Aziridination of cyclic dienes with enantiopure 3-acetoxyamino-quinazolin-4(3H)-ones

Article abstract of DOI:10.1039/b102592a

Aziridination of cyclopentadiene and cyclohepta-1,3-diene with (S)-3-acetoxyamino-2-(3-hydroxy-2,2-dimethyl- propyl)quinazolin-4(3H)-one 6 (Q¹NHOAc) in the presence of titanium(IV) tert-butoxide in dichloromethane takes place highly diastereose

Full text of DOI:10.1039/b102592a

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Aziridination of cyclic dienes with enantiopure 3-acetoxyamino-
quinazolin-4(3H)-ones
Robert S. Atkinson* and Christopher K. Meades
1
Department of Chemistry, Leicester University, Leicester, UK LE1 7RH
Received (in Cambridge, UK) 20th March 2001, Accepted 15th May 2001
First published as an Advance Article on the web 4th June 2001
Aziridination of cyclopentadiene and cyclohepta-1,3-diene with (S)-3-acetoxyamino-2-(3-hydroxy-2,2-dimethyl-
propyl)quinazolin-4(3H)-one 6 (Q1NHOAc) in the presence of titanium() tert-butoxide in dichloromethane takes
place highly diastereoselectively: X-ray structure determinations show that the preferred sense of diastereoselectivity
in both cases is the same as that previously found for aziridination of butadiene with 6. Aziridination of cyclohexa-
1,3-diene with 6 was less diastereoselective in dichloromethane solution but highly diastereoselective in acetonitrile:
in this solvent two diastereoisomeric cis-4-(Q1-amino)cyclohexen-3-ols 27 and 28 were also obtained as by-products.
The same two amino alcohols were obtained by ring-opening of the aziridine with acid and were each converted
into Q1-free oxazolidinones having optical rotations which were similar in magnitude but opposite in sign.
Enantiopure cyclic vinylaziridines 1 are potentially useful
relay compounds for the synthesis of a range of 1,2,3,4-tetra-
substituted cyclic amine derivatives of defined configuration
and (n ϩ 1)-azabicyclo[n.1.0] derivatives 2 by vinylaziridine–
pyrroline rearrangement.1 Because of the dearth of methods for
stereoselective aziridination,2,3 the most direct route to these
compounds 1 from the corresponding dienes (Scheme 1) has not
aziridinates e.g. butadiene or styrene highly diastereoselectively
in the presence of titanium() tert-butoxide (TTB) via a
transition state (TS#) geometry believed to resemble that in 7
(Scheme 3).5
endo-Overlap of the conjugated double bond in butadiene/
styrene with Q1 leads to cis-1,2-disubstituted aziridines 8a or 9a
as the kinetically-formed products: these then spontaneously
N-invert to the more stable trans-1,2-disubstituted 8b or 9b.
The value of these aziridines lies in their potential for conver-
sion to Q1-free chirons by aziridine ring-opening and Q1–N
bond cleavage. Thus the styrene-derived aziridine 9b has been
converted into either of the Boc-protected 1,2-diamines 10 and
enant. 10 (Scheme 4).6
The high diastereoselectivity obtained in the aziridination of
butadiene using Q1NHOAc 6 in the presence of TTB encour-
aged us to examine its use in aziridination of cyclic dienes.
Scheme 1
been explored. Consequently, presently available methods for
synthesis of enantiopure 1 start with enantiopure dienes
(substrate-controlled diastereoselectivity) and are therefore less
general.4
Results
Aziridination of cyclopentadiene
3-Acetoxyaminoquinazolinones
3
(QNHOAc) convert
Since the endo-overlap in TS# 7 requires an s-cis conformation
for the diene, the enforced s-cis diene conformation present in
cyclic dienes should make them reactive towards aziridination
with QNHOAc. Reactions of cyclopentadiene with three
QNHOAc compounds were first examined. With Q2NHOAc
11, aziridine 12 (42%) was obtained as a crystalline solid: the
presence of hexamethyldisilazane (HMDS) in this reaction
scavenges acetic acid and raises the yield.7 Similarly, the use of
Q3NHOAc 13 yielded the corresponding aziridine 14 (55%)
(Scheme 5): the greater stability of Q3NHOAc 13 often leads to
superior yields of aziridination products.8
alkenes into aziridines in a reaction which resembles the con-
version of alkenes into epoxides by peroxyacetic acid 4
(Scheme 2).2 In both cases, 3-membered ring formation takes
Reaction of cyclopentadiene with Q1NHOAc 6 in the pres-
ence of TTB and crystallisation of the crude product from
diethyl ether gave aziridine 16a (25%) (Scheme 6). Although the
yield of aziridine 16a is low, it is isolable without the need for
chromatography because it constitutes the major part of the
recovered product: the fate of the other Q1NHOAc 6-derived
product(s) is unknown. An X-ray crystal structure deter-
mination of 16a9 showed that the relative configuration was
in agreement with the TS# model 15 (cf. 7 for butadiene).
Unexpectedly, this crystal structure also showed that the quin-
azolinone and cyclopentene ring residue were cis in the azirid-
ine: the Q-substituted nitrogen usually undergoes N-inversion
Scheme 2
place stereospecifically with retention of alkene configuration
in the product. However, one advantage in the use of QNHOAc
3 is that high or complete diastereoselectivity is possible using
prochiral alkenes when the R group is chiral (R*) (reagent-
controlled diastereoselectivity).
Thus Q1NHOAc 6, prepared in situ by N-acetoxylation
of the (S)-tert-leucine-derived 5 using lead tetraacetate (LTA),
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This journal is © The Royal Society of Chemistry 2001
DOI: 10.1039/b102592a

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Scheme 3 Reagents and conditions: i, LTA, CH2Cl2, Ϫ20 ЊC; ii, Ti(OBut)4; iii, butadiene or styrene.
present as their exo-N-invertomers but in the light of the
unexpected stability of endo-N-invertomer 16a, samples of each
were heated in deuteriochloroform solution for 1 h at 60 ЊC: no
changes in their NMR spectra were observed. A sample of
aziridine 12, moreover, remained unchanged on heating briefly
to 200 ЊC so it can be concluded that N-inversion from
endo→exo in these aziridines had already occurred in the
aziridination. This conclusion was supported by the chemical
shifts of the olefinic protons (δ 6.06 and 6.21 for 12, δ 6.01
and 6.11 for 14) which resemble closely those in the exo-N-
invertomer 16b (see Scheme 6).
Scheme 4
In aziridine 16a, therefore, for reasons as yet not clear, the
barrier to N-inversion, is significantly higher than in 12 and 14
and endo- and exo-N-invertomers are of comparable stability.
The reaction of aziridine 12 with methylcuprate was briefly
investigated: using methylmagnesium bromide in the presence
of copper() bromide, a mixture of products (71%) (Scheme 7)
was obtained which could not be separated. Treatment of the
mixture with lead tetraacetate (LTA) gave two imines 18 and 19
(68%) in a 1 : 1 ratio whose separation was carried out by
Kieselgel chromatography.
Scheme 5
The presence of two olefinic protons having very similar
multiplicity and coupling constants in imines 18 and 19
suggested that the constitution of each was the same. Their
assignments as different N-invertomers were supported by the
downfield shift of the olefinic proton adjacent to the imine in
the NMR spectrum of 18 and the complementary downfield
shift of the methylene protons in 19 brought about in each case
by the presence of the neighbouring Q group. Support for these
structure assignments to imines 18 and 19 came from their
interconversion on heating at ∼100 ЊC or even on standing at
room temperature over several months.
It appears, therefore, that the mechanism of the cuprate
addition is predominantly SN2Ј but is probably not very
diastereoselective.
Scheme 6
at temperatures <Ϫ20 ЊC but in this case the barrier is raised
sufficiently for the first-formed N-invertomer 16a to be
isolated.6
Aziridination of cyclohexa-1,3-diene
Reaction of cyclohexa-1,3-diene with Q2NHOAc 11 and with
Q3NHOAc 13 in dichloromethane gave the corresponding
aziridines 20 (43%) and 21 (59%) (Scheme 8). An X-ray crystal
structure determination† of aziridine 21 (Fig. 1) confirmed the
expected exo-orientation of the Q3 group. A sample of aziridine
20 was briefly heated to 200 ЊC and its NMR spectrum
was found to be unchanged: the Q2 group of this aziridine,
therefore, can also be assumed to have an exo-orientation.
When aziridine 16a was dissolved in deuteriochloroform and
warmed in an NMR tube for 30 min at 60 ЊC, signals from the
exo-N-invertomer 16b appeared in the NMR spectrum and a
1 : 1 equilibrium ratio of N-invertomers was established which
was unchanged on further heating. The endo→exo inversion
of Q1 is accompanied by a downfield shift for the olefinic
protons (see Scheme 6).
Aziridination of cyclopentadiene with Q1NHOAc 6 in the
absence of TTB gave an unseparated mixture of products
whose NMR spectrum suggested the presence of 16a and its
diastereoisomer.
† CCDC reference number 160871. See http://www.rsc.org/suppdata/
p1/b1/b102592a/ for crystallographic files in. cif or other electronic
format.
Aziridines 12 and 14 had been previously assumed to be
J. Chem. Soc., Perkin Trans. 1, 2001, 1518–1527
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Scheme 7 Reagents and conditions: i, MeMgBr, CuBr; ii, LTA, Ϫ20 ЊC.
When the reaction of cyclohexa-1,3-diene with Q1NHOAc 6
was carried out in acetonitrile as solvent, aziridine 23 was
obtained in high diastereopurity although in lower yield (38%)
(Scheme 9b) together with dienylamine 24 (7%) and two other
products. After separation using Kieselgel chromatography,
these two products were identified by NMR spectroscopy as
cis-(Q1)-amino alcohols 27 and 28. In the NMR spectrum of
each compound there was a coupling of ∼3 Hz between the
protons on adjacent carbons bearing Q1NH and OH groups
suggesting that these two protons are either both equatorial or
equatorial/axial. Since it is likely that the Q1NH group is
equatorial in both compounds, the OH group will be pseudo-
axial and hence the two groups are cis. Confirmation of these
assignments came from conversion of each of these (Q1)-amino
alcohols to the corresponding Q1-free oxazolidinone enanti-
omers (see below).
Scheme 8 Reagents: i, cyclohexa-1,3-diene, HMDS; ii, cyclohexa-1,3-
diene
Higher yields of (Q1)-amino alcohols 27 and 28 were
obtained by reaction of aziridine 23 (dr 5 : 1) with toluene-p-
sulfonic acid in aqueous acetonitrile. After chromatography
on deactivated silica, 27 and 28 were isolated in 49 and 13%
yields respectively (Scheme 11). An additional product isolated
in this reaction was tentatively assigned the cyclic ether
structure 29: this cyclic ether was not formed from a mixture of
(Q1)-amino alcohols 27 and 28 on re-submitting it to the con-
ditions used for the reaction shown in Scheme 11.
Some of the corresponding (Q)-amino alcohol 30 was also
obtained, together with aziridine 20 and quinazolin-4(3H)-one
31 when cyclohexa-1,3-diene and Q2NHOAc 11 were reacted
together in acetonitrile (Scheme 9c).
Aziridination of cyclohepta-1,3-diene and cycloheptatriene
Reaction of Q2NHOAc 11 with cyclohepta-1,3-diene gave a
crystalline aziridine 32 which was isolated in 36% yield without
the need for chromatography. The corresponding reaction of
Q1NHOAc 6–TTB with cyclohepta-1,3-diene gave a crude
product, the major part of which was aziridine 33 (cf. aziridin-
ation of cyclopentadiene) and which crystallised directly from
ethyl acetate–light petroleum in 29% yield.
Fig. 1 Molecular structure of 21, showing the atom label scheme and
30% displacement probability ellipsoids. Hydrogen atoms are shown as
spheres of arbitrary radius.
An X-ray structure determination‡ of this aziridine (Fig. 2)
showed that the relative configuration was the same as that
obtained for aziridine 16a but that the Q1 group is exo.
Aziridine 34 was obtained as a crystalline solid from the
reaction of Q2NHOAc 11 and cycloheptatriene after chrom-
atography: the other isolated product was the quinazolin-
4(3H)-one 31 (Scheme 12b).
A
minor product isolated from the aziridination of
cyclohexa-1,3-diene with Q3NHOAc 13 was identified as the
dienylamine 22 (5%).
Reaction of cyclohexa-1,3-diene with Q1NHOAc 6 in the
presence of TTB gave a mixture of aziridine 23, dienylamine 24
and tert-butoxyaminoquinazolinone 255 (Scheme 9a).
Aziridine 23 was obtained as a mixture of diastereoisomers
in a ratio which varied between 10 : 1 and 4 : 1 in different
experiments. The major diastereoisomer was isolated as a
colourless solid after crystallisation from ether–light petroleum
but with considerable loss in yield. Proof of the stereostructure
and the mechanism of formation of dienylamine 24 (and 22,
Scheme 8) will be discussed elsewhere but in the reaction shown
in Scheme 9a, dienylamine 24 was not separated from tert-
butoxyaminoquinazolinone 25. Neither were the diastereo-
isomers of aziridine 23 separated by chromatography but their
diastereoisomeric relationship was confirmed by the Swern
oxidation–sodium borohydride reduction cycle in Scheme 10: a
sample diastereomeric ratio (dr) 5 : 1 was converted to a single
ketone 26 and then back to a sample of aziridine 23 of dr 3 : 2
showing that the two are epimeric at the aziridine ring chiral
centres.
Discussion
Since aziridines 16a and 33 derived from cyclopentadiene and
cyclohepta-1,3-diene respectively both show the same relative
and absolute configuration it is likely that the major diastereo-
isomer from aziridination of cyclohexadiene is also formed
with the same sense of diastereoselectivity.
Formation of (Q1)-amino alcohols 27, 28 and 30 (Schemes 11
and 9a) by ring-opening of the corresponding aziridines 23 and
21 with retention of configuration is suggestive of the involve-
ment of the Q group in the reaction. Previously, ring-opening
‡ CCDC reference number 160872. See http://www.rsc.org/suppdata/
p1/b1/b102592a/ for crystallographic files in .cif or other electronic
format.
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Scheme 9
Scheme 10 Reagents: i, Swern oxidation; ii, NaBH4, EtOH.
Scheme 12
23 with toluene-p-sulfonic acid in acetonitrile containing
18O-labelled water was interrupted after 45 minutes to allow
recovery of unreacted aziridine. Mass spectroscopy showed
incorporation as expected of 18O label into the alcohol product
but none into the recovered aziridine 23 which supports a
mechanism for quinazolinone participation analogous to that
proposed previously and illustrated for the reaction of the
major aziridine diastereoisomer in Scheme 13.
Scheme 11
Recovery of unlabelled aziridine 23 from this reaction serves
as a control to eliminate the possibility of exchange of the
(Q)C᎐O without its involvement in aziridine ring-opening.
᎐
Much of the 18O label in the amino alcohol products 27 and 28
was lost on silicon chromatography which supports its presence
in the quinazolinone carbonyl group. Scheme 13 also shows a
possible competitive reaction (b in 35) of the allyl cation with
the hydroxy group in the Q1 side-chain giving cyclic ether 29.
Interestingly, the diastereoisomer ratio (dr) of the recovered
aziridine in the experiment above was 10 : 1 and the dr of the
alcohol product (27 : 28) was ∼2 : 1 confirming that the minor
aziridine diastereoisomer was ring-opened approximately twice
as fast as the major one (and providing an expedient route
for purification of the major diastereoisomer 23). In the light
of these results it seems likely that the isolation of only the
major aziridine diastereoisomer 23 from aziridination of
cyclohexa-1,3-diene with Q1NHOAc 6–TTB results from faster
ring-opening of the minor diastereoisomer by a mechanism
resembling that shown in Scheme 13 but mediated by a
titanium-containing species instead of by acid.
Fig. 2 Molecular structure of 33, showing the atom label scheme and
30% displacement probability ellipsoids. Hydrogen atoms are shown as
spheres of arbitrary radius.
of aziridine 8b to the corresponding (Q1)-amino alcohol with
aqueous acetic acid was shown to involve participation of the
Q1 carbonyl oxygen.6
Conversion of (Q1)-amino alcohols 27 and 28 into Q1-free chirons
One of the objectives of this work was to use the products from
aziridination of dienes with enantiopure QNHOAc reagents
Reaction of a 4 : 1 mixture of aziridine diastereoisomers
J. Chem. Soc., Perkin Trans. 1, 2001, 1518–1527
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Scheme 13
to prepare Q-free aziridine ring-opened enantiopure products
containing two or more chiral centres (chirons).
inated highly diastereoselectively by Q1NHOAc 6 and TTB in
dichloromethane and the crystalline products were isolated
without the need for chromatography. Cyclohexa-1,3-diene is
aziridinated highly diastereoselectively by Q1NHOAc 6 and
TTB in acetonitrile and the product 23 is separated by chrom-
atography from cis-Q1-amino alcohols 27 and 28 formed as
by-products.
In a model reaction, Q3-amino alcohol 30 was heated in THF
at reflux with sodium hydride and 1,1Ј-carbonyldiimidazole for
3 h. Chromatography of the crude product gave oxazolidinone
36 (53%) together with unchanged starting material 30 (35%)
(Scheme 14).
These enantiopure aziridines could provide a useful source
of chirons since Q1NH2 5, the precursor of Q1NHOAc 6, is
available from tert-leucine in 43% yield (5 steps) without the
need for chromatography. Thus the two (Q1)-amino alcohols
27 and 28 have been converted into enantiomeric Q1-free
oxazolidinones 39 and enant. 39.
Experimental
For details of instrumentation and other experimental details
see refs. 5 and 6.
General procedure A for aziridination of dienes using Q2NHOAc
11 and Q3NHOAc 13
Dry dichloromethane (1 cm3 for each 0.1 g QNH2) was added
to a round-bottom flask suspended in a dry ice–acetone bath at
Ϫ12 ЊC and magnetically stirred. Lead() acetate (LTA; 1.05
mol equiv.) was added to the flask in one portion. When the
LTA had dissolved, the temperature of the bath was lowered to
Ϫ20 ЊC and the appropriate QNH2 (1.0 mol equiv.) added in
small portions over 10–15 min at this bath temperature, stirring
throughout. The temperature of the bath was allowed to rise to
Ϫ10 ЊC and the solution was filtered into a flask maintained at
Ϫ10 ЊC to remove the lead diacetate produced (on a small scale,
a Pasteur pipette and a cotton wool plug can be used). To this
filtered solution containing the QNHOAc, the diene (1.5–3 mol
equiv.) and (with Q2NH2 only) hexamethyldisilazane (3 mol
equiv.) were added, the cooling bath removed and the temper-
ature allowed to reach ambient (∼15 min) stirring throughout.
The reaction mixture was filtered, the filtrate was washed with
saturated aqueous sodium hydrogencarbonate solution and
water, dried and the solvent evaporated under reduced pressure.
Scheme 14 Reagents and conditions: i, 1,1Ј-carbonyldiimidazole, NaH,
THF, 3 h; ii, SmI2, ButOH, THF.
The similarity in rates of the corresponding reactions of
(Q1)-amino alcohols 27 and 28 with 1,1Ј-carbonyldiimidazole
giving oxazolidinones 37 and 38 respectively supports the
previously drawn conclusion that both have cis-substituted
cyclohexene rings.
Previously we had shown that the presence of a carbonyl
group on the exocyclic 3-aminoquinazolinone facilitated
reductive cleavage of the N–N bond and allowed aluminium
amalgam to be used.10 However, reduction of oxazolidinones 37
and 38 did not take place with aluminium amalgam but was
successful using samarium() iodide in the presence of tert-
butyl alcohol.10 Q1-free oxazolidinones 39 and enant. 39 were
separated from quinazolin-4(3H)-one Q1H 40 by chrom-
atography and found to have optical rotations which were
similar in magnitude but opposite in sign. Assignments of
absolute configuration to oxazolidinones 39 and enant. 39
are based on the assumption that aziridination of cyclohexa-
1,3-diene with Q1NHOAc 6 proceeds preferentially with the
same diastereosense as in aziridination of butadiene, cyclo-
pentadiene and cyclohepta-1,3-diene.
General procedure B for the aziridination of dienes using
Q1NHOAc 6 in the presence of titanium(IV) tert-butoxide5
Procedure A was followed up to and including addition
of Q1NH2 5 and the cold (Ϫ10 ЊC) solution filtered through a
cotton wool plug into a stirred solution of titanium() tert-
butoxide (2.1 equiv.) held at Ϫ20 ЊC. After stirring at this
temperature for 2 min the alkene (2 equiv.) was added and the
temperature of the reaction mixture allowed to rise to ambient
by removal of the cooling bath. Saturated sodium hydrogen-
carbonate solution was added to the vigorously stirred reaction
Summary
Cyclopentadiene and cyclohepta-1,3-diene were mono-azirid-
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mixture and a gelatinous precipitate formed immediately. The
solution was filtered through Celite and the organic layer of the
filtrate was separated, washed with brine, dried, and the solvent
evaporated under reduced pressure to give the crude product.
H-8(Q)], 7.70 [1H, ddd, J 8.2, 6.9, 1.0, H-7(Q)] and 8.17 [1H,
dd, J 8.2, 1.0, H-5(Q)]; δC 26.3 [C(CH3)3], 38.6 (C), 39.4 (CH2),
50.6, 57.0 (2 × C-N), 75.3 (C-OH), 121.9 [CCO(Q)], 126.2,
126.6, 126.8, 127.2, 132.8, 134.0 [4 × CH(Q) and HC᎐CH],
᎐
145.1 [CN᎐C(Q)] and 156.9, 158.2 [CN(Q) and CO(Q)]; m/z(%)
᎐
Aziridination of cyclopentadiene using Q2NHOAc 11
311 (Mϩ, 4) and 176 (100).
General aziridination procedure A was followed using 3-amino-
2-isopropylquinazolin-4(3H)-one11 (300 mg, 1.47 mmol), LTA
(687 mg, 1.55 mmol), HMDS (474 mg, 2.94 mmol) and
cyclopentadiene (194 mg/0.24 cm3, 2.94 mmol) in dichloro-
methane (6 cm3). Crystallisation of the crude product (457 mg)
from ethyl acetate–light petroleum gave aziridine 12 (159 mg,
42%) as a colourless solid, mp 126–128 ЊC (from ethyl acetate–
light petroleum) (Found: C, 71.5; H, 6.4; N, 15.7%. C16H17ON3
requires C, 71.8; H, 6.4; N, 15.7%); νmax/cmϪ1 1670s, 1470m and
1380s; δH 1.40 (3H, d, J 6.6, CH3CHCH3), 1.42 (3H, d, J 6.6,
CH3CHCH3), 2.76 (1H, dddd, J 18.9, 5.0, ∼2 and ∼2, CHH),
2.95 (1H, ddd, J 18.9, ∼2 and ∼2, CHH), 3.60 (1H, br d, J ∼5
and ∼5, azir. NCHCH2), 3.67 [1H, heptet, J 6.6, CH(CH3)2],
Thermal equilibration of endo-aziridine 16a and exo-aziridine
16b
endo-Aziridine 16a (50 mg, 0.16 mmol) was heated in CDCl3 at
60 ЊC for 30 min. On cooling, the NMR spectrum showed, in
addition to the signals above belonging to endo-aziridine 16a,
those assignable to exo-aziridine 16b at δH 1.02 [9H, s, C(CH3)3],
2.74 (1H, dddd, J 18.8, ∼5, ∼2, ∼2, CHH), 2.99 (1H, ddd, J 18.8,
∼5, ∼2, CHH), 3.63 (1H, br d, J ∼6, azir. NCHC᎐C), 3.84 (1H,
᎐
d, J 10.4, CHOH), 3.99 (1H, br dd, J ∼5, ∼5, azir. NCHCH2),
5.01 (1H, d, J 10.4, CHOH), 6.07 (1H, m, CH᎐CH), 6.14 (1H,
᎐
struct. m, CH᎐CH), 8.21 [1H, dd, J 8.2, 1.0, H-5(Q)]; δ 25.9
᎐
C
[C(CH3)3], 32.5 (CH2), 38.1 (C), 51.2, 56.6 (2 × C–N), 75.0
(C–OH), 121.5 [CCO(Q)], 125.8, 126.4, 127.0 [3 × CH(Q)],
3.79 (1H, br d, J ∼5, azir. NCHC᎐C), 6.3–6.9 (1H, struct. m,
᎐
CH᎐CH), 6.21 (1H, dddd, J 5.6, ∼2, ∼2, ∼2, CH᎐CH), 7.40
129.0, 133.6, 139.2 [HC᎐CH and CH(Q)], 144.8 [CN᎐C(Q)] and
157.9, 159.6 [CN(Q), CO(Q)].
᎐
᎐
᎐
᎐
[1H, ddd, J 8.2, 6.9, 1.5, H-6(Q)], 7.59–7.72 [2H, struct. m, H-7,
H-8 (Q)] and 8.19 [1H, dd, J 8.2, 1.0, H-5(Q)]; δC 21.6, 32.7
(2 × CH3), 36.7 (CH2), 49.5 [CH(CH3)2], 52.5, 58.1 (2 × C–N),
121.8 [CCO(Q)], 126.4, 126.5, 127.3, 128.4, 133.9, 138.5
Reaction of aziridine 12 with cuprate
A flame dried 2-necked flask equipped with a septum cap and
3-way tap was flushed with nitrogen, degassed, flushed with
argon, degassed and filled with argon. Using syringes, a suspen-
sion of copper() bromide–dimethyl sulfide (58 mg, 0.28 mmol)
(prepared by the literature procedure12) and dissolved in THF
(1 cm3) was added followed by methylmagnesium bromide (101
mg/0.1 cm3, 0.84 mmol) dissolved in THF (1 cm3). Aziridine
16a (75 mg, 0.28 mmol), dissolved in THF (1 cm3), was then
added dropwise via a syringe to the solution which was stirred
at ambient temperature for 1 h. After addition of ethyl acetate
(5 cm3) the solution was washed with saturated aqueous sodium
hydrogencarbonate (5 cm3) and the solvent separated, dried and
evaporated. Column chromatography (3 : 1 light petroleum–
ethyl acetate) of the crude product (80 mg) gave a mixture of
(Q2)amines 17 (58 mg, 71%) as a yellow oil, Rf 0.28.
[4 × CH(Q) and HC᎐CH], 146.6 [CN᎐C(Q)] and 160.4, 161.8
᎐
᎐
[CN(Q), CO(Q)]; m/z(%) 267 (Mϩ,10), 189 (12), 188 (43), 187
(27) and 173 (100).
Aziridination of cyclopentadiene using Q3 NHOAc 13
3-Amino-2-trifluoromethylquinazolin-4(3H)-one (Q3NH2) was
prepared by the published route7 except that the crude
2-trifluoromethyl-3,1-benzoxazin-4-one was treated with
hydrazine in ethanol directly after removal of trifluoroacetic
anhydride. Following general procedure A, the foregoing
Q3NH2 (300 mg, 1.31 mmol), LTA (609 mg, 1.38 mmol) and
cyclopentadiene (173 mg/0.22 cm3, 2.62 mmol) were reacted in
dichloromethane (6 cm3). Crystallisation of the crude product
(309 mg) from ethyl acetate–light petroleum gave aziridine 14
(212 mg, 55%) as a colourless solid, mp 125–127 ЊC (from ethyl
acetate–light petroleum) (Found: Mϩ 293.0775. C14H10ON3F3
requires M 293.0775); νmax/cmϪ1 1665s, 1470m and 1390s; δH
2.70 (1H, dddd, J 18.8, 5.0, ∼2, ∼2, CHH), 2.85 (1H, ddd,
J 18.8, ∼2, ∼2, CHH), 4.04 (1H, br dd, J ∼5, ∼5, azir.
LTA oxidation of (Q2)amines 17
The above mixture of amines 17 (58 mg, 0.20 mmol) was dis-
solved in dichloromethane (1 cm3) at Ϫ20 ЊC and HMDS (72
mg, 0.45 mmol) was added. LTA (95 mg, 0.21 mmol) was added
in small portions over 10 min and the solution allowed to warm
to ambient temperature. Dichloromethane (10 cm3) was added
and the solution washed with saturated aqueous sodium hydro-
gencarbonate (5 cm3), the organic layer separated, dried and
evaporated to give the crude product as a yellow oil. Column
chromatography (2 : 1 light petroleum–ethyl acetate) gave
N(Q2)-imine 18 (18 mg, 33%) as a colourless oil, Rf 0.43
(Found: Mϩ 281.1529. C17H19ON3 requires M 281.1528);
νmax/cmϪ1 1780 m, 1675s, 1620s and 1595 m; δH 1.13 (3H, d,
J 6.9, CHCH3), 1.29 (3H, d, J ∼7, CHCH3), 1.30 (3H, d, J ∼7,
CHCH3), 2.08 (1H, dd, J 18.6, ∼2, CHH), 2.75 (1H, dd, J 18.6,
∼6, CHH), 3.02 (1H, struct. m, CHMe), 3.31 [1H, heptet, J 6.9,
NCHCH ), 4.28 (1H, br d, J ∼5, azir. NCHC᎐C), 6.01 (1H,
᎐
2
struct. m, CH᎐CH), 6.11 (1H, struct. m, CH᎐CH), 7.59 [1H,
᎐
᎐
ddd, J 8.2, ∼4, ∼4, H-6(Q)], 7.75–7.82 [2H, m, H-7, H-8(Q)] and
8.24 [1H, br d, J 8.2, H-5(Q)]; δC 38.6 (CH2), 49.1, 55.0 (2 ×
C–N), 123.3 [CCO(Q)], 127.0, 128.8, 129.0, 129.5, 134.9, 138.4
[4 × CH(Q) and HC᎐CH], 144.3 [CN᎐C(Q)] and 160.5, 170.2
᎐
᎐
[CN(Q), CO(Q)]; m/z(%) 293 (Mϩ, 7), 215 (100), 214 (70) and
213 (38).
Aziridination of cyclopentadiene using Q1NHOAc 6 and TTB
General aziridination procedure B was followed in this reaction
using Q1NH2 5 (200 mg, 0.80 mmol), LTA (376 mg, 8.50 mmol),
TTB (576 mg, 1.71 mmol) and cyclopentadiene (105 mg/131
cm3, 1.59 mmol) in dichloromethane (5 cm3). Crystallisation of
the crude product from diethyl ether gave endo-aziridine 16a (60
mg, 25%) as a colourless solid, mp 126–128 ЊC (from diethyl
ether–light petroleum). [α]D = ϩ1.3 (c = 1.1, EtOH) (Found: C,
69.1; H, 6.8; N, 13.4%. C18H21O2N3 requires C, 69.4; H, 6.8; N,
13.4%); νmax/cmϪ1 1675s, 1610m and 1590s; δH 1.00 [9H, s,
C(CH3)3], 2.43 (1H, ddd, J 20.1, ∼5, ∼2, CHH), 2.63 (1H, dddd,
J 20.1, 5.5, ∼2, ∼2, CHH), 3.58 (1H, br dd, J ∼5, ∼5, azir.
NCHCH2), 3.85 (1H, d, J 10.6, CHOH), 4.19–4.22 (1H, m,
CH(CH ) ], 6.55 (1H, dd, J 5.7, 2.2, CH᎐CHC᎐N), 7.01 (1H,
᎐
᎐
3
2
br dd, J ∼6, ∼2, N᎐CCH᎐CH), 7.43 [1H, ddd, J ∼8, ∼6, ∼3,
᎐
᎐
H-6(Q)], 7.69–7.73 [2H, m, H-7 and H-8(Q)] and 8.29 [1H, dd,
J 8.2, 1.0, H-5(Q)]; m/z (%) 281 (Mϩ, 78), 266 (100), 187 (81)
and 173 (73).
Further elution gave N(Q2)-imine 19 (19 mg, 35%) as a
colourless oil, Rf 0.36 (Found: Mϩ 281.1529. C17H19ON3
requires M 281.1528); νmax/cmϪ1 1780 m, 1675s, 1620s and 1595
m; δH 1.24 (3H, d, J 6.9, CHCH3), 1.28 (6H, d, J ∼7, 2 ×
CHCH3), 2.55 (1H, dd, J 18.1, ∼2, CHH), 3.14 (1H, struct. m,
CHMe), 3.23 (1H, dd, J 18.1, 6.9, CHH), 3.36 [1H, heptet,
azir. NCHC᎐C), 4.75 (1H, d, J 10.6, CHOH), 5.35–5.41 (1H,
᎐
m, CH᎐CH), 5.65 (1H, dddd, J 5.7, ∼2, ∼2, ∼2, CH᎐CH), 7.42
[1H, ddd, J 8.2, 6.9, 1.0, H-6(Q)], 7.62 [1H, dd, J 8.2, 1.0,
J 6.6, CH(CH ) ], 5.97 (1H, dd, J 5.7, 1.5, CH᎐CHC᎐N), 6.92
᎐ ᎐
3 2
(1H, dd, J 5.7, 2.5, N᎐CCH᎐CH), 7.42 [1H, ddd, J 8.2, 6.9, 1.2,
᎐ ᎐
᎐
᎐
J. Chem. Soc., Perkin Trans. 1, 2001, 1518–1527
1523

View Article Online
H-6(Q)], 7.69–7.73 [2H, m, H-7 and H-8(Q)] and 8.26 [1H, d,
J 8.2, H-5(Q)]; m/z(%) 281 (Mϩ, 71), 266 (100), 188 (53), 187
(96) and 173 (91).
A sample of imine 18 which had been set aside for 18 months
was found to have partially interconverted with imine 19 (ratio
∼2 : 1 respectively).
[CN᎐C(Q)] and 162.4, 168.3 [CN(Q), CO(Q)]; m/z(%) 308
᎐
(MHϩ, 44), 307 (Mϩ, 42), 230 (100) and 229 (50).
Aziridination of cyclohexa-1,3-diene with Q1NHOAc 6–TTB
General aziridination procedure B was followed using Q1NH2 5
(500 mg, 2.01 mmol), LTA (942 mg, 2.12 mmol), TTB (1.42 g,
4.20 mmol) and cyclohexa-1,3-diene (320 mg/0.38 cm3, 4.00
mmol) in dichloromethane (11 cm3). After work up, column
chromatography (8 : 1 light petroleum–ethyl acetate) gave a
mixture of dienylamine 24 (37 mg, 6%) and tert-butoxyamino-
quinazolinone 25 (26 mg, 6%) as a colourless oil, Rf 0.17. For
dienylamine 24: [α]D = ϩ12.9 (c = 1.0, EtOH) (Found: Mϩ
325.1791. C19H23O2N3 requires M 325.1790); νmax/cmϪ1 3500m,
1675s, 1595s and 1470s; δH 0.96 [9H, s, (CH3)3], 2.37 (2H, m,
CH2), 3.61 (1H, d, J 10.4, CHOH), 3.96 (1H, ddd, J ∼12, ∼6,
∼6, CHNH), 5.13 (1H, d, J 10.4, CHOH), 5.37 (1H, d, J 5.9,
Aziridination of cyclohexa-1,3-diene with Q2NHOAc 11
General aziridination procedure A was followed in this reaction
using 3-amino-2-isopropylquinazolin-4(3H)-one11 (600 mg,
2.96 mmol), LTA (1.38 g, 3.11 mmol), HMDS (1.19 g, 7.40
mmol) and cyclohexa-1,3-diene (470 mg/0.55 cm3, 5.92 mmol)
in dichloromethane (12 cm3). Column chromatography of the
crude product (0.68 g) using 2 : 1 light petroleum–ethyl acetate
gave aziridine 20 (0.54 g, 60%) as a colourless solid, Rf 0.41, mp
93–95 ЊC (from light petroleum–ethyl acetate) (Found: MHϩ
282.1606. C17H20ON3 requires MHϩ 282.1607); νmax/cmϪ1 1660s
and 1570s; δH 1.32 (3H, d, J 6.6, CH3CHCH3), 1.35 (3H, d,
J 6.6, CH3CHCH3), 1.69 (1H, struct. m, CH2CHH), 2.13 (1H,
ddd, J ∼18, ∼6, ∼6, CHHCH2), 2.27 (1H, struct. m, incl. J 18.0,
CHHCH2), 2.61 (1H, dddd, J ∼15, ∼7, ∼2, ∼2, CH2CHH), 2.94
(1H, dd, J 7.9, 4.7, azir. NCHCH2), 3.36 (1H, dd, J 7.9, 2, azir.
NH), 5.58 (1H, br dd, J ∼9, ∼5, CH᎐CH), 5.92 (1H, m,
᎐
CH᎐CH), 6.05 (1H, m, CH᎐CH), 6.15 (1H, m, CH᎐CH), 7.48
᎐
᎐
᎐
[1H, ddd, J 8.2, 6.9, 1.0, H-6(Q)], 7.69 [1H, d, J 8.2, H-8(Q)],
7.78 [1H, ddd, J 8.2, 6.9, 1.0, H-7(Q)] and 8.23 [1H, dd, J 8.2,
1.0, H-5(Q)]; δC(75 MHz) 26.3 [(CH3)3], 28.3 (CH2), 38.3
[C(CH3)3], 52.0 (C-N), 75.2 (COH), 120.3 [CCO(Q)], 122.9,
NCHC᎐C), 3.64 [1H, heptet, J 6.6, CH(CH ) ], 6.03 (1H, ddd,
123.8, 126.3, 127.1, 127.2, 127.7, 128.2, 134.9 [2 × HC᎐CH and
᎐
᎐
3
2
J 8.7, ∼6, ∼2, CH᎐CH), 6.23 (1H, ddd, J 8.7, ∼6, ∼4, CH᎐CH),
4 × CH(Q)], 146.9 [CN᎐C(Q)] and 160.6, 161.8 [CN(Q),
᎐
᎐
᎐
7.42 [1H, ddd, J 8.1, 6.3, 1.2, H-6(Q)], 7.60–7.70 [2H, m, H-7
and H-8(Q)] and 8.20 [1H, dd, J 8.1, 1.2, H-5(Q)]; δC 20.4
(CH2), 22.7 (CH3), 23.1 (CH2), 23.4 (CH3), 33.3 [CH(CH3)2],
CO(Q)]; m/z(%) 326 (MHϩ, 52), 248 (48), 233 (100) and 215
(36). 3-tert-Butoxyaminoquinazolinone 25 was identified by
comparison of signals at δ 0.97 and 1.36 (lit.5 0.91 and 1.27) in
its 1H NMR spectrum.
45.8, 50.8 (2 × C–N), 123.3, 123.6 [HC᎐CH, CCO(Q)], 128.3,
᎐
129.2, 135.5, 135.7 [4 × CH(Q)], 148.4 [CN᎐C(Q)] and 162.4,
Further elution gave aziridine 23 (291 mg, 54%) as a colour-
less gum, Rf 0.11, which crystallised from diethyl ether–light
petroleum, mp 106–107 ЊC. [α]D = ϩ16.9 (c = 2.5, EtOH)
(Found: Mϩ 325.1790. C19H23O2N3 requires M 325.1790);
νmax/cmϪ1 3480m, 1660s and 1580s; δH 1.02 [9H, s, C(CH3)3],
1.65 (1H, dddd, J 13.0, 12.5, 7.5, ∼3, CHHCH2), 2.15–2.20 (2H,
m, CH2), 2.66 (1H, dddd, J ∼13, ∼8, ∼2, ∼2, CHHCH2), 2.91
(1H, ddd, J 7.7, 4.7, 1.0, azir. NCHCH2), 3.57 (1H, br d, J 7.7,
᎐
163.7 [CN(Q), CO(Q)]; m/z(%) 282 (MHϩ, 100) and 189 (45).
Aziridination of cyclohexa-1,3-diene with Q3NHOAc 13
General aziridination procedure A was followed using 3-amino-
2-trifluoromethylquinazolin-4(3H)-one (see above; 200 mg,
0.87 mmol), LTA (406 mg, 0.92 mmol) and cyclohexa-1,3-diene
(140 mg/0.16 cm3, 1.75 mmol) in dichloromethane (4 cm3).
Crystallisation of the crude product (246 mg) from ethyl
acetate–light petroleum gave aziridine 21 (170 mg) as a white
solid, mp 103–105 ЊC (Found: C, 58.6; H, 3.85; N, 13.7%.
C15H13ON3F3 requires C, 58.6; H, 3.9; N, 13.7%); νmax/cmϪ1
1690s, 1610s, 1470m and 1380s; δH 1.43 (1H, dddd, J 14.0, 10.0,
6.7, ∼2, CH2CHH), 1.91 (1H, ddd, J 17.5, ∼7, ∼7, CHHCH2),
2.05 (1H, struct. m, incl. J 17.5, CHHCH2), 2.23 (1H, dddd,
J 14.0, 7.8, ∼2, ∼2, CH2CHH), 3.59 (1H, dd, J 7.5, 4.8, azir.
azir. NCHC᎐C), 3.82 (1H, d, J 10.4, CHOH), 5.04 (1H, d,
᎐
J 10.4, CHOH), 6.03 (1H, m, CH᎐CH), 6.22 (1H, m,
᎐
CH᎐CH), 7.44 [1H, ddd, J 8.2, 6.9, 1.0, H-6(Q)], 7.64 [1H, d,
᎐
J 8.0, H-8(Q)], 7.70 [1H, ddd, J 8.0, 6.9, 1.2, H-7(Q)] and 8.21
[1H, dd, J 8.2, 1.2, H-5(Q)]; δC 18.4, 21.6 (2 × CH2), 26.3
[C(CH3)3], 38.5 [C(CH3)3], 45.5, 48.7 (2 × C-N), 75.1 (COH),
120.7, 121.8 [CCO(Q), HC᎐CH], 126.3, 126.7, 127.0, 127.4,
᎐
134.1 [4 × CH(Q), HC᎐CH], 145.0 [CN᎐C(Q)] and 158.0, 159.9
᎐
᎐
[CN(Q), CO(Q)]; m/z(%) 325 (Mϩ, 48), 268 (62), 240 (100), 231
(94) and 215 (80). The NMR spectrum of aziridine 23 before
crystallisation showed the presence of another diastereoisomer
with (observable signals)—δH 0.99 [9H, s, C(CH3)3], 2.47 (1H,
struct. m, CHH), 3.85 (1H, d, J 10.3, CHOH) and 5.02 (1H, d,
J 10.3, CHOH). The ratio of aziridine diastereoisomers ranged
from 10 : 1–4 : 1 in different experiments from comparison of
signals at δ 2.66 and 2.47 in the 1H NMR spectrum of the crude
reaction product.
NCHCH ), 3.82 (1H, d, J 7.5, azir. NCHC᎐C), 5.82 (1H, m,
᎐
2
CH᎐CH), 5.97 (1H, ddd, J 9.5, ∼5, ∼3, CH᎐CH), 7.41 [1H,
᎐
᎐
ddd, J 8.2, 4.9, 3.2, H-6(Q)], 7.60–7.69 [2H, m, H-7 and H-8(Q)]
and 8.04 [1H, dd, J 8.0, 1.0, H-5(Q)]; δC 18.6, 21.2 (2 × CH2),
38.5, 44.1 (2 × C–N), 122.1, 123.3 [CCO(Q), HC᎐CH], 127.2,
᎐
128.6, 129.3 [3 × CH(Q)], 133.1, 134.9 [CH(Q), HC᎐CH], 144.3
᎐
[CN᎐C(Q)], 160.9, 162.3 [CN(Q), CO(Q)]–(CF not visible);
᎐
3
m/z(%) 308 (MHϩ, 100), 230 (24), 215 (46).
Kieselgel chromatography (2 : 1 light petroleum–ethyl
acetate) of the residue after evaporation of the filtrate above
gave more aziridine 21 (13 mg, total 68%), Rf 0.41.
Swern oxidation of aziridine 23
A crystal suitable for X-ray crystallography was prepared by
crystallisation from light petroleum.
DMSO (73 mg/0.07 cm3, 0.93 mmol) was added to dichloro-
methane (1 cm3) pre-cooled to Ϫ78 ЊC followed by dropwise
addition of oxalyl chloride (60 mg, 0.46 mmol). After stirring
for 10 min, aziridine 23 (dr 5 : 1) (100 mg, 0.31 mmol) was
added to a solution of dichloromethane (1 cm3) and the mixture
stirred at Ϫ78 ЊC for 2 h. Triethylamine (219 mg, 2.17 mmol)
was added and the solution warmed to ambient temperature.
After addition of saturated sodium hydrogencarbonate solu-
tion (10 cm3) and extraction with dichloromethane (15 cm3),
drying of the organic layer and evaporation gave the crude
product as a yellow oil. Column chromatography (3 : 1 light
petroleum–ethyl acetate) gave ketone 26 (51 mg, 51%) as a
colourless oil, Rf 0.50 (Found: MHϩ 324.1712. C19H22O2N3
requires MHϩ 324.1712); δH 1.32 [9H, s, (CH3)3], 1.46–1.61
Further elution gave the dienylamine 22 (13 mg, 5%) as a
clear colourless oil, Rf 0.33 (Found: MHϩ 308.1011. C15H13-
ON3F3 requires MHϩ 308.1011); νmax/cmϪ1 1695m and 1610m;
δH 2.31 (1H, dddd, J ∼18, ∼8, ∼4, ∼2, CHH), 2.45 (1H, dddd,
J 18.0, 5.0, 5.0, ∼1.5, CHH), 3.93 (1H, m, incl. J ∼11, CHNH),
5.43 (1H, d, J 11, NH), 5.83 (1H, dd, J 9.6, 5.1, CH᎐CH), 5.90
᎐
(1H, dddd, J 10.5, 5.9, ∼4, ∼2, CH᎐CH), 6.03 (1H, m,
᎐
CH᎐CH), 6.13 (1H, dddd, J 9.6, 5.0, ∼1, ∼1, CH᎐CH), 7.64
᎐
᎐
[1H, ddd, J 8.0, ∼4, ∼4, H-6(Q)], 7.81–7.86 [2H, m, H-7 and H-
8(Q)] and 8.31 [1H, dd, J 8.2, 1.0, H-5(Q)]; δC(75 MHz) 28.3
(CH2), 54.2 (CNH), 122.5 [CCO(Q)], 123.8, 124.0, 126.1, 127.3,
127.6, 129.2, 129.6, 135.5 [4 × CH(Q) and 2 × HC᎐CH], 145.3
᎐
1524
J. Chem. Soc., Perkin Trans. 1, 2001, 1518–1527

View Article Online
(1H), 2.00–2.08 (2H) and 2.30–2.39 (1H) (3 × m, CH2CH2),
3.69 (1H, ddd, J 7.8, 4.8, 1.5, azir. CHCH2), 3.97 (1H, ddd,
dd, J 8.2, 1.0, H-8(Q)], 7.71 [1H, ddd, J 8.2, 6.9, 1.0, H-7(Q)]
and 8.21 [1H, dd, J 8.0 1.0, H-5(Q)]; δC 23.1 (CH2), 26.0
[C(CH3)3], 28.8, 31.7 (2 × CH2), 38.4 [C(CH3)3], 52.4, 54.4
(2 × C-N), 74.5 (COH), 121.5 [CCO(Q)], 121.6, 126.3, 126.7,
J 7.8, ∼2, ∼2, azir. CHC᎐C), 5.88 (1H, m, CH᎐CH), 6.06 (1H,
᎐
᎐
m, CH᎐CH), 7.48 [1H, ddd, J 8.0, 6.6, 1.1, H-6(Q)], 7.66 [1H,
᎐
dd, J 8.0, 1.1, H-8(Q)], 7.75 [1H, ddd, J 8.0, 6.6, 1.3, H-7(Q)]
and 8.21 [1H, dd, J 8.0, 1.3, H-5(Q)]; δC 18.2 (CH3)3, 21.4, 27.1
(2 × CH2), 40.4, 44.9, 45.0 [2 × C-N, C(CH3)3], 122.5, 122.8
126.9, 133.8 [4 × CH(Q), HC᎐CH], 139.5 (HC᎐CH), 144.7
᎐ ᎐
[CN᎐C(Q)] and 157.6, 159.5 [CN(Q), CO(Q)]; m/z(%) 340
᎐
(MHϩ, 100), 307 (78), 289 (39) and 215 (32). A crystal suitable
for X-ray structure determination was obtained from methanol.
[HC᎐CH, CCO(Q)], 126.7, 127.6, 128.0, 132.9, 134.5 [4 ×
᎐
CH(Q), HC᎐CH], 146.2 [CN᎐C(Q)], 153.2, 160.3 [CN(Q),
᎐
᎐
Aziridination of cycloheptatriene with Q2NHOAc 11
CO(Q)] and 204.9 (C᎐O); m/z(%) 324 (MHϩ, 31), 246 (22), 231
᎐
(100) and 215 (44).
Further elution gave unreacted aziridine 23 (19 mg, 19%
recovered), Rf 0.23.
General aziridination procedure A was followed in this reaction
using 3-amino-2-isopropylquinazolin-4(3H)-one11 (300 mg,
1.48 mmol), LTA (687 mg, 1.55 mmol), HMDS (597 mg, 3.69
mmol) and cycloheptatriene (272 mg, 0.29 cm3, 2.96 mmol) in
dichloromethane (6 cm3) to give the crude product as a yellow
oil. Column chromatography (4 : 1 light petroleum–ethyl
acetate) gave aziridine 34 (193 mg, 45%), Rf 0.42, as a colourless
oil which crystallised from ethyl acetate–light petroleum, mp
89–90 ЊC (Found: MHϩ 294.1606. C18H20ON3 requires MHϩ
294.1606); νmax/cmϪ1 1660s and 1590s; δH 1.42 [6H, d, J 6.6,
(CH3)2], 2.84 (1H, m, CHH), 2.99 (1H, dd, J 8.0, 3.7, azir.
Sodium borohydride reduction of ketone 26
Ketone 26 (50 mg, 0.16 mmol) was stirred in ethanol (5 cm3)
with sodium borohydride (3 mg, 0.05 mmol) at ambient tem-
perature for 4 h. Addition of saturated sodium hydrogen-
carbonate solution (10 cm3) and extraction with ethyl acetate
(10 cm3), drying and then evaporation of the organic layer gave
the crude product as a colourless oil. Column chromatography
(3 : 1 light petroleum–ethyl acetate) gave ketone 26 (14 mg, 28%
recovered) as a colourless oil, Rf 0.51.
CHC᎐C), 3.03 (1H, ddd, J 15.6, ∼5, ∼5, CHH), 3.34 (1H, ddd,
᎐
J ∼8, ∼7, 5.0, azir. CHCH2), 3.63 [1H, heptet, J 6.6, CH(CH3)2],
Further elution gave aziridine 23 (18 mg, 36%) as a colourless
oil, Rf 0.30, in which the two aziridine diastereoisomers 23 were
now present in a 3 : 2 ratio from comparison of signals at δ 3.57
and 3.85 in its 1H NMR spectrum.
5.89–6.08 (3H, struct. m, 3 × C᎐CH), 6.47 (1H, dd, J 11.0, 3.7,
᎐
C᎐CH), 7.39 [1H, ddd, J 8.2, 6.6, 1.2, H-6(Q)], 7.58–7.68 [2H,
᎐
m, H-7, H-8(Q)] and 8.17 [1H, dd, J 8.2, 1.0, H-5(Q)]; δC 21.1
[CH(CH3)2], 28.7 (CH2), 30.8 [CH(CH3)2], 48.9, 58.3 (2 × C-N),
121.2 [CCO(Q)], 126.1, 127.0, 127.7, 127.8, 130.6, 130.9
Aziridination of cyclohepta-1,3-diene with Q2NHOAc 11
[3 × CH(Q), 2 × HC᎐CH], 133.5 [CH(Q)], 146.1 [CN᎐C(Q)]
᎐
᎐
and 160.1, 161.1 [CN(Q), CO(Q)]; m/z(%) 294 (MHϩ, 100), 189
The reaction was carried out following general aziridination
procedure A using 3-amino-2-isopropylquinazolin-4(3H)-one11
(300 mg, 1.48 mmol), LTA (689 mg, 1.55 mmol), HMDS (597
mg, 3.70 mmol) and cyclohepta-1,3-diene (272 mg/0.30 cm3,
2.96 mmol) in dichloromethane (6 cm3). After work up the
crude product was obtained as an off-white solid which was
crystallised from ethyl acetate–light petroleum giving aziridine
32 (135 mg, 31%) as a white crystalline solid, mp 230–231 ЊC
(Found: C, 72.9; H, 7.0; N, 14.2%. C18H22ON3 requires C, 73.1;
H, 7.1; N, 14.2%); νmax/cmϪ1 1660s and 1585m; δH 1.40 (3H, d,
J 6.4, CH3CHCH3), 1.42 (3H, d, J 6.4, CH3CHCH3), 1.63–1.84
(2H, struct. m, 2 × CH), 2.04–2.19 (1H, m, 2 × CH), 2.27–2.42
(1H, m, CH), 2.51–2.64 (1H, m, CH), 2.94 (1H, br dd, J 8.0,
∼5, azir. CH), 3.18 (1H, ddd, J 8.0, ∼4, ∼4, azir. CH), 3.65 [1H,
heptet, J 6.4, CH(CH3)2], 5.95 (1H, ddd, J 11.4, 6.6, 3.2,
(39) and 173 (31).
Aziridination of cyclohexa-1,3-diene with Q2NHOAc 11 in
acetonitrile
A modification of general aziridination procedure A was
followed using 3-amino-2-isopropylquinazolin-4(3H)-one (200
mg, 0.98 mmol), LTA (458 mg, 1.04 mmol), HMDS (397 mg,
2.46 mmol) and cyclohexa-1,3-diene (158 mg/0.18 cm3, 1.97
mmol) in acetonitrile (4 cm3). After work up the crude product
was obtained as a yellow oil. Column chromatography (2 : 1
light petroleum–ethyl acetate) gave alcohol 30 (74 mg, 27%)
as a colourless oil, Rf 0.88 (Found: MHϩ 300.1712. C17H22O2N3
requires MHϩ 300.1712); νmax/cmϪ1 3420m, 3300m, 1660s,
1615m and 1590s; δH 1.35 (3H, d, J 6.9, CH3CHCH3), 1.41 (3H,
d, J 6.9, CH3CHCH3), 1.85 (1H, struct. m, CH), 2.05–2.37
(3H, m, CH2CHH), 2.85 (1H, dddd, J ∼10, ∼10, ∼3, ∼3,
CHNH), 3.64 [1H, heptet, J 6.9, CH(CH3)2], 3.96 (1H, br s,
CHOH), 4.83 (1H, br s, OH), 5.78–5.87 (2H, struct. m,
CH᎐CH), 6.13 (1H, br ddd, J 11.4, ∼5, ∼2.5, CH᎐CH), 7.39
᎐
᎐
[1H, ddd, J 8.2, 6.8, 1.0, H-6(Q)], 7.62 [1H, dd, J 8.2, 1.0,
H-8(Q)], 7.67 [1H, ddd, J 8.2, 6.8, 1.2, H-7(Q)] and 8.18 [1H,
dd, J 8.2, 1.2, H-5(Q)]; δC 21.4, 21.5 [CH(CH3)2], 23.7, 28.9
(2 × CH2), 31.1 [CH(CH3)2], 31.9 (CH2), 50.6, 54.7 (2 × C-N),
121.7 [CCO(Q)], 122.9, 126.4, 126.5, 127.3, 133.8, 138.1
CH᎐CH), 5.93 (1H, d, J 10, NH), 7.46 [1H, ddd, J 8.0, 6.6, 1.3,
᎐
H-6(Q)], 7.69–7.76 [2H, m, H-7, H-8(Q)] and 8.23 [1H, dd,
J 8.0, 1.0, H-5(Q)]; δC(CDCl3, 62.9 MHz) 20.5 (CH3CHCH3),
21.6 (CH2), 21.8 (CH3CHCH3), 26.0 (CH2), 30.8 [CH(CH3)2],
45.0 (C-N), 62.6 (C-OH), 119.8 [CCO(Q)], 126.5, 126.6, 127.4,
[4 × CH(Q), HC᎐CH], 146.6 [CN᎐C(Q)] and 160.5, 161.6
᎐
᎐
[CN(Q), CO(Q)]; m/z(%) 296 (MHϩ, 100).
Aziridination of cyclohepta-1,3-diene with Q1NHOAc 6–TTB
131.3, 134.5 [4 × CH(Q), HC᎐CH], 147.2 [CN᎐C(Q)] and
᎐
᎐
162.5, 163.4 [CN(Q), CO(Q)]; m/z(%) 300 (MHϩ, 100), 282 (39),
204 (22), 189 (75) and 188 (50).
General aziridination procedure B was followed in this reaction
using Q1NH2 5 (200 mg, 0.81 mmol), LTA (396 mg, 0.89 mmol),
TTB (576 mg, 1.69 mmol) and cyclohepta-1,3-diene (152 mg/
0.18 cm3, 2.96 mmol) in dichloromethane (5 cm3). Work up in
the normal way gave a light green solid which was crystallised
from ethyl acetate–light petroleum giving aziridine 33 (79 mg,
29%) as a colourless solid, mp 173–174 ЊC. [α]D = ϩ126.9
(c = 1.3, EtOH) (Found: MHϩ 340.2025. C20H26O2N3 requires
MHϩ 340.2026); νmax/cmϪ1 3490m, 1720s and 1580m; δH 1.02
[9H, s, C(CH3)3], 1.69–2.09 (4H, struct. m, 4 × CH), 2.30–2.45
(1H, m, CH), 2.77–2.88 (1H, m, CH), 2.90 (1H, dd, J 8.0, 4.8,
azir. CH), 3.37 (1H, br ddd, J ∼8, ∼5, ∼4, azir. CH), 3.77 (1H, d,
J 10.4, CHOH), 5.08 (1H, d, J 10.4, CHOH), 6.01 (1H, ddd,
Further elution gave aziridine 20 (43 mg, 15%), Rf 0.57,
as a colourless oil identical with that isolated previously and
2-isopropylquinazolin-4(3H)-one 31 (3 mg, 2%), Rf 0.22, as
a colourless solid identical with an authentic sample.11
Aziridination of cyclohexa-1,3-diene with Q1NHOAc 6–TTB in
acetonitrile
A modification of general aziridination procedure B was
followed using Q1NH2 5 (500 mg, 2.01 mmol), LTA (942 mg,
2.12 mmol), TTB (1.42 g, 4.20 mmol) and cyclohexa-1,3-diene
(320 mg/0.38 cm3, 4.00 mmol) in acetonitrile (11 cm3). After
work up, column chromatography (6 : 1 light petroleum–ethyl
acetate) gave dienylamine 24 (19 mg, 7%) as a colourless oil, Rf
J 11.9, 6.2, 2.0, C᎐CHCH ), 6.10 (1H, ddd, J 11.9, 4.8, 2.5,
᎐
2
NCHCH᎐C), 7.45 [1H, ddd, J 8.0, 6.9, 1.0, H-6(Q)], 7.64 [1H,
᎐
J. Chem. Soc., Perkin Trans. 1, 2001, 1518–1527
1525

View Article Online
0.26. Further elution gave aziridine 23 (101 mg, 38%) as a single
diastereoisomer, Rf 0.21. The third fraction eluted, Rf 0.16, was
a mixture which was re-chromatographed using Kieselgel (6 : 1
light petroleum–ethyl acetate) to give the major (Q1)-amino
alcohol diastereoisomer 27 (33 mg, 12%) as a colourless oil, Rf
0.19. [α]D ϩ91.0 (c = 2.0, EtOH) (Found: MHϩ 344.1975.
C19H26O3N3 requires MHϩ 344.1975); νmax/cmϪ1 3460s, 1660s,
1590s and 1470s; δH(400 MHz) 1.05 [9H, s, (CH3)3], 1.65 (1H,
dddd, J ∼13, ∼7, ∼3, ∼3, CHHCN), 1.76 (1H, s, OH), 1.84 (1H,
dddd, J 12.6, 11.9, 10.8, 5.0, CHHCN), 2.04 (1H, m,
Ring-opening of aziridine 23 in acetonitrile containing H218
O
Aziridine 23 (dr 5 : 1) (50 mg, 0.15 mmol) was dissolved in
acetonitrile (1 cm3) and H218O (8 µl, 2.5 equiv.) was added
followed by toluene-p-sulfonic acid (∼2 mg). After stirring for
45 min, ethyl acetate (10 cm3) was added, the solution washed
with saturated aqueous sodium hydrogencarbonate (10 cm3)
and the organic layer separated, dried, and evaporated. An
NMR spectrum of the residue showed the presence of
unchanged aziridine 23 (δ 3.58) and (Q1)-amino alcohol 27 and
28 (δ 3.18 and 2.95; ratio 2 : 1 respectively) in a ratio of 4 : 1.
For this mixture, mass spectrometry showed no 18O incorpor-
ation into the aziridine (MHϩ 326). For the mixture of (Q1)-
amino alcohols 27 and 28 (Found: MHϩ 346.2016. C19H26-
N316O18O requires MHϩ 346.2017) the ratio of 344 : 346 was
2 : 1. Separation of unchanged aziridine 23 and (Q1)-amino
alcohols 27 and 28 using flash silica [base-washed with triethyl-
amine (2%) solution in light petroleum–ethyl acetate] and mass
C᎐CCHH), 2.24 (1H, m, C᎐CCHH), 3.18 (1H, dddd, J ∼12,
᎐
᎐
∼8, ∼3, ∼3, CHNH), 3.62 (1H, br s, OH), 4.17 [1H, m, CH-
(OH)CN], 5.16 (1H, br d, J ∼14, CHOH), 5.75–5.86 (2H, m,
CH᎐CH), 5.90 (1H, d, J 7.6, NH), 7.50 [1H, ddd, J 8.2, 7.1, 1.2,
᎐
H-6(Q)], 7.62 [1H, dd, J 8.2, 1.2, H-8(Q)], 7.72 [1H, ddd, J 8.2,
7.1, 1.0, H-7(Q)] and 8.27 [1H, dd, J 8.2, 1.0, H-5(Q)]; m/z(%)
344 (MHϩ, 100) and 233 (42). Irradiation at δ 4.17 resulted in
loss of J ∼3 Hz from the signal at δ 3.18 and simplification of
spectroscopy on the recovered alcohol 28 showed the 16O : 18
O
the CH᎐CH multiplet.
᎐
ratio was raised to 8 : 1. The recovered aziridine 23 (dr 14 : 1)
was redissolved in acetonitrile (1 cm3) and stirred for a further
2 h with H218O (5 µl, 2.5 equiv.) and toluene-p-sulfonic acid
(∼2 mg). After work up as described above, NMR spectroscopy
showed the presence of alcohol 27 (Found: MHϩ 346.2017.
C19H26N316O18O requires MHϩ 346.2017) with a 344 : 346 ratio
of 1 : 1 (10 : 1 after purification by flash chromatography).
Further elution gave the minor (Q1)-amino alcohol diastereo-
isomer 28 (17 mg, 6%) as a colourless oil, Rf 0.14. [α]D ϩ113.3
(c = 1.2, EtOH) (Found: MHϩ 344.1975. C19H26O3N3 requires
MHϩ 344.1975); νmax/cmϪ1 3420m, 1660s, 1595s and 1470m;
δH(400 MHz) 1.05 [9H, s, (CH3)3], 1.80 (1H, dddd, J ∼12.5, ∼10,
∼3, ∼3, CHHCN), 1.92 (1H, dddd, J 12.5, 12.5, 8.5, 6.8,
CHHCN), 2.19 (1H, struct. m, CHH), 2.31 (1H, struct. m,
CHH), 2.96 (1H, dddd, J ∼13, ∼10, ∼3, ∼3, CHNH), 3.60 (1H,
d, J 10.5, ButCHOH), 3.93 [1H, br dd, J ∼4, ∼3, CH(OH)CN],
4.63 [1H, br d, J ∼4, CH(OH)CN], 5.03 (1H, d, J 10.5,
ButCHOH), 5.79 (1H, dddd, J 9.9, ∼5, ∼1.5, ∼1.5, CH᎐CCH ),
Conversion of (Q2)-amino alcohol 30 into oxazolidinone 36
(Q2)-amino alcohol 30 (60 mg, 0.20 mmol) was heated under
reflux in THF (1 cm3) with sodium hydride (5 mg, 0.22 mmol)
and 1,1Ј-carbonyldiimidazole (45 mg, 0.30 mmol) under
nitrogen for 3 h. After cooling, ethyl acetate (10 cm3) was added
and the solution washed with saturated sodium hydrogen-
carbonate solution (10 cm3), the organic layer was separated,
dried and evaporated to give the crude product as a colourless
solid. Column chromatography (5 : 1 light petroleum–ethyl
acetate) gave unchanged alcohol 30 (21 mg, 35%) as a colour-
less oil, Rf 0.49.
Further elution gave oxazolidinone 36 (35 mg, 53%) as a
colourless solid (Rf 0.33), mp 148–149 ЊC (from ethanol)
(Found: MHϩ 326.1505. C18H20O3N3 requires MHϩ 326.1504);
νmax/cmϪ1 1770s, 1680s and 1600s; δH 1.34 (3H, d, J 6.6,
CH3CHCH3), 1.40 (3H, d, J 6.6, CH3CHCH3), 1.86 (2H, m,
CHH), 2.08–2.21 (1H, m, CHH), 2.24–2.40 (1H, m, CHH),
3.18 [1H, heptet, J 6.6, CH(CH3)3], 4.02–4.15 (1H, m, NCH),
᎐
2
5.84 (1H, d, J 10.0, NH), 5.90 (1H, ddd, J 9.9, ∼5, ∼3,
C᎐CHCH ), 7.55 [1H, ddd, J 8.2, 7.1, 1.2, H-6(Q)], 7.74 [1H,
᎐
2
dd, J 8.0, 1.2, H-8(Q)], 7.83 [1H, ddd, J 8.0, 7.1, 1.2, H-7(Q)]
and 8.30 [1H, dd, J 8.2, 1.2, H-5(Q)]; δC(75 MHz) 22.2, 26.2
(2 × CH2), 26.3 [(CH3)3], 38.5 (CHNH), 62.6 (COH), 75.0
(CHOH), 120.5 [CCO(Q)], 126.5, 127.2, 127.6, 127.7, 131.6,
135.4 [4 × CH(Q), HC᎐CH], 146.3 [CN᎐C(Q)] and 158.8, 163.5
᎐
᎐
[CO(Q), CN(Q)]; m/z(%) 344 (MHϩ, 100) and 233 (30).
Irradiation of the signal at δ 3.93 converted that at δ 4.63 into
a singlet and that at δ 5.79 into a ddd J ∼10, ∼1.5, ∼1.5 Hz, and
that at δ 2.96 into a ddd J 13, 10 and 3.2 . Irradiation of the
signal at δ 2.96 affected only that at δ 3.93 and CH2 signals at
δ 1.80 and 1.92.
Ring-opening of aziridine 23 with CH3CN–H2O–acid
5.00–5.07 (1H, m, HCO), 6.00 (1H, m, incl. J 10.2, CH᎐CH),
᎐
6.26–6.35 (1H, m, incl. J 10.2, CH᎐CH), 7.45 [1H, ddd, J 8.0,
᎐
Aziridine 23 (220 mg, 0.68 mmol) was stirred in acetonitrile
(4 cm3) containing water (1 cm3) and toluene-p-sulfonic acid
(8 mg) at ambient temperature for 2 h. Ethyl acetate (10 cm3) was
added, the solution washed with saturated sodium hydrogen-
carbonate solution (10 cm3) and the organic layer separated,
dried and evaporated. Column chromatography (7 : 1 light
petroleum–ethyl acetate) of the residue gave cyclic ether 29
(53 mg, 24%) as a colourless oil, Rf 0.38. [α]D ϩ 151.5 (c = 1.0,
EtOH) (Found: MHϩ 326.1869. C19H24O2N3 requires MHϩ
326.1868); νmax/cmϪ1 1660s, 1600s, 1520m and 1470s; δH 1.30
[9H, s, (CH3)3], 1.92–2.37 (4H, m, 2 × CH2), 3.23 (1H, struct. m,
CHNH), 4.53 (1H, struct. m, HCO), 4.81 (1H, s, ButCHO),
6.8, 1.4, H-6(Q)], 7.70 [1H, dd, J 8.2, 1.4, H-8(Q)], 7.77 [1H,
ddd, J 8.2, 6.8, 1.1, H-7(Q)] and 8.22 [1H, dd, J 8.0, 1.1,
H-5(Q)]; δC 20.2 (CH2), 21.0 (CH3), 22.8 (CH2), 22.9 (CH3),
30.6 [CH(CH ) ], 54.4 (NCHCH ), 71.1 (C᎐CHCO), 121.4
᎐
3
3
2
[CCO(Q)], 123.2, 127.1, 127.3, 127.9, 133.3, 135.4 [4 × CH(Q),
HC᎐CH], 147.4 [CN᎐C(Q)], 157.6, 159.9 and 163.4 [C᎐O,
᎐
᎐
᎐
CN(Q), CO(Q)]; m/z(%) 326 (MHϩ, 66), 307 (100) and 289 (50).
Conversion of (Q1)-amino alcohol 27 into oxazolidinone 37
(Q1)-amino alcohol 27 (37 mg, 0.11 mmol) was heated under
reflux in THF (1 cm3) with sodium hydride (3 mg, 0.12 mmol)
and 1,1Ј-carbonyldiimidazole (22 mg, 0.14 mmol) under nitro-
gen for 3 h. After cooling, ethyl acetate (10 cm3) was added and
the solution washed with saturated sodium hydrogencarbonate
solution (10 cm3), the organic layer was separated, dried and
evaporated to give the crude product as a colourless solid.
Column chromatography (5 : 1 light petroleum–ethyl acetate)
gave unchanged alcohol 27 (16 mg, 43%) as a colourless oil, Rf
0.18.
5.78 (1H, m, incl. J ∼10, CH᎐CH), 6.06 (1H, struct. m, incl.
᎐
J ∼10, CH᎐CH), 6.60 (1H, br s, NH), 7.48 [1H, ddd, J 8.2, 5.3,
᎐
3.2, H-6(Q)], 7.69–7.76 [2H, m, H-7 and H-8(Q)] and 8.25 [1H,
ddd, J 8.2, 1.2, H-5(Q)]; δC 20.8, 26.3 (2 × CH2), 27.2 [(CH3)3],
34.9 [C(CH3)3], 56.2 (C-N), 74.4, 76.9 (2 × CHO), 120.4
[CCO(Q)], 126.6, 126.9, 127.2, 128.6, 132.4, 134.2 [4 × CH(Q),
HC᎐CH], 146.7 [CN᎐C(Q)] and 154.1, 160.6 [CN(Q), CO(Q)];
᎐
᎐
m/z(%) 326 (MHϩ, 100), 246 (30) and 215 (48).
Further elution gave the major alcohol diastereoisomer 27
(114 mg, 49%) Rf 0.27, and the minor diastereoisomer 28 (31
mg, 13%) Rf 0.14, both as colourless oils identical with those
isolated previously.
Further elution gave oxazolidinone 37 (20 mg, 49%) as a
colourless oil, Rf 0.10. [α]D ϩ39.5 (c = 1.0, EtOH) (Found: MHϩ
370.1766. C20H24O4N3 requires MHϩ 370.1767); νmax/cmϪ1
1790m, 1705m and 1605m; δH 0.99 [9H, s, (CH3)3], 1.67–1.86
1526
J. Chem. Soc., Perkin Trans. 1, 2001, 1518–1527

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(2H, m, CH2), 2.00–2.24 (2H, m, CH2), 3.32 (1H, d, J 10.8,
CHOH), 4.12 (1H, ddd, J 11.6, 6.7, 4.6, NCH), 4.43 (1H, d,
J 10.8, CHOH), 4.89–4.95 (1H, m, HCO), 5.93 (1H, dddd,
residue gave a mixture of products. Subsequent Kieselgel
chromatography (9 : 1 ethyl acetate–methanol) gave quinazolin-
4(3H)-one 40 (5 mg, 72%), Rf 0.71, as a colourless crystalline
solid identical to that isolated previously.
J ∼10, ∼3, ∼3, ∼3, CH᎐CH), 6.18–6.27 (1H, m, CH᎐CH), 7.45
᎐
᎐
[1H, ddd, J 8.0, 6.9, 1.0, H-6(Q)], 7.62 [1H, dd, J 8.0, 1.0,
H-8(Q)], 7.73 [1H, ddd, J 8.0, 6.9, 1.0, H-7(Q)] and 8.21 [1H,
dd, J 8.0, 1.0, H-5(Q)]; m/z(%) 370 (MHϩ, 100), 344 (22), 307
(25), 215 (28).
Further elution gave oxazolidinone enant. 39 (2.5 mg, 60%)
as a colourless solid, mp 87–88 ЊC (from light petroleum–ethyl
acetate). [α]D ϩ13.2 (c = 0.5, EtOH) (Found: MHϩ 140.0711.
C7H9O2N requires MHϩ 140.0712); νmax/cmϪ1 3220m and
1740m; NMR spectrum identical to that of 39 above; m/z(%)
162 (MNaϩ, 100) and 140 (MHϩ, 67).
Conversion of (Q1)-amino alcohol 28 into oxazolidinone 38
(Q1)-amino alcohol 28 (23 mg, 67 µmol) was heated under
reflux in THF (1 cm3) with sodium hydride (2 mg, 73 µmol) and
1,1Ј-carbonyldiimidazole (16 mg, 0.10 mmol) under nitrogen
for 3 h. After work up as described above, column chrom-
atography (3 : 1 light petroleum–ethyl acetate) of the crude
product gave alcohol 28 (11 mg, 48%) as a colourless oil, Rf 0.24.
Further elution gave oxazolidinone 38 (11 mg, 44%) as a
colourless oil, Rf 0.19 (Found: MHϩ 370.1766. C20H24O4N3
requires MHϩ 370.1767); νmax/cmϪ1 1790 m, 1695 m and 1605
m; δH 1.06 [9H, s, (CH3)3], 1.85–2.00 (2H, m, 2 × CH), 2.10–
2.27 (1H, m, CHH), 2.37–2.54 (1H, m, CHH), 2.95 (1H, d,
J 11.2, CHOH), 4.54 (1H, ddd, J ∼8, ∼4, ∼4, NCH), 4.71 (1H,
d, J 11.2, CHOH), 5.23–5.31 (1H, m, HCO), 5.89 (1H, dddd,
Crystal structure determinations of 21 and 33
Data for both compounds were measured on a Siemens P4
diffractometer with graphite monochromated Mo-Kα radiation
(λ = 0.7107 Å) using an ω-scan technique. Three standard
reflections monitored every 100 scans showed no significant
variation in intensity; the reflections were corrected for Lorentz
and polarisation effects.
The structures were solved by direct methods and refined by
full-matrix least squares on F2 using the program SHELXL-97.
All hydrogen atoms were included in calculated positions
(C–H = 0.96 Å) using a riding model. All non-hydrogen atoms
were refined as anisotropic. The absolute configuration of 33 at
C1 is determined by the preparation from the (S)-tert-leucine.
J 13.1, ∼3, ∼3, ∼2, CH᎐C), 6.18–6.27 (1H, m, C᎐CH), 7.52 [1H,
᎐
᎐
ddd, J 8.2, 6.8, 1.1, H-6(Q)], 7.70 [1H, dd, J 8.2, 1.1, H-8(Q)],
7.82 [1H, ddd, J 8.2, 6.8, 1.1, H-7(Q)] and 8.27 [1H, dd, J 8.2,
1.1, H-5(Q)]; δC(75 MHz) 20.3, 21.9 (2 × CH2), 26.3 [(CH3)3],
37.2 [C(CH3)3], 70.9, 74.7 (2 × CH), 121.7 [CCO(Q)], 122.8,
Crystal data for 21. C15H12F3N3O, M = 307.28, monoclinic,
space group C2/c, a = 24.012(3), b = 7.609(1), c = 15.758(2) Å,
β = 105.89(1)Њ, V = 2769.1(6) Å3, T = 200 K, Z = 8, µ(Mo-
Kα) = 0.123 mmϪ1, colourless block, crystal dimensions
0.49 × 0.21 × 0.20 mm. Full matrix least squares based on F2
gave R1 = 0.070 for 808 observed data (F > 4σ(F)) and
wR2 = 0.232 for all 1038 data, GOF = 1.078 for 145 parameters.
127.7, 127.9, 128.0, 133.2, 135.7 [4 × CH(Q), HC᎐CH], 146.2
᎐
[CN᎐C(Q)], 157.2 [OC(O)N] and 159.0, 159.6 [CN(Q), CO(Q)];
᎐
m/z(%) 370 (MHϩ, 100). A COSY spectrum showed the signal
at δ 1.85–2.00 (CH2) coupled with δ 4.54 (NCH) and δ 5.89
(CH᎐CCH ) coupled with δ 5.23–5.31 (HCO).
᎐
2
Crystal data for 33. C20H25N3O2, M = 339.43, tetragonal,
space group P43, a = b = 10.242(2), c = 17.385(3) Å,
V = 1823.7(6) Å3, T = 200 K, Z = 4, µ(Mo-Kα) = 0.08 mmϪ1,
colourless block, crystal dimensions 0.62 × 0.48 × 0.41 mm.
Full matrix least squares based on F2 gave R1 = 0.036 for 1579
observed data (F > 4σ(F)) and wR2 = 0.097 for all 1779 data,
GOF = 1.030 for 226 parameters.
Q1–N reductive cleavage of oxazolidinone 37 with Sm(II) iodide10
A two-necked round bottom flask fitted with a 3-way tap and a
septum cap was flame dried, flushed with argon and oxazolidi-
none 37 (17 mg, 45.9 µmol) dissolved in THF (1 cm3) was added
via a syringe followed by tert-butyl alcohol (0.5 cm3) in THF
(0.5 cm3). Samarium() iodide (0.1 M solution in THF) was
then added dropwise until the dark blue colour of samarium()
persisted (∼1 cm3). Ethyl acetate (5 cm3) was added and the
solution washed with saturated sodium hydrogencarbonate
solution (5 cm3), the organic layer was separated, dried and
evaporated to give the crude product as a yellow semi-solid.
Column chromatography (6 : 1 light petroleum–ethyl acetate)
gave a mixture of products. Subsequent Kieselgel chrom-
atography (9 : 1 ethyl acetate–methanol) gave quinazolin-
4(3H)-one 40 (8 mg, 75%) as a colourless crystalline solid,
identical with a sample isolated previously.5
Further elution gave oxazolidinone 39 (4 mg, 62%) as a
colourless solid, mp 85–86 ЊC (from light petroleum–ethyl
acetate) [lit.13 (racemate) 86–88 ЊC]. [α]D Ϫ10.6 (c = 0.5, EtOH)
(Found: MHϩ 140.0711. C7H9O2N requires MHϩ 140.0712);
νmax/cmϪ1 3220m and 1740m; δH 1.70–1.78 (1H, m, CH), 1.80–
2.05 (2H, m, 2 × CH), 2.15–2.31 (1H, m, CH), 3.89–4.03 (1H,
struct. m, CHNH), 4.87–4.95 (1H, m, HCO), 5.07 (1H, br s,
Acknowledgements
We thank Dr J. Fawcett and Dr D. R. Russell for the X-ray
crystal structure determinations.
References
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᎐
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᎐
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The procedure described above was carried out using oxazo-
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in THF (1 cm3). Samarium() iodide (0.1 M solution in THF)
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metal persisted (∼0.8 cm3). After work up column chrom-
atography (6 : 1 light petroleum–ethyl acetate) of the yellow
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1527