Reaction of electrophilic allyl halides with amines: A reinvestigation

Article abstract of DOI:10.1055/s-2006-942421

The Michael-induced ring closure (MIRC) of amines with 2- bromoalkylidenemalonates has been reinvestigated and the reaction products with primary amines have been identified as (2-iminoethyl)malonates and not 2-aminoalkylidenemalonates as previously repor

Full text of DOI:10.1055/s-2006-942421

2260
PAPER
Reaction of Electrophilic Allyl Halides with Amines: A Reinvestigation
ith Amines Mangelinckx,a Dirk Courtheyn,a Roland Verhé,a Veronique Van Speybroeck,b Michel Waroquier,b
R
eaction of El
v
ectrophilic
A
e
llyl
H
alide
n
s
w
Norbert De Kimpe*a
a
Department of Organic Chemistry, Faculty of Bioscience Engineering, Ghent University, Coupure links 653, 9000 Ghent, Belgium
b
Laboratory of Theoretical Physics, Ghent University, Proeftuinstraat 86, 9000 Ghent, Belgium
Fax +32(9)2646243; E-mail: norbert.dekimpe@UGent.be
Received 4 January 2006
Dedicated to Professor Dieter Hoppe on the occasion of his 65th birthday
O
NH2
Abstract: The Michael-induced ring closure (MIRC) of amines
with 2-bromoalkylidenemalonates has been reinvestigated and the
R
H2O
COOR1
H
COOR1
H
COOR1
H2N
R
R
reaction products with primary amines have been identified as (2-
iminoethyl)malonates and not 2-aminoalkylidenemalonates as pre-
viously reported. The (2-iminoethyl)malonates are formed by ring
opening of the intermediate unstable 2-aminocyclopropane-1,1-di-
carboxylates (b-ACCs) and were characterized spectroscopically
and via chemical transformation.
2
1
Scheme 1
Reinvestigation of the reaction of electrophilic allyl ha-
lides 3 with amines established that indeed formal substi-
tution products 4a–c were cleanly formed with secondary
amines, but that products generated on treatment with pri-
mary amines were not the substitution products 4 as iden-
tified in our earlier report (Table 1 and Scheme 2).4
Careful analysis of the spectra and chemical transforma-
tion showed the presence of an imino function. The major
reaction products (79–100% yield) were identified as (2-
iminoethyl)malonates 5. From the reactions with isopro-
pylamine, g-lactams 6a,d,e and 7a,d were identified as
Key words: Michael additions, ring closure, cyclopropanes, ring
opening, imines
Recently, we described the synthesis of 2-(diphenylmeth-
ylidenamino)- and 2-azidocyclopropane-1,1-dicarboxy-
lates via Michael-induced ring closure (MIRC) of
diphenylmethylideneamine and azide, respectively, to 2-
bromoalkylidenemalonates.1 The former cyclopropanes
are protected derivatives of 2-aminocyclopropanecarbox-
ylates (b-ACCs) 1, which are one of the most conforma-
tionally constrained classes of b-amino acid derivatives
and find applications in the field of b-peptide chemistry
and synthetic organic chemistry.2 However, an appropri-
ate N-protecting group has to be introduced during the
synthesis of b-ACCs to inhibit their ring opening to g-
oxocarboxylates 2, due to the 1,2-push–pull substitution
on the cyclopropane ring (Scheme 1).3 From earlier re-
search, it has been reported that treatment of dimethyl 2-
bromo-2-methylpropylidenemalonate 3a with primary
and secondary amines gave rise to the formation of the
formal substitution products, i.e. 2-aminoalkylidenema-
lonates 4,4 while the reaction of diethyl 2-bromoeth-
ylidenemalonate with proline benzyl ester afforded the
corresponding aminocyclopropane.5 More recently, it has
been described that primary amines give the correspond-
ing Michael adducts in the reaction with diethyl 2,2,2-
trichloroethylidenemalonate.6 The divergent reactivity of
amines with dimethyl 2-bromo-2-methylpropylidenema-
lonate as compared to the reactivity of other N-nucleo-
philes with related electrophilic allyl halides,1,5,7
prompted us to reinvestigate this reaction in order to get
better mechanistic insights.
1
minor side-products based on H NMR and MS analysis
of the reaction mixtures. After the reaction of allyl bro-
mide 3a with benzhydrylamine, some signals were
1
present in the H NMR spectrum of the reaction mixture
corresponding to the presence of about 19% of aziridine
8c [d = 1.17, 1.26 (2 × s, 2 × 3 H), 2.17 (d, J = 9.63 Hz, 1
H), 3.10 (s, 3 H), 3.17 (d, J = 9.63 Hz, 1 H), 3.71 (s, 3 H),
4.22 (s, 1 H)]. A rapid chromatography over a plug of sil-
ica gel was performed to obtain the pure aldimine 5c,
while avoiding hydrolysis to the corresponding aldehyde
10. The unsaturated g-lactam 6c was also isolated in 11%
yield, resulting from the acid-catalyzed ring opening of
aziridine 8c to the corresponding allyl amine 4 [R4 =
(Ph)2CH, R5 = H] and further lactamization.
Spectral analysis allows the discrimination between sub-
stitution products 4 and aldimines 5. Obviously, the aldi-
mines 5a–e have a malonate methine function, not present
in the corresponding substitution products 4. This mal-
onate CH-function resonates at d = 3.67–3.88 ppm in the
1H NMR spectrum (CDCl3), close to the signal of the two
methoxy groups (d = 3.57–3.70 ppm). This CH-proton of
5a and 5b was not detected during the first investigation4
since it did not give a resolved resonance signal in the 1H
NMR spectra obtained with a 60 MHz apparatus. This, to-
gether with the unavailability of 13C NMR explains the in-
correct characterization. However, a clear difference
exists in the chemical shift of the aldimine proton of 5
(d = 7.51–7.86 ppm) and the olefinic proton of 4 (d =
6.88–6.97 ppm). In the latter compounds the two methoxy
SYNTHESIS 2006, No. 13, pp 2260–2264
x
x.
x
x
.
2
0
0
6
Advanced online publication: 12.06.2006
DOI: 10.1055/s-2006-942421; Art ID: C03106SS
© Georg Thieme Verlag Stuttgart · New York

PAPER
Reaction of Electrophilic Allyl Halides with Amines
2261
Table 1 Reaction of 2-Bromoalkylidenemalonates 3 with Two Equivalents of Amine in Diethyl Ether at Reflux Temperature
Time (h) Yield (%)a Ratio of reaction products (%)b,c
Substrate Amine
3
5
4
6
7
8
–
–
8
–
8
3a
3a
3a
3b
3c
3a
3a
3a
i-PrNH2
3
12
5
94
96
–
–
2
–
–
–
9
83 (72)
100
79 (78)
–
9
–
–
t-BuNH2
–
–
(Ph)2CHNH2
i-PrNH2
100
95
–
(11)d
6
19
–
10
16
5
86 (20)
82 (53)
–
i-PrNH2
81
–
18
–
(CH2)4NH
(CH2)5NH
(O(CH2)4)NH
82
100e (53)f
91e (46)f
87e (19)f
6
100
100
4
13
a Crude yield of aldimine 5 or allyl amine 4.
b Based on integration of 1H NMR of reaction crude.
c Parentheses indicate isolated yields.
d g-Lactam 6c was formed from aziridine 8c during purification via chromatography (silica gel).
e Traces of aldehyde 10 and other unidentified side-products were observed in the reaction crude.
f Acid–base extraction afforded the analytically pure amines 4, but the yield dropped due to losses in the aqueous phase.
groups give two separate signals in 1H NMR. Also in the anoborohydride in methanol at room temperature. The al-
IR spectra, a distinction can be made between the aldi- dimine structure of compounds 5 was further proven by
mine function (1660–1666 cm–1) and the C=C bond the hydrolysis of 5a to the known aldehyde 10.8
(1641–1645 cm–1).
The formation of the aldimines 5 and 2-aminoalkylidene-
Besides spectroscopic evidence for the characterization of malonates 4 can be explained via a single mechanistic
the aldimines 5, chemical transformation also allowed to scheme (Scheme 4). Both primary and secondary amines
confirm their structure (Scheme 3). From our experience give 1,4-addition to the 2-bromoalkylidenemalonates 3 to
in the reduction of 2-(diphenylmethylidenamino)cyclo- afford the adducts 11. With primary amines, a further ring
propane-1,1-dicarboxylates to 3-(alkoxycarbonyl)pyrroli- closure via C-alkylation occurs to the corresponding 2-
din-2-ones via the intermediate g-iminodicarboxylates aminocyclopropane-1,1-dicarboxylates 12. The latter b-
5,1a it was expected that treatment of the aldimines 5 with ACC derivatives are however not stable and undergo ring
sodium cyanoborohydride would give the corresponding opening spontaneously to the iminium enolates 13, which
g-lactams. Indeed, 3-(methoxycarbonyl)pyrrolidin-2- suffer proton transfer to form the stable aldimines 5. With
ones 9a and 9c1a were formed in good to excellent yields secondary amines, the addition products 11 probably un-
from reduction of aldimines 5a and 5c with sodium cy- dergo further N-alkylation to the aziridinium compounds
2 equiv R4R5NH
COOMe
R1
R2 Br
COOR3
COOR3
R5R4N
COOMe
Et2O, ∆, 4–6 h
4a (82%) [R4,R5 = (CH2)4]
4b (100%) [R4,R5 = (CH2)5]
4c (100%) [R4,R5 = O(CH2)4]
3a [R1 = R2 = R3 = Me]
3b [R1 = R2 = Me, R3 = Et]
3c [R1,R2 = (CH2)5, R3 = Me]
2 equiv R4NH2
Et2O, ∆, 3–16 h
R4
N
COOR3
O
R4HN
R1
COOR3
O
R4
N
COOR3
COOR3
R1
R2
R1
R2
COOR3
COOR3
+
+
+
R2
N
N
H
R1 R2
R4
R4
5a (94%) [R1 = R2 = R3 = Me, R4 = i-Pr]
5b (96%) [R1 = R2 = R3 = Me, R4 = t-Bu]
5c (78%) [R1 = R2 = R3 = Me, R4 = (Ph)2CH]
5d (95%) [R1 = R2 = Me, R3 = Et, R4 = i-Pr]
5e (81%) [R1,R2 = (CH2)5, R3 = Me, R4 = i-Pr]
7a (not isolated)
7b (not observed)
7c (not observed)
7d (not isolated)
7e (not observed)
8a (not observed)
8b (not observed)
8c (not isolated)
8d (not observed)
8e (not observed)
6a (not isolated)
6b (not observed)
6c (11%)
6d (not isolated)
6e (not isolated)
Scheme 2
Synthesis 2006, No. 13, 2260–2264 © Thieme Stuttgart · New York

2262
S. Mangelinckx et al.
PAPER
ed on a Perkin–Elmer Spectrum One spectrophotometer. Mass
spectra were recorded on an Agilent 1100 Series mass spectrometer
using a direct inlet system (ES, 4000V). Melting points were mea-
sured with a Büchi B-540 apparatus and are uncorrected. Elemental
analyses were measured with a Perkin–Elmer 2400 Elemental Ana-
lyzer. Flash chromatography was performed with silica gel (particle
size 0.035–0.070 mm, pore diameter ca. 6 nm) using a glass col-
umn. The boiling range of petroleum ether used was 40–60 °C.
14 which are prone to ring opening to the stable allyl
amines 4. It is clear that with the primary amines minor
pathways are present, either via compounds 14 or through
ring opening of b-ACCs 12, which lead to the formation
of aziridine 8c and g-lactams 6 and 7. With the secondary
amines, it is also reasonable that cyclopropanes 12, in
equilibrium with the ring-opened compounds 13, are mi-
nor intermediates leading to allyl amines 4 via aziridinium
enolates 15.
Synthesis of 2-(Iminoethyl)malonates 5 and 2-Amino-
alkylidenemalonates 4; General Procedure
To a solution of 2-bromoalkylidenemalonate 39 (2 mmol) in anhyd
Et2O (5 mL) was added the primary or secondary amine (4 mmol).
The reaction mixture was stirred at reflux for 3–16 h. The reaction
mixture was diluted with anhyd Et2O, filtered and concentrated to
give the aldimines 5 as light yellow oils, except for aldimine 5c and
lactam 6c (white crystals), which were obtained by column chroma-
tography (silica gel, PE–EtOAc, 3:7), or allyl amines 4a,b (clear
oils) and 4c (white crystals). Analytically pure samples of the aldi-
mines 5a,d,e were obtained by high-vacuum distillation (5a and 5d)
or Kugelrohr distillation (5e) as clear oils. Analytically pure sam-
ples of the allyl amines 4 were obtained by acid–base extraction (aq
2 N HCl–Et2O–NaOH–CH2Cl2 or Et2O).
R4
R4
1.1 equiv NaCNBH3
N
COOMe
COOMe
N
O
1.1 equiv HOAc
H
MeOH, r.t., 17–21 h
COOMe
5a [R4 = i-Pr]
5c [R4 = (Ph)2CH]
9a (76%)
9c (94%)
1.5 equiv HCl (2 N)
CH2Cl2–H2O (1:1), r.t., 16 h
O
COOMe
COOMe
Dimethyl [(2E)-2-(N-Isopropylimino)-1,1-dimethylethyl]-
malonate (5a)
Bp 76–82 °C/0.8 mmHg.
H
10 (90%) (from 5a)
IR (NaCl): 1757, 1736, 1666 cm–1.
Scheme 3
1H NMR (300 MHz, CDCl3): d = 1.09 (d, J = 6.33 Hz, 6 H), 1.25 (s,
6 H), 3.28 (sept, J = 6.33 Hz, 1 H), 3.70 (s, 6 H), 3.75 (s, 1 H), 7.65
(s, 1 H).
In conclusion, while secondary amines afforded, as al-
ready described, 2-aminoalkylidenemalonates upon reac- 13C NMR (75 MHz, CDCl3): d = 23.8 (4 × CH3), 40.5, 52.0, 58.6,
60.7, 165.8, 168.8.
tion with 2-bromoalkylidenemalonates, primary amines
MS (ES, +ve mode): m/z (%) = 244 (100) [M + H+].
efficiently yielded 2-(iminoethyl)malonates. The latter
compounds are suitably functionalized for further trans-
formations to g-amino acid derivatives and N-heterocy-
clic compounds.
Anal. Calcd for C12H21NO4: C, 59.24; H, 8.70; N, 5.76. Found: C,
59.09; H, 8.59; N, 5.67.
Dimethyl [(2E)-2-(N-tert-Butylimino)-1,1-dimethylethyl]-
malonate (5b)
1H NMR spectra (300 MHz) and 13C NMR spectra (75 MHz or 68
MHz) were recorded on a Jeol Eclipse FT 300 NMR spectrometer
or a Jeol JNM-EX 270 NMR spectrometer. IR spectra were record-
IR (NaCl): 1758, 1736, 1666 cm–1.
1H NMR (300 MHz, CDCl3): d = 1.10 (s, 9 H), 1.23 (s, 6 H), 3.70
R4R5HN
NR4R5
R4
H
R5
N
COOR3
R1
R2 Br
COOR3
COOR3
R4R5NH
R1
COOR3
COOR3
– HBr
R1
R2
COOR3
COOR3
12
O
R2 Br
R1 R2
OR3
11
3
13
– Br
R5 = H
R4
N
R4 R5
N
R4 R5
N
R4
H
O
N
COOR3
R5 = H
R5 = H
R1
R1
R2
R1
COOR3
COOR3
COOR3
COOR3
OR3
COOR3
COOR3
R2
R2
R1 R2
15
5
14
8
COOR3
R1
R2
R5R4N
COOR3
COOR3
R1
R5 = H
– R3OH
O
R2
N
R4
4
6
Scheme 4
Synthesis 2006, No. 13, 2260–2264 © Thieme Stuttgart · New York

PAPER
Reaction of Electrophilic Allyl Halides with Amines
2263
(s, 6 H), 3.80 (s, 1 H), 7.51 (s, 1 H).
Dimethyl (2-Methyl-2-pyrrolidin-1-ylpropylidene)malonate
(4a)4
IR (NaCl): 1735, 1644 cm–1.
13C NMR (75 MHz, CDCl3): d = 23.8, 29.4, 40.8, 51.9, 56.2, 58.4,
162.1, 169.1.
1H NMR (300 MHz, CDCl3): d = 1.24 (s, 6 H), 1.67 (m, 4 H), 2.54
(m, 4 H), 3.76 (s, 3 H), 3.77 (s, 3 H), 6.97 (s, 1 H).
MS (ES, +ve mode): m/z (%) = 258 (100) [M + H+].
Anal. Calcd for C13H23NO4: C, 60.68; H, 9.01; N, 5.44. Found: C,
60.80; H, 9.12; N, 5.22.
13C NMR (75 MHz, CDCl3): d = 23.2, 23.4, 46.1, 51.9, 52.4, 56.0,
126.3, 154.5, 164.9, 167.0.
Dimethyl {(2E)-2-[N-(Diphenylmethyl)imino]-1,1-dimethyl-
ethyl}malonate (5c)
Rf = 0.71 [PE–EtOAc (3:7)].
MS (ES, +ve mode): m/z (%) = 256 (100) [M + H+].
Anal. Calcd for C13H21NO4: C, 61.16; H, 8.29; N, 5.49. Found: C,
60.90; H, 8.41; N, 5.42.
IR (NaCl): 1757, 1736, 1666 cm–1.
Dimethyl (2-Methyl-2-piperidin-1-ylpropylidene)malonate
(4b)4
1H NMR (300 MHz, CDCl3): d = 1.30 (s, 6 H), 3.57 (s, 6 H), 3.88
(s, 1 H), 5.34 (s, 1 H), 7.17–7.32 (m, 10 H), 7.82 (s, 1 H).
IR (NaCl): 1734, 1645 cm–1.
13C NMR (75 MHz, CDCl3): d = 23.8, 41.3, 52.0, 58.4, 77.1, 126.8,
127.5, 128.3, 143.7, 168.7, 168.9.
1H NMR (300 MHz, CDCl3): d = 1.19 (s, 6 H), 1.38 (m, 2 H), 1.51
(m, 4 H), 2.42 (m, 4 H), 3.77 (s, 3 H), 3.82 (s, 3 H), 6.93 (s, 1 H).
MS (ES, +ve mode): m/z (%) = 368 (100) [M + H+].
13C NMR (75 MHz, CDCl3): d = 22.7, 24.8, 26.1, 47.7, 51.9, 52.4,
58.9, 125.8, 155.8, 164.9, 166.8.
Anal. Calcd for C22H25NO4: C, 71.91; H, 6.86; N, 3.81. Found: C,
71.78; H, 6.98; N, 3.70.
MS (ES, +ve mode): m/z (%) = 270 (100) [M + H+].
Methyl 1-(Diphenylmethyl)-5,5-dimethyl-2-oxo-2,5-dihydro-
1H-pyrrole-3-carboxylate (6c)
Mp 192.2–193.2 °C; Rf = 0.46 [PE–EtOAc, (3:7)].
Anal. Calcd for C14H23NO4: C, 62.43; H, 8.61; N, 5.20. Found: C,
62.30; H, 8.72; N, 5.09.
Dimethyl (2-Methyl-2-morpholin-4-ylpropylidene)malonate
(4c)4
Mp 77.3–77.7 °C.
IR (KBr): 1745, 1676, 1629 (w) cm–1.
1H NMR (300 MHz, CDCl3): d = 1.43 (s, 6 H), 3.83 (s, 3 H), 5.64
(s, 1 H), 7.19–7.39 (m, 10 H), 7.79 (s, 1 H).
IR (KBr): 1727, 1641 cm–1.
13C NMR (68 MHz, CDCl3): d = 24.3, 52.2, 60.3, 63.1, 127.3, 128.2,
128.7, 128.8, 139.7, 161.5, 162.5, 164.6.
1H NMR (300 MHz, CDCl3): d = 1.22 (s, 6 H), 2.50 (dd, J = 4.68
Hz, 4 H), 3.65 (dd, J = 4.68 Hz, 4 H), 3.77 (s, 3 H), 3.84 (s, 3 H),
6.88 (s, 1 H).
MS (ES, +ve mode): m/z (%) = 693 (15) [2 × M + Na+], 336 (90) [M
+ H+], 167 (100).
13C NMR (75 MHz, CDCl3): d = 22.5, 46.9, 52.0, 52.5, 58.6, 67.0,
126.3, 154.1, 164.7, 166.8.
Anal. Calcd for C21H21NO3: C, 75.20; H, 6.31; N, 4.18. Found: C,
75.12; H, 6.42; N, 4.10.
MS (ES, +ve mode): m/z (%) = 272 (100) [M + H+].
Diethyl [(2E)-2-(N-Isopropylimino)-1,1-dimethylethyl]-
malonate (5d)
Bp 65–70 °C/0.4 mmHg.
Anal. Calcd for C13H21NO5: C, 57.55; H, 7.80; N, 5.16. Found: C,
57.39; H, 7.83; N, 5.10.
Methyl 1-Isopropyl-4,4-dimethyl-2-oxopyrrolidine-3-carboxy-
late (9a) and Methyl 1-Benzhydryl-4,4-dimethyl-2-oxopyrroli-
dine-3-carboxylate (9c)1a
IR (NaCl): 1753, 1732, 1666 cm–1.
1H NMR (300 MHz, CDCl3): d = 1.09 (d, J = 6.33 Hz, 6 H), 1.25 (s,
6 H), 1.26 (t, J = 7.15 Hz, 6 H), 3.28 (sept, J = 6.33 Hz, 1 H), 3.71
(s, 1 H), 4.17 (q, J = 7.15 Hz, 4 H), 7.68 (s, 1 H).
To a mixture of aldimine 5a or 5c (1 mmol) and MeOH (1 mL) were
added NaCNBH3 (0.07 g, 1.1 mmol) and AcOH (0.07 mL, 1.1
mmol). The reaction mixture was stirred at r.t. for 17–21 h. The re-
action mixture was poured into aq NaOH (0.5 N, 10 mL) and ex-
tracted with CH2Cl2 (3 × 10 mL). After drying of the organic layer
(MgSO4), filtration and evaporation, the pure pyrrolidin-2-ones 9a
(0.16 g, 76%) and 9c (0.32 g, 94%)1a were obtained. An analytically
pure sample of 9a (clear oil) could be obtained upon flash column
chromatography (silica gel, Et2O); Rf = 0.35 (Et2O).
13C NMR (75 MHz, CDCl3): d = 14.1, 23.8, 23.9, 40.4, 59.0, 60.8,
61.0, 166.1, 168.4.
MS (ES, +ve mode): m/z (%) = 272 (100) [M + H+].
Anal. Calcd for C14H25NO4: C, 61.97; H, 9.29; N, 5.16. Found: C,
61.88; H, 9.41; N, 5.07.
Dimethyl {1-[(E)-(N-Isopropylimino)methyl]cyclohexyl}-
malonate (5e)
Kugelrohr distillation: Toven = 80–95 °C/0.01 mbar.
IR (NaCl): 1736, 1686 cm–1.
1H NMR (300 MHz, CDCl3): d = 1.10 (s, 3 H), 1.13 (d, J = 7.15 Hz,
3 H), 1.15 (d, J = 7.15 Hz, 3 H), 1.21 (s, 3 H), 2.96 (d, J = 9.36 Hz,
1 H), 3.05 (s, 1 H), 3.25 (d, J = 9.36 Hz, 1 H), 3.72 (s, 3 H), 4.41
(sept, J = 6.88 Hz, 1 H).
IR (NaCl): 1754, 1737, 1660 cm–1.
1H NMR (300 MHz, CDCl3): d = 1.13 (d, J = 6.33 Hz, 6 H), 1.16–
1.62 (m, 8 H), 1.97–2.08 (m, 2 H), 3.35 (sept, J = 6.33 Hz, 1 H), 3.67
(s, 1 H), 3.69 (s, 6 H), 7.86 (s, 1 H).
13C NMR (75 MHz, CDCl3): d = 19.57, 19.64, 22.7, 28.7, 36.6, 42.6,
52.0, 53.9, 61.1, 169.3, 169.6.
13C NMR (75 MHz, CDCl3): d = 22.2, 23.9, 25.6, 32.5, 43.3, 52.1,
60.5, 61.6, 165.4, 168.3.
MS (ES, +ve mode): m/z (%) = 214 (100) [M + H+].
Anal. Calcd for C11H19NO3: C, 61.95; H, 8.98; N, 6.57. Found: C,
61.72; H, 9.09; N, 6.44.
MS (ES, +ve mode): m/z (%) = 284 (100) [M + H+].
Anal. Calcd for C15H25NO4: C, 63.58; H, 8.89; N, 4.94. Found: C,
63.80; H, 8.78; N, 5.12.
Synthesis 2006, No. 13, 2260–2264 © Thieme Stuttgart · New York

2264
S. Mangelinckx et al.
PAPER
Dimethyl (1,1-Dimethyl-2-oxoethyl)malonate (10)
References
To a mixture of aldimine 5a (122 mg, 0.5 mmol) and H2O (1 mL)
and CH2Cl2 (1 mL) was added aq HCl (2 N, 0.4 mL). The reaction
mixture was stirred at r.t. overnight and extracted with CH2Cl2 (3 ×
3 mL). After drying of the organic layer (MgSO4), filtration and
evaporation, the aldehyde 10 (91 mg, 90%) was obtained. 1H NMR
data were in good agreement with reported data.8
(1) (a) Mangelinckx, S.; De Kimpe, N. Synlett 2005, 1521.
(b) Mangelinckx, S.; De Kimpe, N. Synlett 2006, 369.
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1H NMR (300 MHz, CDCl3): d = 1.24 (s, 6 H), 3.75 (s, 6 H), 3.78
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Acknowledgment
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The authors are indebted to the ‘Institute for the Promotion of Inno-
vation through Science and Technology in Flanders (IWT-Vlaande-
ren)’ and Ghent University (GOA) for financial support of this
research.
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