 1). Reactions were generally per-
formed in toluene at low temperature with (R)-4 (0.55 equiv)
for 3 h followed by column chromatography to isolate the
scalemic aziridine. The selectivity factor (s)[28] was calculated
from the determined yield and enantioselectivity data. Sub-
strates containing an unhindered aliphatic chain underwent
resolution with excellent selectivity (entry 1). A remote
alkene was tolerated with no change in the s-factor
(entry 2). Steric bulk played an important role in both
reactivity and selectivity. The isobutyl substituted aziridine
produced a slight increase in s (entry 3 versus 1). Aziridines
with tertiary substituents were the most selective substrates,
producing nearly enantiopure material under standard con-
ditions (entries 4 and 5). Limitations in the method began to
appear if the aziridine substituent was too small (entry 6) or
too large (entry 7). In fact, the tert-butyl substrate required
The described method is not catalytic in chiral modifier,
and the recovery of BINOL on large scale would greatly
improve reaction utility and lower the cost. The aziridine
resolution was performed on 1 g of racemic 5 (Scheme 3). The
Table 1: Substrate scope for the kinetic resolution of N-acylaziridines
with (R)-4.[a]
Scheme 3. Large-scale resolution of 5 with BINOL recovery.
s-factor decreased on this scale; however, the remaining
aziridine could be isolated in 40% yield and 95% ee. The
BINOL-derived byproduct (7) was isolated as a bright yellow
solid in 38% yield as a single diastereomer. Elucidation of the
new bond connection in 7 was completed by 2D NMR
spectroscopy.[30] Treatment of 7 with 4 equiv of BCl3 at room
temperature led to quantitative conversion over 24 h, and
(R)-4 was recovered in 85% yield without loss of enantio-
purity. BINOL cleavage had occurred by chlorination to
produce the 1,2-chloroamide (8) in high yield. Interestingly,
the reaction occurred stereospecifically, so 8 was generated
with > 98% ee. Chlorination of (R)-5 provided an independ-
ent synthesis of 8, suggesting inversion of stereochemistry
occurred during the BINOL cleavage of 7. Hence, racemic
aziridine can be processed to highly enantioenriched materi-
als in 69% overall yield ((R)-5 + 8).
N-Acylaziridines are synthetically useful because of their
propensity to undergo rearrangement and ring opening
reactions to a series of functionalized molecules. Both
regioisomers of oxazoline can be produced in high yield
with excellent enantioselectivity depending on reaction con-
ditions. Treatment of (R)-5 with catalytic sodium iodide leads
to oxazoline 9 by Heine rearrangement[12a] without loss of
Entry R1
R2
R3
T
[8C]
Yield ee
s[c]
[%][b] [%]
1
2
hexyl
H
H
H
H
ꢀ30 43
ꢀ30 48
ꢀ40 46
ꢀ40 48
ꢀ40 49
ꢀ40 49
25 87
98.8
92.8
98.1
99.4 131
99.4 255
34
44
51
3
4
iBu
iPr
Cy
Me
tBu
H
H
H
H
H
H
H
H
H
H
5[d]
6[e]
7[f]
41.9
5.6
4
2
8[g]
H
H
H
ꢀ30 49
80.4
19
9
nPr
nPr
H
25 61
24.2
79.6
3
10
nBu
Me ꢀ30 48
Et
ꢀ30 48
16
11[g]
H
88.0
28
[a] Conditions: Resolutions were carried out on a 0.3 mmol scale with
racemic aziridine (1.0 equiv), B(OPh)3 (10 mol%), and (R)-4
(0.55 equiv) in toluene (0.2m) at the specified temperature for 3 h. Data
represents a single run; however, runs were repeated a minimum of three
times with the following standard deviations for entries 1–5: yield <2%
and ee <2% (see Supporting Information for details). Entries 6–11 were
reproducible, but had more variable standard deviations. [b] Yield of
unreacted, isolated aziridine. [c] See Ref. [28]. [d] Reaction performed in
2:1 toluene/DCM. [e] Reaction performed for 30 min. [f] Reaction
performed in DCM for 24 h. [g] 20 mol% B(OPh)3 required.
2
www.angewandte.org
ꢀ 2012 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Angew. Chem. Int. Ed. 2012, 51, 1 – 5
These are not the final page numbers!

Angewandte
Chemie
Scheme 5. Proposed mechanism for borate-catalyzed kinetic resolu-
tion.
to harness the unique preference for stereospecific addition to
terminal DNB-protected N-acylaziridines in further Lewis
acid-catalyzed nucleophile additions. Mechanistic studies and
expansion of the substrate scope for kinetic resolution are
underway.
Scheme 4. Ring opening reactions of enantioenriched 5. a) NaI
(10 mol%), THF, 608C, 12 h. b) TfOH (10 mol%), DCM, 0!258C,
2 h. c) Zn(OTf)2 (20 mol%), N-methylindole (4 equiv), DCM, 258C,
18 h. d) Zn(OTf)2 (20 mol%), aniline (4 equiv), DCM, 258C, 18 h.
Received: May 30, 2012
Revised: June 20, 2012
Published online: && &&, &&&&
enantiopurity (Scheme 4). Alternatively, triflic acid (TfOH)
catalyzes the regioisomeric rearrangement to oxazoline
6.[11c,31] Only a very slight erosion of enantiopurity occurs
despite bond formation at the stereogenic carbon.[11d,32] Lewis
acids have been shown to catalyze the addition of nucleo-
philes to N-acylaziridines; however, nucleophilic attack must
beat out rearrangement to 6.[11e] While oxophilic Lewis acids
generally prefer ring opening, the addition of excess indole to
(R)-5 in the presence of catalytic Zn(OTf)2 results in ring
opening at the more substituted aziridine carbon.[33] Trypt-
amine derivative 10 is isolated in 60% yield and 92% ee. The
high regioselectivity and enantiospecificity for indole addition
to the more hindered carbon of terminal N-acylaziridines is
unprecedented.[34] Unprotected anilines are also competent
nucleophiles for aziridine opening[35] with bond formation
occurring on nitrogen to produce 11 in excellent yield and
94% ee. This data represents the first highly stereospecific
example of aniline addition to the stereogenic carbon in
terminal N-acylaziridines.[36]
Keywords: aziridines · BINOL · enantioselective synthesis ·
.
kinetic resolution
[1] V. H. Dahanukar, I. A. Zavialov, Curr. Opin. Clin. Nutr. Metab.
Care 2002, 5, 918 – 927.
[2] a) W. McCoull, F. A. Davis, Synthesis 2000, 1347 – 1365; b) B.
Zwanenburg, P. ten Holte, Top. Curr. Chem. 2001, 216, 93 – 124;
c) J. B. Sweeney, Chem. Soc. Rev. 2002, 31, 247 – 258; d) G.
Cardillo, L. Gentilucci, A. Tolomelli, Aldrichimica Acta 2003, 36,
39 – 50; e) W. K. Lee, H.-J. Ha, Aldrichimica Acta 2003, 36, 57 –
63; f) X. E. Hu, Tetrahedron 2004, 60, 2701 – 2743; g) S. H.
Krake, S. C. Bergmeier, Tetrahedron 2010, 66, 7337 – 7360;
h) P. F. Lu, Tetrahedron 2010, 66, 2549 – 2560.
[3] a) D. A. Evans, M. M. Faul, M. T. Bilodeau, B. A. Anderson,
D. M. Barnes, J. Am. Chem. Soc. 1993, 115, 5328 – 5329; b) Z. Li,
K. R. Conser, E. N. Jacobsen, J. Am. Chem. Soc. 1993, 115,
5326 – 5327; c) K. Omura, M. Murakami, T. Uchida, R. Irie, T.
Katsuki, Chem. Lett. 2003, 32, 354 – 355; d) V. Subbarayan, J. V.
Ruppel, S. Zhu, J. A. Perman, X. P. Zhang, Chem. Commun.
2009, 4266 – 4268.
[4] a) J. Vesely, I. Ibrahem, G. L. Zhao, R. Rios, A. Cordova, Angew.
Chem. 2007, 119, 792 – 795; Angew. Chem. Int. Ed. 2007, 46, 778 –
781; b) T. Hashimoto, N. Uchiyama, K. Maruoka, J. Am. Chem.
Soc. 2008, 130, 14380 – 14381; c) S. Minakata, Y. Murakami, R.
Tsuruoka, S. Kitanaka, M. Komatsu, Chem. Commun. 2008,
6363 – 6365; d) L. Huang, W. D. Wulff, J. Am. Chem. Soc. 2011,
133, 8892 – 8895.
[5] J. C. Antilla, W. D. Wulff, J. Am. Chem. Soc. 1999, 121, 5099 –
5100.
[6] J. E. Jones, J. V. Ruppel, G. Y. Gao, T. M. Moore, X. P. Zhang, J.
Org. Chem. 2008, 73, 7260 – 7265.
[7] J. B. Sweeney in Aziridines and Epoxides in Organic Synthesis
(Ed.: A. K. Yudin), Wiley-VCH, Weinheim, 2006, pp. 117 – 144.
[8] For representative examples of recent kinetic resolutions
producing enantioenriched nitrogen-containing small molecules,
see: a) S. Arseniyadis, A. Valleix, A. Wagner, C. Mioskowski,
Angew. Chem. 2004, 116, 3376 – 3379; Angew. Chem. Int. Ed.
2004, 43, 3314 – 3317; b) A. Berkessel, F. Cleemann, S. Mukher-
A reaction mechanism for kinetic resolution is proposed
in Scheme 5. The amide nitrogen in N-acylaziridines is
pyramidalized because of ring strain, creating the opportunity
for Lewis acid binding at either the amide nitrogen or
oxygen.[37] Addition of B(OPh)3 catalyzes the C O bond
ꢀ
formation with ring opening, likely by Lewis acid activation of
the amide oxygen to generate intermediate 12 followed by
proton transfer to regenerate the catalyst. For highly selective
substrates, (R)-BINOL (4) preferentially attacks the S-con-
figured aziridine enantiomer with inversion of stereochemis-
try at the aziridine carbon. Exchange of BINOL with phenol
ligands on boron occurs at room temperature[25] and cannot be
ruled out; however, we have never isolated phenol addition to
aziridines suggesting B(OPh)3 remains intact during the
reaction.
In conclusion, a unique method for kinetic resolution of
N-acylaziridines is disclosed. The consumed enantiomer of
aziridine can be further processed to enantioenriched 1,2-
chloroamides with BINOL recovery. We are actively working
Angew. Chem. Int. Ed. 2012, 51, 1 – 5
ꢀ 2012 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.angewandte.org
3
These are not the final page numbers!

.
Angewandte
Communications
jee, Angew. Chem. 2005, 117, 7632 – 7635; Angew. Chem. Int. Ed.
2005, 44, 7466 – 7469; c) D. Minato, Y. Nagasue, Y. Demizu, S.
Onomura, Angew. Chem. 2008, 120, 9600 – 9603; Angew. Chem.
Int. Ed. 2008, 47, 9458 – 9461; d) C. K. De, E. G. Klauber, D.
Seidel, J. Am. Chem. Soc. 2009, 131, 17060 – 17061; e) M.
Binanzer, S. Y. Hsieh, J. W. Bode, J. Am. Chem. Soc. 2011, 133,
19698 – 19701; f) V. D. Bumbu, V. B. Birman, J. Am. Chem. Soc.
2011, 133, 13902 – 13905; g) P. Maity, S. D. Lepore, Angew.
Chem. 2011, 123, 8488 – 8491; Angew. Chem. Int. Ed. 2011, 50,
8338 – 8341.
E. M. F. Loh, K. W. Huang, C. H. Tan, Chem. Commun. 2011, 47,
3897 – 3899.
[22] B. Wu, J. C. Gallucci, J. R. Parquette, T. V. RajanBabu, Angew.
Chem. 2009, 121, 1146 – 1149; Angew. Chem. Int. Ed. 2009, 48,
1126 – 1129.
[23] B. Wu, J. R. Parquette, T. V. RajanBabu, Science 2009, 326, 1662.
[24] A. Martin, K. Casto, W. Morris, J. B. Morgan, Org. Lett. 2011, 13,
5444 – 5447.
[25] K. Ishihara, M. Miyata, K. Hattori, T. Tada, H. Yamamoto, J.
Am. Chem. Soc. 1994, 116, 10520 – 10524.
[9] During the preparation of this manuscript, a more efficient
resolution of N-tosylaziridines was published: a) K. Ohmatsu, Y.
Hamajima, T. Ooi, J. Am. Chem. Soc. 2012, 134, 8794 – 8797. For
previous examples, see: b) S. Calet, F. Urso, H. Alper, J. Am.
Chem. Soc. 1989, 111, 931 – 934; c) M. Bucciarelli, A. Forni, I.
Moretti, F. Prati, G. Torre, Tetrahedron: Asymmetry 1993, 4,
903 – 906; d) V. Alezra, C. Bouchet, L. Micouin, M. Bonin, H. P.
Husson, Tetrahedron Lett. 2000, 41, 655 – 658; e) W. H. Leung,
W. L. Mak, E. Y. Y. Chan, T. C. H. Lam, W. S. Lee, H. L. Kwong,
L. L. Yeung, Synlett 2002, 1688 – 1690; f) S. Minakata, Y.
Murakami, M. Satake, I. Hidaka, Y. Okada, M. Komatsu, Org.
Biomol. Chem. 2009, 7, 641 – 643.
[10] a) M. Tokunaga, J. F. Larrow, F. Kakiuchi, E. N. Jacobsen,
Science 1997, 277, 936 – 938; For an example leading to the
synthesis of enantioenriched aziridines, see: b) S. K. Kim, E. N.
Jacobsen, Angew. Chem. 2004, 116, 4042 – 4044; Angew. Chem.
Int. Ed. 2004, 43, 3952 – 3954.
[26] a) M. Pineschi, F. Bertolini, R. M. Haak, P. Crotti, F. Macchia,
Chem. Commun. 2005, 1426 – 1428; b) M. Pineschi, F. Bertolini,
P. Crotti, F. Macchia, Org. Lett. 2006, 8, 2627 – 2630.
[27] Non-racemic BINOL is a cheap source of chiral material when
compared to the cost of achiral stoichiometric reagents used for
asymmetric aziridination, such as tosyl azide ($5864/mol,
Aldrich) and ethyl diazoacetate ($403/mol, Aldrich). For this
study, we purchased (R)-BINOL from D-L Chiral Chemicals for
$149/mol.
[28] Selectivity factor (s) is defined as s = ln[(1ꢀC)(1ꢀee)]/ln[(1ꢀC)-
(1+ee)] where C = (100ꢀyield of recovered aziridine)/100 and
ee = %ee/100. A practical resolution is considered to be s > 10,
see: a) H. B. Kagan, J. C. Fiaud, Top. Stereochem. 1988, 18, 249 –
330; b) E. L. Eliel, S. H. Wilen, L. N. Mander, Stereochemistry of
Organic Compounds, Wiley-Interscience, New York, 1994; c) E.
Vedejs, M. Jure, Angew. Chem. 2005, 117, 4040 – 4069; Angew.
Chem. Int. Ed. 2005, 44, 3974 – 4001.
[11] a) H. W. Heine, Z. Proctor, J. Org. Chem. 1958, 23, 1554 – 1556;
b) T. Nishiguchi, H. Tochio, A. Nabeya, Y. Iwakura, J. Am.
Chem. Soc. 1969, 91, 5835 – 5841; c) T. Nishiguchi, H. Tochio, A.
Nabeya, Y. Iwakura, J. Am. Chem. Soc. 1969, 91, 5841 – 5846;
d) K. Hori, T. Nishiguchi, A. Nabeya, J. Org. Chem. 1997, 62,
3081 – 3088; e) D. Ferraris, W. J. Drury, C. Cox, T. Lectka, J. Org.
Chem. 1998, 63, 4568 – 4569; f) G. Cardillo, L. Gentilucci, G. P.
Mohr, Eur. J. Org. Chem. 2001, 3545 – 3551.
[12] a) H. W. Heine, M. E. Fetter, E. M. Nicholson, J. Am. Chem.
Soc. 1959, 81, 2202 – 2204; b) P. Thyrum, A. R. Day, J. Med.
Chem. 1965, 8, 107 – 111; c) J. W. Lown, T. Itoh, N. Ono, Can. J.
Chem. 1973, 51, 856 – 869; d) F. W. Eastwood, P. Perlmutter, Q.
Yang, J. Chem. Soc. Perkin Trans. 1 1997, 35 – 42; e) B. F. Bonini,
M. Fochi, M. Comes-Franchini, A. Ricci, L. Thijs, B. Zwanen-
burg, Tetrahedron: Asymmetry 2003, 14, 3321 – 3327.
[29] We have found that synthetically useful 2-aryl and trisubstituted
DNB-protected aziridines readily rearrange to the correspond-
ꢀ
ing oxazolines at the activated benzylic or tertiary C N bond.
Other terminal N-acyl and N-acyloxyaziridines undergo ring
opening under our optimized conditions, but DNB-protected
aziridines displayed superior selectivity factors.
[30] See Supporting Information for spectra and stereochemical
rational. We propose an absolute configuration of R for the
stereogenic carbon in 7.
[31] C. U. Pittman, S. P. McManus, J. Org. Chem. 1970, 35, 1187 –
1190.
[32] S. P. McManus, R. A. Hearn, C. U. Pittman, J. Org. Chem. 1976,
41, 1895 – 1898.
[33] K. Sato, A. P. Kozikowski, Tetrahedron Lett. 1989, 30, 4073 –
4076.
[13] For an example of desymmetrization by N-acylaziridine isomer-
ization, see: Z. Da Zhang, R. Scheffold, Helv. Chim. Acta 1993,
76, 2602 – 2615.
[14] C. Schneider, Angew. Chem. 2009, 121, 2116 – 2118; Angew.
Chem. Int. Ed. 2009, 48, 2082 – 2084.
[15] a) M. Hayashi, K. Ono, H. Hoshimi, N. Oguni, J. Chem. Soc.
Chem. Commun. 1994, 2699 – 2700; b) M. Hayashi, K. Ono, H.
Hoshimi, N. Oguni, Tetrahedron 1996, 52, 7817 – 7832.
[16] a) T. Mita, I. Fujimori, R. Wada, J. Wen, M. Kanai, M. Shibasaki,
J. Am. Chem. Soc. 2005, 127, 11252 – 11253; b) I. Fujimori, T.
Mita, K. Maki, M. Shiro, A. Sato, S. Furusho, M. Kanai, M.
Shibasaki, J. Am. Chem. Soc. 2006, 128, 16438 – 16439; c) Y. J.
Xu, L. Q. Lin, M. Kanai, S. Matsunaga, M. Shibasaki, J. Am.
Chem. Soc. 2011, 133, 5791 – 5793.
[34] For indole additions to N-acylaziridines, see: a) J. Legters,
J. G. H. Willems, L. Thijs, B. Zwanenburg, Recl. Trav. Chim.
Pays-Bas 1992, 111, 59 – 68; b) L. Dubois, A. Mehta, E. Tourette,
R. H. Dodd, J. Org. Chem. 1994, 59, 434 – 441; c) M. Bucciarelli,
A. Forni, I. Moretti, F. Prati, G. Torre, Tetrahedron: Asymmetry
1995, 6, 2073 – 2080; for a stereospecific example with N-
nosylaziridines, see: d) R. N. Farr, R. J. Alabaster, J. Y. L.
Chung, B. Craig, J. S. Edwards, A. W. Gibson, G. J. Ho, G. R.
Humphrey, S. A. Johnson, E. J. J. Grabowski, Tetrahedron:
Asymmetry 2003, 14, 3503 – 3515.
[35] For examples of aniline additions to N-acylaziridines, see: a) K.
Nakajima, T. Tanaka, K. Morita, K. Okawa, Bull. Chem. Soc.
Jpn. 1980, 53, 283 – 284; b) S. Peruncheralathan, M. Henze, C.
Schneider, Synlett 2007, 2289 – 2291; for aniline additions to
aziridines catalyzed by metal triflate salts, see: c) M. Meguro, N.
Asao, Y. Yamamoto, Tetrahedron Lett. 1994, 35, 7395 – 7398;
d) G. Sekar, V. K. Singh, J. Org. Chem. 1999, 64, 2537 – 2539.
[36] For a stereospecific example with an N-tosylaziridine, see: M. K.
Ghorai, A. K. Sahoo, S. Kumar, Org. Lett. 2011, 13, 5972 – 5975.
[37] a) F. A. L. Anet, J. M. Osyany, J. Am. Chem. Soc. 1967, 89, 352 –
356; b) G. R. Boggs, J. T. Gerig, J. Org. Chem. 1969, 34, 1484 –
1486; c) G. V. Shustov, G. K. Kadorkina, S. V. Varlamov, A. V.
Kachanov, R. G. Kostyanovsky, A. Rauk, J. Am. Chem. Soc.
1992, 114, 1616 – 1623.
[17] Y. Fukuta, T. Mita, N. Fukuda, M. Kanai, M. Shibasaki, J. Am.
Chem. Soc. 2006, 128, 6312 – 6313.
[18] a) E. B. Rowland, G. B. Rowland, E. Rivera-Otero, J. C. Antilla,
J. Am. Chem. Soc. 2007, 129, 12084 – 12085; b) S. E. Larson, J. C.
Baso, G. L. Li, J. C. Antilla, Org. Lett. 2009, 11, 5186 – 5189.
[19] a) G. Della Sala, A. Lattanzi, Org. Lett. 2009, 11, 3330 – 3333;
b) M. Senatore, A. Lattanzi, S. Santoro, C. Santi, G. Della Sala,
Org. Biomol. Chem. 2011, 9, 6205 – 6207.
[20] T. Mita, E. N. Jacobsen, Synlett 2009, 1680 – 1684.
[21] a) A. Lattanzi, G. Della Sala, Eur. J. Org. Chem. 2009, 1845 –
1848; b) Y. Zhang, C. W. Kee, R. Lee, X. A. Fu, J. Y. T. Soh,
4
www.angewandte.org
ꢀ 2012 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Angew. Chem. Int. Ed. 2012, 51, 1 – 5
These are not the final page numbers!

Angewandte
Chemie
Communications
Enantioselective Synthesis
J. Cockrell, C. Wilhelmsen, H. Rubin,
A. Martin, J. B. Morgan*
&&&& — &&&&
Enantioselective Synthesis and
Stereoselective Ring Opening of N-
Acylaziridines
Kinetic resolution of N-acylaziridines by
nucleophilic ring opening was achieved
with (R)-BINOL as the chiral modifier
under boron-catalyzed conditions (see
scheme; Ar=3,5-dinitrophenyl). The
consumed enantiomer of aziridine can be
further converted to an enantioenriched
1,2-chloroamide with recovery of (R)-
BINOL.
Angew. Chem. Int. Ed. 2012, 51, 1 – 5
ꢀ 2012 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.angewandte.org
5
These are not the final page numbers!