Synthesis and characterization of a diaziridinium ion. Conversion of 3,4-dihydroisoquinolines to 4,5-dihydro-3H-benzo[2,3]diazepines via a formal N-insertion process

Article abstract of DOI:10.1016/j.tet.2014.03.015

A diaziridinium ion has been synthesized in high yield and its structure unambiguously confirmed by X-ray crystal analysis. The predicted N-transfer reactivity with olefins of this species was not observed. Instead, upon heating, the diaziridinium ion underwent ring opening to produce a dihydrobenzodiazepene product in good yield, thus achieving a formal N-insertion of the starting dihydroisoquinoline substrate. This process has been demonstrated on 11 total substrates.

Full text of DOI:10.1016/j.tet.2014.03.015

Tetrahedron xxx (2014) 1e7
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Tetrahedron
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Synthesis and characterization of a diaziridinium ion. Conversion of
3,4-dihydroisoquinolines to 4,5-dihydro-3H-benzo[2,3]diazepines
via a formal N-insertion process
*
Julia M. Allen, Tristan H. Lambert
Department of Chemistry, Columbia University, 3000 Broadway, New York, NY 10027, United States
a r t i c l e i n f o
a b s t r a c t
Article history:
A diaziridinium ion has been synthesized in high yield and its structure unambiguously confirmed
by X-ray crystal analysis. The predicted N-transfer reactivity with olefins of this species was not ob-
served. Instead, upon heating, the diaziridinium ion underwent ring opening to produce a dihy-
Received 23 January 2014
Received in revised form 1 March 2014
Accepted 5 March 2014
Available online xxx
drobenzodiazepene product in good yield, thus achieving
dihydroisoquinoline substrate. This process has been demonstrated on 11 total substrates.
Ó 2014 Published by Elsevier Ltd.
a formal N-insertion of the starting
Keywords:
Diaziridinium
N-transfer
N-insertion
Diazepine
Isoquinoline
1. Introduction
Diheterocyclic three-membered rings participate in a number of
useful reactivity modes including ring-opening and atom-transfer
reactions. Within the broader class, dioxiranes,1 oxaziridines,2,3
diaziridines,4,5 and oxaziridiniums6 have all been well-
characterized and productively employed. In contrast, diazir-
idinium ions have yet to succumb to unambiguous synthesis and
characterization.7 Especially intriguing is the expectation that
diaziridinium ions might participate in N-transfer chemistry,8
analogous to the O-transfer reactivity of their kindred oxazir-
idinium ions.6 In this article, we describe a high-yielding synthesis
of a diaziridinium ion, which has been characterized by X-ray
structural analysis, a development that should enable the in-depth
study of these intriguing species. Additionally, as part of an in-
vestigation of the reactivity of these ions, we have also developed
Fig. 1. Diheterocyclic three-membered rings.
diaziridines,11 although these procedures were low yielding and
definitive structural characterization was not possible. Thus the
isolation of significant quantities of diaziridinium ions for the
purposes of characterization and reactivity studies has not been
reported. In order to enable the study and development of these
ions, particularly with the goal of probing the potential of these
ions to serve as novel N-transfer agents, we set out to synthesize
and characterize a diaziridinium ion.
a
formal N-insertion process for the conversion of dihy-
droisoquinolines to 4,5-dihydrobenzo[2,3]diazepines, an un-
2. Synthesis
derdeveloped pharmacophore9 (Fig. 1).
Diaziridinium ions have been postulated as reactive in-
termediates in the protic or alkylative decomposition of diazir-
idines.10 Schmitz reported the preparation of protic salts of
For our first attempt at diaziridinium synthesis, we sought to
execute a strategy analogous to one that had been successful for the
synthesis of oxaziridiniums ions6 from their corresponding imi-
niums. Specifically we treated 3,4-dihydroisoquinoline N-methyl
iminium ion 2 with hydroxylamine-O-sulfonic acid in the presence
of triethylamine. Unfortunately, this procedure did not result in the
production of readily identifiable reaction products. For our next
* Corresponding author. Tel.: þ1 212 854 1438; e-mail address: tl2240@columbia.
edu (T.H. Lambert).
0040-4020/$ e see front matter Ó 2014 Published by Elsevier Ltd.
http://dx.doi.org/10.1016/j.tet.2014.03.015
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2
J.M. Allen, T.H. Lambert / Tetrahedron xxx (2014) 1e7
attempt, we decided to reverse the steps by first converting 3,4-
dihydroisoquinoline (1) to its corresponding diaziridine 212 and
then alkylating with trimethyloxonium tetrafluoroborate. Although
alkylation of the sterically less-hindered nitrogen might have been
expected, in fact we observed clean conversion to diaziridinium ion
3, which was isolated as a crystalline solid in 72% yield after puri-
fication by recrystallization. Structural verification of ion 3 was
achieved by X-ray diffraction (Fig. 2). To the best of our knowledge,
this work provides the first high-yielding synthesis and X-ray
structural characterization of a diaziridinium ion.
modifications to the diaziridinium framework (e.g., electron-
withdrawing groups to disfavor carbocation formation at C1)
could suppress this pathway, although to date such efforts have
been unsuccessful (Scheme 1).
Scheme 1. Attempted N-transfer from diaziridinium 3. Formation of benzodiazepine 4.
4. Synthesis of [2,3]benzodiazepines via a formal N-insertion
process
The conversion of dihydroisoquinolines, which are readily
available via BischlereNapieralski condensation, to [2,3]benzodi-
azepines represents an intriguing formal N-insertion process of
potential value. The [2,3]benzodiazepine substructure has been of
interest to the pharmaceutical community for drug design,9 es-
pecially because it offers a scaffold isomeric to the common [1,4]
benzodiazepine framework. The current standard for the prepa-
ration of [2,3]benzodiazepines is via the condensation of hydra-
zine with benzylic ketones.13 We felt that the strategy represented
by the conversion of 1 to 4 offered a unique and potentially ad-
vantageous alternative to this standard route, and thus we de-
cided to further explore this formal N-insertion process in more
depth.
Fig. 2. Synthesis of diaziridinium ion 4.
Under argon, diaziridinium ion 3 can be stored indefinitely at
5 ꢀC with no observed decomposition. The stability of diaziridinium
ion 3 was somewhat surprising, given the tendency of related
structures to undergo rapid decomposition. At room temperature,
however, 3 slowly underwent decomposition, primarily to struc-
ture 4 as described below (Fig. 3).
In contrast to the parent compound, which required heat for
facile rearrangement (entry 1), methyldiaziridine 5 rearranged
spontaneously to the corresponding diazepine 6 upon treatment
with Meerwein’s salt, even at reduced temperature (entry 2).
Structural variation of the benzo ring (entry 3) and the saturated
portion (entries 4 and 5) of the scaffold was well tolerated. Phenyl
substitution on the diaziridine carbon resulted in a very facile ring-
opening process (entry 6), presumably a result of the ability of the
bisbenzylic 1-carbon to readily accommodate positive charge. In-
terestingly, while we found the standard method for synthesis of
the 1-unsubstituted and 1-methyl diazepines provided serviceable
yields (entries 1e5), the yield of this process for the 1-phenyl
substrate 13 was exceedingly low (entry 6). Thus, although it pro-
vided us with sufficient material to explore the ring-opening re-
action, a more efficient diaziridine preparation will obviously be
required for this type of substrate to be practically employed.
Similarly, both the synthesis and rearrangement of the
trifluoromethyl-substituted substrate 15 were viable although less
than optimal (entry 7) (Table 1).
We also found that the ring-opening process could be achieved
via acylation of diaziridine substrates. For example, treatment of
diaziridine 2 or 5 with acetyl chloride resulted in highly efficient
production of the N-acyl diazepines 17 and 18 in 82 and 84%
yields, respectively (entries 8 and 9). In addition, treatment of
diaziridine 5 with CbzCl produced diazepine 19, which should
provide the opportunity for straightforward N-deprotection (entry
10). Finally, we found that the use of a more complex acid chloride
was productive for the formation of diazepine 20 in high yield
(entry 11).
Fig. 3. Molecular structure of diaziridinium 3. The BFꢁ4 counterion has been removed
for clarity.
3. Attempted N-transfer studies
With diaziridinium ion 3 in hand, we next sought to investigate
the reactivity of this species. Specifically, we were interested in
exploring the potential of this structure to engage in N-transfer
chemistry for the aziridination of olefins. Notably, Washington,
Houk, and Armstrong have offered theoretical support for the no-
tion that diaziridiniums might participate in N-transfer with both
electron-rich and electron-deficient olefins.8 Unfortunately, ion 3
did not undergo any reaction at room temperature with electron-
rich, electron-deficient, or strained alkenes, including 4-phenyl-1-
butene, cis- or trans-stilbene,
a-pinene, 3-carene, styrene, cyclo-
dodecene, methyl acrylate, or norbornene. Instead, at elevated
temperatures, 3 underwent facile conversion to the corresponding
benzodiazepine 4 in 74% yield. Of course, the failure to observe N-
transfer reactivity says nothing against the validity of the theoret-
ical predictions, only that in this context the ring-opening pathway
to form 4 is more facile. It is entirely plausible that structural
5. Conclusions
It has long been speculated that the diaziridinium ion functional
group would offer an interesting reactivity profile for synthetic
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J.M. Allen, T.H. Lambert / Tetrahedron xxx (2014) 1e7
3
Table 1
6. Experimental section
6.1. General information
Formal N-insertion process for the conversion of dihydroisoquinolines to
benzodiazepinesa
All reactions were performed using oven-dried glassware under
atmosphere of dry argon. Non-aqueous reagents were transferred
by syringe under argon. Organic solutions were concentrated using
a Buchi rotary evaporator. Acetonitrile (MeCN) and methylene
chloride (DCM) were dried using a J.C. Meyer solvent purification
system. Reactions using trimethyloxonium tetrafluoroborate
(Me3OBF4) were set up in a glove box under inert atmosphere.
Trimethyloxonium tetrafluoroborate and all other commercially
available reagents were used as provided. Flash column chroma-
Entry
1
Diaziridine
% Yield Electrophile
Diazepineb
% Yield
74
58
63
Me3OBF4
Me3OBF4
2
3
82
93
tography was performed employing 32e63 mm silica gel (Dynamic
Adsorbents Inc). Thin-layer chromatography (TLC) was performed
on silica gel 60 F254 plates (EMD). Dihydroisoquinolines were pre-
pared according to established procedures.14 Diaziridines were
prepared according to the procedure of Alper.15
71
68
Me3OBF4
Me3OBF4
1H and 13C NMR were recorded in CDCl3 on a Bruker DRX-300
spectrometer. Data for 1H NMR are reported as follows: chemical
shift
(d
ppm), multiplicity (s¼singlet, br s¼broad singlet,
4
89
d¼doublet, t¼triplet, q¼quartet, m¼multiplet), integration, cou-
pling constant (Hz), and assignment. Data for 13C NMR are reported
in terms of chemical shift. Low-resolution mass spectra (LRMS)
were acquired on a JEOL JMS-LCmate liquid chromatography mass
spectrometer system using a Clþ ionization technique. IR spectra
were recorded on a Nicolet Avatar 370 DTGS (Thermo) using NaCl
salt plates.
5
6
65
Me3OBF4
Me3OBF4
87
84
6.2. Synthetic procedures
3
6.2.1. 1,2,3,7b-Tetrahydro-1,1a-diazacyclopropa[a]-naphthalene
(compound 2). A solution of NH4OH (5.7 mL) in MeOH (13 mL) was
cooled to ꢁ20 ꢀC, and hydroxylamine-O-sulfonic acid (4.65 g,
41.1 mmol) was added portionwise to the mixture. After stirring the
suspension for about 30 min at ꢁ20 ꢀC, a solution of 3,4-
dihydroisoquinoline (1) (4.82 g, 36.7 mmol) in MeOH (13 mL)
was added dropwise. The reaction mixture was stirred at 0 ꢀC
overnight. Upon warming to room temperature, the reaction mix-
ture was filtered, and the filtrate was concentrated. The crude
yellow oil was purified directly by silica gel chromatography (50%
EtOAc/hexanes) to yield diaziridine 2 as a white solid (3.10 g,
7
8
35
Me3OBF4
AcCl
24
82
2
5
9
AcCl
84
64
21.21 mmol, 58% yield). 1H NMR (300 MHz, CDCl3)
d 7.43e7.08 (m,
4H, ArH), 4.06 (d, J¼6.9 Hz, 1H, CHN), 3.61e3.54 (ddd, J¼12.9, 6.0,
and 1.2 Hz, 1H, ArCH2CH2N), 3.01e2.89 (td, J¼15.6 and 6.0 Hz, 1H,
ArCH2), 2.76e2.67 (td, J¼12.8 and 4.2 Hz,1H, ArCH2), 2.43e2.37 (dd,
J¼15.3 and 3.6 Hz, 1H, ArCH2CH2N), 2.29 (d, J¼6.6 Hz, 1H, NH).
10
5
2
CbzCl
6.2.2. N-methyltetrahydroisoquinoline
diaziridinium
tetra-
fluoroborate (compound 3). A solution of Me3OBF4 (213 mg,
1.37 mmol) in DCM (3 mL) was cooled to 0 ꢀC. Then a solution of 2
(200 mg, 1.44 mmol) in DCM (2 mL) was added to the solution of
Meerwein’s salt at 0 ꢀC. The reaction mixture was stirred at 0 ꢀC for
30 min. The reaction mixture was then concentrated under reduced
pressure. The crude oily yellow solid was recrystallized by dis-
solving in a minimal amount of a 1:1 mixture of hot EtOAc/DCM
followed by the addition of hexanes, providing 3 as colorless
crystals (243 mg, 0.980 mmol, 72% yield). 1H NMR (300 MHz,
11
ArCOCl
91
a
Percent yields refer to isolated and purified materials.
Temperatures for the formation of diazepines: 4: 80 ꢀC; 6, 8, 10, 12: ꢁ40 ꢀC;
b
17e20: 0 ꢀC.
CD3CN)
d
7.68e7.65 (dd, J¼7.5 and 1.5 Hz, 1H, ArH), 7.54e7.49 (td,
chemists. The high-yielding synthesis and unambiguous charac-
terization described in this communication should facilitate a de-
tailed study of these intriguing species. Although we have yet to
confirm the N-transfer reactivity of these ions, appropriate struc-
tural modifications, particularly those that suppress the ring-
opening process we have described, may help to enable this type
of reactivity.
J¼7.5 and 1.5 Hz, 1H, ArH), 7.46e7.40 (td, J¼7.5 and 0.9 Hz, 1H, ArH),
7.31 (d, J¼7.2 Hz, 1H, ArH), 5.30e5.23 (m, 2H, NH and ArCH),
4.07e4.00 (ddd, J¼6.06, 6.15, and 1.2 Hz, 1H, ArCH2CH2N), 3.73 (s,
3H, NCH3), 3.48e3.39 (td, J¼12.2 and 4.5 Hz, 1H, ArCH2CH2N),
3.31e3.12 (td, J¼12.8 and 6.0 Hz, 1H, ArCH2CH2N), 2.91e2.84 (dd,
J¼16.2 and 4.2 Hz, 1H, ArCH2CH2N). 13C NMR (300 MHz, CD3CN)
d
133.3, 132.0, 131.0, 129.4, 128.3, 125.8, 63.8, 52.3, 50.7, 25.0. IR
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4
J.M. Allen, T.H. Lambert / Tetrahedron xxx (2014) 1e7
(neat) 3625, 3238, 3052, 1635, 1453, 1296, 1064, 819, 765 cmꢁ1
.
MeOH (1.80 mL) was cooled to ꢁ20 ꢀC, and hydroxylamine-O-
sulfonic acid (0.870 g, 7.68 mmol) was added portionwise to the
mixture. After stirring the suspension for about 30 min at ꢁ20 ꢀC,
a solution of 8-bromo-1-methyl-3,4-dihydroisoquinoline (1.15 g,
5.12 mmol) in MeOH (1.80 mL) was added dropwise. The reaction
mixture was gradually warmed to room temperature and stirred
for 2 days. The reaction mixture was filtered, and the filtrate was
concentrated. The crude red oil was purified directly by silica gel
chromatography (35% EtOAc/hexanes) to yield 7 as a yellow solid
LRMS (APClþ) mass calcd for C10H13Nþ2 (Mþ) requires m/z 161.11,
found m/z 161.50.
6.2.3. (Z)-3-methyl-4,5-dihydro-3H-benzo[d][1,2]diazepine
(com-
pound 4). diaziridinium 3 (42 mg, 0.169 mmol) was dissolved in
MeCN (0.50 mL), and the reaction mixture was heated at 80 ꢀC
under Ar for 12 h. After cooling to room temperature, the reaction
mixture was diluted with EtOAc (2 mL) and washed with NaHCO3
(2 mL), brine (2 mL), and dried over Na2SO4. The solution was
concentrated, and the crude material was purified directly by silica
gel chromatography (20% EtOAc/hexanes) to yield benzodiazepine
4 as a yellow oil (20 mg, 0.125 mmol, 74% yield). 1H NMR (300 MHz,
(874 mg, 3.66 mmol, 71% yield). 1H NMR (300 MHz, CDCl3)
d 7.65 (s,
1H, ArH), 7.37 (d, J¼8.1 Hz, 1H, ArH), 6.97 (d, J¼8.1 Hz, 1H, ArH),
3.55e3.49 (dd, J¼5.7, 12.5 Hz, 1H, ArCH2CH2N), 2.95e2.84 (td,
J¼5.7, 12.6 Hz, 1H, ArCH2CH2N), 2.79e2.70 (td, J¼3.0, 12.8 Hz, 1H,
ArCH2CH2N), 2.39 (d, J¼14.4 Hz, 1H, ArCH2CH2N), 1.96 (br s, 1H,
CDCl3)
(m, 2H, ArCH2CH2N), 3.25e3.22 (m, 2H, ArCH2CH2N), 3.16 (s, 3H,
NCH3). 13C NMR (300 MHz, CDCl3)
139.7, 135.2, 132.4, 132.2, 129.1,
d
7.31e7.16 (m, 4H, ArH), 7.11 (s, 1H, ArC(¼N)H), 3.40e3.37
NH), 1.83 (s, 3H, ArC(CH3)). 13C NMR (300 MHz, CDCl3)
d 136.9,
d
134.2, 130.5, 130.3, 129.7, 119.7, 53.8, 46.1, 24.6, 24.0. IR (neat) 3194,
2937, 1595, 1487, 1444, 1423, 1381, 1330, 1226, 1187, 1118, 1046, 908,
883, 818, 790, 775, 756, 732, 711, 684 cmꢁ1. LRMS (APClþ) mass
127.5, 126.3, 54.1, 48.3, 37.7. IR (neat) 3060, 3017, 2955, 2905, 2854,
1586, 1563, 1494, 1444, 1422, 1400, 1309, 1258, 1204, 1149, 1115,
1065, 1022, 946, 924, 873, 780, 757, 728, 700 cmꢁ1. LRMS (APClþ)
mass calcd for C10H13Nþ2 (MHþ) requires m/z 161.11, found m/z
161.50.
calcd for C10H12BrN2 (MHþ) requires m/z 240.12, found m/z
þ
240.84.
6.2.7. (Z)-1,3-Dimethyl-4,5-dihydro-9-bromo-3H-benzo[d][1,2]dia-
zepine (compound 8). A solution of Me3OBF4 (32 mg, 0.219 mmol)
in MeCN-d3 (0.60 mL) was cooled to ꢁ40 ꢀC. Then a solution of
diaziridine 7 (50 mg, 0.209 mmol) in MeCN-d3 (0.60 mL) was added
slowly. The reaction mixture was stirred for 30 min at ꢁ40 ꢀC, and
then the reaction mixture was quenched with NaHCO3 (1 mL). The
product was extracted with EtOAc (3ꢂ2 mL), and the combined
organic layers were washed with brine (2 mL) and dried over
Na2SO4. The crude dark orange oily solid was purified by silica gel
chromatography (5% MeOH/DCM) to furnish 8 (49 mg, 0.194 mmol,
6.2.4. 1-methyl-1,2,3,7b-tetrahydro-1,1a-diazacyclopropa[a]naph-
thalene (compound 5). A solution of NH4OH (0.35) in MeOH
(0.85 mL) was cooled to ꢁ20 ꢀC, and hydroxylamine-O-sulfonic acid
(0.290 g, 2.57 mmol) was added portionwise to the mixture. After
stirring the suspension for about 30 min at ꢁ20 ꢀC, a solution of 1-
methyl-3,4-dihydroisoquinoline (0.330 g, 2.27 mmol) in MeOH
(0.85 mL) was added dropwise. The reaction mixture was gradually
warmed to room temperature and stirred for 2 days. The reaction
mixture was then filtered, and the filtrate was concentrated. The
crude red oil was purified directly by silica gel chromatography
(50% EtOAc/hexanes) to yield diaziridine 5 as a dark yellow solid
(231 mg, 1.44 mmol, 63% yield). 1H NMR (300 MHz, CDCl3)
93% yield). 1H NMR (300 MHz, CDCl3)
d 7.41e7.39 (m, 2H, ArH), 7.10
(d, J¼8.4 Hz,1H, ArH), 3.32 (t, J¼6.9 Hz, 2H, ArCH2CH2N), 2.67 (s, 3H,
NCH3), 2.62 (t, J¼6.9 Hz, 2H, ArCH2CH2N), 2.31 (s, 3H, ArC(CH3)]N).
d
7.57e7.54 (m, 1H, ArH), 7.29e7.23 (m, 2H, ArH), 7.12e7.09 (m, 1H,
13C NMR (300 MHz, CDCl3)
d 159.9, 139.0, 138.2, 132.0, 129.3, 128.8,
ArH), 3.57e3.51 (ddd, J¼6.5, 6.9, and 1.5 Hz, 1H, ArCH2CH2N),
3.05e2.94 (td, J¼13.8 and 6.0 Hz, 1H, ArCH2CH2N), 2.85e2.75 (td,
J¼12.9 and 3.9 Hz, 1H, ArCH2CH2N), 2.47e2.41 (dd, J¼15.0 and
3.3 Hz, 1H, ArCH2CH2N), 1.95 (br s, 1H, NH), 1.87 (s, 3H, ArCHCH3).
120.4, 63.3, 47.2, 31.8, 23.1. IR (neat) 2949, 2848, 2793, 1585, 1561,
1480, 1439, 1391, 1371, 1297, 1257, 1220, 1195, 1138, 1109, 1079,1050,
1029, 880, 824, 786, 771, 749, 718, 702, 671 cmꢁ1. LRMS (APClþ)
mass calcd for C11H14BrN2 (MHþ) requires m/z 254.15, found m/z
þ
13C NMR (300 MHz, CDCl3)
d
135.2, 134.4, 128.1, 127.6, 127.3, 126.3,
254.88.
54.1, 46.2, 25.1, 24.2. IR (neat) 3218, 3068, 2987, 2944, 2919, 2857,
1497, 1458, 1439, 1381, 1345, 1313, 1271, 1229, 1189, 1149, 1114, 1076,
1064, 1047, 1028, 980, 907, 785, 766, 749, 724, 634 cmꢁ1. LRMS
(APClþ) mass calcd for C10H13N2þ (MHþ) requires m/z 161.11, found
m/z 161.44.
6.2.8. 1,4-Dimethyl-1,2,3,7b-tetrahydro-1,1a-diazacyclopropa[a]
naphthalene (compound 9). A solution of NH4OH (0.60) in MeOH
(1.40 mL) was cooled to ꢁ20 ꢀC, and hydroxylamine-O-sulfonic
acid (0.663 g, 5.86 mmol) was added portionwise to the
mixture. After stirring the suspension for about 30 min at ꢁ20 ꢀC,
6.2.5. (Z)-1,3-Dimethyl-4,5-dihydro-3H-benzo[d][1,2]-diazepine
(compound 6). A solution of Me3OBF4 (29 mg, 0.197 mmol) in
MeCN-d3 (0.40 mL) was cooled to ꢁ40 ꢀC. Then a solution of dia-
ziridine 5 (30 mg, 0.187 mmol) in MeCN-d3 (0.40 mL) was added
slowly. The reaction mixture was stirred for 30 min at ꢁ40 ꢀC, and
then the reaction mixture was quenched with NaHCO3 (1 mL). The
product was extracted with EtOAc (3ꢂ2 mL), and the combined
organic layers were washed with brine (2 mL) and dried over
Na2SO4 to furnish 6 as a yellow oil (26 mg, 0.149 mmol, 82% yield).
a solution of 1,4-dimethyl-3,4-dihydroisoquinoline (0.622 g,
3.91 mmol) in MeOH (2.0 mL) was added dropwise. The sus-
pension was gradually warmed to room temperature and stirred
for 2 days. The reaction mixture was then filtered, and the filtrate
was concentrated. The crude red oil was purified directly by silica
gel chromatography (35% EtOAc/hexanes) to yield the title com-
pound as a 4:1 mixture of diastereomers (460 mg, 2.64 mmol,
68% yield). 1H NMR (300 MHz, CDCl3)
d
7.57 (d, J¼7.5 Hz, 2H,
major and minor ArH), 7.37e7.17 (m, 6H, major and minor ArH),
3.51e3.45 (dd, J¼5.7, 12.9 Hz, 1H, major ArCH(CH3)CH2N),
3.34e3.28 (dd, J¼5.6, 13.3 Hz, 1H, minor ArCH(CH3)CH2N),
3.11e3.03 (m, 3H, major ArCH(CH3)CH2N, minor ArCH(CH3)CH2N,
minor ArCH(CH3)CH2N), 2.51 (t, J¼11.7 Hz, 1H, major ArCH(CH3)
CH2N), 2.19 (br s, 1H, minor NH), 1.98 (br s, 1H, major NH), 1.88 (s,
3H, major ArC(CH3)(NH)N), 1.83 (s, 3H, minor ArC(CH3)(NH)N),
1.42 (d, J¼7.2 Hz, 3H, minor ArCH(CH3)CH2N), 1.28 (d, J¼6.9 Hz,
1H NMR (300 MHz, CDCl3)
d 7.33e7.31 (m, 4H, ArH), 3.38 (t,
J¼7.2 Hz, 2H, ArCH2CH2N), 2.71e2.67 (m, 5H, NCH3 and
ArCH2CH2N), 2.36 (s, 3H, ArC(CH3)]N). 13C NMR (300 MHz, CDCl3)
d
162.0, 139.2, 137.1, 129.2, 127.5, 126.5, 125.8, 63.8, 47.2, 32.2, 23.2.
IR (neat) 3065, 3022, 2987, 2948, 2916, 2846, 2790, 1609, 1490,
1438, 1370, 1295, 1279, 1220, 1202, 1107, 1055, 1041, 958, 765,
754 cmꢁ1. LRMS (APClþ) mass calcd for C11H15N2 (MHþ) requires
þ
m/z 175.12, found m/z 175.58.
3H, major ArCH(CH3)CH2N). 13C NMR (300 MHz, CDCl3)
d 139.9,
134.0, 127.8, 127.3, 126.0, 124.5, 54.4, 26.6, 24.8, 15.1. IR (neat)
3199, 3065, 3037, 2963, 2930, 2871, 1493, 1449, 1381, 1354, 1230,
1116, 1067, 1034, 957, 920, 892, 734, 704, 664 cmꢁ1. LRMS (APClþ)
6.2.6. 1-Methyl-8-bromo-1,2,3,7b-tetrahydro-1,1a-diazacyclopropa
[a]naphthalene (compound 7). A solution of NH4OH (0.80 mL) in
Please cite this article in press as: Allen, J. M.; Lambert, T. H., Tetrahedron (2014), http://dx.doi.org/10.1016/j.tet.2014.03.015

J.M. Allen, T.H. Lambert / Tetrahedron xxx (2014) 1e7
5
mass calcd for C11H15N2 (MHþ) requires m/z 175.25, found m/z
d 159.8, 141.8, 139.8, 136.2, 129.3, 128.9, 127.1, 127.0, 126.5, 126.1,
þ
175.00.
77.2, 68.3, 48.3, 47.5, 23.5. IR (neat) 3410, 3061, 3027, 2992,
2950, 2917, 2847, 2795, 1604, 1553, 1493, 1451, 1371, 1297, 1231,
1207, 1147, 1114, 1063, 1042, 1020, 983, 880, 758, 701 cmꢁ1. LRMS
6.2.9. (Z)-1,3,5-Trimethyl-4,5-dihydro-3H-benzo[d][1,2]-diazepine
(compound 10). A solution of Me3OBF4 (45 mg, 0.301 mmol) in
MeCN-d3 (0.60 mL) was cooled to ꢁ40 ꢀC. Then a solution of dia-
ziridine 9 (50 mg, 0.287 mmol) in d3-MeCN (0.60 mL) was added
slowly to the reaction. The reaction mixture was stirred for 30 min
at ꢁ40 ꢀC, and then quenched with NaHCO3 (1 mL). The product
was extracted with EtOAc (3ꢂ2 mL), and the combined organic
layers were washed with brine (2 mL) and dried over Na2SO4. The
crude oil was purified by silica gel chromatography (5% MeOH/
DCM) to yield the title compound as a yellow oil (48 mg,
(APClþ) mass calcd for C17H19N2 (MHþ) requires m/z 251.35,
þ
found m/z 251.67.
6.2.12. 1-Phenyl-1,2,3,7b-tetrahydro-1,1a-diazacyclopropa[a]naph-
thalene (compound 13). A solution of NH4OH (0.95 mL) in MeOH
(2.2 mL) was cooled to ꢁ20 ꢀC, and hydroxylamine-O-sulfonic acid
(0.776 g, 6.86 mmol) was added portionwise to the mixture. After
stirring the suspension for about 30 min at ꢁ20 ꢀC, a solution of
1-phenyl-3,4-dihydroisoquinoline (1.27 g, 6.13 mmol) in MeOH
(2.2 mL) was added dropwise. The reaction mixture was stirred at
0.255 mmol, 89% yield). 1H NMR (300 MHz, CDCl3)
d 7.37e7.26 (m,
4H, ArH), 3.30e3.25 (dd, J¼10.95, 6.9 Hz, ArCH(CH3)CH2), 3.05 (t,
J¼10.5 Hz, 1H, ArCH(CH3)CH2), 2.93e2.85 (m, 1H, ArCH(CH3)CH2),
2.66 (s, 3H, NCH3), 2.34 (s, 3H, ArC(CH3)¼N), 1.28 (d, J¼6.9 Hz, 3H,
0
ꢀC overnight. Upon warming to room temperature, the reaction
mixture was filtered, and the filtrate was concentrated. The crude
oil was purified directly by silica gel chromatography (20% EtOAc/
hexanes) to yield diaziridine 13 (35 mg, 0.157 mmol, 3% yield, 50%
yield BRSM) and starting material (0.80 g, 3.86 mmol). 1H NMR
ArCH(CH3)CH2). 13C NMR (300 MHz, CDCl3)
d 161.3, 142.8, 137.0,
129.1, 126.3, 125.6, 124.2, 71.2, 47.2, 35.0, 23.2, 15.9. IR (neat) 2954,
2844, 2790, 1610,1487,1436,1374,1286,1155, 1070,1043, 980 cmꢁ1
.
(300 MHz, CDCl3)
d
7.51e6.89 (m, 9H, ArH), 3.74e3.67 (ddd, J¼6.3,
LRMS (APClþ) mass calcd for C12H17N2þ (MHþ) requires m/z 189.28,
found m/z 189.06.
5.6, and 1.8 Hz, 1H, ArCH2CH2N), 3.22e2.94 (m, 2H, ArCH2CH2N),
2.59e2.52 (m, 2H, ArCH2CH2N and NH). 13C NMR (300 MHz, CDCl3)
d
140.2, 135.5, 134.1, 130.0, 128.8, 128.7, 128.4, 128.2, 128.1, 128.0,
6.2.10. 1-Methyl-4-Phenyl-1,2,3,7b-tetrahydro-1,1a-diazacyclopropa
[a]naphthalene (compound 11). A solution of NH4OH (0.85) in
127.7, 126.0, 60.8, 46.7, 25.1. IR (neat) 3240, 3061, 3028. 2938, 2862,
1654, 1602, 1587, 1538, 1488, 1448, 1424, 1337, 1224, 1185, 1149,
1095, 1074, 1025, 963, 899, 876, 831þ, 772, 754, 734, 700 cmꢁ1. LRMS
(APClþ) mass calcd for C15H15N2 (MHþ) requires m/z 223.12,
found m/z 223.10.
MeOH (2.0 mL) was cooled to ꢁ20 ꢀC, and hydroxylamine-O-sul-
fonic acid (0.928 g, 8.21 mmol) was added portionwise to the
mixture. After stirring the suspension for about 30 min at ꢁ20 ꢀC,
a solution of 1-methyl-4-phenyl-3,4-dihydroisoquinoline (1.21 g,
5.47 mmol) in MeOH (2.0 mL) was added dropwise. The suspension
was gradually warmed to room temperature and stirred for 3 days.
The reaction mixture was then filtered, and the filtrate was con-
centrated. The crude red oil was purified directly by silica gel
chromatography (35% EtOAc/hexanes) to yield diaziridine 11 as
a 2.7:1 mixture of diastereomers (740 mg, 3.13 mmol, 65% yield). 1H
6.2.13. (Z)-3-Methyl-1-phenyl-4,5-dihydro-3H-benzo[d][1,2]-dia-
zepine (compound 14). A solution of Me3OBF4 (25 mg, 0.165 mmol)
in MeCN-d3 (0.50 mL) was cooled to ꢁ40 ꢀC. Then a solution of
diaziridine 13 (35 mg, 0.157 mmol) in MeCN-d3 (0.50 mL) was
added slowly. The reaction mixture was stirred for 30 min at
ꢁ40 ꢀC, and then the reaction mixture was quenched with NaHCO3
(1 mL). The product was extracted with EtOAc (3ꢂ2 mL), and the
combined organic layers were washed with brine (2 mL) and dried
over Na2SO4 to furnish 14 as a yellow oil (31 mg, 0.131 mmol, 84%
NMR (300 MHz, CDCl3)
d
7.65 (d, J¼7.5 Hz, 2H, major and minor
ArH), 7.43e7.12 (m,14H, major and minor ArH), 6.94 (d, J¼7.5 Hz,1H,
minor ArH), 6.75 (d, J¼7.8 Hz, 1H, major ArH), 4.27e4.21 (m, 2H,
major ArCH(Ph)CH2N and minor ArCH(Ph)CH2N), 3.72e3.66 (dd,
J¼6.0, 13.2 Hz, 2H, major ArCH(Ph)CH2N and minor ArCH(Ph)CH2N),
3.52e3.46 (dd, J¼6.9,1H, 12.9 Hz,1H, minor ArCH(Ph)CH2N), 3.04 (t,
J¼12.0 Hz, 1H, major ArCH(Ph)CH2N), 2.26 (br s, 1H, minor NH), 2.11
(br s, 1H, major NH), 1.98 (s, 3H, major ArC(CH3)), 1.85 (s, 3H, minor
yield). 1H NMR (300 MHz, CDCl3)
d 7.62e7.59 (m, 2H, ArH),
7.39e7.25 (m, 6H, ArH), 7.09 (d, 1H, J¼7.8 Hz, ArH), 3.54 (t, J¼6.9 Hz,
2H, ArCH2CH2N), 2.83 (s, 3H, NCH3), 2.79 (t, 2H, J¼7.2 Hz,
ArCH2CH2N). 13C NMR (300 MHz, CDCl3)
d 161.9, 141.2, 138.3, 135.4,
129.4, 129.2, 128.7, 128.6, 128.1, 127.3, 126.2, 65.2, 47.8, 32.2. IR
(neat) 3212, 3038, 2952, 2872, 1500, 1459, 1428, 1378, 1349, 1284,
1248, 1173, 1064, 1036, 972, 921, 887, 840, 79þ1, 756, 741, 721,
656 cmꢁ1. LRMS (APClþ) mass calcd for C16H17N2 (MHþ) requires
m/z 237.14, found m/z 237.89.
ArC(CH3)). 13C NMR (300 MHz, CDCl3)
d 143.7, 140.7, 138.7, 137.4,
135.4, 134.3, 129.6, 128.6, 128.5, 128.2, 127.5, 127.4, 127.1, 126.9,
126.2, 77.2, 56.5, 54.7, 54.2, 53.9, 43.1, 40.0, 25.9, 24.4. IR (neat)
3200, 3061, 3029, 2968, 2925, 2861, 1602, 1493, 1451, 1381, 1351,
1361, 1269, 1232, 1157, 1116, 1071, 1032, 925, 875, 7þ94, 757, 725, 702,
682 cmꢁ1. LRMS (APClþ) mass calcd for C16H17N2 (MHþ) requires
m/z 237.32, found m/z 236.71.
6.2.14. 1-(Trifluoromethyl)-1,2,3,7b-tetrahydro-1,1a-diazacyclopropa
[a]naphthalene (compound 15). A solution of NH4OH (1.2 mL) in
MeOH (5 mL) was cooled to ꢁ20 ꢀC, and hydroxylamine-O-sul-
fonic acid (1.703 g, 15.06 mmol) was added portionwise to the
mixture. After stirring the suspension for about 30 min at ꢁ20 ꢀC,
a solution of 1-(trifluoromethyl)-3,4-dihydroisoquinoline (1.50 g,
7.53 mmol) in MeOH (5 mL) was added dropwise. The reaction
mixture was stirred at room temperature for 5 days. The reaction
mixture was then filtered, and the filtrate was concentrated. The
crude oil was purified directly by silica gel chromatography (5%
EtOAc/hexanes) to yield 15 as a yellow oil (0.566 g, 2.64 mmol, 35%
6.2.11. (Z)-1,3-Dimethyl-5-phenyl-4,5-dihydro-3H-benzo[d][1,2]dia-
zepine (compound 12). A solution of Me3OBF4 (33 mg, 0.222 mmol)
in MeCN-d3 (0.60 mL) was cooled to ꢁ40 ꢀC. Then a solution of
diaziridine 11 (50 mg, 0.212 mmol) in MeCN-d3 (0.60 mL) was
added slowly to the reaction. The reaction mixture was stirred for
30 min at ꢁ40 ꢀC, and then quenched with NaHCO3 (1 mL). The
product was extracted with EtOAc (3ꢂ2 mL), and the combined
organic layers were washed with brine (2 mL) and dried over
Na2SO4. The crude red oil was purified by silica gel chromatography
(5% MeOH/DCM) to yield benzodiazepine 12 as an orange oil
(46 mg, 0.184 mmol, 87% yield). 1H NMR (300 MHz, CDCl3)
yield). 1H NMR (300 MHz, CDCl3)
d 7.78e7.76 (m, 1H, ArH),
7.37e7.16 (m, 3H, ArH), 3.52 (d, J¼12.0 Hz, ArCH2CH2N), 3.03e2.84
(m, 2H, ArCH2CH2N), 2.75 (s, 1H, NH), 2.53 (d, J¼12.6 Hz, 1H,
d
7.44e7.21 (m, 8H, ArH), 6.93 (d, J¼7.8 Hz, 1H, ArH), 4.22e4.16 (dd,
ArCH2CH2N). 13C NMR (300 MHz, CDCl3)
d 136.0, 128.9, 128.6,
J¼7.2, 10.8 Hz, 1H, ArCH(Ph)CH2N), 3.79 (t, J¼11.1 Hz, 1H, ArCH(Ph)
CH2N), 3.51e3.45 (dd, J¼7.2, 11.3 Hz, 1H, ArCH(Ph)CH2N), 2.79 (s,
3H, NCH3), 2.44 (s, 3H, ArC(CH3)]N). 13C NMR (300 MHz, CDCl3)
127.8, 126.7, 126.0, 125.5, 121.8, 46.3, 24.8. IR (neat) 3213, 2951,
2360, 1500, 1459, 1428, 1378, 1348, 1284, 1247, 1172, 1151, 1064,
1036, 971, 920, 887, 840, 791, 756, 740, 721, 656 cmꢁ1. LRMS
Please cite this article in press as: Allen, J. M.; Lambert, T. H., Tetrahedron (2014), http://dx.doi.org/10.1016/j.tet.2014.03.015

6
J.M. Allen, T.H. Lambert / Tetrahedron xxx (2014) 1e7
(APClþ) mass calcd for C10H10F3N2 (MHþ) requires m/z 215.08,
found m/z 215.23.
white solid precipitate after approximately 10 min. After stirring at
ꢀC for a total of 30 min, the reaction mixture was diluted with
þ
0
ethyl acetate (1 mL), washed with NaHCO3 (1 mL) and brine (1 mL),
and dried over Na2SO4. The solution was concentrated, and the
crude red oil was purified by silica gel chromatography (35% EtOAc/
hexanes) to yield benzodiazepine 19 as a white solid (35 mg,
6.2.15. (Z)-3-Methyl-1-(trifluoromethyl)-4,5-dihydro-3H-benzo[d]
[1,2]diazepine (compound 16). A solution of Me3OBF4 (30 mg,
0.187 mmol) in MeCN-d3 (0.40 mL) was cooled to ꢁ40 ꢀC. Then
a solution of diaziridine 15 (40 mg, 0.205 mmol) in MeCN-d3
(0.40 mL) was added slowly. The reaction mixture was stirred for
30 min at ꢁ40 ꢀC, and then the reaction mixture was quenched
with NaHCO3 (1 mL). The product was extracted with EtOAc
(3ꢂ2 mL), and the combined organic layers were washed with
brine (2 mL) and dried over Na2SO4. The crude yellow oil was pu-
rified by silica gel chromatography (5% EtOAc/hexanes) to furnish
benzodiazepine 16 (10 mg, 0.044 mmol, 24% yield). 1H NMR
0.119 mmol, 64% yield). 1H NMR (300 MHz, CDCl3)
d 7.34e7.22 (m,
9H, ArH), 5.15 (s, 2H, NC(]O)OCH2Ar), 4.15 (t, J¼6.6 Hz, 2H,
ArCH2CH2N), 2.82 (t, J¼6.6 Hz, 2H, ArCH2CH2N), 2.46 (s, 3H, ArC(]
N)CH3). 13C NMR (300 MHz, CDCl3)
d 168.4, 155.3, 138.3, 136.6,
135.8, 130.0, 128.3, 128.0, 127.8, 126.9, 126.8, 77.2, 67.3, 54.4, 31.7,
24.1. IR (neat) 2924, 2870, 1697, 1613, 1491, 1447, 1400, 1347, 1327,
1289, 1233, 1210, 1157, 1106, 1010, 764, 698 cmꢁ1. LRMS (APClþ)
mass calcd for C18H19N2O2þ (MHþ) requires m/z 295.36, found m/z
295.14.
(300 MHz, CDCl3)
d
7.59 (t, J¼1.8 Hz, 1H, ArH), 7.30e7.20 (m, 3H,
ArH), 7.08 (t, J¼6.3 Hz, 1H, ArH), 3.71 (t, J¼4.2 Hz, 2H, ArCH2CH2N),
3.32 (s, 3H, NCH3), 3.06 (t, J¼4.5 Hz, 2H, ArCH2CH2N). 13C NMR
6.2.19. (Z)-(6-Chloropyridin-3-yl)(4,5-dihydro-3H-benzo[d][1,2]dia-
zepin-3-yl)methanone (compound 20). A solution of diaziridine 2
(30 mg, 0.187 mmol) in MeCN (1 mL) was cooled to 0 ꢀC. To this
solution was added 6-chloronicotinoyl chloride (35 mg,
0.196 mmol). The reaction mixture was stirred at 0 ꢀC for 20 min,
and at this time yellow precipitate was observed. The reaction
mixture was diluted with ethyl acetate (1 mL), washed with
NaHCO3 (1 mL) and brine (1 mL), and then dried over Na2SO4. The
solution was concentrated, and the crude solid was purified by
silica gel chromatography (20% EtOAc/hexanes) to yield benzodi-
azepine 20 as a white solid (49 mg, 0.171 mmol, 91% yield). 1H NMR
(300 MHz, CDCl3)
d 141.5, 128.4, 127.7, 127.4, 126.4, 58.3, 49.2, 35.5.
IR (neat) 2924, 1725, 1584, 1566, 1495, 1452, 1381, 1335, 1307, 1275,
1227, 1166, 1096, 1067, 1037, 990, 974, 926, 830, 793, 7þ64, 746, 730,
691 cmꢁ1. LRMS (APClþ) mass calcd for C11H12F3N2 (MHþ) re-
quires m/z 229.09, found m/z 229.12.
6.2.16. (Z)-1-(4,5-Dihydro-3H-benzo[d][1,2]diazepin-3-yl)ethanone
(compound 17). A solution of diaziridine 2 (30 mg, 0.205 mmol) in
MeCN (1 mL) was cooled to 0 ꢀC. To this solution was added acetyl
chloride (15 mL, 0.215 mmol). After stirring the reaction mixture for
30 min at 0 ꢀC, the reaction mixture was diluted with EtOAc (1 mL),
washed with NaHCO3 (1 mL) and brine (1 mL), and dried over
Na2SO4. The solution was concentrated, and the crude product was
purified on a silica gel column (50% EtOAc/hexanes) to provide the
title compound as a yellow solid (32 mg, 0.170 mmol, 82% yield). 1H
(300 MHz, CDCl3) d 8.75 (s, 1H, NC(]O)CeCH]Ne), 8.02e7.99 (dd,
J¼2.4, 8.3 Hz, NC(]O)C]CHeCHe), 7.45e7.25 (m, 6H, ArH and
ArCH]N), 4.37e4.34 (m, 2H, ArCH2CH2N), 3.28e3.25 (m, 2H,
ArCH2CH2N). 13C NMR (300 MHz, CDCl3)
d 167.3, 152.7, 150.9, 143.4,
141.3, 140.0, 134.2, 130.7, 130.3, 129.9, 129.4, 127.0, 123.2, 44.7, 36.5.
IR (neat) 2923, 1657, 1600, 1581, 1494, 1447, 1391, 1359, 1281, 1200,
1166, 1140, 1103, 1046, 991, 931, 891, 838, 776, 759 cmꢁ1. LRMS
(APClþ) mass calcd for C15H13ClN3Oþ (MHþ) requires m/z 286.74,
found m/z 287.07.
NMR (300 MHz, CDCl3)
d 7.44e7.40 (m, 2H, ArH and ArCH]N),
7.32e7.20 (m, 3H, ArH), 4.19e4.16 (m, 2H, ArCH2CH2N), 3.11 (t,
J¼4.8 Hz, 2H, ArCH2CH2N), 2.40 (s, 3H, NC(]O)CH3). 13C NMR
(300 MHz, CDCl3)
d 172.4, 141.5, 141.4, 133.8, 131.1, 129.6, 129.3,
126.7, 43.6, 36.6, 21.7. IR (neat) 2943, 1669, 1597, 1570, 1497, 1449,
1427, 1385, 1362, 1308, 1259, 1205, 1162, 1040, 985, 955, 909, 873,
763, 734 cmꢁ1. LRMS (APClþ) mass calcd for C11H13N2Oþ (MHþ)
requires m/z 189.23, found m/z 189.16.
Acknowledgements
This work was supported by the National Science Foundation
(_100000001) under CHE-0953259. We thank Daniella Buccella,
Ahmed Al-Harbi, and the Parkin Group for X-ray structure de-
termination, and the National Science Foundation (CHE-0619638)
is thanked for acquisition of an X-ray diffractometer.
6.2.17. (Z)-1-(1-Methyl-4,5-dihydro-3H-benzo[d][1,2]diazepin-3-yl)
ethanone (compound 18). A solution of diaziridine 5 (30 mg,
0.187 mmol) in MeCN (1 mL) was cooled to 0 ꢀC. To this solution
was added acetyl chloride (14 mL, 0.197 mmol) dropwise via mi-
croliter syringe. The clear and yellow solution gradually formed
white solid precipitate after approximately 10 min. After stirring at
0 ꢀC for an additional 10 min, the reaction mixture was diluted with
ethyl acetate (1 mL) and washed with NaHCO3 (1 mL) and brine
(1 mL). The organic layer was dried over Na2SO4, and concentrated
to yield the title compound as a yellow oil (32 mg, 0.158 mmol, 84%
Supplementary data
NMR spectra and crystallographic data. Supplementary data
related to this article can be found at http://dx.doi.org/10.1016/
j.tet.2014.03.015.
yield). 1H NMR (300 MHz, CDCl3)
d 7.47e7.44 (m, 1H, ArH),
References and notes
7.32e7.29 (m, 2H, ArH), 7.20e7.17 (m, 1H, ArH), 4.19 (t, J¼5.7 Hz, 2H,
ArCH2CH2N(COCH3), 2.91 (t, J¼5.7 Hz, 2H, ArCH2CH2N(COCH3)),
2.46 (s, 3H, ArCCH3), 2.21 (s, 3H, ArCH2CH2N(COCH3)). 13C NMR
1. For reviews, see: (a) Murray, R. W. Chem. Rev. 1989, 89, 1187; (b) Frohn, M.; Shi,
Y. Synthesis 2000, 14, 1979; (c) Adam, W.; Curci, R.; Edwards, J. O. Acc. Chem. Res.
1989, 22, 205; (d) Shi, Y. Acc. Chem. Res. 2004, 37, 488; (e) Yang, D. Acc. Chem.
Res. 2004, 37, 497.
2. For selected reviews, see: (a) Davis, F. A.; Sheppard, A. C. Tetrahedron 1989, 45,
5703; (b) Davis, F. A.; Chen, B.-C. Chem. Rev. 1992, 92, 919.
3. For selected examples of oxaziridine reactions, see: (a) Davis, F. A.; Harakal, M.
E.; Awad, S. B. J. Am. Chem. Soc. 1983, 105, 3123; (b) Davis, F. A.; Vishwakarma, L.
C.; Billmers, J. G.; Finn, J. J. Org. Chem. 1984, 49, 3241; (c) Morizawa, Y.; Yasuda,
A.; Uchida, K. Tetrahedron Lett. 1986, 27, 1833; (d) Evans, D. A.; Morrissey, M. M.;
Dorow, R. L. J. Am. Chem. Soc. 1985, 107, 4346; (e) Davis, F. A.; Sheppard, A. C.;
Chen, B.-C.; Haque, M. S. J. Am. Chem. Soc. 1990, 112, 6679; (f) Adams, A. M.; Du
Bois, J. Chem. Sci. 2014, 5, 656; (g) Litvinas, N. D.; Brodsky, B. H.; Du Bois, J.
Angew. Chem., Int. Ed. 2009, 48, 4513; (h) Williamson, K. S.; Yoon, T. P. J. Am.
Chem. Soc. 2012, 134, 12370; (i) Benkovics, T.; Guzei, I. A.; Yoon, T. P. Angew.
Chem., Int. Ed. 2010, 49, 9153; (j) Williamson, K. S.; Yoon, T. P. J. Am. Chem. Soc.
2010, 132, 4570; (k) Partridge, K. M.; Guzei, I. A.; Yoon, T. P. Angew. Chem., Int. Ed.
(300 MHz, CDCl3)
d 172.0, 156.5, 140.5, 134.4, 129.9, 128.3, 128.1,
126.8, 50.0, 33.1, 25.5, 22.0. IR (neat) 2925, 1670, 1491, 1389, 1370,
1288, 1238, 1192, 1041, 1005, 981, 930, 768, 708 cmꢁ1. LRMS (APClþ)
mass calcd for C12H15N2Oþ (MHþ) requires m/z 203.26, found m/z
203.18.
6.2.18. (Z)-Benzyl 1-methyl-4,5-dihydro-3H-benzo[d][1,2]diazepine-
3-carboxylate (compound 19). A solution of diaziridine 5 (30 mg,
0.187 mmol) in MeCN (1 mL) was cooled to 0 ꢀC. To this solution
was added benzyl chloroformate (28
mL, 0.197 mmol) dropwise via
microliter syringe. The solution gradually became opaque with
Please cite this article in press as: Allen, J. M.; Lambert, T. H., Tetrahedron (2014), http://dx.doi.org/10.1016/j.tet.2014.03.015

J.M. Allen, T.H. Lambert / Tetrahedron xxx (2014) 1e7
7
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Please cite this article in press as: Allen, J. M.; Lambert, T. H., Tetrahedron (2014), http://dx.doi.org/10.1016/j.tet.2014.03.015