Diastereoselective control through hydrogen bonding in the aziridination of the chiral allylic alcohols by acetoxyaminoquinazolinone

Article abstract of DOI:10.1021/jo902092s

(Chemical Equation Presented) A high diastereoselectivity (up to >99:1) is found for the aziridinations of chiral allylic alcohols with acetoxyaminoquinazolinone (Q-NHOAc). The selectivity is explained in terms of hydrogen bonding between the hydroxy func

Full text of DOI:10.1021/jo902092s

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Diastereoselective Control Through Hydrogen Bonding in the
Aziridination of the Chiral Allylic Alcohols by
Acetoxyaminoquinazolinone
Murat Cakici,† Semistan Karabuga,§ Hamdullah Kilic,*,† Sabri Ulukanli,‡ Ertan S-ahin,†
and Fatma Sevin
†Faculty of Sciences, Department of Chemistry, Ataturk University, 25240 Erzurum, Turkey,
§Faculty of Science and Letters, Department of Chemistry, Kilis 7 Aralꢀık University, Kilis Turkey,
‡Faculty of Science and Letters, Department of Chemistry, Korkut Ata University, Osmaniye,
Turkey, and Faculty of Sciences, Department of Chemistry, Hacettepe University, Ankara, Turkey
hkilic@atauni.edu.tr
Received October 7, 2009
A high diastereoselectivity (up to >99:1) is found for the aziridinations of chiral allylic alcohols with
acetoxyaminoquinazolinone (Q-NHOAc). The selectivity is explained in terms of hydrogen bonding
between the hydroxy functionality of the allylic alcohol and the remote carbonyl group of the quinazolinone.
Introduction
has documented that olefin aziridination by 2 is hydroxy-
directed as are peracid epoxidations.4 For example, treat-
ment of cyclohex-3-en-1-ol with this reagent furnishes the syn
isomer 3 in high stereoselectivity. (Scheme 1); peroxyacid
epoxidation of this homoallylic alcohol is hardly diastereo-
selective at all.
The oxidation of N-amino heterocycles1 such as 3-amino-
2-ethylquinazolin-4(3H)-one (Q-NH2) (1) with lead tetraa-
cetate in the presence of olefinic substrates provides a general
method for the synthesis of the N-aminoaziridines (oxidative
aminoaziridination of olefins). Atkinson showed that the
active aziridinating species is the corresponding N-acetoxy-
lated hydrazine derivatives, rather than nitrenes.2 The reac-
tion of Q-NH2 1 with lead tetraacetate at low temperature
generates the corresponding 3-(acetoxyamino)-2-ethylqui-
nazolin-4(3H)-one (Q-NHOAc) (2) as a relatively stable
intermediate.3 This compound, and its analogues, convert
alkenes into aziridines in a reaction which resembles the
conversion of alkenes into epoxides by peracids. Atkinson
Reaction of geraniol occurs preferentially at the double
bond proximal to the hydroxy group (92:8), whereas that of
geranyl chloride proceeds predominantly at the site distant
from the heteroatom (85:15).5 Definitely, Q-NHOAc 2 is
subject to stronger directivity effects than m-CPBA 4,
although the structural similarities between Q-NHOAc 2
and the m-CPBA 4 are clearly evident (Figure 1). Thus, it
should be of mechanistic importance to understand what
structural and geometrical factors control the hydroxy-
group directivity in the aziridination of the allylic alcohol
(e.g., geraniol) by Q-NHOAc 2. For this purpose, the chiral
allylic alcohols 5 were chosen as a stereochemical probe. By
comparison of the observed diastereoselectivity with those of
the established oxidant m-CPBA, these stereolabeled allylic
alcohols should serve as a mechanistic tool to define the
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Che, C. M. Org. Lett. 2005, 7, 5801–5804. (c) Li, J. Y.; Liang, J. L.; Chan, P.
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9452 J. Org. Chem. 2009, 74, 9452–9459
Published on Web 11/16/2009
DOI: 10.1021/jo902092s
r
2009 American Chemical Society

Cakici et al.
JOCArticle
SCHEME 1. Atkinson’s Aziridination
TABLE 1. Aziridination of the Allylic Alcohols 5 by Q-NHOAc 2
Generated in situ from Q-NH2 1 and Pb(OAc)4 and Comparison with
m-CPBAa
FIGURE 1. Comparison of the Q-NHOAc 2 and m-CPBA 4
structures.
transition-state structure of the aziridination process.6
Herein we report that the chiral allylic alcohols 5 undergo
highly diastereoselective (up to >99:1) aziridination with
Q-NHOAc 2. The diastereoselectivity is controlled by
hydrogen bonding with the remote quinazolinone carbonyl
group rather than the acetoxy functionality.
diastereoselectivityb
threo/erythro
convnb yield
entry substrate R1 R2 R3
[%]
[%] Q-NHOAc 2 m-CPBAc4
1
2
3
4
5
6
7
8
5a
5b
5c
5d
5e
5f
H
H
H
H
H
H
100
100
100
100
78
78
42
95
82
90
84
87
97:3
95:5
60:40
64:36
45:55
48:52
95:5
H
CH3
CH3
H
95:5d
97:3e
>99:1
>99:1
95:5
CH3 CH3
Results
H
H
CH3 100
CH3 CH3 100
CH3 100
H
CH3
95:5
90:10
90:10
The aziridinations (Table 1) were conducted at ca. -25 °C
in CH2Cl2, at the 1/allylic alcohol/Pb(OAc)4/hexamethyldisi-
lazane (HDMS)7 ratio of 2:1:2.2:4. The diastereoselectivities
5g
5h
H
CH3 CH3 CH3 100
97:3
aStoichiometric amounts: allylic alcohol 5 (1 mmol); Q-NH2
1
(2 mmol); Pb(OAc)4 (2.2 mmol); HMDS (4 mmol); CH2Cl2 (5 mL).
bConversion of the allylic alcohol 5 after complete consumption of 1
(determined by TLC); an aliquot of the crude reaction mixture was
taken, and the conversions and threo-6/erythro-6 ratios were assessed
by 1H NMR analysis. cReference 6. dRatio of threo invertomers 5:1
determined by 1H NMR. eRatio of erythro invertomers 3:1 determined
by 1H NMR.
(3) (a) Atkinson, R. S.; Darrah, C. M.; Kelly, B. J. Tetrahedron Lett. 1987,
28, 1711–1712. (b) Atkinson, R. S.; Grimshire, M. J.; Kelly, B. J. Tetrahedron
1989, 45, 2875–2886. (c) Atkinson, R. S.; Kelly, B. J. J. Chem. Soc., Perkin
Trans. 1 1989, 1627–1630. (d) Atkinson, R. S.; Kelly, B. J. J. Chem. Soc.,
Perkin Trans. 1 1989, 1657–1661. (e) Atkinson, R. S.; Kelly, B. J. J. Chem.
Soc., Chem. Commun. 1989, 836–837. (f) Atkinson, R. S.; Kelly, B. J.;
Williams, J. Tetrahedron 1992, 48, 7713–7730. (g) Atkinson, R. S.; Coogan,
M. P.; Cornell, C. L. J. Chem. Soc., Chem. Commun. 1993, 1215–1216.
(h) Atkinson, R. S.; Fawcett, J.; Russell, D. R.; Williams, P. J. J. Chem. Soc.,
Chem. Commun. 1994, 2031–2032. (i) Atkinson, R. S.; Barker, E. J. Chem.
Soc., Chem. Commun. 1995, 819–820. (j) Atkinson, R. S.; Fawcett, J.; Russell,
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S.; Coogan, M. P.; Cornell, C. L. J. Chem. Soc., Perkin Trans. 1 1996, 157–
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205–211. (m) Atkinson, R. S.; Williams, P. J. J. Chem. Soc., Perkin Trans. 1
1996, 2661–2661. (n) Atkinson, R. S.; Williams, P. J. J. Chem. Soc., Perkin
Trans. 1 1996, 1951–1959. (o) Atkinson, R. S.; Barker, E.; Meades, C. K.;
Albar, H. A. Chem. Commun. 1998, 29–30. (p) Atkinson, R. S.; Barker, E.;
Ulukanli, S. J. Chem. Soc., Perkin Trans. 1 1998, 583–589. (q) Atkinson, R.
S.; Claxton, T. A.; Lochrie, I. S. T.; Ulukanli, S. Tetrahedron Lett. 1998, 39,
5113–5116. (r) Atkinson, R. S.; Ulukanli, S. J. Chem. Soc., Perkin Trans. 2
1999, 771–776. (s) Atkinson, R. S.; Ulukanli, S.; Williams, P. J. J. Chem. Soc.,
Perkin Trans. 1 1999, 2121–2128. (t) Al-Sehemi, A. G.; Atkinson, R. S.;
Fawcett, J.; Russell, D. R. Tetrahedron Lett. 2000, 41, 2239–2242. (u) Al-
Sehemi, A. G.; Atkinson, R. S.; Fawcett, J.; Russell, D. R. Tetrahedron Lett.
2000, 41, 2243–2246. (v) Atkinson, R. S.; Ayscough, A. P.; Gattrell, W. T.;
Raynham, T. M. J. Chem. Soc., Perkin Trans. 1 2000, 3096–3106.
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1515–1519. (b) Atkinson, R. S.; Kelly, B. J.; Mcnicolas, C. J. Chem. Soc.,
Chem. Commun. 1989, 562–564.
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611–614.
(7) (a) Atkinson found that decomposition of in situ generated QNHOAc 2
was retarded by the removal of acetic acid, a byproduct both in acetoxylation of the
3-aminoquinazolinone 1 with lead tetraacetate (LTA) and in the aziridination of
alkenes by QNHOAc 2, and thus, in the presence of HMDS scavenging AcOH, the
yields of aziridines from reaction of Q-NHOAc 2 and alkenes were improved,
especially for otherwise less reactive alkenes. (b) Karabuga, S.; Kazaz, C.; Kilic,
H.; Ulukanli, S.; Celik, A. Tetrahedron Lett. 2005, 46, 5225–5227.
for the chiral allylic alcohols 5a-h are listed in Table 1,
together with the literature data for the m-CPBA6 epoxidation
for comparison. The results in Table 1 reveal that the in situ
generated Q-NHOAc 2 aziridinates the allylic alcohols 5 in
excellent conversions (100%) to the aziridine alcohols 6. As
demonstrated by the eight preparative runs, the aziridine
alcohols 6a-h were isolated in 42-95% yields. For the
azirinidation of the cis- and trans-allylic alcohols 5b,d,e,g,
the configuration around the CdC bond was retained in
the corresponding aziridine alcohols (Table 1, entries 2, 4, 5,
and 7), suggesting that radical intermediates are not involved
in the present aziridination. The aziridinations of substrates
5a,b (entries 1 and 2) without allylic strain, as well as the
substrates 5c,d (entries 3 and 4) with 1,2-allylic strain, displays
already excellent (ca. 95%) threo selectivity, which is difficult
to improve. Nevertheless, the 1,3-allylic strain present in the
derivatives 5e,f (entries 5 and 6) induces expectedly perfect
(>99:1) threo preference.
From a green chemistry point of view, the aziridination of
alkenes with Q-NH2 2 generated in situ from QNH2 1 and
nontoxic hypervalent iodine reagent diacetoxy(phenyl)-λ3-
iodane (PIDA)1c,e in place of Pb(OAc)4 (LTA) is very
attractive. For comparison, the aziridinations of the allylic
alcohols 5a-d,f,g were repeated by using PIDA in place of
J. Org. Chem. Vol. 74, No. 24, 2009 9453

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SCHEME 2. Synthesis of Aziridine Alcohols
TABLE 2. Aziridination of the Allylic Alcohols 5 by Q-NHOAc 2
mixtures obtained in the aziridination (Scheme 2). The
structures of the compounds 6a-h were assigned by 1H
NMR, 13C NMR, mass, and IR spectra. The assignment of
the relative configuration of the products was made by
comparison of the chemical shift for the methine proton
(Ha) on the hydroxy-bearing carbon atom and X-ray analy-
sis. Thus, the Ha proton of the erythro-configurated isomer 6
absorbs at lower field than that of the corresponding threo
isomer. For example, the resonances of the Ha proton of the
erythro-configurated aziridine alcohols 6 are shifted as much
as 1.24 ppm downfield relative to those of the corresponding
threo diastereomer. This upfield chemical shift is most
pronounced for the signals of the carbon atom which bears
the Ha proton (ΔδC up to 5.9 ppm). This trend is general,
as observed for the threo epoxy alcohols 59 and aziridine
alcohols 6.10 The configurations of diastereomerically pure threo
aziridine alcohols 6d and 6e (as p-nitrobenzoate derivative 8a)
were also established by X-ray analysis (see Supporting
Information).
Generated in Situ from Q-NH2 1 and PhI(OAc)2 (PIDA)a
diastereoselectivityb
convnb mbc
entry substrate R1
R2
R3
[%]
[%]
threo/erythro
1
2
3
4
5
6
5a
5b
5c
5d
5f
H
H
CH3
CH3 CH3
H
CH3 H
H
CH3
H
H
90
100
90
100
100
100
77
88
65
91
95
95
96:4
95:5
82:18
95:5
>99:1
96:4
H
H
H
CH3 CH3
CH3
5g
aStoichiometric amounts: allylic alcohol 5 (1 mmol); Q-NH2
1
(2 mmol); K2CO3 (4 mmol); PhI(OAc)2 (2.2 mmol) and 4 mL of CH2Cl2.
bConversion of the allylic alcohol 5 after complete consumption of the
Q-NH2 1 (determined by TLC). An aliquot was taken of the crude
reaction mixture, and the conversions and diastereomeric ratios were
assessed by 1H NMR analysis with diphenylmethane as internal
Discussion
These stereochemical results in Tables 1 and 2 disclose that
allylic strain is not decisive in the stereocontrol of the
nitrogen transfer to the chiral acyclic allylic alcohols 5.
Consequently, the conformationally mobile acyclic sub-
strates 5a,b (Table 1, entries 1 and 2) without allylic strain
are comparable (g95%) to the conformationally restrained
acyclic chiral substrates 5g,h (Table 1, entries 7 and 8) with
both 1,2- and 1,3-allylic strain in threo-stereoselective azir-
idination. This strong threo preference (g95%) in the azir-
idination of the substrates 5a,b without allylic strain is to be
contrasted with the modest threo selectivity (ca. 60%) of the
m-CPBA epoxidation (Table 1, entries 1 and 2). Mechan-
istically equally significant are the substrates 5c and 5d with
1,2-allylic strain, for which also excellent threo diastereos-
electivity (g95%) is expressed in the aziridination, but
essentially none (ca. 45:55) in the m-CPBA6 epoxidation
(Table 1, entries 3 and 4). The composite set of selectivity
data unequivocally proclaims that the observed hydroxy-
group directivity derives from hydrogen bonding between
the carbonyl group in Q-NHOAc 2 and the hydroxy func-
tionality in the allylic alcohols 5. The hydroxy-protected
derivative of mesitylol (5f), namely, the benzoate ester 5i,
displayed a reversed diastereoselectivity (erythro) in this
aziridination by 2 (Scheme 3). This favorable hydroxy-
directing effect accelerates the reaction rate because the
hydroxyl-protected derivative 5i is less efficiently aziridi-
nated (convn 50%) than the parent allylic alcohol 5f
(Table 1, entry 6). Moreover, the substrates 5i possess no
c
standard; error ca. (5% of the stated values. Mass balance refers to
the characterized products threo-6 and erythro-6 and recovered allylic
alcohol 5.
LTA and gave almost identical results as shown in Table 2.
The threo-aziridine alcohols 6 were formed preferentially
in the aziridination of chiral allylic alcohols 5a-d,f,g with
Q-NH2 1 and PIDA as the oxidant. Conversions and mass
balances were high to excellent in every case. For the
aziridination of cis- and trans-allylic alcohols, the configura-
tions around the CdC moieties were retained in the corre-
sponding aziridine alcohols (Table 2, entries 2, 4 and 6). The
allylic alcohols 5a and 5b without allylic strain were aziridi-
nated in high threo diastereoselectivities (entries 1 (96%) and
2 (95%)). For the substrates 5c,d (Table 2, entries 3 and 4)
with 1,2-allylic strain, also a high, significant threo diaster-
eoselectivity was found, suggesting no influence of 1,2-allylic
strain. Aziridination of the allylic alcohol 5f possessing 1,3-
allylic strain proceeded with high threo diastereoselectivity
(entry 5). The threo-aziridine alcohol was dominantly
produced (96:4) for the aziridination of the stereochemical
probe (Z)-3-methyl-3-penten-2-ol (5g) with both 1,2- and
1,3-allylic strains (Table 2, entry 6).
To confirm the diastereoisomeric authenticity of the azir-
idine alcohols 6a-h, we synthesized all diastereoisomers by
the Swern oxidation8 of the aziridine alcohol to the corre-
sponding aziridinyl ketones 7a-h. Subsequent reduction of
each of the resulting aziridinyl ketones 7a-h with sodium
borohydride regenerated the diastereomeric mixtures of the
aziridine alcohols 6a-h for comparison with the product
(9) (a) Adam, W.; Richter, M. J. Acc. Chem. Res. 1994, 27, 57–62.
(b) Prein, M.; Adam, W. Angew. Chem., Int. Ed. Engl. 1996, 35, 477–494.
(c) Adam, W.; Peters, K.; Renz, M. J. Org. Chem. 1997, 62, 3183–3189.
(10) Hwang, G. I.; Chung, J. H.; Lee, W. K. J. Org. Chem. 1996, 61, 6183–
6188.
(8) Mancuso, A. J.; Huang, S.-L.; Swern, D. J. Org. Chem. 1978, 43,
2480–2482.
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Cakici et al.
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SCHEME 3. Aziridination of Hydroxy-Protected Allylic
Alcohol Derivative 5i
in the aziridination even without the assistance of allylic
strain. To assess this, DFT calculations (B3LYP/6-31G*) of
the model substrate 5c with 1,2-allylic strain were carried
out. The hydrogen-bonding conformer (structure A in
Figure 2) is favored by 5.0 kcal/mol over B. The novelty of
the present contribution is the realization that favorable
bonding conditions combined with optimal geometrical
provisions may obviate conformational impositions.
Experimental Section
hydrogen-bonding donors, and hence, since there is no
hydroxy-group directivity, steric effects promote erythro
(63%) diastereoselectivity.
Representative Procedure for Aziridination of Allylic Alcohols
by Using LTA. 3-Amino-2-ethyl-3H-quinazolin-4-one
5
(Q-NH2) (1) (0.75 g, 4 mmol) was added in small portions within
10 min to a vigorously stirred solution of acetic acid free lead
tetraacetate (LTA) (1.95 g, 4.4 mmol) in 10 mL of CH2Cl2 at
-25 °C, and stirring was continued for a further 10 min to give a
solution of the 3-acetoxy-aminoquinazolinone (Q-NHOAc) (2).
Then, a solution of allylic alcohol 5 (2 mmol) and hexamethyl-
disilazane (HMDS) (1.29 g, 8 mmol) in CH2Cl2 (2 mL) was
added, and the final mixture was stirred for 30 min. The
temperature of the solution was then allowed to rise to ambient
over 20-25 min with stirring throughout. The mixture
was extracted with CH2Cl2 (2 ꢀ 15 mL), washed with water
(2 mL), and saturated NaHCO3 (2 ꢀ 10 mL). The organic layer
was dried over anhydrous Na2SO4, filtered, and concentrated
under reduced pressure (20 °C, 450 Torr), and the conversion
and diastereoselectivity were determined by 1H NMR analysis
directly on the crude mixture (Table 1).
FIGURE 2. Transition-state structures for the aziridination by 2.
This mechanistic rationale of hydrogen bonding constitu-
tes an unprecedented fact for the aziridination with
Q-NHOAc 2, which reflects valuable geometrical informa-
tion about the transition-state structure. The dihedral angle
(R) between the π plane of the double bond and the hydroxy
group in the CdC;C;O structural fragment of the allylic
system is definitive (Figure 2). This dihedral angle
(R) assumes characteristic values, ideally about 120°, in the
stoichiometric epoxidations of chiral allylic alcohols with
allylic strain.6,11 Hence, we propose the transition-state
structure A in Figure 2 to account for the stereochemical
course in the aziridination of the chiral allylic alcohols 5,
irrespective of whether these acyclic substrates possess allylic
strain or not. In view of the high threo selectivity (g95%)
observed in the present aziridination, we presume that the
dihedral angle (R) in the CdC;C;O fragment is ca. 120°.
This value is inferred from the m-CPBA epoxidation of chiral
allylic alcohols 5, which are diastereocontrolled by 1,3-allylic
strain.6,11f In the threo TS (structure A in Figure 2), the
π system is oriented favorably for hydrogen bonding12 with
the quinazoline carbonyl functionality.
Representative Procedure for Aziridination of Allylic Alcohols
5 by Using PIDA. Into a 10-mL, one-necked, round-bottomed
flask, equipped with a magnetic stirrer were placed 4 mL of
CH2Cl2, allylic alcohol (1 mmol), Q-NH2 1 (378 mg, 2 mmol),
anhydrous K2CO3 (552 mg, 4 mmol), and diphenylmethane
(1 mmol) (as internal standard) at room temperature. The reaction
was initiated by addition of PIDA (708 mg, 2.2 mmol), while the
reaction progress was monitored by TLC. After completion of the
reaction (2-4 h), the reaction mixture was passed through a short
silica gel column (150 mg) and the solvent was removed under
reduced pressure (25 °C, 450 Torr). The conversion, mass balance,
1
and diastereoselectivities were determined by H NMR analysis
directly on the crude mixture (Table 2).
2-Ethyl-3-(2-(1-hydroxyethyl)aziridin-1-yl)quinazolin-4(3H)-
one (6a). A mixture of the diastereoisomeric aziridines (threo-6a
and erythro-6a in a 97:3 ratio by integration of the signals at
3.56 and 4.54 ppm respectively) was chromatographed on a
silica gel column to give the major diastereoisomer threo-6a
(395 mg, 1.53 mmol) in a yield of 76%.
threo-6a. Recrystallization from EtOAc-hexane gave a white
powder. Rf 0.11 (hexane-EtOAc = 2:1); mp 95-97 °C; 1H
NMR (400 MHz, CDCl3): δ 8.18 (dd, J = 8.1, 1.4 Hz, 1H), 7.70
(ddd, J = 8.3, 7.0, 1.4 Hz, 1H), 7.63 (d, J = 8.3 Hz, 1H), 7.43
(ddd, J = 8.1, 7.0, 1.2 Hz, 1H), 5.09 (bs, -OH, 1H), 3.56 (dqd,
J = 8.2, 6.4, 1.2 Hz, 1H), 3.15 (dq, J = 16.5, 7.3 Hz, 1H, A part
of AB system), 2.97 (dq, J = 16.5, 7.3 Hz, 1H, B part of AB
system), 2.84 (td, J = 8.2, 5.8 Hz, 1H), 2.52 (dd, J = 5.8, 1.7 Hz,
1H), 2.31 (dd, J = 8.2, 1.7 Hz, 1H), 1.43 (t, J = 7.3 Hz, 3H), 1.32
(d, J = 6.4 Hz, 3H); 13C NMR (100 MHz, CDCl3): δ 160.8,
156.5, 146.3, 134.2, 127.1, 126.7, 126.4, 120.9, 69.9, 52.1, 40.5,
27.3, 20.0, 10.9; IR (KBr, cm-1) 3385, 2975, 2936, 1667, 1592,
1471, 1365, 1278, 1253, 1155, 1044; MS (FAB) m/z 260 (MHþ);
HRMS (FAB) calcd for C14H18N3O2 (MHþ) 260.1399, found
260,1395. Anal. Calcd for C14H17N3O2: C, 64.85; H, 6.61;
N, 16.20. Found: C, 64.63; H, 6.64; N, 16.23. erythro-6a: Color-
For comparison, in the erthro TS (structure B in Figure 2),
the hydroxy group is located away from the carbonyl group
and hydrogen bonding is not possible. Thus, the threo
conformer is preferentially populated through efficient hy-
drogen bonding to affect very high threo diastereoselectivity
(11) (a) Adam, W.; Alsters, P. L.; Neumann, R.; Saha-Moller, C. R.;
Sloboda-Rozner, D.; Zhang, R. J. Org. Chem. 2003, 68, 1721–1728. (b)
Adam, W.; Corma, A.; Reddy, T. I.; Renz, M. J. Org. Chem. 1997, 62, 3631–
3637. (c) Adam, W.; Degen, H. G.; Saha-Moller, C. R. J. Org. Chem. 1999,
64, 1274–1277. (d) Adam, W.; Mitchell, C. M.; Saha-Moller, C. R. J. Org.
Chem. 1999, 64, 3699–3707. (e) Adam, W.; Smerz, A. K. J. Org. Chem. 1996,
61, 3506–3510. (f) Adam, W.; Wirth, T. Acc. Chem. Res. 1999, 32, 703–710.
(g) Hoffmann, R. W. Chem. Rev. 1989, 89, 1841–1860. (h) Adam, W.; Bach,
R. D.; Dmitrenko, O.; Saha-Moller, C. R. J. Org. Chem. 2000, 65, 6715–
6728.
1
less oil. Rf 0.09 (hexane-EtOAc = 2:1); H NMR (400 MHz,
CDCl3): δ 8.16 (ddd, J = 8.1, 1.5, 0.6 Hz, 1H), 7.69 (ddd, J =
8.3, 7.0, 1.5 Hz, 1H), 7.62 (ddd, J = 8.3, 1.2, 0.6 Hz, 1H),
7.41 (ddd, J = 8.1, 7.0, 1.2 Hz, 1H), 4.58-4.49 (m, 1H), 3.27
(12) Hoveyda, A. H.; Evans, D. A.; Fu, G. C. Chem. Rev. 1993, 93, 1307–
1370.
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(d, J = 3.2 Hz, -OH, 1H), 3.20-3.07 (m, 2H), 2.98 (dq,
J = 16.5, 7.3 Hz, 1H, B part of AB system), 2.70 (dd, J = 5.9,
1.5 Hz, 1H), 2.28 (dd, J = 8.1, 1.5 Hz, 1H), 1.43 (t, J = 7.3, Hz,
3H), 1.22 (d, J = 6.5 Hz, 3H); 13C NMR (100 MHz, CDCl3):
δ 160.4, 157.1, 146.3, 134.0, 127.1, 126.6, 126.3, 121.2, 64.0, 49.7,
38.6, 27.4, 18.6, 10.9; IR (KBr, cm-1) 3424, 2976, 2935, 1672,
1595, 1473, 1369, 1337, 1288, 1224, 1065; MS (FAB) m/z 260
(MHþ); HRMS (FAB) calcd for C14H18N3O2 (MHþ) 260.1399,
found 260.1394. Anal. Calcd for C14H17N3O2: C, 64.85; H, 6.61;
N, 16.20. Found: C, 64.73; H, 6.60; N, 15.33.
274.1556, found 274.1551. Anal. Calcd for C15H19N3O2: C,
65.91; H, 7.01; N, 15.37. Found: C, 65.68; H, 7.12; N, 15.42.
erythro-6c: Colorless oil. Rf 0.13 (hexane-EtOAc = 2:1); H
1
NMR (400 MHz, CDCl3): δ 8.17 (dd, J = 8.1, 1.5 Hz, 1H), 7.70
(ddd, J = 8.3, 7.0, 1.5 Hz, 1H), 7.63 (dd, J = 8.3, 1.2 Hz, 1H),
7.42 (ddd, J = 8.1, 7.0, 1.2 Hz, 1H), 4.24 (q, J = 6.2 Hz, 1H),
3.22 (bs, OH, 1H), 3.07-2.79 (m, 3H), 2.49 (bs, 1H), 1.40 (t, J =
7.3 Hz, 3H), 1.24 (d, J = 6.2 Hz, 3H), 1.20 (s, 3H); 13C NMR
(100 MHz, CDCl3): δ 161.0, 157.5, 146.2, 133.9, 127.0, 126.5,
126.4, 121.2, 67.5, 53.2, 41.1, 27.6, 18.5, 15.4, 10.9; IR (KBr,
cm-1) 3430, 2976, 2936, 1674, 1593, 1568, 1472, 1369, 1276,
1222, 1116; MS (FAB) m/z 274 (MHþ); HRMS (FAB) calcd for
C15H20N3O2 (MHþ) 274.1556, found 274.1550. Anal. Calcd for
C15H19N3O2: C, 65.91; H, 7.01; N, 15.37. Found: C, 65.54; H,
7.07; N, 15.23.
(E)-2-Ethyl-3-(2-(1-hydroxyethyl)-2,3-dimethylaziridin-1-yl)-
quinazolin-4(3H)-one (6d). A mixture of the diastereoisomeric
aziridines (threo-6d and erythro-6d in a 97:3 ratio by integration
of the signals at 8.21 and 8.12 ppm respectively) was chromato-
graphed on a silica gel column to give the major diastereoisomer
threo-6d (528 mg, 1.84 mmol) in a yield of 92%.
threo-6d: Recrystallization from EtOAc-hexane gave color-
less needles. Rf 0.22 (hexane-EtOAc = 2:1); mp 125-128 °C;
1H NMR (400 MHz, CDCl3): δ 8.21 (ddd, J = 8.1, 1.5, 0.5 Hz,
1H), 7.71 (ddd, J = 8.3, 7.0, 1.5 Hz, 1H), 7.64 (ddd, J = 8.3, 1.2,
0.5 Hz, 1H), 7.43 (ddd, J = 8.1, 7.0, 1.2 Hz, 1H), 3.70 (bs, OH,
1H), 3.16-2.83 (m, 3H), 2.23 (s, 1H), 1.49 (s, 3H), 1.49 (d, J =
5.6 Hz, 3H), 1.41 (t, J = 7.3 Hz, 3H), 1.17 (d, J = 6.5 Hz, 3H);
13C NMR (100 MHz, CDCl3): δ 162.3, 157.3, 146.2, 134.2,
126.9, 126.6, 126.5, 120.6, 67.6, 57.6, 49.2, 28.2, 20.3, 12.3, 10.9,
10.8; IR (KBr, cm-1) 3436, 2975, 2935, 1655, 1594, 1472, 1369,
1338, 1221, 1137, 1083; MS (FAB) m/z 288 (MHþ); HRMS
(FAB) calcd for C16H22N3O2 (MHþ) 288.1712, found 288.1707.
Anal. Calcd for C16H21N3O2: C, 66.88; H, 7.37; N, 14.62.
Found: C, 66.54; H, 7.29; N, 14.69. erythro-6d: Recrystalliza-
tion from EtOAc-hexane gave a white powder. Rf 0.11
(hexane-EtOAc = 2:1); mp 116-118 °C; 1H NMR (400
MHz, CDCl3): (Two invertomers = 3:1) major invertomer δ
8.12 (dd, J = 8.1, 1.5 Hz, 1H), 7.62 (ddd, J = 8.4, 7.0, 1.5 Hz,
1H), 7.56 (ddd, J = 8.4, 1.2, 0.6 Hz, 1H), 7.34 (ddd, J = 8.1, 7.0,
1.2 Hz, 1H), 3.99-3.87 (m, 1H), 3.59 (bs, 1H), 3.14-2.94 (m,
1H), 2.94-2.75 (m, 1H), 1.48 (d, J = 5.9 Hz, 3H), 1.39 (t, J = 7.4
Hz, 3H), 1.38 (s, 3H), 1.21 (d, J = 6.3 Hz, 3H); minor invertomer
(observable signals) δ 7.69 (ddd, J = 8.4, 7.0, 1.5 Hz, 1H), 7.40
(ddd, J = 8.1, 7.0, 1.2 Hz, 1H), 4.26 (dq, J = 6.3, 1.5 Hz, 1H),
3.38 (bs, 1H), 1.36 (t, J = 7.4 Hz, 3H), 1.18 (d, J = 6.8 Hz, 3H),
1.13 (d, J = 6.3 Hz, 3H), 1.10 (s, 3H); 13C NMR (100 MHz,
CDCl3): (Two invertomers) major invertomer δ 160.7, 157.8,
146.2, 133.4, 126.8, 126.3, 126.0, 121.4, 68.6, 56.1, 44.1, 28.2,
22.5, 15.4, 13.1, 11.0; minor invertomer (observable signals) δ
161.8, 133.8, 126.2, 126.2, 68.7, 53.9, 42.5, 28.0, 17.8, 13.3, 11.3,
10.0; IR (KBr, cm-1) 3415, 2974, 2930, 1672, 1593, 1473, 1370,
1289, 1226, 1140, 1059; MS (FAB) m/z 288 (MHþ); HRMS
(FAB) calcd for C16H22N3O2 (MHþ) 288.1712, found 288.1707.
Anal. Calcd for C16H21N3O2: C, 66.88; H, 7.37; N, 14.62.
Found: C, 66.56; H, 7.20; N, 14.67.
(E)-2-Ethyl-3-(2-(1-hydroxyethyl)-3-methylaziridin-1-yl)quina-
zolin-4(3H)-one (6b). A mixture of the diastereoisomeric aziri-
dines (threo-6b and erythro-6b in a 95:5 ratio by integration of the
signals at 3.61 and 4.48 ppm respectively) was chromatographed
on a silica gel column to give the major diastereoisomer threo-6b
(404 mg, 1.48 mmol) in a yield of 74%.
1
threo-6b: Colorless oil. Rf 0.19 (hexane-EtOAc = 2:1); H
NMR (400 MHz, CDCl3): δ 8.15 (ddd, J = 8.1, 1.5, 0.5 Hz, 1H),
7.69 (ddd, J = 8.3, 7.0, 1.5 Hz, 1H), 7.62 (ddd, J = 8.3, 1.3, 0.5
Hz, 1H), 7.40 (ddd, J = 8.1, 7.0, 1.3 Hz, 1H), 4.72 (d, J = 2.1 Hz,
OH, 1H), 3.61 (dqd, J = 8.2, 6.4, 2.1, 1H), 3.13 (dq, J = 16.1, 7.3
Hz, 1H, A part of AB system), 2.86 (dq, J = 16.1, 7.3 Hz, 1H, B
part of AB system), 2.81 (dd, J = 8.2, 5.4 Hz, 1H), 2.69-2.61 (m,
1H), 1.39 (t, J = 7.3 Hz, 3H), 1.33 (d, J = 6.4 Hz, 3H), 1.15 (d,
J = 5.8 Hz, 3H); 13C NMR (100 MHz, CDCl3): δ 161.5, 158.0,
146.3, 133.9, 127.1, 126.5, 126.3, 121.2, 69.4, 57.2, 45.1, 27.6,
20.2, 13.0, 11.0; IR (KBr, cm-1) 3450, 2973, 2935, 1661, 1594,
1472, 1368, 1218, 1143, 1078; MS (FAB) m/z 274 (MHþ);
HRMS (FAB) calcd for C15H20N3O2 (MHþ) 274.1556, found
274.1551. Anal. Calcd for C15H19N3O2: C, 65.91; H, 7.01; N,
15.37. Found: C, 65.97; H, 6.98; N, 15.34. erythro-6b: Colorless
oil. Rf 0.13 (hexane-EtOAc = 2:1); 1H NMR (400 MHz,
CDCl3): δ 8.15 (ddd, J = 8.1, 1.5, 0.5 Hz, 1H), 7.69 (ddd, J =
8.3, 7.0, 1.5 Hz, 1H), 7.63 (ddd, J = 8.3, 1.2, 0.5 Hz, 1H), 7.41
(ddd, J = 8.1, 7.0, 1.2 Hz, 1H), 4.48 (q, J = 6.4 Hz, 1H), 3.21 (bs,
OH, 1H), 3.19-3.08 (m, 2H), 2.86 (dq, J = 16.2, 7.4 Hz, 1H, B
part of AB system), 2.79 (p, J = 5.8 Hz, 1H), 1.40 (t, J = 7.4 Hz,
1H), 1.24 (d, J = 6.4 Hz, 1H), 1.15 (d, J = 5.8 Hz, 1H); 13C
NMR (100 MHz, CDCl3): δ 161.3, 158.4, 146.4, 133.9, 127.1,
126.4, 126.3, 121.4, 64.4, 55.2, 43.2, 27.7, 18.7, 13.0, 10.9; IR
(KBr, cm-1) 3372, 2980, 2924, 1671, 1592, 1466, 1401, 1357,
1158, 1057; MS (FAB) m/z 274 (MHþ); HRMS (FAB) calcd for
C15H20N3O2 (MHþ) 274.1556, found 274,1551. Anal. Calcd for
C15H19N3O2: C, 65.91; H, 7.01; N, 15.37. Found: C, 65.04; H,
6.95; N, 15.15.
2-Ethyl-3-(2-(1-hydroxyethyl)-2-methylaziridin-1-yl)quina-
zolin-4(3H)-one (6c). A mixture of the diastereoisomeric aziri-
dines (threo-6c and erythro-6c in a 95:5 ratio by integration of
the signals at 3.57 and 4.24 ppm respectively) was chromato-
graphed on a silica gel column to give the major diastereoisomer
threo-6c (218 mg, 0.8 mmol) in a yield of 40%.
1
threo-6c: Colorless oil. Rf 0.21 (hexane-EtOAc = 2:1); H
NMR (400 MHz, CDCl3): (Two invertomers = 5:1) major
invertomer δ 8.17 (ddd, J = 8.1, 1.5, 0.6 Hz, 1H), 7.69 (ddd,
J = 8.4, 7.0, 1.5 Hz, 1H), 7.62 (ddd, J = 8.4, 1.2, 0.6 Hz, 1H),
7.41 (ddd, J = 8.1, 7.0, 1.2 Hz, 1H), 4.91 (bs, OH, 1H), 3.57 (q,
J = 6.6 Hz, 1H), 3.14-2.91 (m, 2H), 2.64 (d, J = 1.9 Hz,
1H), 2.20 (bs, 1H), 1.39 (t, J = 7.3 Hz, 3H), 1.25 (d, J = 6.6 Hz,
3H), 1.19 (s, 3H); minor invertomer (observable signals) δ 8.21
(ddd, J = 8.1, 1.5, 0.6 Hz, 1H), 2.71 (d, J = 1.9 Hz, 1H), 2.02 (bs,
1H), 1.55 (s, 3H), 1.40 (t, J = 7.3 Hz, 3H), 1.20 (d, J = 6.6 Hz,
3H); 13C NMR (100 MHz, CDCl3): (Two invertomers) major
invertomer δ 161.9, 156.9, 146.3, 134.0, 126.9, 126.5, 126.4,
120.5, 73.3, 54.6, 44.4, 27.6, 18.3, 11.2, 11.0; minor invertomer
(observable signals) δ 162.2, 157.3, 146.3, 134.2, 126.7, 126.5,
66.7, 55.0, 45.7, 20.2, 15.8, 10.9; IR (KBr, cm-1) 3430, 2976,
2937, 1662, 1593, 1569, 1472, 1371, 1286, 1223, 1114; MS (FAB)
m/z 274 (MHþ); HRMS (FAB) calcd for C15H20N3O2 (MHþ)
(Z)-2-Ethyl-3-(2-(1-hydroxyethyl)-3-methylaziridin-1-yl)quina-
zolin-4(3H)-one (6e). A mixture of the diastereoisomeric aziri-
dines (threo-6e and erythro-6e in a 97:3 ratio by integration of
the signals at 3.81 and 4.49 ppm respectively) was chromato-
graphed on a silica gel column to give the major diastereoisomer
threo-6e (448 mg, 1.64 mmol) in a yield of 82%.
threo-6e: Recrystallization from EtOAc-hexane gave color-
less needles. Rf 0.26 (hexane-EtOAc = 2:1); mp 138-140 °C;
1H NMR (400 MHz, CDCl3): δ 8.18 (dd, J = 8.1, 1.4 Hz, 1H),
7.70 (ddd, J = 8.3, 7.1, 1.4 Hz, 1H), 7.62 (d, J = 8.1 Hz, 1H),
7.42 (ddd, J = 8.1, 7.1, 1.1 Hz, 1H), 5.58 (bs, OH, 1H), 3.81
(dqd, J = 9.1, 6.5, 1.1 Hz, 1H), 3.10 (dq, J = 16.5, 7.3 Hz, 1H,
9456 J. Org. Chem. Vol. 74, No. 24, 2009

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A part of AB system), 2.90 (dq, J = 16.5, 7.3 Hz, 1H, B part of
AB system), 2.71 (t, J = 8.9 Hz, 1H), 2.51 (dq, J = 8.6, 6.1 Hz,
1H), 1.47 (d, J = 6.1 Hz, 3H), 1.44 (t, J = 7.3 Hz, 3H), 1.29 (d,
J = 6.5 Hz, 3H); 13C NMR (100 MHz, CDCl3): δ 160.7, 156.4,
146.1, 134.1, 127.0, 126.6, 126.4, 120.9, 66.3, 55.4, 47.7, 27.8,
20.4, 12.1, 10.7; IR (KBr, cm-1) 3436, 2972, 2936, 1659, 1594,
1569, 1472, 1365, 1286, 1223, 1115, 1079; MS (FAB) m/z 274
(MHþ); HRMS (FAB) calcd for C15H20N3O2 (MHþ) 274.1556,
found 274.1552. Anal. Calcd for C15H19N3O2: C, 65.91; H, 7.01;
N, 15.37. Found: C, 65.71; H, 7.06; N, 15,27. erythro-6e: Color-
3.12-2.72 (m, 2H), 2.36 (bs, 1H), 1.49 (d, J = 6.0 Hz, 3H), 1.41
(t, J = 7.3 Hz, 3H), 1.25 (d, J = 6.5 Hz, 3H), 1.16 (s, 3H); 13
C
NMR (100 MHz, CDCl3): δ 162.0, 156.7, 146.2, 134.1, 126.9,
126.5, 126.5, 120.5, 69.8, 57.1, 51.4, 28.1, 18.7, 12.4, 12.3, 10.9;
IR (KBr, cm-1) 3450, 2973, 2934, 1661, 1594, 1472, 1367, 1337,
1219, 1144, 1078; MS (FAB) m/z 288 (MHþ); HRMS (FAB)
calcd for C16H22N3O2 (MHþ) 288.1712, found 288.1706. Anal.
Calcd for C16H21N3O2: C, 66.88; H, 7.37; N, 14.62. Found: C,
66.62; H, 7.61; N, 14.63. erythro-6g: Colorless oil. Rf 0.17
1
(hexane-EtOAc = 2:1); H NMR (400 MHz, CDCl3): δ 8.17
1
less oil. Rf 0.14 (hexane-EtOAc = 2:1); H NMR (400 MHz,
(dd, J = 8.1, 1.5 Hz, 1H), 7.70 (ddd, J = 8.3, 7.0, 1.5 Hz, 1H),
7.63 (dd, J = 8.3, 1.2 Hz, 1H), 7.42 (ddd, J = 8.1, 7.0, 1.2 Hz,
1H), 4.31 (q, J = 6.4 Hz, 1H), 3.03 (bs, OH, 1H), 2.98-2.88 (m,
1H), 2.87-2.77 (m, 2H), 1.72 (d, J = 6.1 Hz, 3H), 1.41 (t, J = 7.3
Hz, 3H), 1.37 (d, J = 6.4 Hz, 3H), 1.12 (s, 3H); 13C NMR (100
MHz, CDCl3): δ 161.0, 157.5, 146.2, 133.9, 127.0, 126.4, 126.4,
121.4, 68.5, 56.6, 51.0, 27.6, 18.8, 16.9, 12.8, 10.9; IR (KBr,
cm-1) 3444, 2975, 2930, 1656, 1594, 1472, 1368, 1334, 1214,
1137; MS (FAB) m/z 288 (MHþ); HRMS (FAB) calcd for
C16H22N3O2 (MHþ) 288.1712, found 288.1707. Anal. Calcd
for C16H21N3O2: C, 66.88; H, 7.37; N, 14.62. Found: C, 66.08;
H, 7.32; N, 14.56.
CDCl3): δ 8.15 (ddd, J = 8.1, 1.5, 0.5 Hz, 1H), 7.68 (ddd, J =
8.3, 7.0, 1.5 Hz, 1H), 7.61 (ddd, J = 8.3, 1.2, 0.5 Hz, 1H), 7.40
(ddd, J = 8.1, 7.0, 1.2 Hz, 1H), 4.55-4.42 (m, 1H), 3.07 (dq, J =
16.3, 7.4 Hz, 1H, A part of AB system), 2.99-2.86 (m, 2H), 2.62
(dq, J = 8.3, 6.1 Hz, 1H), 2.56 (bs, OH, 1H), 1.61 (d, J = 6.1 Hz,
3H), 1.44 (d, J = 6.5 Hz, 3H), 1.43 (t, J = 7.4 Hz, 3H); 13C NMR
(100 MHz, CDCl3): δ 160.3, 157.3, 146.2, 133.9, 127.0, 126.4,
126.3, 121.4, 64.9, 52.6, 47.2, 27.9, 20.5, 12.5, 10.9; IR (KBr,
cm-1) 3436, 2973, 2936, 1659, 1594, 1569, 1472, 1365, 1287,
1223, 1119, 1079; MS (FAB) m/z 274 (MHþ); HRMS (FAB)
calcd for C15H20N3O2 (MHþ) 274.1556, found 274.1550. Anal.
Calcd for C15H19N3O2: C, 65.91; H, 7.01; N, 15.37. Found: C,
65.71; H, 7.08; N, 15.30.
2-Ethyl-3-(2-(1-hydroxyethyl)-2,3,3-trimethylaziridin-1-yl)-
quinazolin-4(3H)-one (6h). A mixture of the diastereoisomeric
aziridines (threo-6h and erythro-6h in a 97:3 ratio by integration
of the signals at 3.92 and 4.37 ppm respectively) was chromato-
graphed on a silica gel column to give the major diastereoisomer
threo-6h (524 mg, 1.74 mmol) in a yield of 87%.
2-Ethyl-3-(3-(1-hydroxyethyl)-2,2-dimethylaziridin-1-yl)quina-
zolin-4(3H)-one (6f). A mixture of the diastereoisomeric aziri-
dines (threo-6f and erythro-6f in a 99:1 ratio by integration of the
signals at 3.76 and 4.31 ppm respectively) was chromatographed
on a silica gel column to give the major diastereoisomer threo-6f
(522 mg, 1.82 mmol) in a yield of 91%.
1
threo-6h: Colorless oil. Rf 0.19 (hexane-EtOAc = 2:1); H
NMR (400 MHz, CDCl3): δ 8.14 (dd, J = 8.1, 1.4 Hz, 1H), 7.70
(ddd, J = 8.3, 7.1, 1.4 Hz, 1H), 7.62 (dd, J = 8.3, 1.2 Hz, 1H),
7.41 (ddd, J = 8.1, 7.1, 1.2 Hz, 1H), 5.32 (bs, OH, 1H), 3.92 (q,
J = 6.6 Hz, 1H), 2.97 (dq, J = 14.8, 7.4 Hz, 1H, A part of AB
system), 2.78 (dq, J = 14.8, 7.4 Hz, 1H, B part of AB system),
1.50 (s, 3H), 1.37 (t, J = 7.4 Hz, 3H), 1.19 (d, J = 6.6 Hz, 3H),
1.12 (s, 3H), 1.07 (s, 3H); 13C NMR (100 MHz, CDCl3): δ 162.6,
158.4, 146.1, 134.0, 126.8, 126.3, 126.3, 120.8, 71.0, 57.5, 50.5,
28.1, 20.9, 18.4, 18.1, 11.2, 9.5; IR (KBr, cm-1) 3438, 2977, 2935,
1666, 1593, 1568, 1472, 1378, 1285, 1210, 1109, 1055; MS (FAB)
m/z 302 (MHþ); HRMS (FAB) calcd for C17H24N3O2 (MHþ)
302.1869, found 302.1862. Anal. Calcd for C17H23N3O2: C,
67.75; H, 7.69; N, 13.94. Found: C, 67.12; H, 7.50; N, 14.03.
threo-6f: Recrystallization from EtOAc-hexane gave a white
1
powder. Rf 0.19 (hexane-EtOAc = 2:1); mp 144-146 °C; H
NMR (400 MHz, CDCl3): δ 8.15 (dd, J = 8.0, 0.9 Hz, 1H), 7.69
(t, J = 7.6 Hz, 1H), 7.62 (d, J = 8.1 Hz, 1H), 7.41 (t, J = 7.5 Hz,
1H), 5.42 (bs, OH, 1H), 3.76 (m, 1H), 3.07 (dq, J = 14.8, 7.4 Hz,
1H, A part of AB system), 2.76 (dq, J = 14.8, 7.4 Hz, 1H, B part
of AB system), 2.70 (d, J = 9.0 Hz, 1H), 1.45 (s, 3H), 1.39 (t, J =
7.4 Hz, 3H), 1.29 (d, J = 6.4 Hz, 3H), 1.15 (s, 3H); 13C NMR
(100 MHz, CDCl3): δ 161.4, 158.0, 146.0, 134.1, 127.0, 126.6,
126.4, 121.1, 67.2, 59.3, 51.4, 27.9, 20.8, 20.8, 19.2, 10.8; IR
(KBr, cm-1) 3449, 2972, 2934, 1659, 1594, 1472, 1364, 1337,
1220, 1158, 1109, 1074; MS (FAB) m/z 288 (MHþ); HRMS
(FAB) calcd for C16H22N3O2 (MHþ) 288.1712, found 288.1707.
Anal. Calcd for C16H21N3O2: C, 66.88; H, 7.37; N, 14.62.
Found: C, 66.50; H, 7.38; N, 14.63. erythro-6f: Colorless oil.
Rf 0.10 (hexane-EtOAc = 2:1); 1H NMR (400 MHz, CDCl3): δ
8.14 (d, J = 8.0 Hz, 1H), 7.67 (t, J = 7.5 Hz, 1H), 7.62 (d, J =
7.7 Hz, 1H), 7.39 (t, J = 7.4 Hz, 1H), 4.31 (m, 1H), 3.04-3.13
(m, 2H), 2.74 (dq, J = 14.9, 7.4, Hz, 1H, B part of AB system),
2.48 (bs, OH, 1H), 1.58 (s, 3H), 1.48 (d, J = 6.5 Hz, 3H), 1.39 (t,
J = 7.4, Hz, 3H), 1.13 (s, 3H); 13C NMR (100 MHz, CDCl3): δ
160.7, 158.5, 146.1, 133.7, 127.0, 126.3, 121.5, 65.9, 57.1, 51.2,
27.9, 21.3, 20.6, 19.3, 10.8; IR (KBr, cm-1) 3421, 2976, 2933,
1677, 1595, 1472, 1366, 1336, 1221, 1156, 1107, 1077; MS (FAB)
m/z 288 (MHþ); HRMS (FAB) calcd for C16H22N3O2 (MHþ)
288.1712, found 288.1706. Anal. Calcd for C16H21N3O2: C,
66.88; H, 7.37; N, 14.62. Found: C, 67.06; H, 7.44; N, 14.57.
(Z)-2-Ethyl-3-(2-(1-hydroxyethyl)-2,3-dimethylaziridin-1-yl)-
quinazolin-4(3H)-one (6g). A mixture of the diastereoisomeric
aziridines (threo-6g and erythro-6g in a 95:5 ratio by integration
of the signals at 3.86 and 4.31 ppm respectively) was chromato-
graphed on a silica gel column to give the major diastereoisomer
threo-6g (460 mg, 1.60 mmol) in a yield of 80%.
1
erythro-6h: Colorless oil. Rf 0.16 (hexane-EtOAc = 2:1); H
NMR (400 MHz, CDCl3): δ 8.11 (ddd, J = 8.1, 1.5, 0.5 Hz, 1H),
7.68 (ddd, J = 8.3, 7.0, 1.5 Hz, 1H), 7.61 (ddd, J = 8.3, 1.2,
0.5 Hz, 1H), 7.39 (ddd, J = 8.1, 7.0, 1.2 Hz, 1H), 4.37 (q, J =
6.4 Hz, 1H), 3.05 (bs, OH, 1H), 2.91 (dq, J = 14.8, 7.4 Hz, 1H, A
part of AB system), 2.77 (dq, J = 14.8, 7.4 Hz, 1H, B part of AB
system), 1.69 (s, 3H), 1.36 (t, J = 7.4 Hz, 3H), 1.35 (d, J = 6.4
Hz, 3H), 1.12 (s, 3H), 1.06 (s, 3H); 13C NMR (100 MHz,
CDCl3): δ 161.6, 158.7, 146.2, 133.8, 126.8, 126.2, 121.4, 70.3,
55.6, 50.8, 28.0, 20.9, 19.2, 18.1, 14.9, 11.2; IR (KBr, cm-1) 3445,
2977, 2937, 1688, 1593, 1568, 1472, 1374, 1287, 1211, 1108, 1054;
MS (FAB) m/z 302 (MHþ); HRMS (FAB) calcd for
C17H24N3O2 (MHþ) 302.1869, found 302.1861. Anal. Calcd
for C17H23N3O2: C, 67.75; H, 7.69; N, 13.94. Found: C, 67.29;
H, 7.47; N, 14.03.
4-Methylpent-3-en-2-yl 4-Nitrobenzoate (5i). To a stirred so-
lution of 4-methylpent-3-en-2-ol (5f) (300 mg, 3 mmol) in 20 mL
of ethyl acetate were added p-nitrobenzoyl chloride (2.78 g,
15 mmol), anhydrous K2CO3 (2.07 g, 15 mmol), and N,N-
dimethyl-amino pyridine (DMAP) (18 mg, 0.15 mmol). The
reaction mixture was stirred at room temperature for 12 h. The
mixture was filtered by suction using a sintered glass funnel, and
the solid residue was washed with 2 ꢀ 15 mL portions of EtOAc.
The organic layer was concentrated under reduced pressure, and
the residue was chromatographed on a silica gel column by elu-
tion with hexane-EtOAc (95:5) to give 4-methylpent-3-en-2-yl
threo-6g: Recrystallization from EtOAc-hexane gave a white
1
powder. Rf 0.19 (hexane-EtOAc = 2:1); mp 103-105 °C; H
NMR (400 MHz, CDCl3): δ 8.18 (d, J = 8.1 Hz, 1H), 7.70 (ddd,
J = 8.3, 7.0, 1.3 Hz, 1H), 7.63 (d, J = 7.8 Hz, 1H), 7.42 (t, J =
7.5 Hz, 1H), 5.40 (bs, OH, 1H), 3.86 (q, J = 6.5, Hz, 1H),
J. Org. Chem. Vol. 74, No. 24, 2009 9457

Cakici et al.
JOCArticle
4-nitrobenzoate (5i) (0.68 g, 2.71 mmol, 90%). Recrystalliza-
tion from hexane-EtOAc afforded colorless needles. Rf 0.58
1596, 1471, 1362, 1287, 1222, 1186, 1130; MS (FAB) m/z 258
(MHþ); HRMS (FAB) calcd for C14H16N3O2 (MHþ) 258.1243,
found 258.1239. Anal. Calcd for C14H15N3O2: C, 65.35; H, 5.88;
N, 16.33. Found: C, 65.01; H, 5.64; N, 15.67.
1
(hexane-EtOAc = 19:1); mp 67-70 °C; H NMR (400 MHz,
CDCl3): δ 8.27 (d, J = 9.0 Hz, 2H, A part of AB system), 8.20 (d,
J = 9.0 Hz, 2H, B part of AB system), 5.86 (dq, J = 9.0, 6.4 Hz,
1H), 5.35-5.16 (m, 1H), 1.78 (s, 3H), 1.75 (s, 3H), 1.42 (d, J = 6.4
Hz, 3H); 13C NMR (100 MHz, CDCl3): δ 164.3, 150.6,
137.5, 136.6, 130.9, 124.5, 123.6, 70.4, 25.9, 21.2, 18.6; IR (KBr,
cm-1) 3112, 2973, 2918, 1714, 1608, 1525, 1445, 1352, 1331, 1276,
1104, 1064.
1-(1-(2-Ethyl-4-oxoquinazolin-3(4H)-yl)-3,3-dimethylaziridin-
2-yl)ethyl 4-Nitrobenzoate (8b). A mixture of the diastereo-
isomeric aziridines (threo-8b and erythro-8b in a 37:63 ratio by
integration of the signals at 3.70 and 3.66 ppm respectively) was
chromatographed on a silica gel column to give the diastereo-
isomers 8b (170 mg, 0.39 mmol) in a yield of 78%.
(E)-3-(2-Acetyl-3-methylaziridin-1-yl)-2-ethylquinazolin-
4(3H)-one (7b). Colorless oil, Rf 0.23 (hexane-EtOAc = 2:1);
1H NMR (400 MHz, CDCl3): (Two invertomers = 3.5:1) major
invertomer δ 8.09 (ddd, J = 8.1, 1.5, 0.6 Hz, 1H), 7.73-7.60 (m,
2H), 7.38 (ddd, J = 8.1, 7.0, 1.5 Hz, 1H), 3.53 (d, J = 4.7 Hz,
1H), 3.20-3.00 (m, 1H), 2.89 (m, 2H), 2.48 (s, 3H), 1.55 (d, J =
5.7 Hz, 3H), 1.44 (t, J = 7.3 Hz, 3H); minor invertomer
(observable signals) δ 8.17 (ddd, J = 8.1, 1.5, 0.6 Hz, 1H),
7.43 (ddd, J = 8.1, 7.0, 1.5 Hz, 1H), 3.64 (d, J = 5.0 Hz, 1H),
2.45 (s, 3H), 1.41 (t, J = 7.3 Hz, 3H), 1.23 (d, J = 5.9 Hz, 3H);
13C NMR (100 MHz, CDCl3): (Two invertomers) major inver-
tomer δ 198.1, 160.0, 155.7, 146.1, 133.7, 127.1, 126.3, 126.3,
121.1, 52.3, 49.7, 31.0, 27.7, 16.3, 10.7; minor invertomer
(observable signals) δ 160.7, 157.6, 146.3, 134.0, 127.2, 126.6,
threo-8b: Recrystallization from EtOH afforded pale yellow
1
needles. Rf 0.44 (hexane-EtOAc = 2:1); mp 157-159 °C; H
NMR (200 MHz, CDCl3): δ 8.46 (d, J = 9.0 Hz, 2H, A part of
AB system), 8.30 (d, J = 9.0 Hz, 2H, B part of AB system), 8.14
(d, J = 8.0 Hz, 1H), 7.72-7.57 (m, 2H), 7.44-7.36 (m, 1H), 5.15
(dq, J = 9.1, 6.5 Hz, 1H), 3.70 (d, J = 9.1 Hz, 1H), 3.12 (dq, J =
16.5, 7.3 Hz, 1H, A part of AB system), 2.71 (dq, J = 16.5, 7.3
Hz, 1H, B part of AB system), 1.55 (s, 3H), 1.53 (d, J = 6.5 Hz,
3H), 1.37 (t, J = 7.3 Hz, 3H), 1.18 (s, 3H); 13C NMR (50 MHz,
CDCl3): δ 166.5, 162.3, 160.2, 152.5, 147.9, 138.3, 135.5, 133.2,
128.8, 128.3, 128.1, 125.4, 123.6, 73.6, 56.8, 51.2, 29.8, 22.5, 21.5,
20.1, 12.5; IR (KBr, cm-1) 2982, 2930, 1724, 1674, 1596, 1528,
1472, 1339, 1270, 1165, 1102; HRMS (FABþ) calcd for
C23H25N4O5 [MþH]þ 437.1825, found 437.1820. erythro 8b:
Recrystallization from EtOH afforded pale yellow needles. Rf
126.4, 121.4, 54.7, 46.0, 27.6, 24.0, 12.7, 10.9; IR (KBr, cm-1
)
2969, 2924, 1701, 1671, 1593, 1472, 1351, 1292, 1161, 1055; MS
(FAB) m/z 272 (MHþ); HRMS (FAB) calcd for C15H18N3O2
(MHþ) 272.1399, found 272.1394. Anal. Calcd for C15H17N3O2:
C, 66.40; H, 6.32; N, 15.49. Found: C, 66.94; H, 6.35; N, 15.09.
3-(2-Acetyl-2-methylaziridin-1-yl)-2-ethylquinazolin-4(3H)-one
(7c). Colorless oil. Rf 0.23 and 0.36 (hexane-EtOAc = 2:1);
(Two invertomers = 1:1) 1H NMR (400 MHz, CDCl3): δ 8.17
(ddd, J = 8.1, 1.5, 0.5 Hz, 1H), 8.07 (ddd, J = 8.1, 1.5, 0.5 Hz,
1H), 7.71 (ddd, J = 8.4, 7.0, 1.5 Hz, 1H), 7.66 (ddd, J = 8.4, 7.0,
1.5 Hz, 1H), 7.65-7.61 (m, 1H), 7.43 (ddd, J = 8.1, 7.0, 1.2 Hz,
1H), 7.37 (ddd, J = 8.1, 7.0, 1.2 Hz, 1H), 3.36 (bs, 1H), 3.33 (bs,
1H), 3.07 (s, 1H), 3.05 (dq, J = 16.3, 7.3 Hz, 1H), 2.97 (dq, J =
16.3, 7.3 Hz, 1H), 2.82 (dq, J = 16.3, 7.3 Hz, 1H), 2.66 (s, 1H),
2.62 (dq, J = 16.3, 7.3 Hz, 1H), 2.44 (s, 3H), 2.21 (s, 3H), 1.90 (s,
3H), 1.43 (t, J = 7.3 Hz, 3H), 1.36 (t, J = 7.3 Hz, 3H), 1.26 (s,
3H); 13C NMR (100 MHz, CDCl3): (Two invertomers) δ 205.5,
199.4, 160.4, 160.2, 157.5, 155.6, 146.3, 146.2, 134.1, 133.6, 127.2,
127.1, 126.6, 126.5, 126.3, 126.1, 121.5, 121.1, 54.2, 51.2, 49.1,
1
0.80 (hexane-EtOAc = 2:1); mp 122-124 °C; H NMR (200
MHz, CDCl3): δ 8.34-8.16 (m, 5H), 7.75-7.61 (m, 2H), 7.42
(ddd, J = 8.2, 6.6, 1.7 Hz, 1H), 5.17 (dq, J = 8.2, 6.5 Hz, 1H),
3.66 (d, J = 8.2 Hz, 1H), 3.10 (dq, J = 16.4, 7.3 Hz, 1H, A part
of AB system), 2.73 (dq, J = 16.4, 7.3 Hz, 1H, B part of AB
system), 1.86 (d, J = 6.5 Hz, 3H), 1.50 (s, 3H), 1.41 (t, J = 7.3
Hz, 3H), 1.15 (s, 3H); 13C NMR (50 MHz, CDCl3): δ 165.7,
162.5, 160.2, 152.6, 147.9, 137.7, 135.7, 132.8, 128.9, 128.2,
125.6, 123.5, 74.0, 56.3, 52.7, 29.9, 22.3, 21.3, 20.6, 12.6; IR
(KBr, cm-1) 2986, 2924, 1724, 1675, 1596, 1528, 1468, 1334,
1270, 1163, 1102. Anal. Calcd for C23H24N4O5: C, 63.29; H,
5.54; N, 12.84. Found: C, 62.53; H, 5.53; N, 12.79.
45.2, 27.7, 27.6, 27.2, 23.9, 19.9, 12.8, 10.8, 10.7; IR (KBr, cm-1
)
2981, 2938, 1701, 1672, 1594, 1472, 1360, 1297, 1225, 1149; MS
(FAB) m/z 272 (MHþ); HRMS (FAB) calcd for C15H18N3O2
(MHþ) 272.1399, found 272.1394. Anal. Calcd for C15H17N3O2:
C, 66.40; H, 6.32; N, 15.49. Found: C, 66.82; H, 6.49; N, 15.03.
(E)-3-(2-Acetyl-2,3-dimethylaziridin-1-yl)-2-ethylquinazolin-
4(3H)-one (7d). Recrystallization from EtOAc-hexane gave a
white powder. Rf 0.23 (hexane-EtOAc = 2:1); mp 140-142 °C;
1H NMR (400 MHz, CDCl3): δ 8.07 (d, J = 8.0 Hz, 1H),
7.69-7.60 (m, 2H), 7.37 (ddd, J = 8.0, 6.3, 1.9 Hz, 1H), 3.28 (q,
J = 5.9 Hz, 1H), 2.91 (q, J = 7.3 Hz, 2H), 2.40 (s, 3H), 1.82 (s,
3H), 1.49 (d, J = 5.9 Hz, 3H), 1.43 (t, J = 7.3 Hz, 3H); 13C NMR
(100 MHz, CDCl3): δ 200.1, 160.1, 155.6, 146.1, 133.6, 127.1,
126.3, 126.1, 121.0, 54.3, 53.5, 27.8, 15.4, 12.6, 10.6; IR (KBr,
cm-1) 2980, 2935, 1695, 1668, 1592, 1471, 1348, 1262, 1166,
1090; MS (FAB) m/z 286 (MHþ); HRMS (FAB) calcd for
C16H20N3O2 (MHþ) 286.1556, found 286.1550. Anal. Calcd
for C16H19N3O2: C, 67.35; H, 6.71; N, 14.73. Found: C, 67.68;
H, 6.88; N, 14.61.
(Z)-3-(2-Acetyl-3-methylaziridin-1-yl)-2-ethylquinazolin-4(3H)-
one (7e). Recrystallization from EtOAc-hexane gave a white
powder. Rf 0.29 (hexane-EtOAc = 2:1); mp 96-98 °C; 1H
NMR (400 MHz, CDCl3): δ 8.14 (d, J = 8.0 Hz, 1H), 7.68 (t,
J = 7.5 Hz, 1H), 7.61 (d, J = 8.1 Hz, 1H), 7.40 (t, J = 7.5 Hz,
1H), 3.54 (d, J = 8.6 Hz, 1H), 3.16-3.09 (m, 1H), 3.06-2.88 (m,
2H), 2.42 (s, 3H), 1.47 (d, J = 5.9 Hz, 3H), 1.42 (t, J = 7.3 Hz,
3H); 13C NMR (100 MHz, CDCl3): δ 202.9, 160.0, 157.0, 146.2,
134.1, 127.2, 126.6, 126.3, 121.4, 53.8, 48.3, 29.8, 27.6, 12.5, 10.8;
IR (KBr, cm-1) 2977, 2936, 1704, 1671, 1594, 1472, 1357, 1290,
1228, 1182, 1158, 1059; MS (FAB) m/z 272 (MHþ); HRMS
(FAB) calcd for C15H18N3O2 (MHþ) 272.1399, found 272.1394.
Representative Procedure for Swern Oxidation of Aziridine
Alcohols to Aziridinyl Ketones 7. To a solution of oxalyl chloride
(115 mg, 1.1 mmol) in 1 mL of CH2Cl2 under a nitrogen
atmosphere at -60 °C was added DMSO (390 mg, 5 mmol) in
1 mL of CH2Cl2. The solution was stirred for 10 min at -60 °C,
and threo-6 (1 mmol) in 1 mL of CH2Cl2 was added to the above
solution. Then the resulting mixture was stirred for 5 min. To the
above reaction mixture was added Et3N (232 mg, 2.3 mmol) at
-60 °C. The mixture was stirred for another 15 min and warmed
to room temperature. The mixture was treated with 3.0 mL of
water, and the aqueous layer was separated and extracted with
CH2Cl2 (3 ꢀ 5.0 mL). The combined organic extracts were
washed with saturated NaHCO3 and 10 mL of brine, dried over
anhydrous MgSO4, filtered, and concentrated in vacuo. Purifi-
cation by column chromatography (hexane-EtOAc = 2:1)
provided the corresponding aziridinyl ketone 7.
3-(2-Acetylaziridin-1-yl)-2-ethylquinazolin-4(3H)-one (7a).
1
Colorless oil. Rf 0.25 (hexane-EtOAc = 2:1); H NMR (400
MHz, CDCl3): δ 8.14 (ddd, J = 8.1, 1.5, 0.5 Hz, 1H), 7.72-7.66
(ddd, J = 8.3, 7.0, 1.5 Hz, 1H), 7.61 (ddd, J = 8.3, 1.2, 0.5 Hz,
1H), 7.40 (ddd, J = 8.1, 7.0, 1.2 Hz, 1H), 3.57 (dd, J = 8.1, 5.2
Hz, 1H), 3.01 (m, 3H), 2.91 (dd, J = 5.2, 1.4 Hz, 1H), 2.34 (s,
3H), 1.40 (t, J = 7.3 Hz, 3H); 13C NMR (100 MHz, CDCl3): δ
203.3, 160.1, 157.2, 146.3, 134.2, 127.2, 126.6, 126.3, 121.4, 48.4,
39.3, 27.6, 27.1, 10.9; IR (KBr, cm-1) 2975, 2936, 1706, 1675,
9458 J. Org. Chem. Vol. 74, No. 24, 2009

Cakici et al.
JOCArticle
Anal. Calcd for C15H17N3O2: C, 66.40; H, 6.32; N, 15.49.
Found: C, 66.35; H, 6.38; N, 15.50.
dry CH3OH (3 mL) was added NaBH4 (1 mol equiv) in small
portions over 10 min, and the reaction mixture stirred until the
starting material aziridinyl ketone disappeared as monitored by
TLC (10 min). The reaction mixture was poured into water
(3 mL), and the bulk of the methanol was removed by evapora-
tion under reduced pressure. The residual solution was extracted
with CH2Cl2 (2 ꢀ 10 mL), and the combined organic layers were
dried over Na2SO4. After removal of the solvent, threo and
erythro diastereoisomers were separated on a silica gel column
by elution with hexane-EtOAc.
3-(3-Acetyl-2,2-dimethylaziridin-1-yl)-2-ethylquinazolin-4(3H)-
one (7f). Recrystallization from EtOAc-hexane gave a white
1
powder. Rf 0.24 (hexane-EtOAc = 2:1); mp 126-127 °C; H
NMR (400 MHz, CDCl3): δ 8.13 (d, J = 8.0 Hz, 1H), 7.69 (t,
J = 7.5 Hz, 1H), 7.62 (d, J = 8.0 Hz, 1H), 7.41 (t, J = 7.5 Hz,
1H), 3.59 (s, 1H), 3.08 (dq, J = 14.7, 7.3 Hz, 1H), 2.74 (dq, J =
14.7, 7.3 Hz, 1H), 2.45 (s, 3H), 1.44 (s, 3H), 1.41 (t, J = 7.3 Hz,
3H), 1.25 (s, 3H); 13C NMR (100 MHz, CDCl3): δ 203.9, 160.5,
157.6, 146.1, 134.0, 127.1, 126.5, 126.3, 121.4, 58.4, 53.7, 29.5,
27.7, 20.2, 19.6, 10.7; IR (KBr, cm-1) 2981, 2937, 1709, 1675,
1595, 1472, 1379, 1354, 1218, 1182, 1107; MS (FAB) m/z 286
(MHþ); HRMS (FAB) calcd for C16H20N3O2 (MHþ) 286.1556,
found 286.1550. Anal. Calcd for C16H19N3O2: C, 67.35; H, 6.71;
N, 14.73. Found: C, 67.07; H, 6.65; N, 14.74.
threo-1-(2-Ethyl-4-oxoquinazolin-3(4H)-yl)-3-methylaziridin-
2-yl)ethyl 4-Nitrobenzoate (8a). To a stirred solution of threo-6e
(45 mg, 0.16 mmol) in dichloromethane (2 mL) were added
pyridine (19 mg, 0.24 mmol) and p-nitrobenzoyl chloride
(92 mg, 0.49 mmol) at 0 °C. The final mixture was stirred at
room temperature for 6 h and quenched by the addition of
saturated aqueous sodium bicarbonate. The aqueous layer was
extracted with dichloromethane (3 ꢀ 3 mL). The combined
organic layers were washed with brine, dried over MgSO4,
filtered, and concentrated under vacuum. Further purification
by chromatography on silica gel (hexane-EtOAc = 2:1) gave
threo-8a (55 mg, 0.13 mmol) in a yield of 81%. Recrystalli-
zation from EtOH afforded pale yellow needles. Rf 0.40
(hexane-EtOAc = 2:1); mp 129-131 °C; 1H NMR (200
MHz, CDCl3): δ 8.39-8.27 (m, 4H), 8.13 (dd, J = 8.1, 1.4
Hz, 1H), 7.72-7.57 (m, 2H), 7.43-7.35 (m, 1H), 5.22 (dq, J =
9.1, 6.5 Hz, 1H), 3.57 (t, J = 8.6 Hz, 1H), 3.22-2.95 (m, 3H),
1.54 (d, J = 6.0, 3H), 1.51 (d, J = 6.5 Hz, 3H), 1.29 (t,
J = 7.3 Hz, 3H); 13C NMR (50 MHz, CDCl3): δ 166.1, 162.5,
160.4, 152.7, 148.1, 137.9, 135.7, 132.9, 128.8, 128.1, 125.4,
(Z)-3-(2-Acetyl-2,3-dimethylaziridin-1-yl)-2-ethylquinazolin-
4(3H)-one (7g). Recrystallization from EtOAc-hexane gave a
white powder. Rf 0.33 (hexane-EtOAc = 2:1); mp 98-100 °C;
1H NMR (400 MHz, CDCl3): δ 8.16 (d, J = 7.6 Hz, 1H), 7.70 (t,
J = 7.6, Hz, 1H), 7.63 (d, J = 8.1 Hz, 1H), 7.42 (t, J = 7.5 Hz,
1H), 3.05 (bs, 1H), 2.93 (dq, J = 14.7, 7.3 Hz, 1H), 2.71 (dq, J =
14.7, 7.3 Hz, 1H), 2.40 (s, 3H), 1.55 (d, J = 5.9 Hz, 3H), 1.40 (t,
J = 7.3 Hz, 3H), 1.34 (bs, 3H); 13C NMR (100 MHz, CDCl3):
δ 206.1, 160.6, 157.2, 146.2, 134.0, 127.1, 126.5, 126.4, 121.3,
60.0, 53.4, 28.2, 27.8, 15.3, 13.6, 10.9; IR (KBr, cm-1) 2981,
2938, 1682, 1595, 1569, 1472, 1357, 1284, 1223, 1132, 1060;
MS (FAB) m/z 286 (MHþ); HRMS (FAB) calcd for
C16H20N3O2 (MHþ) 286.1556, found 286.1550. Anal. Calcd
for C16H19N3O2: C, 67.35; H, 6.71; N, 14.73. Found: C, 67.69;
H, 6.70; N, 14.66.
123.7, 73.4, 50.7, 44.4, 29.8, 20.1, 14.7, 12.8; IR (KBr, cm-1
)
3-(2-Acetyl-2,3,3-trimethylaziridin-1-yl)-2-ethylquinazolin-
4(3H)-one (7h). Recrystallization from EtOAc-hexane gave a
white powder. Rf 0.34 (hexane-EtOAc = 2:1); mp 144-146 °C;
1H NMR (400 MHz, CDCl3): δ 8.11 (dd, J = 8.1, 1.5 Hz, 1H),
7.69 (ddd, J = 8.3, 7.1, 1.5 Hz, 1H), 7.62 (dd, J = 8.3, 1.2 Hz,
1H), 7.40 (ddd, J = 8.1, 7.1, 1.2 Hz, 1H), 2.92 (dq, J = 14.8, 7.3
Hz, 1H), 2.79 (dq, J = 14.8, 7.3 Hz, 1H), 2.54 (s, 3H), 1.41 (s,
3H), 1.39 (t, J = 7.3 Hz, 3H), 1.26 (s, 3H), 1.15 (s, 3H); 13C
NMR (100 MHz, CDCl3): δ 208.8, 161.4, 158.1, 146.2, 133.9,
126.8, 126.3, 126.2, 121.3, 59.8, 51.7, 28.3, 28.0, 22.5, 17.2, 14.1,
11.1; IR (KBr, cm-1) 2986, 2939, 1683, 1594, 1568, 1471, 1354,
1295, 1211, 1167, 1106, 1071; MS (FAB) m/z 300 (MHþ);
HRMS (FAB) calcd for C17H22N3O2 (MHþ) 300.1712, found
300.1707. Anal. Calcd for C17H21N3O2: C, 68.20; H, 7.07; N,
14.04. Found: C, 67.94; H, 6.97; N, 14.03.
2980, 2936, 1724, 1676, 1597, 1528, 1473, 1340, 1268, 1102; MS
(FAB) m/z 423 (MHþ); HRMS (FAB) calcd for C22H23N4O5
(MHþ) 423.1668, found 423.1662. Anal. Calcd for C22H22N4O5:
C, 62.55; H, 5.25; N, 13.26. Found: C, 62.32; H, 5.36; N, 13.25.
Acknowledgment. Financial support by the Scientific and
Technological Research Council of Turkey (TUBITAK)
(TBAG-108T116) is gratefully acknowledged. In addition
the authors would like to thank Dr. Graham Eaton from
Leicester University for HRMS measurements. M.C. would
like to thank TUBITAK for a scholarship.
Supporting Information Available: X-ray structures and
crystallographic data for compounds threo-6d and threo-8a,
DFT calculations, and copies of the 1H-13C NMR spectra for
all new compounds. This material is available free of charge via
the Internet at http://pubs.acs.org.
Representative Procedure for Reduction of Aziridinyl Ketone 7
with Sodium Borohydride to threo- and erythro-Aziridine Alco-
hols 6. To a stirred solution of aziridinyl ketone 7 (1 mol equiv) in
J. Org. Chem. Vol. 74, No. 24, 2009 9459