Lithiation of 2-(1-chloroethyl)-2-oxazolines: Synthesis of substituted oxazolinyloxiranes and oxazolinylaziridines

Article abstract of DOI:10.1055/s-2001-18447

Lithiation of 2-(1-chloroethyl)-4,4-dimethyl-2-oxazoline 2 leads to lithiated derivative 3, which is quite stable and can be deuterated, methylated and silylated to give oxazolines 4a-c. The reaction of 3 with carbonyl compounds and imines furnishes good to excellent yields of oxazolinylepoxides 6a-m and aziridines 17a-f, respectively. Methylation and NaBH₄ reduction of epoxides 6 afford oxazolidines 7 highly stereoselectively. Acylepoxides can be obtained by hydrolysis of the oxazolidine moiety.

Full text of DOI:10.1055/s-2001-18447

PAPER
2299
Lithiation of 2-(1-Chloroethyl)-2-oxazolines: Synthesis of Substituted
Oxazolinyloxiranes and Oxazolinylaziridines
S
ynthesis of Subst
i
itute
d
O
t
xazoli
o
nyloxiranes and O
Ca
a
Centro C.N.R. “M.I.S.O.”, Dipartimento Farmaco-Chimico, Università di Bari, Via E. Orabona 4, 70126 Bari, Italy
Fax +39(080)5442231; E-mail: florio@farmchim.uniba.it
b
Dipartimento di Biologia, Università di Lecce, Via Monteroni, 73100 Lecce, Italy
Received 27 July 2001; revised 19 September 2001
azoline 1 with t-butylhypochlorite.4 Treatment of 2 with
lithium diisopropylamide (LDA) afforded lithiated deriv-
ative 3. The formation of 3 was confirmed by its trapping
with electrophiles (deuteration, methylation and trimeth-
Abstract: Lithiation of 2-(1-chloroethyl)-4,4-dimethyl-2-oxazo-
line 2 leads to lithiated derivative 3, which is quite stable and can be
deuterated, methylated and silylated to give oxazolines 4a–c. The
reaction of 3 with carbonyl compounds and imines furnishes good
to excellent yields of oxazolinylepoxides 6a–m and aziridines 17a– ylsilylation) to give compounds 4a–c (Scheme 1,
f, respectively. Methylation and NaBH4 reduction of epoxides 6 af-
ford oxazolidines 7 highly stereoselectively. Acylepoxides can be
Table 1).
The reaction of 3 with acetone (Scheme 2) afforded a very
good yield of chlorohydrin 5a that was quantitatively
transformed into oxazolinylepoxide 6a upon treatment
obtained by hydrolysis of the oxazolidine moiety.
Key words: oxazolinyloxiranes, oxazolinylaziridines, carbanion,
nucleophilic addition
N
CH3
Lithiated 2-halomethyl-2-oxazolines are useful but ex-
tremely reactive intermediates for undergoing smooth ho-
O
1
t-BuOCl
mocoupling reaction to give trans-bis(oxazolinyl)ethenes
and trans-tris(oxazolinyl)cyclopropanes.1 The capture of
Cl
Cl
Li
N
such lithiated oxazolines by electrophiles is made possible
by adding the electrophile soon after their generation or
by generating them in the presence of the electrophile
(Barbier’s conditions).2 Lithiated –haloethyloxazolines
are quite stable at low temperature even for long times so
that for some of them a spectroscopic investigation per-
formed to elucidate the structural features has been report-
ed.3 In the present paper we report on the generation of
some lithiated 2-(1-chloroethyl)-2-oxazolines and their
reactions with electrophiles.
N
LDA
CH3
CH3
-80°C
O
O
2
3
70-95 %
E
E
4
a
b
c
E
Cl
D
N
CH3
CH3
O
(CH3)3Si
4
2-(1-Chloroethyl)-4,4-dimethyl-2-oxazoline (2) has been
prepared by chlorination of 2-ethyl-4,4-dimethyl-2-ox-
Scheme 1
Table 1 Oxazolines 4 Prepared from Lithiated 2-(1-chloroethyl)-2-oxazoline (3)
Product a
Yield (%)
95 b
IR (film, cm–1)
1663
1H NMR (CDCl3/TMS) , J (Hz)
13C NMR (CDCl3)
4a
1.24 (s, 3 H), 1.25 (s, 3 H), 1.67 (s, 3
H), 3.97 (s, 2 H)
22.1, 28.2, 67.6, 80.0, 164.3
4b
4c
95 b
70 c
1655
1660
1.24 (s, 6 H), 1.76 (s, 6 H), 3.98 (s, 2
H)
28.1, 30.7, 61.6, 67.6, 80.0, 166.8
0.14 (s, 9 H), 1.23 (s, 3 H), 1.26 (s, 3
H), 1.71 (s, 3 H), 3.94 (s, 2 H)
2.4, 24.4, 28.1, 53.8, 67.3, 79.7,
167.0
a Satisfactory microanalyses.
b Yield determined by 1H NMR analysis of the crude reaction mixture.
c Yield of isolated material.
Synthesis 2001, No. 15, 12 11 2001. Article Identifier:
1437-210X,E;2001,0,15,2299,2306,ftx,en;Z08901SS.pdf.
© Georg Thieme Verlag Stuttgart · New York
ISSN 0039-7881

2300
V. Capriati et al.
PAPER
with NaOH in i–PrOH. Similarly, the reaction of 3 with tereoselective were the reactions of 6c with vinyl, allyl
cyclohexanone provided chlorohydrin 5b and then ep- and ethynyl magnesium halides (Table 5). A highly stere-
oxide 6b (Tables 2, 3). In the case of benzophenone, the oselective reduction took place with cyclohexylmagne-
epoxide 6c was obtained straightforwardly.
sium chloride to give 7b. In comparison, the reaction with
NaBH4 was much less stereoselective (dr = 75:25).
Methylation of 6c with CF3SO3CH3 followed by the addi-
tion of MeMgBr/2 HMPT furnished an excellent yield of The coupling reaction of 3 with aldehydes was also stud-
oxazolidine 7a (Scheme 3) with a satisfactory diastereo- ied. Thus, the reaction of 3 with benzaldehyde produced
selection (dr = 80:20). HMPT plays an important role in an almost 1:1 mixture of diastereomeric (syn+anti) chlo-
the oxazoline-oxazolidine transformation. Due to its rohydrins 5d–e (Table 3) in good yields. Chlorohydrins
strong solvating effect it prevents the Grignard reagent 5d and 5e were then separated by column chromatography
from the double addition to the C–N double bond that and stereospecifically cyclized to the corresponding ep-
would provoke ring opening of the formed oxazolidine oxides 6d and 6e (Table 4) upon treatment with NaOH/i-
moiety.5 Comparable results were obtained with other PrOH. Comparable results were obtained with other alde-
Grignard reagents (Scheme 3). In particular, highly dias- hydes (Scheme 2). In particular, diastereomeric oxazoli-
Table 2 Chlorohydrins 5 Prepared from Lithiated 2-(1-chloroethyl)-2-oxazoline (3)
Prod-
ucta,b
Yield
(%)c
Mp (°C)
–
IR (KBr,
cm–1)
1H NMR (CDCl3/TMS) , J (Hz)
13C NMR (CDCl3)
5a
5b
5d
5e
5h
5i
83
76
61e
1648d
1651
1650
1650
1650
1655
1.25 (s, 3 H), 1.27 (s, 3 H), 1.32 (s, 3 H), 1.38 (s, 3 H),
1.76 (s, 3 H), 4.01–3.94 (2 d, AB system, 2 H, J =
8.2 Hz), 4.87 (s, 1 H, exchanges with D2O)
24.8, 25.0, 27.8, 27.9, 67.7, 71.1,
74.9, 79.1, 165.8
61–63
1.25 (s, 3 H), 1.26 (s, 3 H), 1.77 (s, 3 H), 1.98 1.00
(m, 10 H), 4.00–3.98 (2 d, AB system, 2 H, J = 8.2
Hz), 4.30 (s, 1 H, exchanges with D2O)
21.5, 21.7, 24.6, 25.7, 27.9, 28.0,
31.3, 31.6, 67.7, 72.3, 75.5, 79.1,
165.7
89–91
1.17 (s, 3 H), 1.25 (s, 3 H), 1.57 (s, 3 H), 4.00 (s, 2 H),
4.65–4.64 (s broad, 1 H, exchanges with D2O), 5.09
(s, 1 H), 7.25 7.50 (m, 5 H)
23.5, 28.0, 28.2, 67.6, 68.9, 78.0,
79.6, 127.9, 128.1, 128.5, 137.6,
165.8
104–106
130–132
88–90
1.24 (s, 3 H), 1.30 (s, 3 H), 1.60 (s, 3 H), 4.05 (s, 2 H),
4.66 (s, 1 H, exchanges with D2O), 5.12 (s, 1 H),
7.25 7.47 (m, 5 H)
23.5, 27.8, 28.0, 67.5, 68.5, 77.8,
79.4, 127.7, 128.4, 137.1, 165.6
47e
1.29 (s, 3 H), 1.33 (s, 3 H),1.57 (s, 3 H), 4.03 (s, 2 H),
5.30–5.10 (s broad, 1 H, exchanges with D2O), 6.24
(s, 1 H), 7.42 7.90 (m, 4 H)
21.4, 27.7, 28.0, 65.1, 67.6, 70.6,
79.7, 124.1, 128.9, 130.2, 131.3,
131.8, 166.4
1.24 (s, 3 H), 1.27 (s, 3 H), 1.61 (s, 3 H), 4.06 (s, 2 H),
5.60–5.70 (s broad, 1 H, exchanges with D2O), 6.29
(s, 1 H), 7.56 7.64 (m, 1 H), 7.70 7.80 (m, 1 H)
7.88 7.82 (m, 1 H), 8.20 7.94 (m, 1 H)
21.4, 27.4, 27.43, 66.3, 67.6,
69.5, 79.6, 124.0, 129.3, 130.8,
132.0, 132.9, 164.9
5j
69e
129–131
81–83
1650
1655
1645
1650
1.33 (s, 3 H), 1.35 (s, 3 H), 1.74 (s, 3 H), 4.04 (s, 2 H),
5.20 5.17 (s, 1 H), 5.73 5.75 (s, 1 H), 7.22 7.65 (m,
4 H)
22.9, 27.8, 28.1, 66.2, 67.6, 74.2,
79.3, 126.3, 129.3, 129.6, 129.7,
134.5, 136.0, 165.5
5k
5l
1.33 (s, 3 H), 1.34 (s, 3 H), 1.60 (s, 3 H), 4.06 (s, 2 H),
5.50 5.65 (s broad, 1 H, exchanges with D2O), 5.65
(s, 1 H), 7.24 7.92 (m, 4 H)
14.1, 22.6, 31.6, 60.4, 67.5, 72.6,
79.5, 126.5, 128.4, 128.9, 129.5,
131.3, 135.1, 165.5
67e
87–89
1.33 (s, 6 H), 1.70 (s, 3 H), 3.83 (s, 3 H), 4.02 (s, 2 H),
4.90 5.30 (s broad, 1 H, exchanges with D2O), 5.56
(s, 1 H), 6.85 7.53 (m, 4 H)
14.1, 23.3, 27.9, 28.0, 55.4, 67.3,
73.9, 79.3, 110.8, 120.2, 126.4,
129.3, 129.5, 157.3, 165.5
5m
87–89
1.30 (s, 3 H), 1.33 (s, 3 H), 1.55 (s, 3 H), 3.82 (s, 3 H),
4.03 (s, 2 H), 5.27 (s 1 H, exchanges with D2O), 5.58
(s, 1 H), 6.83 7.80 (m, 4 H)
15.3, 24.1, 27.9, 28.1, 55.3, 65.9,
70. 6, 79.4, 110.0, 120.4, 125.8,
129.2, 130.3, 156.7, 166.6
a Satisfactory microanalyses.
b Spectroscopic data of chlorohydrins 5f and 5g have been reported in ref. 6a
c Yield of isolated material.
d Film in this case.
e Overall yields of isolated diastereomeric chlorohydrins (syn + anti) separable by flash chromatography (see experimental). Diastereomeric
ratio determined by weighing the isolated syn and anti diastereomers: dr 5d/5e = 56/44; 5f/5g = 57/43; 5h/5i = 55/45; 5j/5k = 49/51; 5l/5m
= 42/58.
Synthesis 2001, No. 15, 2299–2306 ISSN 0039-7881 © Thieme Stuttgart · New York

PAPER
Synthesis of Substituted Oxazolinyloxiranes and Oxazolinylaziridines
2301
Table 3 Oxazolinylepoxides 6 Prepared from Lithiated 2-(1-chloroethyl)-2-oxazoline (3)
Producta
Yield (%)b
IR (KBr,
cm–1)
1H NMR (CDCl3/TMS) , J (Hz)
13C NMR (CDCl3)
6a
6b
6c
83
76
66
1670c
1657
1666
1.08 (s, 3 H), 1.09 (s, 3 H), 1.14 (s, 3 H), 1.17 (s,
3 H), 1.34 (s, 3 H), 3.74–3.82 (m, 2 H)
17.3, 20.1, 20.6, 28.3, 60.3, 62.7, 67.5, 79.3,
164.4
1.16 (s, 6 H), 1.43 (s, 3 H), 1.21–1.64 (m, 10 H),
3.84 (s, 2 H)
16.8, 24.7, 24.9, 25.5, 28.2, 28.3, 30.2, 31.0,
60.7, 66.9, 67.6, 79.2, 164.4
0.87 (s, 3 H), 1.07 (s, 3 H), 1.43 (s, 3 H), 3.54 (d,
1 H, J = 8.0 Hz), 3.69 (d, 1 H, J = 8.0 Hz), 7.18
7.34 (m, 6 H), 7.47–7.51 (m, 4 H)
17.6, 27.7, 27.9, 62.9, 67.3, 70.4, 79.2, 127.1,
125.5, 127.7, 127.8, 128.3, 137.9, 138.5,
163.0
a Satisfactory microanalyses.
b Yield of isolated material.
c Film in this case
CH3
N
O
CH3
H
N
O
CH3
O
Cl
O
R
O
NaOH
RR1C=O
N
R
3
CH3
N
H
i-PrOH
O
R1
CH3
R1
HO
O
6
5
CH3
6g
6f
R
R1
5,6
1) CF3SO3CH3
2) CH3MgCl / HMPT
1) CF3SO3CH3
2) CH3MgCl / HMPT
CH3
a
b
c
d
e
f
g
h
i
CH3
- (CH2)5
-
CH3
Ph
H
Ph
H
Ph
Ph
H
O
CH3
H
CH3
O
CH3
p-CH3C6H4
H
o-NO2C6H4
H
o-ClC6H4
H
N
p-CH3C6H4
CH3
CH3
H
N
H
O
CH3
o-NO2C6H4
j
k
l
O
CH3
H
8b
8a
o-ClC6H4
o-CH3OC6H4
m
H
o-CH3OC6H4
(COOH)2
(COOH)2
THF/H2O
THF/H2O
H
H
CH3
Scheme 2
O
CH3
CH3
O
CH3
CH3
O
H3C
N
Ph
Ph
O
O
R
H3C
Ph
Ph
1) CF3SO3CH3
2) RMgX / HMPT
H
H3C
CH3
O
N
9a
9b
O
O
6c
7
Scheme 4
7
RMgX
dr
R
a
b
c
d
e
f
CH3MgCl
CyMgBr
CH2=CHCH2MgBr
C4H9MgCl
CH2=CHMgBr
CH CMgBr
PhCH2MgCl
PhMgBr
80/20
95/5
90/10
8020
95/5
95/5
75/25
60/40
CH3
H
CH2=CH-CH2
C4H9
CH2=CH
CH C
The hydrolysis of (Z)-oxazolidinyloxirane 8a carried out
with oxalic acid (8 equiv) in THF/H2O afforded a low
yield (40%) of the expected acetyltolyloxirane 9a6a after 7
days. The (E)-acetyltolyloxirane 9b6a was obtained start-
ing from the (E)-oxazolidinyloxirane 8b (11 equiv of ox-
alic acid, THF/H2O; 3 days). The acetyloxirane 10 does
form when the oxazolidinyloxirane 7a is treated with ox-
alic acid, but it was not possible to isolate it due to its
isomerization to 3,3-diphenyl-2,4-pentanedione 12.
g
h
PhCH2
Ph
Scheme 3
nyloxiranes 6f and 6g were converted into the Moreover, the reaction of 7a with MeI in acetone fur-
oxazolidines 8a6a and 8b6a upon N-methylation with nished 1,1-diphenyl-2-propanone 13 (Scheme 5). In con-
CF3SO3CH3 followed by the addition of MeMgBr/ trast, oxazolidine 7b could be easily hydrolyzed to the
2 HMPT with good to excellent diastereoselection corresponding formyloxirane 11 upon treatment with ox-
(Scheme 4).
alic acid in THF/H2O.6a
Synthesis 2001, No. 15, 2299–2306 ISSN 0039-7881 © Thieme Stuttgart · New York

2302
V. Capriati et al.
PAPER
Table 4 Oxazolinylepoxides 6 prepared from lithiated 2-(1-chloroethyl)-2-oxazoline (3)
Producta,b
Yield (%)c
61
IR (film,
cm–1)
1H NMR (CDCl3/TMS) , J (Hz)
13C NMR (CDCl3) , J (Hz)
6d
1665
1.30 (s, 6 H), 1.32 (s, 3 H), 4.00 (s,
2 H), 4.40 (s, 1 H), 7.24 7.35 (m, 5
H)
13.7 (CH3C–O), 28.2 (2 CH3C–N), 57.4, 63.6 (CH–
O), 67.7, 79.5 (CH2–O), 126.6, 126.8, 128.0, 128.1,
128.4, 134.2, 164.2
6e
1665
0.96 (s, 3 H), 1.03 (s, 3 H), 1.72 (s,
3 H), 3.66 (s, 2 H), 4.02 (s, 1 H),
7.25 7.39 (m, 5 H),
20.5 (qd, CH3C–O 1Jq = 128.9 Hz, 3Jd = 2.0 Hz), 27.6
(2 CH3C–N), 59.6, 63.9 (d with fine structure, 1Jd =
175.7 Hz, CH-O), 67.3, 79.2 (t with fine structure, 1Jt
= 144.7 Hz, CH2–O), 126.6, 127.7, 127.9, 134.1, 161.6
6h
47
69
67
1655d
1650d
1655
1670
1650
1.30 (s, 3 H), 1.40 (s, 6 H), 4.10 (s,
2 H), 4.87 (s, 1 H), 7.30 8.30 (m, 4
H)
14.3 (q, 1Jq = 129.0 Hz, CH3C–O), 28.0 (CH3C–N),
28.3 (CH3C–N), 58.0, 61.8 (d with fine structure 1Jd =
186.5 Hz, CH–O), 68.0, 79.7 (t with fine structure, 1Jt
= 149.2 Hz, CH2–O), 124.9, 129.1, 129.4, 131.7,
134.1, 147.0, 163.5
6i
0.65 (s, 3 H), 1.01 (s, 3 H), 1.80 (s,
3 H), 3.55–3.57 (2 d, AB system,
2 H, J = 8.2 Hz), 4.51 (s, 1 H),
7.44 8.14 (m, 4 H)
19.9 (qd, 1Jq = 129.2 Hz, 3Jd = 1.8 Hz, CH3C–O), 27.7
(2 CH3C–N), 59.1, 62.8 (d with fine structure, 1Jd =
186.8 Hz, CH-O), 67.1, 79.4 (t with fine structure, 1Jt
= 149.6 Hz, CH2-O), 124.0, 128.7, 130.2, 131.4, 133.6,
147.1, 161.4
6j
6k
6l
1.27 (s, 3 H), 1.30 (s, 3 H), 1.31 (s,
3 H), 4.05–3.98 (2 d, AB system,
2 H, J = 8.1 Hz), 4.47 (s, 1 H),
7.21 7.37 (m, 4 H)
14.0 (q, 1Jq = 129.1 Hz, CH3C-O), 28.2 (2 CH3C-N),
57.3, 61.1 (d with fine structure, 1Jd = 181.9 Hz, CH-
O), 67.9, 79.6 (t with fine structure, 1Jt = 149.3 Hz,
CH2-O), 128.1, 128.9, 129.0, 129.1, 132.8, 132.9,
163.8
0.76 (s, 3 H), 0.98 (s, 3 H), 1.71 (s,
3 H), 3.58 3.52 (2 d, AB system,
2 H, J = 7.9 Hz), 4.07 (s, 1 H),
7.10 7.40 (m, 4 H)
19.9 (qd, 1Jq = 129.0 Hz, 3Jd = 1.8 Hz, CH3C-O), 27.8
(CH3C-N), 27.9 (CH3C-N), 59.1, 62.5 (d with fine
structure, 1Jd = 180.6 Hz, CH–O), 67.2, 79.3 (t with
fine structure, 1Jt = 149.3 Hz, CH2–O), 126.0, 128.3,
128.8, 129.0, 132.4, 132.9, 161.6
1.30 (s, 3 H), 1.31 (s, 6 H), 3.80 (s,
3 H), 4.01 (s, 2 H), 4.47 (s, 1 H),
6.83 7.27 (m, 4 H)
13.9 (q, 1Jq = 128.8 Hz, CH3C–O), 28.2 (CH3C-N),
26.3 (CH3C-N), 55.4 (q, 1Jq = 144.1 Hz, CH3O–Ar),
57.2, 59.7 (d with fine structure, 1Jd = 180.3 Hz, CH–
O), 67.8, 79.4 (t with fine structure, 1Jt = 149.3 Hz,
CH2–O), 109.9, 120.1, 123.0, 127.5, 129.0, 157.8,
164.5
6m
1665
0.89 (s, 3 H), 1.00 (s, 3 H), 1.71 (s,
3 H), 3.60 (s, 2 H), 3.80 (s, 3 H),
4.14 (s, 1 H), 6.76 7.31 (m, 4 H)
20.3 (qd, 1Jq = 128.8 Hz, 3Jd = 1.9 Hz, CH3C–O), 27.9
(CH3C–N), 28.0 (CH3C–N), 55.5 (q, 1Jq = 144.1 Hz,
CH3O–Ar), 59.1, 61.0 (d with fine structure, 1Jd =
183.1 Hz, CH–O), 67.2, 79.1 (t with fine structure, 1Jt
= 149.2 Hz, CH2–O), 109.6, 119.7, 122.7, 127.6,
128.8, 157.9, 162.1
a Satisfactory microanalyses.
b The E and Z configuration of epoxides 6d–m was established on the basis of the 3JCH coupling constant value between the oxirane ring
hydrogen and the CH3 on the adjacent ring carbon as discussed in ref. 6b Spectroscopic data of oxazolinylepoxides 6f and 6g have been
reported in ref. 6a
c Overall yields of isolated diastereomeric epoxides (E + Z) separable by flash chromatography (see experimental). Diastereomeric ratio
determined by weighing the isolated E and Z diastereomers: dr 6d/6e = 56/44; 6f/6g = 57/43; 6h/6i = 55/45; 6j/6k = 49/51; 6l/6m = 42/58.
d KBr in this case.
On the basis of previous results, the Darzens reaction of the expected lithiated species 15b that was stable at low
chiral 2-(1-chloroethyl)-2-oxazolines with carbonyl com- temperature and could be captured with ketones (3-pen-
pounds has also been examined.7,8 Lithiation (LDA, THF, tanone, cyclohexanone, cyclododecanone) to give a high
–78 °C) of a 1:1 diastereomeric mixture of (1R,4’S,5’S) yield of the corresponding tetrasubstituted epoxides 16a–
and (1S,4’S,5’S)-2-(1-chloroethyl)-4-methoxymethyl-5- c as a diastereomeric mixture (Table 6) that could not be
phenyl-2-oxazoline 15a, (Scheme 6) prepared by chlori- separated by chromatography. The diastereomeric ratios
1
nation of the corresponding 2-ethyl derivative 14 with were measured by H NMR and no diastereoselectivity
t-butylhypochlorite (see experimental section), afforded was observed (Scheme 6).
Synthesis 2001, No. 15, 2299–2306 ISSN 0039-7881 © Thieme Stuttgart · New York

PAPER
Synthesis of Substituted Oxazolinyloxiranes and Oxazolinylaziridines
2303
Table 5 Oxazolidine Derivatives 7 Prepared from Oxazolinylepoxide (6c) with RMgX
Pro-
Yield
(%)b
IR (film
cm–1)
drc
1H NMR (CDCl3/TMS) , J (Hz)
13C NMR (CDCl3)
ducta
7a
95
1444
1096
80:20d
minor: 0.88 (s, 3 H), 1.02 (s, 3 H), 1.13 (s, 3 H), 1.18 (s,
3 H), 1.91 (s, 3 H), 3.62 (d, 1 H, J = 7.7 Hz), 3.69 (d, 1
H, J = 7.7 Hz), 7.10–7.60 (3 m, 10 H);
major: 0.97 (s, 3 H), 1.04 (s, 3 H), 1.20 (s, 3 H), 1.37 (s,
3 H), 2.33 (s, 3 H), 3.28 (d, J = 7.5 Hz, 1 H), 3.76 (d, 1
H, J = 7.5 Hz), 7.22 7.53 (3 m, 10 H)
minor: 18.6, 20.4, 21.7, 24.9, 27.2,
75.8, 77.3 78.0, 79.0, 98.6, 126.9,
127.0, 127.3, 127.9, 128.2, 128.7,
142.0; major: 18.2, 21.1, 21.4, 24.2,
60.2, 68.3, 72.4 74.6, 77.3, 96.0,
126.4, 126.9, 127.1, 127.2, 127.9,
128.7, 142.5, 143.9
7b
7c
51
95
1447e
1069
≥ 95:5
0.81 (s, 3 H), 1.10 (s, 3 H), 1.16 (s, 3 H), 2.21 (s, 3 H),
3.49 (s, 1 H), 3.62 (s, 2 H), 7.16 7.35 (m, 6 H), 7.57
7.44 (m, 4 H)
12.9, 16.5, 23.3, 57.8, 60.0, 68.1,
69.3, 79.4, 95.6, 127.4, 127.7,
127.8, 128.0, 128.6, 128.7, 140.4,
141.3
1638
1488
1055
90:10
0.98 (s, 3 H major + 3 H minor), 1.14 (s, 3 H major + 3
H minor), 1.17 (s, 3 H major + 3 H minor), 2.46 (s, 3 H
major + 3 H minor), 2.48 2.59 (m, 1 H major, 2 H mi-
nor), 2.68 (dd, 1 H major, 2J = 14.4 Hz, 3J = 7.9 Hz),
3.18 3.20 (d, 1 H major, J = 7.4 Hz), 3.49 3.65 (2 d,
AB system, 2 H minor), 3.80 3.82 (d, 1 H major, J = 7.4
Hz), 5.04 5.24 (m, 2 H major + 2 H minor), 5.87 6.01
(m, 1 H major + 1 H minor), 7.10 7.30 (m, 5 H major +
5 H minor), 7.40 7.55 (m, 5 H major + 5 H minor)
major + minor: 96.6, 117.5, 126.0,
126.1, 126.4, 126.5, 126.9, 127.0,
127.6, 127.9, 128.5, 134.6, 134.9,
141.4, 143.0
7d
87
1446
1060
80:20
0.88–1.00 (m, 3 H major + 3 H minor), 0.98 (s, 3 H ma- major + minor: 18.7, 19.7, 22.4,
jor), 1.14 (s, 3 H major), 1.15 (s, 3 H major), 1.16 (s, 3
H minor), 1.19 (s, 3 H minor), 1.23 1.37 (m, 4 H major
+ 4 H minor), 1.58 1.90 (m, 2 H major + 2 H minor),
2.44 (s, 3 H major + 3 H minor), 3.15 (d, 1 H major, J =
7.2 Hz), 3.42 3.59 (2 d, AB system, 2 H minor, J = 7.7
Hz), 3.81 (d, 1 H major, J = 7.2 Hz), 7.05 7.55 (m, 10
H major + 10 H minor)
23.4, 23.6, 23.7, 23.8, 25.1, 26.4,
26.9, 27.3, 33.8, 35.2, 59.5, 61.0,
72.9, 74.2, 75.3, 76.9, 77.9, 97.5,
99.4, 126.4, 126.7, 127.0, 127.2,
127.3, 127.7, 127.9, 128.3, 128.7
7e
93
1444e
1066
≥ 95:5
0.80 (s, 3 H), 0.90 (s, 3 H), 1.21 (s, 3 H), 2.25 (s, 3 H),
3.41 3.77 (2 d, AB system, 2 H J = 7.2 Hz), 5.28 (dd,
1 H, 3J = 10.8 Hz, 2J = 1.9 Hz), 5.39 (dd, 1 H, 3J = 17.3
Hz, 2J = 1.9 Hz), 5.95 (dd, 1 H, 3J = 17.30 Hz, 3J = 10.9
Hz), 7.01 7.46 (m, 10 H)
18.5, 20.6, 23.7, 30.1, 57.8, 60.5,
72.0, 72.9, 96.4, 116.6, 126.4,
127.1, 127.2, 127.3, 127.6, 128.7,
137.4, 142.2, 143.9
7f
83
85
3303e
1445
1079
≥ 95:5
0.60 (s, 3 H), 1.00 (s, 3 H), 1.31 (s, 3 H), 2.26 (s, 3 H),
2.66 (s, 1 H), 3.47 3.56 (2 d, AB system, 2 H, J = 7.14
Hz), 7.06 7.54 (m, 10 H)
18.2, 19.6, 23.1, 60.9, 72.2, 72.6,
78.0, 78.4, 81.6, 93.5, 126.5, 126.9,
127.4, 128.0, 128.8, 124.0, 137.3,
143.57
7g
1447
1075
75:25
0.49 (s, 3 H minor), 0.65 (s, 3 H major), 1.17 (s, 3 H mi- major + minor: 18.9, 20.1, 21.7,
nor), 1.19 (s, 3 H minor), 1.20 (s, 3 H major), 1.38 (s, 3
H major), 1.96 (s, 3 H minor), 2.69 (s, 3 H major), 2.85
(s, 2 H minor), 3.08 3.32 (2 x d, AB system, 2 H major,
J = 13.8 Hz), 3.12 (d, 1 H major, J = 7.2 Hz), 3.36 3.51
(2 d, AB system, 2 H minor, J = 7.7 Hz), 3.80 (d, 1 H
23.5, 24.3, 24.73, 27.7, 30.2, 40.1,
41.2, 59.4, 59.9, 68.8, 73.4, 73.8,
74.8, 77.6, 77.7, 97.8, 100.6, 126.3,
126.6, 126.7, 127.0, 127.1, 127.2,
127.3, 127.7, 128.1, 128.3, 128.5,
major, J = 7.2 Hz), 7.05 7.75 (m, 10 H major + 10 H mi- 128.7, 128.8, 132.0, 132.5, 137.9,
nor) 138.6, 141.7, 142.5, 143.9, 144.0
7h
77
1600
1444
1066
60:40
0.46 (s, 3 H major), 0.79 (s, 3 H major), 0.87 (s, 3 H mi- 20.0, 20.6, 21.2, 22.4, 23.0, 24.1,
nor), 1.13 (s, 3 H major), 1.17 (s, 3 H minor), 1.18 (s, 3
H minor), 1.20 (s, 3 H minor), 2.05 (s, 3 H major), 3.78
(d, 1 H major, J = 7.3 Hz), 3.87 (d, 1 H major, J = 7.3
Hz), 3.92 (d, 1 H minor, J = 7.5 Hz), 4.23 (d, 1 H minor,
J = 7.5 Hz), 7.03 7.24 (m, 4 H major + 4 H minor),
7.30 7.41 (m, 6 H major + 6 H minor), 7.47 7.68 (m, 5
H major + 5 H minor)
60.7, 62.2, 68.6, 71.0, 73.9, 74.3,
77.8, 78.2, 97.8, 100.7, 126.1,
126.6, 126.8, 127.1, 127.3, 127.4,
127.4, 127.8, 128.0, 128.1, 128.1,
128.5, 128.7, 128.8, 140.2, 140.5,
142.1, 142.2, 144.0, 144.4.
a Satisfactory microanalyses.
b Yield of isolated material.
c Diastereomeric ratio, determined by 1H NMR on the crude reaction mixture; 5 % error of the stated value.
d Separated by column chromatography on silica gel (petroleum ether–AcOEt, 9:1).
e KBr in this case.
Synthesis 2001, No. 15, 2299–2306 ISSN 0039-7881 © Thieme Stuttgart · New York

2304
V. Capriati et al.
PAPER
Table 6 Oxazolinylepoxides 16 Prepared from Lithiated 2-(1-chloroethyl)-2-oxazoline (15b)
Producta
Yield (%)b
86
IR (film,
cm–1)
1H NMR (CDCl3/TMS) , J (Hz)
13C NMR (CDCl3)
16a
1673
0.94 1.40 (2 t, 6 H major + 6 H minor), 1.50–
1.84 (m, 4 H major + 4 H minor), 1.63 (s, 3 H major
9.5, 17.2, 17.6, 22.7, 23.4, 23.8, 59.3,
59.5, 61.6, 61.8, 69.6, 69.7, 74.0,
+ 3 H minor), 3.37 (s, 3 H minor), 3.38 (s, 3 H ma- 74.2, 74.5, 74.7, 84.2, 125.8, 125.9,
jor), 3.42–3.52 (m, 1 H major + 1 H minor), 3.60– 128.5, 129.0, 140.5, 140.9, 167.0
3.67 (m, 1 H major + 1 H minor), 4.16–4.22 (m, 1
H major + 1 H minor), 5.37 (d, 1 H major + 1 H mi-
nor, J = 6.9 Hz), 7.27–7.38 (m, 5 H major + 5 H mi-
nor)
16b
16c
75
75
1672
1670
1.40–1.80 (m, 10 H major + 10 H minor), 1.61 (s,
3 H minor),1.62 (s, 3 H major), 3.35 (s, 3 H major),
3.37 (s, 3 H minor), 3.40–3.52 (m, 1 H major + 1 H
minor), 3.55–3.64 (m, 1 H major + 1 H minor),
4.14–4.25 (m, 1 H major + 1 H minor), 5.35 (d, 1
H major + 1 H minor, J = 6.9 Hz), 7.27–7.38 (m, 5
H major + 5 H minor)
16.8, 17.1, 25.1, 25.14, 25.2, 25.7,
30.4, 30.5, 31.2, 31.4, 59.3, 59.5,
61.2, 61.4, 67.3, 67.5, 74.0, 74.2,
74.5, 74.7, 84.2, 84.3, 125.8, 126.0,
126.1, 128.5, 128.53, 129.0, 140.5,
140.8, 166.8, 167.0
1.20–1.80 (m, 22 H major + 22 H minor), 1.63 (s,
3 H major + 3 H minor), 3.37 (s, 3 H major), 3.38
17.4, 17.8, 20.3, 20.4, 20.5, 22.4,
22.5, 26.3, 26.6, 26.61, 27.2, 28.0,
(s, 3 H minor), 3.40–3.52 (m, 1 H major + 1 H mi- 59.4, 61.1, 61.3, 68.8, 74.0, 74.2,
nor), 3.55–3.64 (m, 1 H major + 1 H minor), 4.17– 74.5, 74.7, 84.0, 125.8, 126.0, 126.1,
4.21 (m, 1 H major + 1 H minor), 5.37 (d, 1 H ma- 128.5, 128.9, 129.0, 140.5, 140.9,
jor, J = 6.9 Hz), 5.38 (d, 1 H minor, J = 6.6 Hz),
167.0, 167.2
7.27–7.38 (m, 5 H major + 5 H minor)
a Satisfactory microanalyses.
b Isolated yields.
We found that 2-lithio-(1-chloroethyl)-2-oxazoline 3 re-
acts efficiently with imines (Scheme 7). Indeed, satisfac-
tory to very good yields of oxazolinylaziridines 17a–f
could be obtained when 3 was treated with the appropriate
Schiff’s bases.9 It is worth noting that in some cases the
coupling reaction proceeded with complete E diastereose-
lection affording oxazolinylaziridines 17d–f, while 17c
was found to be a mixture of E and Z diastereoisomers
(Table 7).
O
O
O
O
Ph
Ph
Ph
Ph
CH3
H
CH3
CH3
10
11
O
O
O
Ph
Ph
CH3
Ph
CH3
CH3
Ph
12
13
In conclusion, this paper describes a simple preparation of
oxazolinyl- and oxazolidinylepoxides and oxazolinylazir-
idines, which look like useful synthetic intermediates.
Scheme 5
OCH3
(S)
Li
CH3
Cl
Ph(S)
Cl
OCH3
N
CH3
dr
N
OCH3
LDA; -78 °C
THF
R2C=O
N
O
R
R
O
CH3
(S)
(S)
O
75 - 86 %
(S)
(S)
O
15a
15b
16
Ph
Ph
t-BuOCl 92%
OCH3
R
R
16
1:1.26
1:1
a
b
c
CH3CH2
CH3CH2
N
- (CH2)5
-
CH3
1:1.1
(S)
(S)
O
- (CH2)11
-
14
Ph
Scheme 6
Synthesis 2001, No. 15, 2299–2306 ISSN 0039-7881 © Thieme Stuttgart · New York

PAPER
Synthesis of Substituted Oxazolinyloxiranes and Oxazolinylaziridines
2305
points are uncorrected. TLC was performed on Merck silica gel
plates with F-254 indicator; visualization was accomplished with
UV light (254 nm). Column chromatography was performed by us-
ing silica gel (70–230 mesh) with petroleum ether–Et2O (or AcOEt)
mixtures as the eluent. A –80 °C bath refers to a mixture of liquid
nitrogen and EtOH; the temperature was controlled with a spirit
filled low-temperature thermometer (Aldrich) and kept at a fixed
value by adding liquid nitrogen from time to time. All reactions in-
volving air sensitive reagents were performed under N2 in oven–
dried glassware using syringe septum cap techniques.
R2
R
Cl
CH3
O
N
1) LDA, THF, -80 °C
2) RR1C=NR2
N
N
CH3
O
R1
2
17
17
R
R1
R2
a
b
c
d
e
f
CH3
CH3
Ph
Ph
Ph
- (CH2)5
-
CH3
Ph
C2H5
H
PhCh2
PhSo2
Ph
Ph
Ph
H
CH3
Reaction of 2-(1-chloroethyl)-4,4-dimethyl-2-oxazoline Lithium
Derivative (3) with Electrophiles; General Procedure for the
Synthesis of 4a–c.
Scheme 7
Procedure for a 2 mmol scale: A solution of 2.4 mmol of lithium di-
isopropylamide (LDA) (from diisopropylamine (347 L ) and 2.5 M
n-BuLi (960 L) in anhyd THF (10 mL) was prepared under N2 and
stirred at 0 °C for 15 min. To this solution, pre-cooled to –80 °C
with an EtOH-liquid N2 bath, 2-(1-chloroethyl)-4,4-dimethyl-2-ox-
azoline (2) (323 mg, 2.0 mmol) in anhyd THF (5 mL ) was added
dropwise and the resulting yellow solution stirred at this tempera-
ture for 20 min. The electrophile (CD3OD, CH3I or (CH3)3SiCl) (5
mmol) was then added and the resulting solution warmed to r.t. The
reaction mixture was then quenched with sat. aq. NH4Cl and ex-
tracted with Et2O (3 30 mL). Combined organic layers were dried
(Na2SO4) and concentrated in vacuo. In the case of compound 4c,
the crude mixture was flash-chromatographed (silica gel; petroleum
ether–AcOEt ,9:1) and the product isolated. The crude mixture of
4a and 4b was instead analyzed without further purification.
Tetrahydrofuran (THF) was freshly distilled under N2 from sodium
benzophenone ketyl. Petroleum ether refers to the 40–60 °C boiling
fraction. Commercial hexanes solutions of n-BuLi and Grignard re-
agents (Et2O solutions) were purchased from Aldrich and were ti-
trated by using N-pivaloyl-o-toluidine prior to use.10 All other
chemicals were of commercial grade (Aldrich) and distilled just pri-
or to use. 2-(1-Chloroethyl)-4,4-dimethyl-2-oxazoline was pre-
pared as reported.3,9 NMR Varian EM 390, Varian XL 200 (200
MHz and 50.3 MHz for 1H and 13C, respectively), Bruker (300 MHz
1
1
for H) were used for NMR spectroscopic determination. For H
NMR, CDCl3 was used as solvent, ( H = 7.24) and TMS as internal
standard; for 13C NMR, CDCl3
(
C = 77.0) and [D6] acetone
(
C = 20.83). IR spectra were recorded on Perkin Elmer 283 and
FTIR spectra on Perkin Elmer 1600. GC-MS spectrometry analyses
were performed with a HP 5995C gas chromatograph (dimethylsil-
icon capillary column, 30 m, 0.25 mm i.d.) equipped with a mass se-
lective detector operating at 70 eV (EI). Microanalyses were
performed with a Carlo Erba Mod. 1106 C, H, N analyzer. Melting
Reaction of 2-(1-chloroethyl)-4,4-dimethyl-2-oxazoline Lithium
Derivative (3) with Carbonyl compounds; General Procedure
for the Synthesis of the Chlorohydrins (5a–b, 5d–m).
Procedure for a 2 mmol scale: A solution of 2.4 mmol of LDA (from
diisopropylamine (347 L) and 2.5 M n-BuLi (960 L) in anhyd
Table 7 Oxazolinylaziridines 17 Prepared from Lithiated 2-(1-chloroethyl)-2-oxazoline (3)
Producta,b
Yield (%)c
IR (film,
cm–1)
1H NMR (CDCl3/TMS) , J (Hz)
13C NMR (CDCl3)
17a
60
1660, 1500
1670, 1500
1650, 1500
1650, 1500
1.21 (s, 3 H), 1.32 (s, 6 H), 1.38 (s, 3 H), 1.42
(s, 3 H), 4.0 (s, 2 H), 6.74 7.25 (m, 5 H)
13.6, 16.3, 23.2, 28.1, 28.2, 44.5, 45.3,
67.2, 79.0, 120.2, 120.8, 128.3, 145.5,
165.6
17b
55
85
80
1.29 (s, 3 H), 1.31 (s, 3 H), 1.45 (s, 3 H),
1.10 1.80 (m, 10 H), 3.98 (s, 2 H), 6.75 7.26
(m, 5 H)
14.2, 25.5, 25.9, 26.5, 28.9, 29.0, 34.6,
45.4, 51.5, 68.0, 79.7, 121.0, 121.5, 129.0,
146.3, 166.5
17cd
17de
1.0–1.8 (m, 17 H), 3.9 4.0 (m, 2 H), 6.7 7.3
(m, 5 H)
10.3, 12.8, 13.6, 14.0, 19.8, 24.6, 28.3,
28.40, 28.42, 29.5, 29.6, 49.2, 67.4, 79.0,
120.0, 121.0, 128.5, 145.7, 165.5
1.20 (s, 3 H), 1.26 (s, 3 H), 1.28 (s, 3 H), 3.65
(s, 1 H), 3.85 (d, 1 H, J = 14.0 Hz), 3.90 (d, 1
H, J = 14.0 Hz), 3.92 (s, 2 H), 7.25 7.46 (m,
10 H)
16.7, 28.3, 28.6, 43.1, 50.8, 56.4, 67.4,
78.8, 126.7, 126.9, 127.8, 127.9, 128.0,
136.5, 139.5, 163.5
17ee
55
1670, 1450
1.29 (s, 3 H), 1.40 (s, 6 H), 4.09 4.19 (2 d,
AB system, 2 H, J = 7.9 Hz), 4.87 (s, 1 H),
7.16 7.48 (m, 5 H), 7.50 7.62 (m, 3 H),
8.00 8.05 (m, 2 H)
16.6, 27.5, 27.8, 50.2, 50.6, 67.6, 79.7,
126.0, 127.0, 128.0, 128.2, 128.9, 132.3,
133.0, 140.0, 161.0
a Satisfactory microanalyses.
b Spectroscopic data and the E configuration of aziridine 17f have been reported in ref. 9
c Isolated yields.
d E + Z diastereomeric mixture.
e The E configuration of aziridine 17d has been discussed in ref. 9. The E configuration of aziridine 17e was established on the basis of the
vanishing 3JCH ~ 0 Hz between the aziridine ring hydrogen and the CH3 on the adjacent carbon according to ref. 6b
Synthesis 2001, No. 15, 2299–2306 ISSN 0039-7881 © Thieme Stuttgart · New York

2306
V. Capriati et al.
PAPER
THF (10 mL)) was prepared under N2 and stirred at 0 °C for 15 min.
To this solution, cooled to –80 °C, 2-(1-chloroethyl)-4,4-dimethyl-
2-oxazoline (2) (323 mg, 2.0 mmol) in anhyd THF (5 mL) was add-
ed dropwise and the resulting yellow solution stirred at this temper-
ature for 20 min. The carbonyl compound (2.4 mmol in 5 mL of
anhyd THF) was then added dropwise at –80 °C and the resulting
solution stirred for further 30 min. The reaction mixture was
quenched with sat. aq. NH4Cl and extracted with Et2O (3 30 mL).
Combined organic layers were dried (Na2SO4) and concentrated in
vacuo. The crude mixture was flash-chromatographed (silica gel;
petroleum ether–AcOEt, 6:4) to give pure chlorohydrins 5a–b, 5d–
m.
warmed to r.t. The reaction mixture was quenched with sat aq.
NH4Cl and extracted with AcOEt (3 30 mL). Combined organic
layers were dried (Na2SO4) and concentrated in vacuo. The crude
mixture was flash-chromatographed (silica gel; petroleum ether–
AcOEt, 6:4) to give pure epoxides 16a–c.
Addition of Grignard Reagents to the Oxazolinylepoxide 6c;
General Procedure for the Synthesis of Oxazolidines 7a–h
Procedure for a 1 mmol scale: To a solution of the oxazolinylep-
oxide 6c (245 mg, 1 mmol) in anhyd THF (2 mL) under N2 at 0 °C,
methyl triflate (CH3SO3CF3, 170 L, 1.5 mmol) was added. After
30 min, to the resulting N-methyloxazolinium salt, the Grignard re-
agent (1.1 mmol) mixed with hexamethylphosphorous triamide
(HMPT, 400 L, 2.2 mmol) in anhyd THF (2 mL) was added drop-
wise at r.t. The reaction mixture was stirred for 50 min, quenched
with sat aq. NH4Cl and extracted with Et2O (3 10 mL). Combined
organic layers were dried (Na2SO4) and concentrated in vacuo. The
crude mixture was purified by flash-chromatography (silica gel; pe-
troleum ether–Et2O, 9:1) to give 7a–h.
Preparation of Oxazolinylepoxides 6a–m
The chlorohydrins 5a–m were cyclized quantitatively to epoxides
6a–m, respectively, in NaOH/i-PrOH.11 The epoxides were purified
by flash chromatography (silica gel; petroleum ether–AcOEt, 6:4).
Reaction of 2-(1-chloroethyl)-4,4-dimethyl-2-oxazoline Lithium
derivative (3) with Schiff’s Bases; General Procedure for the
Synthesis of the Oxazolinylaziridines 17a–f
Acknowledgement
Procedure for a 2 mmol scale: A solution of 2.4 mmol of LDA (from
diisopropylamine (347 L) and of 2.5 M n-BuLi (960 L) in anhyd
THF(10 mL)) was prepared under N2 and stirred at 0 °C for 15 min.
To this solution, cooled to –80 °C, 2-(1-chloroethyl)-4,4-dimethyl-
2-oxazoline (2) (323 mg, 2.0 mmol) in anhyd THF (5 mL) was add-
ed dropwise and the resulting yellow solution stirred at this temper-
ature for 20 min. The Schiff’s base (2.0 mmol in 5 mL of anhyd
THF) was then added dropwise over 20 min at –80 °C and the re-
sulting solution stirred for a time variable between 3–5 h (TLC
monitoring). The reaction mixture was quenched with sat. aq.
NH4Cl and extracted with Et2O (3 30 mL). Combined organic lay-
ers were dried (Na2SO4) and concentrated in vacuo. The crude mix-
ture was separated by flash-chromatography (silica gel; petroleum
ether–Et2O, 1:1) to give oxazolinylaziridines 17a–f.
This work was carried out under the framework of the National Pro-
ject “Stereoselezione in Sintesi Organica. Metodologie ed Applica-
zioni” supported by the Ministero dell’Università e della Ricerca
Scientifica e Tecnologica (MURST, Rome) and by the University
of Bari and CNR (Rome).
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Chem. 1987, 40, 39. (b) Liddell, J. R.; Whiteley, C. G. S.
Afr. J. Chem. 1991, 44, 35.
(1R,4’S,5’S/1S,4’S,5’S)-2-(1-Chloroethyl)-4-methoxymethyl-5-
phenyl-2-oxazoline (15a)
Chlorination of the 2-ethyl derivative 1412 was carried out as report-
ed in ref.4 to give oxazoline 15a as a mixture of diastereoisomers af-
ter flash chromatography (petroleum ether–AcOEt, 4:1).
Colorless oil, 92% yield.
IR (film): 3064, 1667, 1496, 1397, 1129, 1086, 699 cm–1.
1H NMR: = 1.77 (d, 3 H, J = 7.5 Hz), 1.83 (d, 3 H, J = 7.5 Hz),
3.40 (s, 3 H), 3.43–3.58 (m, 1 H), 3.60–3.70 (m, 1H), 4.10–4.80 (2
q, 1 H, J = 7.5 Hz), 5.40 (d, 1 H, J = 7.3 Hz) 7.25–7.45 (m, 5 H).
13C NMR: = 22.0, 48.6, 48.8, 59.3, 73.8, 74.4, 74.5, 84.1, 125.3,
127.6, 128.2, 128.8, 140.2, 140.3, 166.3.
GC MS (70 eV) m/z (%): 254 (4, M+), 208 (34), 146 (26), 119 (53),
112 (69), 91 (62), 77 (27), 45 (100).
Reaction of (1R,4’S,5’S/1S,4’S,5’S)-2-(1-chloroethyl)-4-
methoxymethyl-5-phenyl-2-oxazoline Lithium Derivative (15b)
with Carbonyl Compounds; General Procedure for the
Synthesis of the Oxazolinylepoxides 16a–c
Procedure for a 2 mmol scale: A solution of 2.4 mmol of LDA (from
diisopropylamine (347 L) and 2.5 M n-BuLi (960 L) in anhyd
THF (10 mL )) was prepared under N2 and stirred at 0 °C for 15 min.
To this solution, cooled to –78 °C, oxazoline 15a (507 mg, 2.0
mmol) in anhyd THF (5 mL) was added dropwise and the resulting
yellow solution was stirred at this temperature for 20 min. The car-
bonyl compound (2.4 mmol in 5 mL of anhyd THF) was then added
dropwise at –78 °C and the resulting solution stirred for 1 h and
(9) Florio, S.; Troisi, L.; Capriati, V.; Ingrosso, G. Tetrahedron
Lett. 1999, 40, 6101.
(10) Suffert, J. J. Org. Chem. 1989, 54, 509.
(11) Florio, S.; Capriati, V.; Russo, V. Gazz. Chim. Ital. 1997,
127, 587.
(12) Meyers, A. I.; Knaus, G.; Kamata, K.; Ford, M. E. J. Am.
Chem. Soc. 1976, 98, 567.
Synthesis 2001, No. 15, 2299–2306 ISSN 0039-7881 © Thieme Stuttgart · New York