Synthesis of hexahydro-1H-benzo[c]chromen-1-amines via the intramolecular ring-opening reactions of aziridines by π-nucleophiles

Article abstract of DOI:10.1055/s-2008-1072561

The intramolecular cyclization of aziridines with π-nucleophiles can be a useful route to a number of heterocyclic and carbocyclic systems. This methodology has been applied to the synthesis of hexahydro-1H-benzo[c]chromen-1- amines, the basic skeleton of many amaryllidaceae alkaloids. The success of the aziridine cyclization is largely dependent on the N-substitution of aziridine, with activated aziridines not undergoing the cyclization reaction. Only N-H-, N-alkyl- and N-arylaziridines underwent the cyclization reaction. The ring opening of an unactivated aziridines with a π-nucleophile is one of the first examples of such a reaction. Georg Thieme Verlag Stuttgart.

Full text of DOI:10.1055/s-2008-1072561

1420
PAPER
Synthesis of Hexahydro-1H-benzo[c]chromen-1-amines via the
Intramolecular Ring-Opening Reactions of Aziridines by p-Nucleophiles
I
ntramolecular Cyc
r
lization
a
s
of
A
ziridi
v
nes
w
ith
p
-N
i
ucleop
n
hile
s
da B. Pulipaka, Stephen C. Bergmeier*
Department of Chemistry & Biochemistry, Clippinger Laboratory, Ohio University, Athens, OH 45701, USA
E-mail: bergmeis@ohio.edu
Received 13 December 2007; revised 16 January 2008
examples of such an aziridine ring opening via a p-nucleo-
phile have used an electron-stabilizing group on the nitro-
gen of the aziridine ring.
Abstract: The intramolecular cyclization of aziridines with p-nu-
cleophiles can be a useful route to a number of heterocyclic and car-
bocyclic systems. This methodology has been applied to the
synthesis of hexahydro-1H-benzo[c]chromen-1-amines, the basic
skeleton of many amaryllidaceae alkaloids. The success of the azir-
idine cyclization is largely dependent on the N-substitution of azir-
idine, with activated aziridines not undergoing the cyclization
reaction. Only N-H-, N-alkyl- and N-arylaziridines underwent the
cyclization reaction. The ring opening of an unactivated aziridines
with a p-nucleophile is one of the first examples of such a reaction.
We were interested in using this methodology for the syn-
thesis of more complex polycyclic molecules such as the
amaryllidaceae alkaloid homolycorane.6 Such structures
could come from an acid-catalyzed cyclization of an azir-
idine such as 3. This reaction could also provide a route
for the synthesis of pancratistatin and related alkaloids.7
For example, Keck has reported on the synthesis of pan-
cratistatin via benzochromenes such as 4.8
Key words: heterocycles, electrophilic additions, ring opening,
ethers, amines
Since there were no reports of a fused-ring aziridine/
p-nucleophile cyclization, we first prepared and attempt-
ed the cyclization of aziridine 7 (Scheme 2). Treatment of
3-bromocyclohexene with phenethylmagnesium bromide
provided 6 in excellent yield.9 The olefin was then azirid-
inated in 54% yield using PhI=NTs and CuClO4.10 Cy-
clization of 7 was then carried out using standard
conditions and was complete in less than one hour to pro-
vide the octahydrophenanthrene 8 in 70% yield.
Aziridines are versatile building blocks for the synthesis
of biologically active natural and synthetic compounds.
These are well-known electrophiles and capable of react-
ing with a variety of nucleophiles including heteroatom
nucleophiles (amines, azides, alcohols, etc.) and carbon
nucleophiles (aryl groups, enolates, etc.).1,2
We, and others have reported on the use of p-nucleophiles
such as allylsilanes,3 olefins4 and aromatic rings5 to open
aziridine rings. Recently we reported on the intramolecu-
lar cyclization of aziridines with simple p-nucleophiles
such as aromatic rings, and substituted olefins
(Scheme 1).4d
Br
Ph
MgBr
Ph
PhI=NTs
CuClO4
MeCN
0 °C to r.t., 2 h
54%
THF
0 °C to r.t., 8 h
87%
6
5
The reaction is believed to proceed via an initial acid-cat-
alyzed nucleophilic attack of the p-bond on the more sub-
stituted carbon of the aziridine. All of the reported
BF3⋅OEt2
CH2Cl2
1 h, 0 °C
70%
NTs
NHTs
NHTs
7
NTs
8
BF3⋅OEt2, CH2Cl2,
Scheme 2 Intramolecular cyclization of a carbon-linked fused-ring
aziridine
r.t., 1 h
97%
1
2
Confident that the use of a fused-ring aziridine was not
detrimental to the cyclization we proceeded to prepare the
appropriate ether linked aziridine 11 (Scheme 3). The use
of PhI=NTs as an aziridination reagent provided very low
yields of the desired aziridine 11. Significant amounts of
the debenzylated alcohol were also obtained. The
chloramine-T with NBS system provided moderately bet-
ter yields of 11. The use of our standard cyclization con-
ditions (100 mol% BF3·OEt2, 0 °C, CH2Cl2)4d with 11
gave only the starting material. Increasing the temperature
and increasing the amount of BF3·OEt2 only led to the for-
mation of 12 and 13, presumably via the reaction of ad-
O
O
X
X
acid
Y
Y
NR
NHR
3
4
Scheme 1 Previously reported example of an aziridine/p-nucleo-
phile cyclization and proposed possible oxygen-linked cyclization
SYNTHESIS 2008, No. 9, pp 1420–1430
Advanced online publication: 27.03.2008
x
x
.
x
x
.2
0
0
8
DOI: 10.1055/s-2008-1072561; Art ID: M09007SS
© Georg Thieme Verlag Stuttgart · New York

PAPER
Intramolecular Cyclizations of Aziridines with p-Nucleophiles
1421
ventitious water with the aziridine ring. None of the this system is the ether oxygen, and not the NTs of the
expected product 4 was isolated. An examination of other aziridine.
acids [e.g., B(C6F5)3, silica gel], heating, or the presence
Clearly the nitrogen of the aziridine must be made more
of electron-donating groups on the benzene ring (e.g.,
basic for the reaction to proceed as planned. As the use of
OMe) did not provide any of the required product.
other electron-stabilizing groups on the nitrogen was not
expected to significantly change the basicity of the aziri-
OH
OBn
dine, we decided to examine an unsubstituted aziridine.
While the nucleophilic ring-opening reactions of aziri-
dines which lack an electron-stabilizing group are well
known,14 there have been no reports on the use of weaker
p-nucleophiles reacting with such a nonactivated aziri-
dine.
PhCH2Cl
chloramine-T⋅xH2O
NaH, DMF
0 °C to r.t.
90%
10 mol% NBS, 4 Å MS, MeCN,
r.t., 8 h, 30%
9
10a
OBn
OBn
O
The requisite aziridine is readily prepared from alkene
10a (Scheme 4).15 Epoxidation of 10a with perbenzimidic
acid, generated in situ from PhCN and H2O2,provided cis-
epoxide 16a in 75% yield after purification.16 Reaction of
16a with sodium azide provides a mixture of regioisomer-
ic azido alcohols. This mixture was then directly cyclized
to unsubstituted aziridine 17. Treatment of 17 with 100
mol% of B(C6F5)3 cleanly provided cyclization product 18
in 70% isolated yield.
NHTs
OH
OH
Lewis acid
NTs
NHTs
11
12
13
Scheme 3 Synthesis and attempted cyclization of an oxygen-linked
N-tosylaziridine
Given the facile nature of the carbon-linked aziridine
(Scheme 2), we were puzzled as to why a simple modifi-
cation of the substrate inhibited the cyclization reaction.
We wished to find out where the Lewis acid was com-
plexed in both the all-carbon system as well as the ether-
linked system. This complexation should be measurable
via NMR spectroscopy.11 Tosylaziridine 14 was chosen as
our test aziridine as it had no p-nucleophile that could
open the aziridine under Lewis acid catalysis. Aziridine
14 was readily prepared via tosylation of the commercial-
ly available 2-methylaziridine and treated with 100 mol%
O
Ar
O
Ar
O
1) NaN3, NH4Cl
PhCN, H2O2
MeOH
0 °C to r.t.,
8 h, 75%
MeOH–H2O (8:1)
reflux, 36 h, 75%
2) Ph3P, THF,
10a, Ar = Ph
16a, Ar = Ph
reflux, 1 h, 82%
O
O
B(C6F5)3
CH2Cl2
0 °C to r.t., 8 h
70%
NH
1
of BF3·OEt2 in CDCl3. Although the H NMR spectrum
NH2
showed some Lewis acid induced changes, there was suf-
ficient overlap so as to make any type of quantification
difficult. We thus examined the 13C NMR spectrum and
were able to cleanly determine the Dd (relative to the un-
complexed aziridine) as shown in Figure 1.12
17
18
Scheme 4 First successful ring opening of an unactivated aziridine
with a p-nucleophile
This ring-opening of an unactivated aziridine with a p-nu-
cleophile is one of the first examples of such a reaction.
This reaction enhances the utility as no deprotection of the
resulting amine is required for further transformations.
∆δ
2
1
∆δ
0.007
0.077
1
4
3
0.02
0.04
1.20
0.05
C1
C2
C3
C4
2
C1
C2
Ph
O
N
NTs
Ts
15
14
Given the ease of the cyclization with the unsubstituted
aziridine, we wished to examine the scope of this cycliza-
tion reaction. To this end, a series of N-alkyl- and O-aryl-
methyl-substituted aziridines were prepared by the
general route shown in Scheme 5. The results of these re-
actions are summarized in Table 1.
Figure 1 Dd values of aziridines in CH2Cl2 with 100 mol%
BF3·OEt2
Based upon these results, we next examined the simple
aziridine 15 containing an ether linkage.11a This com-
pound was readily prepared via the aziridination of allyl
benzyl ether with Chloramine-T and NBS.13 Again a solu-
tion of 15 was treated with 100 mol% of BF3·OEt2 and the
13C NMR spectrum was recorded. This experiment
showed clear differences when compared to the all-carbon
aziridine 14. The C2 showed a negligible Dd and C3, ad-
jacent to the ether oxygen showed a large Dd of >1 ppm.
Clearly the primary site of Lewis acid complexation in
O
Ar
N
O
1) LiBr, RNH2,
r.t., 8 h
X
B(C6F5)3
16
R
2) Ph3P, DIAD
r.t., 8 h
R
N
H
19
20
Scheme 5 General method for the synthesis of 1-aminochromenes
Synthesis 2008, No. 9, 1420–1430 © Thieme Stuttgart · New York

1422
A. B. Pulipaka, S. C. Bergmeier
Table 1 Hexahydro-1H-benzo[c]chromen-1-amines 20
Entry ArCH2X Alkene 10, Epoxide 16, RNH2
PAPER
Aziridine 19,
Product
Yield (%)
yield (%)
yield (%)
yield (%)
O
10a
90
16a
75
19a
49
1
2
3
PhCH2Cl
PhCH2Cl
PhCH2Cl
n-C6H13
PhCH2
Ph
20a
20b
20c
80
90
70
n-C6H13
N
H
O
O
10a
90
16a
75
19b
44
Bn
N
H
10a
90
16a
75
19c
51
Ph
N
H
Me
O
O
10b
65
16b
84
19d
55
4
5
3-MeC6H4CH2Cl
4-MeC6H4CH2Cl
n-C6H13
20d
20e
72
60
n-C6H13
N
H
10c
92
16c
81
19e
65
n-C6H13
Me
n-C6H13
N
H
OMe
O
10d
89
16d
84
19f
61
6
2-MeOC6H4CH2Cl
n-C6H13
20f
64
n-C6H13
N
H
OMe
O
O
O
10e
84
16e
72
19g
63
7
8
9
3-MeOC6H4CH2Cl
4-MeOC6H4CH2Cl
4-BrC6H4CH2Br
n-C6H13
n-C6H13
n-C6H13
20g
20h
20i
75
25
45
n-C6H13
N
H
10f
88
16f
75
19h
57
OMe
n-C6H13
N
H
10g
64
16g
48
19i
53
Br
n-C6H13
N
H
Synthesis 2008, No. 9, 1420–1430 © Thieme Stuttgart · New York

PAPER
Intramolecular Cyclizations of Aziridines with p-Nucleophiles
Table 1 Hexahydro-1H-benzo[c]chromen-1-amines 20 (continued)
Entry ArCH2X Alkene 10, Epoxide 16, RNH2
1423
Aziridine 19,
Product
Yield (%)
yield (%)
yield (%)
yield (%)
CF3
O
10h
81
16h
37
19j
25
10
2-CF3C6H4CH2Cl
n-C6H13
20j
0
n-C6H13
N
H
OMe
O
10i
60
16i
61
19k
66
11
12
3,4-(MeO)2C6H3CH2Br
n-C6H13
20k
20l
40
46
OMe
n-C6H13
N
H
O
10j
80
16j
58
19l
66
C10H7CH2Br
n-C6H13
n-C6H13
N
H
Cyclohexenol (9) was alkylated with a series of substitut- with this system was the loss of the 4-methoxybenzyl
ed benzyl halides to provide ethers 10b–j. As before group under the acidic reaction conditions. We were quite
(Scheme 4) the olefin was epoxidized with perbenzimidic pleased to note that the 4-bromobenzyl (entry 9) provided
acid to generate the cis-epoxides 16b–j. The epoxides the expected product in a low (but acceptable) yield of
were then opened using a primary amine and LiBr. This 45%. The 2-OMe benzyl substrate 19f, also provided the
provided a mixture of regioisomeric amino alcohols. This expected product 20f in 64% yield.
mixture was directly cyclized to form aziridines 19a–l.
A key question in these cyclizations was the regioselectiv-
We first examined the cyclizations of aziridines 19a–c ity of the cyclization reaction when an unsymmetrical
carrying a small substituent on the aziridine nitrogen. The substrate was used. In a simpler cyclization system, (i.e.,
n-hexylaziridine 19a smoothly cyclized to chromene 20a compound 1 with a 3-OMe group on the aromatic ring,
in 80% yield. The benzylaziridine provided product 20b Scheme 1) we observed a roughly 3:1 mixture of regioiso-
in an excellent 90% isolated yield. We were concerned meric cyclization products.4d
that two possible p-nucleophiles were present in this mol-
In this study, we examined three compounds with 3-sub-
ecule: one, the expected nucleophile of the benzyl ether,
stituted benzyl ethers. Two possible regioisomeric prod-
and the other, the benzyl on the aziridine ring. Only the
ucts can be formed (para or ortho to the 3-substituent). We
benzyl ether nucleophile opened the aziridine. This is
were quite pleased to observe a single product being
likely due to the unfavorable 5-endo-tet transition state
that would be required for the N-benzyl group to open the
aziridine ring. We next converted aziridine 19c into 20c in
excellent yield. We were pleased to note that the reduced
basicity of the N-phenylaziridine relative to the N-H- or
N-alkylaziridines was not detrimental to the cyclization.
formed in all cases (entries 4, 7 and 11). The regiochem-
1
istries of these products were determined by H NMR
spectra. These compounds show a clear singlet in the aro-
matic region, which is possible only for regioisomers 20d,
20g, and 20k. If the other regioisomer were to be formed,
none of the aromatic protons would be singlets. In addi-
Satisfied that the range of substitution on the aziridine ni- tion to the methyl- and methoxy-substituted aromatic ring,
trogen was acceptably broad, we turned our attention to a polycyclic aromatic (2-naphthalene) was examined.
substitution on the aromatic ring. We chose to use only the Again, a single regioisomer was isolated. Although the
n-hexyl substitution on the aziridine ring due to the lack yields for these cyclizations were not as high compared to
of interfering peaks in the aromatic region of the 1H NMR others, none of the regioisomeric products were found.
spectra. We then examined a variety of substitution pat- Only starting material and decomposition products were
terns and electron-donating and electron-withdrawing observed. Clearly, the greater steric bulk of the fused-ring
substitution on the aromatic ring.
aziridine has improved the regioselectivity of the cycliza-
tion reaction.
Cyclization of a symmetrical 4-substituted aromatic ring
was relatively uneventful with the 4-Me and 4-OMe Most of the aromatic substituents examined have been
(Table 1, entries 5 and 8) providing the expected products electron-donating groups. The CF3 substituted benzyl
20e and 20h. We were disappointed to see that the 4-OMe substrate 19j, provided no cyclized product. Even after
provided the product 20h in only 25% yield. A problem extended reaction times (>24 h), heating (reflux), or the
Synthesis 2008, No. 9, 1420–1430 © Thieme Stuttgart · New York

1424
A. B. Pulipaka, S. C. Bergmeier
PAPER
centrated, and chromatographed (EtOAc–hexanes, 10:90) to pro-
vide 0.41 g (54%) of 7 as a colorless oil; Rf = 0.5 (EtOAc–hexanes,
15:85).
1H NMR (300 MHz, CDCl3): d = 7.6 (m, 4 H), 7.3 (m, 3 H), 7.0 (m,
2 H), 3.0 (m, 1 H), 2.75 (m, 1 H), 2.4 (m, 4 H), 2.3 (m, 2 H), 2.0 (m,
2 H), 1.85 (m, 6 H), 1.3 (m, 3 H).
addition of more acid (300 mol%) only starting material
and some decomposition products were isolated. This is in
contrast to our previous results using a simpler carbon-
linked system in which the CF3 substituted arene provided
cyclized product in good yield.4d
In conclusion, we have demonstrated the first example of
an unactivated aziridine/p-nucleophile cyclization. The
scope of the reaction in terms of the N-substitution ap-
pears very good, with N-H-, N-alkyl- and N-arylaziridines
undergoing the reaction. The allowed substitution on the
arene is reasonably broad with a variety of electron-donat-
ing groups. As might be expected for an electrophilic aro-
matic substitution reaction, substitution of the aromatic
ring with a strongly electron-withdrawing group is not tol-
erated. The regioselectivity of the cyclization when using
an unsymmetrical arene is excellent with a single regio-
isomer being isolated. This method should be an excellent
route to amaryllidaceae alkaloids and other bioactive ni-
trogen-containing molecules.
13C NMR (75 MHz, CDCl3): d = 142.5, 137.7, 136.5, 129.4, 128.5,
128.2, 127, 42, 41.7, 33.7, 33.2, 33, 32.6, 28.5, 24.7, 20.5.
HRMS (ESI): m/z calcd for C21H25NO2S + Na [M + Na]+: 375.1504;
found: 378.1501.
1,2,3,4,4a,9,10,10a-Octahydro-N-tosylphenanthren-4-amine(8)
BF3·OEt2 (18 mL, 0.140 mmol) was added to a 0 °C solution of azir-
idine 7 (50 mg, 0.14 mmol) in CH2Cl2 (1 mL), and the mixture was
warmed to r.t. After 1 h, the mixture was diluted with CH2Cl2 (5
mL) and washed with sat. aq NaHCO3 (5 mL), brine (5 mL), and
H2O (5 mL), concentrated, and chromatographed (EtOAc–hexanes,
15:85) to provide 35 mg (70%) of 8 as a colorless oil; Rf = 0.2
(EtOAc–hexanes, 15:85).
1H NMR (300 MHz, CDCl3): d = 7.4 (d, J = 7.7 Hz, 2 H), 7.3 (m, 1
H), 7.1 (d, J = 7.4 Hz, 1 H), 7.0 (d, J = 8.3 Hz, 2 H), 7.05 (d, J = 7.6
Hz, 2 H), 4.6 (d, J = 11.5 Hz, 1 H), 3.4 (m, 1 H), 2.7 (t, J = 9.5 Hz,
2 H), 2.55 (m, 1 H), 2.5 (s, 3 H), 2.2 (m, 1 H), 2.0 (m, 1 H), 1.95 (m
1 H), 1.52 (m, 4 H), 1.4 (m, 1 H).
All chemicals were purchased from the usual commercial suppliers
and used without further purification, unless otherwise noted. THF
and CH2Cl2 were dried using a column purification system. IR spec-
tra were obtained neat. Rf values were obtained by TLC on alumi-
num backed, silica coated, TLC plates containing a fluorescent (254
nm) indicator. Spots were identified via UV or staining with an eth-
anolic solution of ninhydrin, followed by heating. Compounds were
purified by either an automated flash purification system utilizing
silica gel or by flash chromatography using 32-63D 60Å silica gel
according to the method of Still.17 NMR spectra were obtained at
300 (1H) or 75 MHz (13C).
13C NMR (75 MHz, CDCl3): d = 142.6, 137.1, 136.5, 129.3, 128.2,
127.1, 126.6, 126.5, 125.3, 53.3, 45.7, 32.7, 29.2, 27.1, 24.0, 20.2.
HRMS-(ESI): m/z calcd for C21H25NO2S [M + H]+: 356.1684;
found: 356.1690.
Arylmethyl Cyclohexenyl Ethers 10; General Procedure
Cyclohexenol (9; 5.08 mmol, 100 mol%) in DMF (10 mL, 0.5 M)
was added to suspension of NaH (15.3 mmol, 300 mol%, previously
washed with hexanes (20 mL)] in DMF (20 mL) and the mixture
was stirred at 0 °C for 10 min. The desired benzyl halide (5.08
mmol, 100 mol%) in DMF (10 mL) was slowly added to the alkox-
ide solution. The mixture was warmed to r.t. and stirred 16 h. The
mixture was quenched by the addition H2O (100 mL) and the aque-
ous layer extracted with Et2O (3 × 50 mL). The organic layers were
combined, washed with brine (50 mL), dried (MgSO4), concentrat-
ed, and chromatographed (EtOAc in hexanes) to provide the desired
ether.
2-(Benzyloxy)-7-tosyl-7-azabicyclo[4.1.0]heptane (11)
To a solution of 10a (0.2 g, 1.06 mmol), NBS (38 mg, 0.213 mmol),
and chloramine-T (0.24 g, 1.06 mmol) in anhyd MeCN (3 mL) was
added molecular sieves (4 Å, 200 mg) and the mixture was stirred
at r.t. for 8 h. The mixture was filtered, concentrated, and chromato-
graphed (EtOAc–hexanes, 8:92) to provide 114 mg (30%) of aziri-
dine 11 as a colorless oil; Rf = 0.5 (EtOAc–hexanes, 20:80).
1H NMR (300 MHz, CDCl3): d = 7.78 (d, J = 8.0 Hz, 2 H), 7.20 (m,
7 H), 4.50 (d, J = 11.5 Hz, 1 H), 4.39 (d, J = 11.5 Hz, 1 H), 3.52 (m,
1 H), 3.06 (m, 1 H), 2.98 (d, J = 6.5 Hz, 1 H), 2.43 (s, 3 H), 1.8 (m,
1 H), 1.68 (m, 2 H), 1.42 (m, 1 H), 1.17 (m, 2 H).
1-[(Cyclohex-2-enyloxy)methyl]benzene (10a)
Benzyl chloride provided 0.86 g (90%) of 10a; Rf = 0.8 (EtOAc–
hexanes, 5:95).
13C NMR (75 MHz, CDCl3): d = 162.5, 144.3, 142, 140.7, 138.8,
128.3, 127.6, 127.4, 72.6, 69.1, 42, 40.4, 26.6, 22.6, 21.6, 15.1.
1H NMR (300 MHz, CDCl3): d = 7.8 (m, 5 H), 5.94 (m, 2 H), 4.71
(dd, J = 13.3, 12.0 Hz, 2 H), 4.0 (m, 1 H), 2.2 (m, 5 H), 1.7 (m, 1 H).
13C NMR (75 MHz, CDCl3): d = 139.2, 130.8, 128.4, 128.3, 127.9,
127.8, 127.6, 127.3, 72.3, 70.0, 28.5, 25.3, 19.3.
1-[2-(Cyclohex-2-enyl)ethyl]benzene (6)
To a suspension of Mg turnings (0.12 g, 4.96 mmol) in anhyd THF
(5 mL) was slowly added a solution of phenethyl bromide (0.861 g,
4.65 mmol) in THF (5 mL). The mixture was stirred at r.t. for 30
min and then added dropwise to a solution of 5 (0.5 g, 3.1 mmol) in
THF (1 mL) and the mixture stirred for 8 h. The mixture was
quenched with sat. aq NH4Cl (5 mL) and extracted with Et2O
(3 × 10 mL). The combined organic layers were washed with brine
(5 mL), dried (MgSO4), concentrated, and chromatographed (hex-
anes) to provide 0.5 g (87%) of 6 as colorless oil which matched the
reported spectra.3
HRMS (EI): m/z calcd for C13H16O [M+]: 188.1201; found:
188.1203.
1-[(Cyclohex-2-enyloxy)methyl]-3-methylbenzene (10b)
3-Methylbenzyl chloride provided 0.67 g (65%) of 10b; Rf = 0.8
(EtOAc–hexanes, 5:95).
1H NMR (300 MHz, CDCl3): d = 7.14 (m, 4 H), 5.8 (m, 2 H), 4.57
(dd, J = 11.9, 8.2 Hz, 2 H), 4.02 (m, 1 H), 2.4 (s, 3 H), 1.8 (m, 5 H),
1.62 (m, 1 H).
13C NMR (75 MHz, CDCl3): d = 139.0, 137.9, 130.9, 128.5, 128.4,
2-Phenethyl-7-tosyl-7-azabicyclo[4.1.0]heptane (7)
128.2, 127.9, 124.8, 72.3, 70.1, 28.5, 25.3, 21.5, 19.4.
PhINTs (1.2 g, 3.2 mmol) was added slowly to a 0 °C solution of
CuClO4 (35 mg, 0.32 mmol) and olefin 6 (0.4 g, 2.15 mmol) in
MeCN (10 mL), and the mixture was stirred for 2 h at 0 °C and 45
min at r.t. The mixture was filtered through a plug of silica gel, con-
HRMS (ESI): m/z calcd for C14H18O + Na [M + Na]+: 225.1255;
found: 225.1249.
Synthesis 2008, No. 9, 1420–1430 © Thieme Stuttgart · New York

PAPER
Intramolecular Cyclizations of Aziridines with p-Nucleophiles
1425
1-[(Cyclohex-2-enyloxy)methyl]-4-methylbenzene (10c)
4-Methylbenzyl chloride provided 0.95 g (92%) of 10c; Rf = 0.3
(EtOAc–hexanes, 4:96).
1H NMR (300 MHz, CDCl3): d = 7.18 (d, J = 7.9 Hz, 2 H), 7.30 (d,
J = 7.8 Hz, 2 H), 5.84 (m, 2 H), 4.52 (dd, J = 11.9, 7.4 Hz, 2 H), 3.99
(m, 1 H), 2.4 (s, 3 H), 1.8 (m, 5 H), 1.62, (m, 1 H).
13C NMR (75 MHz, CDCl3): d = 135.8, 134.8, 129.6, 127.8, 126.7,
126.5, 70.7, 68.6, 27.2, 24.0, 19.9, 18.1.
HRMS (ESI): m/z calcd for C14H18O + Na [M + Na]+: 225.1255;
found: 225.1249.
1H NMR (300 MHz, CDCl3): d = 7.51 (m, 4 H), 5.95 (m, 2 H), 4.65
(m, 2 H), 4.06 (m, 1 H), 1.84 (m, 5 H), 1.62 (m, 1 H).
13C NMR (75 MHz, CDCl3): d = 132.1, 131.9, 131.0, 129.0, 128.3,
127.5, 125.9, 120.2, 72.9, 65.9, 28.3, 24.1, 19.2.
HRMS (EI): m/z calcd for C14H15F3O [M+]: 256.1075; found:
256.1081.
4-[(Cyclohex-2-enyloxy)methyl]-3,4-dimethoxybenzene (10i)
3,4-Dimethoxybenzyl bromide18 provided 0.76 g (60%) of 10i;
Rf = 0.3 (EtOAc–hexanes, 4:96).
1H NMR (300 MHz, CDCl3): d = 6.79 (m, 3 H), 5.77 (m, 2 H), 4.45
(dd, J = 11.7, 7.5 Hz, 2 H), 3.93 (m, 1 H), 3.88 (s, 3 H), 3.85 (s, 3
H), 1.6 (m, 5 H), 1.4 (m, 1 H).
13C NMR (75 MHz, CDCl3): d = 148.9, 148.4, 131.7, 130.9, 127.8,
120.1, 111.0, 110.9, 71.9, 69.9, 55.9, 55.8, 28.4, 25.2, 19.3.
HRMS (ESI): m/z calcd for C15H20O3 + Na [M + Na]+: 271.1310;
found: 271.1307.
1-[(Cyclohex-2-enyloxy)methyl]-2-methoxybenzene (10d)
2-Methoxybenzyl chloride provided 0.99 g (89%) of 10d; Rf = 0.3
(EtOAc–hexanes, 4:96).
1H NMR (300 MHz, CDCl3): d = 7.51 (d, J = 7.4 Hz, 1 H), 7.28 (t,
J = 8.0, 7.4 Hz, 1 H), 7.0 (t, J = 7.4 Hz, 1 H), 6.89 (d, J = 8.2 Hz, 1
H), 5.9 (m, 2 H), 4.65 (dd, J = 12.8, 6.5 Hz, 2 H), 4.06 (m, 1 H), 3.87
(s, 3 H), 1.84 (m, 5 H), 1.62 (m, 1 H).
13C NMR (75 MHz, CDCl3): d = 130.7, 128.7, 128.5, 128.3, 128.2,
2-[(Cyclohex-2-enyloxy)methyl]naphthalene (10j)
2-(Bromomethyl)naphthalene provided 0.97 g (80%) of 10j;
Rf = 0.3 (EtOAc–hexanes, 2:98).
1H NMR (300 MHz, CDCl3): d = 7.88 (m, 4 H), 7.51 (m, 3 H), 5.96
(m, 2 H), 4.76 (dd, J = 12.2, 7.1 Hz, 2 H), 4.08 (m, 1 H), 1.86 (m, 5
H), 1.6 (m, 1 H).
13C NMR (75 MHz, CDCl3): d = 136.7, 133.4, 133.0, 131.1, 128.1,
127.9, 127.9, 127.8, 126.3, 126.1, 125.9, 125.8, 72.3, 70.2, 28.5,
25.4, 19.4.
120.5, 110.1, 72.6, 67.7, 64.8, 55.3, 28.5, 25.4, 19.4.
HRMS (ESI): m/z calcd for C14H18O2 + Na [M + Na]+: 241.1204;
found: 241.1201.
1-[(Cyclohex-2-enyloxy)methyl]-3-methoxybenzene (10e)
3-Methoxybenzyl chloride provided 0.93 g (84%) of 10e; Rf = 0.3
(EtOAc–hexanes, 4:96).
1H NMR (300 MHz, CDCl3): d = 7.25 (t, J = 8.1, 7.98 Hz, 1 H),
6.97 (m, 2 H), 6.83 (d, J = 8.3 Hz, 1 H), 5.83 (m, 2 H), 4.54 (dd,
J = 12.1, 6.8 Hz, 2 H), 3.98 (m, 1 H), 3.84 (s, 3 H), 1.77 (m, 5 H),
1.57 (m, 1 H).
HRMS (ESI): m/z calcd for C17H18O + Na [M + Na]+: 261.1255;
found: 261.1252.
13C NMR (75 MHz, CDCl3): d = 159.7, 140.8, 130.9, 129.3, 127.8,
Epoxides 16, General Procedure
119.9, 113.1, 112.9, 72.2, 69.9, 55.2, 28.4, 25.3, 19.5.
A solution of the olefin 10 (3.95 mmol, 100 mol%) in MeOH (10
mL) was added to a mixture of PhCN (23.7 mmol, 600 mol%), 30%
H2O2 (23.7 mmol, 600 mol%), and KHCO3 (2.95 mmol, 75 mol%)
in MeOH (10 mL) at 0 °C and the mixture was warmed to r.t. and
stirred for 18 h. H2O (100 mL) was added and the mixture was ex-
tracted with Et2O (3 × 50 mL). The organic layers were combined,
washed with brine (50 mL), dried (MgSO4), concentrated and chro-
matographed (EtOAc in hexanes) to provide the desired epoxide.
HRMS (ESI): m/z calcd for C14H18O2 + Na [M + Na]+: 241.1204;
found: 241.1205.
1-[(Cyclohex-2-enyloxy)methyl]-4-methoxybenzene (10f)
4-Methoxybenzyl chloride provided 0.98 g (88%) of 10f; Rf = 0.3
(EtOAc–hexanes, 4:96).
1H NMR (300 MHz, CDCl3): d = 7.31 (d, J = 8.9 Hz, 2 H), 6.90 (d,
J = 4.7 Hz, 2 H), 5.85 (m, 2 H), 4.5 (dd, J = 11.5, 7.9 Hz, 2 H), 3.97
(m, 1 H), 3.82 (s, 3 H), 1.8 (m, 5 H), 1.62 (m, 1 H).
13C NMR (75 MHz, CDCl3): d = 158.2, 130.3, 129.9, 128.4, 127.1,
112.9, 71.1, 68.9, 54.4, 27.6, 24.4, 18.7.
HRMS (ESI): m/z calcd for C14H18O2 + Na [M + Na]+: 241.1204;
2-(Benzyloxy)-7-oxabicyclo[4.1.0]heptane (16a)
Olefin 10a (1 g, 5.31 mmol) provided 0.81 g (75%) of 16a; Rf = 0.5
(EtOAc–hexanes, 30:70).
1H NMR (300 MHz, CDCl3): d = 7.43 (m, 5 H), 4.70 (s, 2 H), 3.84
(m, 1 H), 3.32 (m, 2 H), 1.84 (m, 2 H), 1.64 (m, 3 H), 1.31 (m, 1 H).
13C NMR (75 MHz, CDCl3): d = 138.8, 128.3, 127.5, 74.7, 70.2,
found: 241.1205.
53.9, 53.4, 24.9, 23.1, 19.7.
1-[(Cyclohex-2-enyloxy)methyl]-4-bromobenzene (10g)
4-Bromobenzyl bromide provided 0.87 g (64%) of 10g; Rf = 0.28
(EtOAc–hexanes, 2:98).
HRMS (ESI): m/z calcd for C13H16O2 + Na [M + Na]+: 227.1048;
found: 227.1045.
1H NMR (300 MHz, CDCl3): d = 7.46 (d, J = 8.4 Hz, 2 H), 7.24 (d,
J = 8.3 Hz, 2 H), 5.83 (m, 2 H), 4.53 (dd, J = 11.5, 6.4 Hz, 2 H), 3.94
(m, 1 H), 2.0 (m, 2 H), 1.77 (m, 3 H), 1.58 (m, 1 H).
13C NMR (75 MHz, CDCl3): d = 138.2, 131.4, 131.2, 129.2, 127.6,
121.2, 72.5, 69.3, 28.4, 25.3, 19.3.
2-(3-Methylbenzyloxy)-7-oxabicyclo[4.1.0]heptane (16b)
Olefin 10b (0.5 g, 2.47 mmol) provided 0.45 g (84%) of 16b;
Rf = 0.5 (EtOAc–hexanes, 30:70).
1H NMR (300 MHz, CDCl3): d = 7.18 (m, 3 H), 7.1 (m, 1 H), 4.70
(s, 2 H), 3.84 (m, 1 H), 3.32 (m, 1 H), 3.3 (m, 1 H), 2.4 (s, 3 H), 1.8
(m, 2 H), 1.54 (m, 3 H), 1.31 (m, 1 H).
HRMS (EI): m/z calcd for C13H15BrO [M+]: 266.0306; found:
13C NMR (75 MHz, CDCl3): d = 138.8, 128.3, 127.5, 74.7, 70.2,
266.0307.
53.9, 53.4, 24.9, 23.1, 19.7.
1-[(Cyclohex-2-enyloxy)methyl]-2-(trifluoromethyl)benzene
(10h)
2-(Trifluoromethyl)benzyl chloride provided 1.05 g (81%) of 10h;
Rf = 0.2 (EtOAc–hexanes, 4:96).
HRMS (ESI): m/z calcd for C14H18O2 + Na [M + Na]+: 241.1204;
found: 241.1206.
Synthesis 2008, No. 9, 1420–1430 © Thieme Stuttgart · New York

1426
A. B. Pulipaka, S. C. Bergmeier
PAPER
2-(4-Methylbenzyloxy)-7-oxabicyclo[4.1.0]heptane (16c)
Following the general procedure olefin 10c (0.6 g, 2.96 mmol) pro-
vided 0.52 g (81%) of 16c; Rf = 0.5 (EtOAc–hexanes, 30:70).
1H NMR (300 MHz, CDCl3): d = 7.81 (m, 2 H), 7.4 (m, 2 H), 4.88
(s, 2 H), 3.83 (m, 1 H), 3.35 (m, 1 H), 3.29 (m, 1 H), 1.80 (m, 2 H),
1.55 (m, 3 H), 1.23 (m, 1 H).
1H NMR (300 MHz, CDCl3): d = 7.29 (d, J = 7.9 Hz, 2 H), 7.16 (d,
J = 7.9 Hz, 2 H), 4.67 (s, 2 H), 3.79 (s, 2 H), 3.26 (m, 1 H), 3.3 (m,
1 H), 2.36 (s, 3 H), 1.8 (m, 2 H), 1.42 (m, 3 H), 1.22 (m, 1 H).
13C NMR (75 MHz, CDCl3): d = 137.2, 135.6, 129.1, 127.8, 74.4,
70.1, 54.1, 53.5, 24.9, 23.0, 21.2, 19.7.
13C NMR (75 MHz, CDCl3): d = 131.9, 129.0, 128.60, 127.4, 127.1,
75.8, 68.3, 54.2, 53.3, 24.8, 22.9, 19.7.
HRMS (ESI): m/z calcd for C14H15F3O2 + Na [M + Na]+: 295.0908;
found: 295.0922.
2-[(3,4-Dimethoxy)benzyloxy]-7-oxabicyclo[4.1.0]heptane (16i)
Olefin 10i (1 g, 4.02 mmol) provided 0.65 g (61%) of 16i; Rf = 0.5
(EtOAc–hexanes, 30:70).
HRMS (ESI): m/z calcd for C14H18O2 + Na [M + Na]+: 241.1204;
found: 241.1206.
2-(2-Methoxybenzyloxy)-7-oxabicyclo[4.1.0]heptane (16d)
Following the general procedure olefin 10d (0.6 g, 2.74 mmol) pro-
vided 0.54 g (84%) of 16d; Rf = 0.45 (EtOAc–hexanes, 30:70).
1H NMR (300 MHz, CDCl3): d = 7.48 (d, J = 7.4 Hz, 1 H), 7.24 (t,
J = 8.0, 7.6 Hz, 1 H), 6.95 (t, J = 7.5, 7.4 Hz, 1 H), 6.8 (d, J = 8.2
Hz, 1 H), 4.75 (s, 2 H), 3.84 (s, 3 H), 3.82 (m, 1 H), 3.35 (m, 1 H),
3.27 (m, 1 H), 1.80 (m, 2 H), 1.55 (m, 3 H), 1.23 (m, 1 H).
1H NMR (300 MHz, CDCl3): d = 6.95 (s, 1 H), 6.88 (d, J = 8.1 Hz,
1 H), 6.81 (d, J = 8.1 Hz, 1 H), 4.61 (s, 2 H), 3.85 (s, 3 H), 3.82 (s,
3 H), 3.75 (m, 1 H), 3.24 (m, 2 H), 1.77 (m, 2 H), 1.47 (m, 3 H), 1.19
(m, 1 H).
13C NMR (75 MHz, CDCl3): d = 149.0, 148.5, 131.2, 120.2, 111.0,
110.9, 74.3, 70.1, 55.9, 55.9, 54.1, 53.5, 24.9, 22.9, 19.7.
HRMS (ESI): m/z calcd for C15H20O4 + Na [M + Na]+: 287.1259;
found: 287.1259.
13C NMR (75 MHz, CDCl3): d = 154.6, 126.4, 126.1, 124.8, 118.1,
72.8, 62.6, 52.9, 51.7, 51.2, 22.5, 20.6, 17.5.
2-(2-Napthylmethyloxy)-7-oxabicyclo[4.1.0]heptane (16j)
Olefin 10j (0.3 g, 1.25 mmol) provided 0.185 g (58%) of 16j;
Rf = 0.4 (EtOAc–hexanes, 20:80).
HRMS (ESI): m/z calcd for C14H18O3 + Na [M + Na]+: 257.1154;
found: 257.1146.
2-(3-Methoxybenzyloxy)-7-oxabicyclo[4.1.0]heptane (16e)
Olefin 10e (0.6 g, 2.74 mmol) provided 0.462 g (72%) of 16e;
Rf = 0.5 (EtOAc–hexanes, 30:70).
1H NMR (300 MHz, CDCl3): d = 7.8 (m, 4 H), 7.54 (d, J = 8.7 Hz,
1 H), 7.40 (m, 2 H) 4.85 (s, 2 H), 3.83 (m, 1 H), 3.34 (m, 1 H), 3.28
(m, 1 H), 1.82 (m, 2 H), 1.59 (m, 3 H), 1.22 (m, 1 H).
1H NMR (300 MHz, CDCl3): d = 7.48 (m, 3 H), 6.9 (s, 1 H), 4.74
(s, 2 H), 3.75 (s, 3 H), 3.73 (m, 1 H), 3.25 (m, 1 H), 3.22 (m, 1 H),
1.80 (m, 2 H), 1.55 (m, 3 H), 1.23 (m, 1 H).
13C NMR (75 MHz, CDCl3): d = 159.8, 140.3, 129.4, 128.6, 119.9,
113.2, 74.6, 70.1, 55.2, 54.1, 53.5, 24.9, 22.9, 19.7.
13C NMR (75 MHz, CDCl3): d = 136.2, 133.3, 133.0, 128.2, 127.9,
127.7, 126.4, 126.1, 125.8, 74.6, 70.3, 54.1, 53.5, 24.9, 23.0, 19.7.
HRMS (ESI): m/z calcd for C17H18O2 [M + Na]+: 277.1204; found:
277.1195.
2-(Benzyloxy)-7-azabicyclo[4.1.0]heptane (17)
HRMS (ESI): m/z calcd for C14H18O3 + Na [M + Na]+: 257.1154;
A solution of epoxide 16a (2 g, 9.8 mmol) in MeOH (36 mL) and
H2O (4 mL) was added to a mixture of NaN3 (6.3 g, 98 mmol) and
NH4Cl (1.04 g, 19.6 mmol) and the mixture was heated to reflux for
36 h. The mixture was diluted with H2O (50 mL) and the aqueous
layer was extracted with EtOAc (3 × 50 mL), dried (MgSO4), and
concentrated to give 1.8 g (75%) of a regioisomeric mixture of azido
alcohols which were directly carried on to the next step.
found: 257.1144.
2-(4-Methoxybenzyloxy)-7-oxabicyclo[4.1.0]heptane (16f)
Olefin 10f (0.6 g, 2.74 mmol) provided 0.482 g (75%) of 16f;
Rf = 0.5 (EtOAc–hexanes, 30:70).
1H NMR (300 MHz, CDCl3): d = 7.31 (d, J = 8.6 Hz, 2 H), 6.87 (d,
J = 7.7 Hz, 2 H), 4.62 (s, 2 H), 3.80 (s, 3 H), 3.79 (m, 1 H), 3.28 (m,
1 H), 3.25 (m, 1 H), 1.78 (m, 2 H), 1.51 (m, 3 H), 1.21 (m, 1 H).
13C NMR (75 MHz, CDCl3): d = 159.16, 130.7, 129.3, 113.8, 74.2,
69.8, 55.3, 54.1, 53.5, 24.9, 23.0, 19.7.
HRMS (ESI): m/z calcd for C14H18O3 + Na [M + Na]+: 257.1154;
found: 257.1149.
Rf = 0.5 (EtOAc–hexanes, 30:70).
1H NMR (300 MHz, CDCl3): d = 7.41 (m, 5 H), 4.68 (dd, J = 11.6
Hz, 2 H), 3.87 (m, 1 H), 3.68 (m, 1 H), 3.51 (dd, J = 3.1, 5.8 Hz, 1
H), 2.59 (br s, 1 H), 2.2 (m, 2 H), 1.8 (m, 2 H), 1.4 (m, 2 H).
13C NMR (75 MHz, CDCl3): d = 128.5, 127.9, 127.7, 77.1, 74.5,
71.0, 62.8, 29.1, 26.9, 18.4.
2-(4-Bromobenzyloxy)-7-oxabicyclo[4.1.0]heptane (16g)
Olefin 10f (0.5 g, 1.87 mmol) provided 0.25 g (48%) of 16g;
Rf = 0.5 (EtOAc–hexanes, 25:75).
1H NMR (300 MHz, CDCl3): d = 7.45 (d, J = 8.4 Hz, 2 H), 7.26 (d,
J = 8.5 Hz, 2 H), 4.63 (s, 2 H), 3.77 (m, 1 H), 3.26 (m, 2 H), 1.80
(m, 2 H), 1.59 (m, 3 H), 1.22 (m, 1 H).
Ph3P (1.91 g, 7.28 mmol) was added to a solution of the above azido
alcohol (1.8 g, 7.28 mmol) in MeCN (10 mL) and the mixture was
heated to reflux for 1 h. The mixture was concentrated and chro-
matographed (MeOH–CH2Cl2, 10:90) to yield 1.2 g (82%) of aziri-
dine 17 as a colorless oil.
Rf = 0.4 (MeOH–CH2Cl2, 10:90).
13C NMR (75 MHz, CDCl3): d = 137.8, 131.5, 128.4, 121.4, 74.9,
1H NMR (300 MHz, CDCl3): d = 7.27 (m, 5 H), 4.54 (s, 2 H), 3.61
(dd, J = 2.3, 5.3 Hz, 1 H), 2.4 (s, 2 H), 1.71 (m, 3 H), 1.39 (m, 1 H),
1.23 (m, 2 H).
13C NMR (75 MHz, CDCl3): d = 128.4, 127.6, 127.5, 74.6, 70.8,
36.8, 33.4, 30.0, 24.2, 15.2.
69.4, 54.1, 53.3, 24.9, 22.9, 19.6.
HRMS (ESI): m/z calcd for C13H15BrO2 + Na [M + Na]+: 305.0153;
found: 305.0138.
2-[(2-Trifluoromethyl)benzyloxy]-7-oxabicyclo[4.1.0]heptane
(16h)
Olefin 10h (0.3 g, 0.12 mmol) provided 0.12 g (37%) of 16h;
HRMS (ESI): m/z calcd for C13H17NO [M + H]+: 204.1388; found:
204.1379.
Rf = 0.4 (EtOAc–hexanes, 30:70).
Synthesis 2008, No. 9, 1420–1430 © Thieme Stuttgart · New York

PAPER
Intramolecular Cyclizations of Aziridines with p-Nucleophiles
1427
2,3,4,4a,6,10b-Hexahydro-1H-benzo[c]chromen-1-amine (18)
B(C6F5)3 (126 mg, 0.246 mmol) was added to aziridine 17 (50 mg,
0.246 mmol) in CH2Cl2 (1 mL) at 0 °C. The mixture was then
warmed to r.t. and stirred overnight. The mixture was diluted with
CH2Cl2 (10 mL) and washed with sat. aq K2CO3 (10 mL), brine (10
mL), and H2O (10 mL). The organic layer was dried (MgSO4), con-
centrated, and chromatographed (MeOH–CH2Cl2, 10:90) to provide
35 mg (70%) of amine 18; Rf = 0.39 (MeOH–CH2Cl2, 10:90).
1H NMR (300 MHz, CDCl3): d = 7.23 (m, 6 H), 7.11 (m, 2 H), 6.8
(t, J = 8.4 H, 2 H), 4.65 (s, 2 H), 3.81 (t, J = 7.6 Hz, 1 H), 2.37 (s, 2
H), 1.99 (m, 1 H), 1.78 (m, 2 H), 1.30 (m, 1 H), 1.19 (m, 2 H).
13C NMR (75 MHz, CDCl3): d = 133.9, 128.9, 128.7, 128.5, 127.7,
127.6, 122.2, 120.2, 74.4, 71.2, 42.4, 39.6, 29.7, 27.4, 24.4, 15.9.
HRMS (ESI): m/z calcd for C19H21NO [M + H]+: 280.1701; found:
280.1691.
1H NMR (300 MHz, CDCl3): d = 7.36 (m, 5 H), 4.71 (dd, J = 11.5,
11.5 Hz, 2 H), 3.29 (m, 1 H), 3.09 (m, 1 H), 2.53 (m, J = 9.3 Hz, 1
H), 2.41(br s, 2 H), 2.18 (m, 1 H), 1.99 (m, 1 H), 1.80 (m, 1 H), 1.34
(m, 3 H).
13C NMR (75 MHz, CDCl3): d = 128.4, 127.8, 127.7, 81.9, 73.4,
71.1, 61.9, 32.6, 29.6, 20.1.
N-Hexyl-2-(3-methylbenzyloxy)-7-azabicyclo[4.1.0]heptane
(19d)
Epoxide 16b (0.4 g, 1.83 mmol) and n-hexylamine (0.185 g, 1.83
mmol) provided 0.30 g of aziridine 19d (55%); Rf = 0.63 (EtOAc–
hexanes, 30:70).
1H NMR (300 MHz, CDCl3): d = 7.17 (m, 3 H), 7.1 (d, J = 7.3 Hz,
1 H), 4.51 (s, 2 H), 3.57 (dd, J = 5.2, 2.7 Hz, 1 H), 2.28 (s, 3 H), 2.14
(t, J = 7.1 Hz, 2 H), 1.18 (m, 15 H), 0.79 (t, J = 6.9 Hz, 3 H).
HRMS (ESI): m/z calcd for C13H17NO [M + H]+: 204.1388; found:
204.1381.
13C NMR (75 MHz, CDCl3): d = 138.6, 137.9, 128.4, 128.3, 128.2,
124.8, 74.5, 70.8, 61.2, 42.1, 39.1, 31.8, 29.7, 27.3, 27.1, 24.1, 22.6,
21.4, 16.1, 14.0.
HRMS (ESI): m/z calcd for C20H31NO [M + H]+: 302.2484; found:
302.2483.
Conversion of Epoxides 16 into Aziridines 19; General Proce-
dure
A mixture of epoxide 16 (1.47 mmol, 100 mol%), LiBr (0.147
mmol, 10 mol%) and amine (1.47 mmol, 100 mol%) were stirred at
r.t. for 5 h. This crude mixture was dissolved in H2O (10 mL) and
extracted with EtOAc (3 × 20 mL). The combined organic layers
were washed with brine (20 mL), dried (MgSO4) and concentrated
to provide the amino alcohol as a mixture of regioisomers. This
mixture was used directly in the next reaction. To a solution of PPh3
(1.06 mmol, 106 mol%) in THF (5 mL) was added DIAD (1.06
mmol, 106 mol%) in THF (2 mL) at 0 °C. After 5 min, a solution of
the above amino alcohol (1 mmol, 100 mol%) in THF (2 mL) was
added, warmed to r.t. and stirred for 8 h. This mixture was concen-
trated and chromatographed (EtOAc in hexanes) to provide the de-
sired aziridine 19.
N-Hexyl-2-(4-methylbenzyloxy)-7-azabicyclo[4.1.0]heptane
(19e)
Epoxide 16c (0.5 g, 2.29 mmol) and n-hexylamine (0.23 g, 2.29
mmol) provided 0.45 g of aziridine 19e (65%); Rf = 0.65 (EtOAc–
hexanes, 30:70).
1H NMR (300 MHz, CDCl3): d = 7.27 (d, J = 7.9 Hz, 2 H), 7.16 (d,
J = 7.9 Hz, 2 H), 4.6 (s, 2 H), 3.66 (dd, J = 5.2, 2.7 Hz, 1 H), 2.36
(s, 3 H), 2.22 (m, 2 H), 1.2 (m, 15 H), 0.89 (t, J = 7.0 Hz, 3 H).
13C NMR (75 MHz, CDCl3): d = 137.1, 135.7, 129.0, 127.7, 74.3,
61.2, 42.1, 39.0, 31.9, 29.7, 27.3, 27.1, 24.1, 22.6, 21.1, 16.1, 14.1.
HRMS (ESI): m/z calcd for C20H31NO [M + H]+: 302.2484; found:
302.2477.
2-(Benzyloxy)-N-hexyl-7-azabicyclo[4.1.0]heptane (19a)
Epoxide 16a (0.3 g, 1.47 mmol) and n-hexylamine (0.15 g, 1.47
mmol) provided 0.33 g (75%) of amino alcohol, 0.3 g (0.98 mmol)
of which afforded 0.21 g of aziridine 19a (73%); overall yield: 49%;
Rf = 0.65 (EtOAc–hexanes, 30:70).
1H NMR (300 MHz, CDCl3): d = 7.29 (m, 5 H), 4.5 (s, 2 H), 3.54
(m, 1 H), 2.09 (t, J = 7.3 Hz, 2 H), 1.2 (m, 18 H).
13C NMR (75 MHz, CDCl3): d = 138.8, 128.3, 127.6, 127.4, 74.6,
70.7, 61.2, 53.3, 42.1, 39, 31.8, 298.7, 27.2, 27.1, 24.9, 24.2, 23,
22.6, 19.7, 16.1, 14.0.
N-Hexyl-2-(2-methyloxybenzyloxy)-7-azabicyclo[4.1.0]heptane
(19f)
Epoxide 16d (0.5 g, 2.13 mmol) and n-hexylamine (0.22 g, 2.13
mmol) provided 0.412 g of aziridine 19f (61%); Rf = 0.65 (EtOAc–
hexanes, 30:70).
1H NMR (300 MHz, CDCl3): d = 7.44 (d, J = 7.4 Hz, 1 H), 7.23 (t,
J = 8.0 Hz, 1 H), 6.94 (t, J = 7.4 Hz, 1 H), 6.85 (d, J = 8.2 Hz, 1 H),
4.68 (s, 2 H), 3.84 (s, 3 H), 3.69 (dd, J = 5.2, 2.8 Hz, 1 H), 2.23 (t,
J = 7.4 Hz, 2 H), 1.29 (m, 15 H), 0.88 (t, J = 7.0 Hz, 3 H).
HRMS (ESI): m/z calcd for C19H29NO [M + H]+: 288.2327; found:
288.2314.
13C NMR (75 MHz, CDCl3): d = 154.5, 126.3, 125.9, 124.8, 118.0,
107.6, 72.3, 63.0, 58.8, 52.8, 39.7, 36.7, 29.4, 27.2, 24.9, 24.7, 21.7,
20.1, 13.7, 11.6.
HRMS (ESI): m/z calcd for C20H31NO2 [M + H]+: 318.2433; found:
318.2438.
N-Benzyl-2-(benzyloxy)-7-azabicyclo[4.1.0]heptane (19b)
Epoxide 16a (0.3 g, 1.47 mmol) and benzylamine (0.16 g, 1.47
mmol) provided 0.34 g (75%) of amino alcohol, 0.3 g of which
(0.96 mmol) afforded 0.189 g of aziridine 19b (67%); overall
yield: 44%; Rf = 0. 65 (EtOAc–hexanes, 30:70).
1H NMR (300 MHz, CDCl3): d = 7.23 (m, 10 H), 4.47 (s, 2H), 3.61
(t, J = 7.5 Hz, 1 H), 3.49 (d, J = 13.9 Hz, 1 H), 3.33 (d, J = 13.9 Hz,
1 H), 1.69 (m, 5 H), 1.37 (m, 1 H), 1.19 (m, 2 H).
13C NMR (75 MHz, CDCl3): d = 139.6, 138.7, 128.3, 128.2, 127.6,
127.4, 126.7, 74.3, 70.6, 64.1, 42.1, 39.7, 29.7, 27.4, 24.1, 16.1.
HRMS (ESI): m/z calcd for C20H23NO [M + H]+: 294.1858; found:
294.1845.
N-Hexyl-2-(3-methyloxybenzyloxy)-7-azabicyclo[4.1.0]heptane
(19g)
Epoxide 16e (0.4 g, 1.7 mmol) and n-hexylamine (0.17 g, 1.7 mmol)
provided 0.34 g of aziridine 19g (63%); Rf = 0.65 (EtOAc–hexanes,
30:70).
1H NMR (300 MHz, CDCl3): d = 7.25 (t, J = 8.2 Hz, 1 H), 6.85 (d,
J = 7.2 Hz, 2 H), 6.82 (dd, J = 6.9, 1.2 Hz, 1 H), 4.62 (s, 2 H), 3.83
(s, 3 H), 3.66 (dd, J = 5.2, 2.6 Hz, 1 H), 2.23 (t, J = 7.3 Hz, 2 H),
1.27 (m, 15 H), 0.88 (t, J = 7.1 Hz, 3 H).
13C NMR (75 MHz, CDCl3): d = 129.3, 119.8, 113.1, 113.0, 74.5,
70.6, 61.2, 55.2, 42.1, 39.1, 31.8, 29.7, 27.3, 27.2, 24.1, 22.6, 16.1,
14.1.
2-(Benzyloxy)-N-phenyl-7-azabicyclo[4.1.0]heptane (19c)
Epoxide 16a (0.3 g, 1.47 mmol) and aniline (0.14 g, 1.47 mmol)
provided 0.33 g (76%) of amino alcohol, 0.3 g (1 mmol) of which
afforded 0.21 g of aziridine 19c (75%); overall yield: 51%;
Rf = 0.65 (EtOAc–hexanes, 30:70).
Synthesis 2008, No. 9, 1420–1430 © Thieme Stuttgart · New York

1428
A. B. Pulipaka, S. C. Bergmeier
PAPER
N-Hexyl-2-(2-napthylbenzyloxy)-7-azabicyclo[4.1.0]heptane
HRMS (ESI): m/z calcd for C20H31NO2 [M + H]+: 318.2433; found:
318.2441.
(19l)
Following the general procedure epoxide 16j (0.15 g, 0.589 mmol)
and n-hexylamine (60 mg, 0.589 mmol) provided 0.131 g of aziri-
dine 19l (66%); Rf = 0.68 (EtOAc–hexanes, 30:70).
1H NMR (300 MHz, CDCl3): d = 7.82 (m, 2 H), 7.46 (m, 3 H), 7.25
(d, J = 8.6 Hz, 2 H), 4.58 (s, 2 H), 3.64 (dd, J = 5.2, 2.5 Hz, 1 H).
13C NMR (75 MHz, CDCl3): d = 137.8, 136.2, 133.3, 132.9, 128.1,
127.8, 127.6, 126.3, 126.0, 125.8, 125.7, 121.3, 74.7, 70.9, 61.2,
41.9, 39.0, 31.8, 29.7, 27.3, 24.1, 22.6, 16.1, 14.0.
N-Hexyl-2-(4-methyloxybenzyloxy)-7-azabicyclo[4.1.0]heptane
(19h)
Epoxide 16f (0.4 g, 1.7 mmol) and n-hexylamine (0.17 g, 1.7 mmol)
provided 0.31 g of aziridine 19h (57%); Rf = 0.63 (EtOAc–hexanes,
30:70).
1H NMR (300 MHz, CDCl3): d = 7.2 (d, J = 8.5 Hz, 2 H), 6.78 (d,
J = 8.5 Hz, 2 H), 4.47 (s, 2 H), 3.72 (s, 3 H), 3.55 (dd, J = 5.2, 2.6
Hz, 1 H), 2.12 (t, J = 7.4 Hz, 2 H), 1.08 (m, 15 H), 0.78 (t, J = 6.5
Hz, 3 H).
13C NMR (75 MHz, CDCl3): d = 159.1, 130.8, 129.2, 113.8, 74.2,
61.2, 55.2, 42.1, 39.1, 31.9, 27.4, 27.3, 27.1, 24.1, 22.6, 16.1, 14.0.
HRMS (ESI): m/z calcd for C20H31NO2 + Na [M + Na]+: 340.2252;
HRMS (ESI): m/z calcd for C23H31NO + Na [M + Na]+: 360.2303;
found: 360.2296.
Cyclization of Aziridines 19 to Chromenes 20; General Proce-
dure
found: 340.2243.
To a solution of aziridine 19 (0.006 mmol, 100 mol%) in CH2Cl2 (1
mL) was added B(C6F5)3 (0.006 mmol, 100 mol%) at 0 °C. After 10
min, the mixture was warmed to r.t. and stirred for 8 h. The organic
layer was diluted with CH2Cl2 (10 mL), washed with sat. aq Na2CO3
(5 mL), brine (5 mL), dried (MgSO4), concentrated, and chromato-
graphed (MeOH–CH2Cl2, 10:90) to provide amine 20.
2-(4-Bromobenzyloxy)-N-hexyl-7-azabicyclo[4.1.0]heptane
(19i)
Epoxide 16g (0.2 g, 0.71 mmol) and n-hexylamine (71 mg, 0.71
mmol) provided 0.137 g of aziridine 19i (53%); Rf = 0.6 (EtOAc–
hexanes, 30:70).
N-Hexyl-2,3,4,4a,6,10b-hexahydro-1H-benzo[c]chromen-1-
amine (20a)
Aziridine 19a (20 mg, 0.0695 mmol) provided 16 mg (80%) of
1H NMR (300 MHz, CDCl3): d = 7.47 (d, J = 8.3 Hz, 2 H), 7.25 (d,
J = 8.6 Hz, 2 H), 3.64 (m, 1 H), 2.22 (t, J = 7.4 Hz, 2 H), 1.18 (15
H), 0.88 (t, J = 6.9 Hz, 3 H).
13C NMR (75 MHz, CDCl3): d = 137.8, 131.4, 129.2, 121.3, 74.8,
70.0, 61.2, 42, 39, 31.9, 29.7, 27.2, 27.1, 24.1, 22.6, 16.1, 14.1.
HRMS (ESI): m/z calcd for C19H28BrNO [M + H]+: 366.1433;
found: 366.1443.
amine 20a; Rf = 0.25 (MeOH–CH2Cl2, 5:95).
1H NMR (300 MHz, CDCl3): d = 7.18 (m, 4 H), 4.58 (d, J = 11.6
Hz, 1 H), 4.32 (d, J = 11.5 Hz, 1 H), 3.18 (m, 1 H), 2.51 (m, 2 H),
2.24 (t, J = 9.6 Hz, 1 H), 1.96 (m, 1 H), 1.7 (m, 1 H), 1.67 (m, 1 H),
1.17 (m, 14 H), 0.77 (m, 4 H).
13C NMR (75 MHz, CDCl3): d = 138.5, 128.4, 127.7, 127.6, 78.3,
70.7, 70.2, 67.3, 45.6, 32.2, 31.7, 30.9, 30.2, 29.6, 26.9, 24.6, 22.6,
19.9, 13.9.
2-(2-Trifluoromethylbenzyloxy)-N-hexyl-7-azabicy-
clo[4.1.0]heptane (19j)
Epoxide 16h (0.1 g, 0.37 mmol) and n-hexylamine (37 mg, 0.37
mmol) provided 33 mg of aziridine 19j (25%); Rf = 0.62 (EtOAc–
hexanes, 30:70).
Anal. Calcd for C19H29NO: C, 79.39; H, 10.17; N, 4.87. Found: C,
79.00; H, 10.12; N, 4.70.
1H NMR (300 MHz, CDCl3): d = 7.67 (d, J = 7.8 Hz, 1 H), 7.55 (d,
J = 7.8 Hz, 1 H), 7.45 (t, J = 7.6 Hz, 1 H), 7.27 (t, J = 7.7 Hz, 1 H),
4.73 (s, 2 H), 3.60 (dd, J = 5.1, 2.7 Hz, 1 H), 2.17 (m, 2 H), 1.14 (m,
15 H), 0.80 (t, J = 7.0 Hz, 3 H).
13C NMR (75 MHz, CDCl3): d = 137.6, 131.9, 129, 127.2, 125.7,
125.6, 75.2, 66.6, 66.5, 61.2, 41.8, 39.1, 31.8, 29.6, 27.2, 27.1, 24.1,
22.5, 16.0, 14.0.
N-Benzyl-2,3,4,4a,6,10b-hexahydro-1H-benzo[c]chromen-1-
amine (20b)
Aziridine 19b (20 mg, 0.068 mmol) provided 18 mg (90%) of amine
20b; Rf = 0.2 (MeOH–CH2Cl2, 5:95).
1H NMR (300 MHz, CDCl3): d = 7.18 (m, 9 H), 4.63 (d, J = 11.5
Hz, 1 H), 4.37 (d, J = 11.5 Hz, 1 H), 3.93 (d, J = 12.6 Hz, 1 H), 3.69
(d, J = 12.5 Hz, 1 H), 3.28 (m, 1 H), 2.38 (t, J = 9.5 Hz, 1 H), 2.15
(m, 1 H), 1.94 (m, 1 H), 1.71 (m, 1 H), 1.18 (m, 6 H).
HRMS (ESI): m/z calcd for C20H28F3NO [M + H]+: 356.2201;
found: 356.2205.
13C NMR (75 MHz, CDCl3): d = 137.2, 127.2, 126.9, 126.52,
126.5125.8, 75.3, 69.3, 66.14, 49.5, 31, 28.9, 28.4, 18.6.
N-Hexyl-2-(3,4-dimethoxybenzyloxy)-7-azabicyclo[4.1.0]hep-
tane (19k)
Epoxide 16i (0.6 g, 2.26 mmol) and n-hexylamine (0.23 g, 2.26
mmol) provided 0.52 g of aziridine 19k (66%); Rf = 0.62 (EtOAc–
hexanes, 30:70).
1H NMR (300 MHz, CDCl3): d = 6.90 (d, J = 9.1 Hz, 2 H), 6.82 (d,
J = 7.9 Hz, 1 H), 4.56 (s, 2 H), 3.9 (s, 3 H), 3.88 (s, 3 H), 3.64 (dd,
J = 5.1, 2.8 Hz, 1 H), 2.21 (t, J = 7.4 Hz, 2 H), 1.18 (m, 15 H), 0.86
(t, J = 7.1 Hz, 3 H).
13C NMR (75 MHz, CDCl3): d = 149.0, 148.5, 131.9, 120.2, 11.0,
110.9, 74.3, 70.7, 61.2, 55.9, 55.8, 42.1, 39.1, 31.87, 29.7, 27.3,
27.1, 24.1, 22.6, 22.3, 21.9, 16.1, 14.0.
Anal. Calcd for C20H23NO: C, 81.87; H, 7.90; N, 4.77. Found: C,
81.60; H, 7.84; N, 4.63.
N-Phenyl-2,3,4,4a,6,10b-hexahydro-1H-benzo[c]chromen-1-
amine (20c)
Aziridine 19c (20 mg, 0.071 mmol) provided 14 mg (70%) of amine
20c; Rf = 0.22 (MeOH–CH2Cl2, 5:95).
1H NMR (300 MHz, CDCl3): d = 7.25 (m, 3 H), 7.2 (m, 2 H), 7.05
(m, 1 H), 6.8 (m, 2 H), 4.5 (d, J = 11.5 Hz, 1 H), 4.35 (d, J = 12.6
Hz, 1 H), 3.2 (m, 3 H), 3.0 (s, 1 H), 2.1 (m, 2 H), 1.8 (m, 1 H), 1.2
(m, 3 H).
13C NMR (75 MHz, CDCl3): d = 148.8, 138.2, 129.2, 128.2, 127.6,
127.6, 127.5, 118.3, 114.4, 80.1, 72.9, 70.9, 64, 31.6, 29.8, 19.2.
HRMS (ESI): m/z calcd for C19H21NO [M + H]+: 280.1691; found:
HRMS (ESI): m/z calcd for C21H33NO3 + Na [M + Na]+: 370.2358;
found: 370.2366.
280.1701.
Synthesis 2008, No. 9, 1420–1430 © Thieme Stuttgart · New York

PAPER
Intramolecular Cyclizations of Aziridines with p-Nucleophiles
1429
N-Hexyl-2,3,4,4a,6,10b-hexahydro-8-methyl-1H-ben-
zo[c]chromen-1-amine (20d)
Aziridine 19d (50 mg, 0.165 mmol) provided 36 mg (72%) of amine
20d; Rf = 0.2 (MeOH–CH2Cl2, 5:95).
1H NMR (300 MHz, CDCl3): d = 7.14 (d, J = 7.29 Hz, 2 H), 7.07 (s,
1 H), 4.58 (d, J = 11.4 Hz, 1 H), 4.28 (d, J = 11.4 Hz, 1 H), 3.18 (m,
2 H), 2.58 (m, 1 H), 2.46 (m, 1 H), 2.28 (s, 3 H), 2.15 (m, 1 H), 2.12
(m, 1 H), 1.92 (m, 1 H), 1.18 (m, 10 H), 0.80 (m, 3 H).
1H NMR (300 MHz, CDCl3): d = 7.20 (d, J = 8.0 Hz, 1 H), 7.15 (s,
1 H), 6.74 (d, J = 7.9 Hz, 1 H), 4.50 (d, J = 11.4 Hz, 1 H), 4.13 (d,
J = 11.3 Hz, 1 H), 3.71 (s, 3 H), 3.57 (m, 2 H), 2.78 (m, 1 H), 2.63
(m, 1 H), 2.15 (t, J = 7.6 Hz, 1 H), 2.10 (m, 1 H), 1.43 (m, 1 H), 1.18
(m, 11 H), 0.76 (m, 3 H).
13C NMR (75 MHz, CDCl3): d = 157.7, 143.1, 129.3, 125.5, 114.2,
113.8, 73.6, 70.6, 70.2, 68.2, 55.2, 46.0, 33.7, 31.7, 29.7, 27.0, 22.5,
19.2, 14.0.
13C NMR (75 MHz, CDCl3): d = 129.4, 128.5, 128.4, 128.3, 125.3,
124.9, 78.0, 70.8, 70.1, 67.2, 45.3, 32.1, 31.8, 31.0, 29.7, 27.0, 22.6,
21.4, 19.9, 14.0.
HRMS (ESI): m/z calcd for C20H31NO2 [M + H]+: 318.2433; found:
318.2427.
9-Bromo-N-hexyl-2,3,4,4a,6,10b-hexahydro-1H-ben-
zo[c]chromen-1-amine (20i)
Following the general procedure, aziridine 19i (50 mg, 0.136 mmol)
provided 22.5 mg (45%) of amine 20i; Rf = 0.22 (MeOH–CH2Cl2,
5:95).
1H NMR (300 MHz, CDCl3): d = 7.38 (d, J = 8.6 Hz, 1 H), 7.19 (s,
1 H), 7.05 (d, J = 8.3 Hz, 1 H), 4.52 (d, J = 11.3 Hz, 1 H), 4.18 (d,
J = 11.4 Hz, 1 H), 3.55 (m, 2 H), 3.38 (m, 1 H), 3.17 (m, 1 H), 2.14
(t, J = 7.5 Hz, 1 H), 2.10 (m, 1 H), 1.45 (m, 1 H), 1.20 (m, 11 H),
0.76 (m, 3 H).
13C NMR (75 MHz, CDCl3): d = 131.7, 130.6, 129.1, 128.7, 128.5,
127.9, 78.7, 70.8, 70.5, 67.9, 46.4, 33.1, 31.5, 31.3, 29.5, 27.2, 22.8,
20.8, 14.0.
HRMS (ESI): m/z calcd for C20H31NO [M + H]+: 302.2484; found:
302.2476.
N-Hexyl-9-methyl-2,3,4,4a,6,10b-hexahydro-1H-ben-
zo[c]chromen-1-amine (20e)
Aziridine 19e (50 mg, 0.165 mmol) provided 30 mg (60%) of amine
20e; Rf = 0.2 (MeOH–CH2Cl2, 5:95).
1H NMR (300 MHz, CDCl3): d = 7.07 (m, 3 H), 4.55 (d, J = 11.6
Hz, 1 H), 4.17 (d, J = 11.6 Hz, 1 H), 3.31 (m, 2 H), 2.58 (m, 1 H),
2.63 (m, 1 H), 2.26 (s, 3 H), 2.19 (m, 1 H), 2.12 (m, 1 H), 1.18 (m,
11 H), 0.80 (m, 3 H).
13C NMR (75 MHz, CDCl3): d = 129.7, 129.6, 129.1, 128.4, 128.3,
127.9, 78.7, 70.3, 70.5, 67.8, 45.4, 32.1, 31.3, 31.1, 29.7, 27.3, 22.6,
21.8, 19.9, 14.0
HRMS (ESI): m/z calcd for C19H28BrNO [M + H]+: 366.1433;
found: 366.1433.
HRMS (ESI): m/z calcd for C20H31NO [M + H]+: 302.2484; found:
302.2487.
8,9-Dimethoxy-N-hexyl-2,3,4,4a,6,10b-hexahydro-1H-ben-
zo[c]chromen-1-amine (20k)
Following the general procedure, aziridine 19k (50 mg, 0.143
mmol) provided 20 mg (40%) of amine 20k; Rf = 0.19 (MeOH–
CH2Cl2, 5:95).
1H NMR (300 MHz, CDCl3): d = 6.89 (s, 1 H), 6.80 (s, 1 H), 4.37
(d, J = 11.2 Hz, 1 H), 4.25 (d, J = 11.4 Hz, 1 H), 3.91 (s, 3 H), 3.86
(s, 3 H), 3.29 (m, 2 H), 3.03 (m, 1 H), 3.17 (m, 1 H), 2.18 (t, J = 7.6
Hz, 1 H), 2.10 (m, 1 H), 1.45 (m, 1 H), 1.20 (m, 11 H), 0.76 (m, 3 H).
13C NMR (75 MHz, CDCl3): d = 157.3, 138.1, 127.4, 117.9, 112.3,
111.0, 78.4, 70.6, 70.1, 67.2, 66.4, 54.1, 43.5, 31.1, 30.8, 29.0, 27.4,
21.6, 19.6, 14.0.
N-Hexyl-7-methoxy-2,3,4,4a,6,10b-hexahydro-1H-ben-
zo[c]chromen-1-amine (20f)
Aziridine 19f (50 mg, 0.157 mmol) provided 32 mg (64%) of amine
20f; Rf = 0.18 (MeOH–CH2Cl2, 5:95).
1H NMR (300 MHz, CDCl3): d = 7.18 (m, 1 H), 6.87 (m, 1 H), 6.79
(d, J = 8.2 Hz, 1 H), 4.60 (d, J = 11.9 Hz, 1 H), 4.28 (d, J = 11.9 Hz,
1 H), 3.76 (s, 3 H), 3.23 (m, 2 H), 2.57 (m, 1 H), 2.48 (m, 1 H), 2.24
(t, J = 9.6 Hz, 1 H), 2.12 (m, 1 H), 1.92 (m, 1 H), 1.18 (m, 11 H),
0.80 (t, J = 7.2 Hz, 3 H).
13C NMR (75 MHz, CDCl3): d = 157.1, 130.8, 129.2, 128.9, 126.9,
120.4, 110.2, 78.3, 70.3, 67.3, 65.8, 55.3, 45.5, 32.2, 31.8, 30.9,
30.3, 27.0, 22.6, 20.0, 14.1.
HRMS (ESI): m/z calcd for C21H33NO3 [M + H]+: 348.2539; found:
348.2530.
HRMS (ESI): m/z calcd for C20H31NO2 [M + H]+: 318.2433; found:
318.2424.
N-Hexyl-2,3,4,4a,6,12b-hexahydro-1H-naphtho[2,3-c]chrom-
en-1-amine (20l)
Aziridine 19l (50 mg, 0.148 mmol) provided 23 mg (46%) of amine
N-Hexyl-8-methoxy-2,3,4,4a,6,10b-hexahydro-1H-ben-
zo[c]chromen-1-amine (20g)
Aziridine 19g (50 mg, 0.157 mmol) provided 37.5 mg (75%) of
amine 20g; Rf = 0.18 (MeOH–CH2Cl2, 5:95).
1H NMR (300 MHz, CDCl3): d = 7.19 (s, 1 H), 6.81 (d, J = 8.1 Hz,
1 H), 6.74 (d, J = 7.9 Hz, 1 H), 4.56 (d, J = 11.7 Hz, 1 H), 4.28 (d,
J = 11.7 Hz, 1 H), 3.74 (s, 3 H), 3.18 (m, 2 H), 2.60 (m, 1 H), 2.49
(m, 1 H), 2.24 (t, J = 9.6 Hz, 1 H), 2.10 (m, 1 H), 1.96 (m, 1 H), 1.18
(m, 11 H), 0.80 (t, J = 6.9 Hz, 3 H).
13C NMR (75 MHz, CDCl3): d = 159.7, 140.1, 129.4, 119.9, 113.3,
113.0, 78.2, 70.6, 70.1, 67.3, 55.1, 45.5, 32.1, 31.8, 31.0, 27.0, 22.6,
19.9, 14.0.
20l; Rf = 0.23 (MeOH–CH2Cl2, 5:95).
1H NMR (300 MHz, CDCl3): d = 7.85 (s, 1 H), 7.49 (m, 3 H), 7.22
(d, J = 8.3 Hz, 2 H), 4.63 (d, J = 11.8 Hz, 1 H), 4.25 (d, J = 11.8 Hz,
1 H), 3.31 (m, 2 H), 2.72 (m, 1 H), 2.55 (m, 1 H), 2.34 (t, J = 9.6 Hz,
1 H), 2.18 (m, 1 H), 2.03 (m, 1 H), 1.81 (m, 1 H), 1.28 (m, 11 H),
0.76 (t, J = 7.4 Hz, 3 H).
13C NMR (75 MHz, CDCl3): d = 129.2, 128.1, 127.8, 127.6, 126.3,
126.0, 125.8, 125.7, 74.6, 70.0, 61.2, 53.4, 442.1, 39.1, 31.8, 29.7,
27.2, 24.1, 22.6, 16.1, 14.0.
HRMS (ESI): m/z calcd for C23H31NO [M + H]+: 338.2484; found:
338.2473.
HRMS (ESI): m/z calcd for C20H31NO2 [M + H]+: 318.2433; found:
318.2429.
Acknowledgment
N-Hexyl-9-methoxy-2,3,4,4a,6,10b-hexahydro-1H-ben-
zo[c]chromen-1-amine (20h)
Aziridine 19h (50 mg, 0.157 mmol) provided 12.5 mg (25%) of
We thank the National Science Foundation (CHE-9816208) and the
National Institutes on Drug Abuse at the NIH (DA 013939) for par-
tial support of this work. We also thank the Ohio University
BioMolecular Innovation and Technology project for support.
amine 20h; Rf = 0.18 (MeOH–CH2Cl2, 5:95).
Synthesis 2008, No. 9, 1420–1430 © Thieme Stuttgart · New York

1430
A. B. Pulipaka, S. C. Bergmeier
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Synthesis 2008, No. 9, 1420–1430 © Thieme Stuttgart · New York