Regioselective addition of aldimines to the 2-propenyl-1,3-dithiane anion

Article abstract of DOI:10.1016/0022-328X(90)85507-U

The allyllithium generated from 2-propenyl-1,3-dithiane reacts exclusively at the γ-site with aldimines, but the BF3-mediated reaction with aliphatic aldimines occurs predominantly at the α-site.

Full text of DOI:10.1016/0022-328X(90)85507-U

219
Journal of Organometallic Chemistry, 398 (1990) 219-224
Elsevier Sequoia S.A., Lausanne
JOM 21256
Regioselective addition of aldimines
to the
anion
J im-Min Fang *, Same-Ting
and I-Hui
Department of Chemistry, National Taiwan University, Taipei 10764 (Taiwan)
(Received May llth, 1990)
The allyllithium generated from
y-site with aldimines, but the
predominantly at the a-site.
reacts exclusively at the
reaction with aliphatic aldimines occurs
Introduction
Although the reactions of heteroatom-substituted allylic organometallic com-
pounds have been extensively studied the controlling factors of
mistry are not fully understood. We and others have found that the regioselectivity
in the reaction of an unsymmetric allylic organometallic compound is dependent on
several factors, such as the attacking electrophile
hexamethylphosphoramide
the additive of
So
and the complexation with Lewis acids
far, related reactions with alkyl halides and carbonyl compounds have been in-
tensely investigated, but the corresponding reaction with is rarely examined
In continuation of the study on dithio-substituted allylic organometallic
compounds, we now report that regioselectivity for the allyllithium 1 in reaction
with aldimines can be manipulated by mediation of
Results and discussion
As shown in Table 1, the crotyllithium generated from
THF solution reacts exclusively at the y-site with aldimines. On the other hand,
a-addition occurs predominantly when the ethereal crotyllithium solution is treated
in
with
aliphatic aldehyde
of propylidene butylamine and
before the addition of the
(prepared from butylamine and an
is retained when a mixed ethereal solution
is added to the crotyllithium 1, to give
The
exclusively the a-adduct 3. THF should not be used as solvent in the presence of
because undergoes a ring-opening reaction As we previously proposed, the
a-site in the crotyllithium 1 is harder than the y-site, so the regioselectivity is best
0022-328X/90/$03.50
1990 Elsevier Sequoia S.A.

Table 1
Addition reactions of
with the crotyllithium 1
solvent
THF
(equiv.)
Products (yield,
4 (73)
0
2
3
4
5
6
7
THF
THF
THF
THF
0
1
0
1
0
1
0
1
6 (74)
5 (64) + 6 (4)
8
(60)
7 (72) + 8 (5)
10 (35)
9 (36) + 10 (54)
12 (93)
9
10
PhCH=NPh
PhCH=NPh
1 2 (5 5 )
The product was obtained as a diasterwmeric mixture.
= 66 34,
=
69 31,
addition of the
the
=
= 15 85,
mixture or addition of the
reaction was warmed to room temperature for 1 h
= 42 58. Either
to the
mixture to
give the single product 3.
before quenching by
No addition product formed at
Either addition mode, as
described in entry 2, yields products of similar composition, viz.,
9 and 10
= 67 33).
= 94 6.
Li
+
1
2
4
Pr”,
Bu”
Bu”
Bu”
Ph
6
8
7
Ph
Ph
9
1 0
12
11
s
s
a
B
Ph.
Bu”
Scheme 1.

accounted for by the hard and soft acid and base principle
relatively soft electrophile of aliphatic aldimine prefers reaction at the y-site.
However, the would become much harder when coordinated with Thus,
with reaction at the hard a-site was realized. Owing to the delocalizing effect of
the phenyl group, an increase in hardness would be less profound in the complex of
a benzaldehyde and this is reflected in reactions (entries 8 and 10) which
Accordingly, the
both give a- and y-addition products.
The y-addition reaction of allyllithium 1 with the complex of
probably
involves the acyclic transition state A (Scheme 1). The antiperiplanar mode of
reaction can account for the selectivity of y-addition products i.e.
=
and
=
(entries 8 and 10). The
y treated with trifluoroacetic
18,191. The P-methyls of
to give y-lactams 13 and
respective diastereomers of 10 and 12 were
acid and
13-h and
compounds appeared at unusually high fields of 0.62 and 0.72
in NMR spectra owing to the shielding effect by the adjacent phenyl group
When allyllithium 1 was pretreated with
allylboron or as an “ate” complex
the possibility of it behaving as an
cannot be excluded. However, the
selectivity of its y-reaction with aldimines may deduced from either transition state,
A or B (M is boron). The y-additions in entries 1, 3, 5 also show that
isomers are preferentially formed
probably proceed via the chair-like cyclic transition state
lithium coordinates with the nitrogen atom to the
in the reactions, entries 7 and 9
= 1.5 to 2.2). These reactions
(M is lithium), in which
group Abnormal
B
selectivity for benzaldehyde
= 0.18 and 0.72) was observed as reported previously
transition state is unclear.
although the nature of
Use of dithiane as an umpolung of carbonyl group is well documented
Our
present method furnishes the dithianes containing additional functional groups
(amino and double bond) suitable for further elaboration in many aspects.
Experimental
Elemental analyses were carried out with a Perkin-Elmer
elemental analyzer.
Infrared spectra were recorded on a Perkin-Elmer 985 infrared spectrophotometer.
The nuclear magnetic resonance spectra were recorded on a Bruker AM-300WB or
AC-200 spectrometer. Mass spectra were recorded on a Finnigan TSQ
spec-
trometer operating at an ionizing voltage of 70 Merck silica gel 60 F sheets were
used for the analytical thin-layer chromatography. Reaction products were sep-
arated by flash chromatography by elution with a gradient of
Further purification was carried out by a Waters Association M45 high-pres-
sure
of
on a
procedure for the addition reaction of I to aldimines.
(1.6 M in hexane) under was added
column (0.78 cm X 25 cm).
A solution of 0.8 ml
to a solution of
(160 mg, 1.0 mmol) in THF (0.5 ml) at
30°C. The
mixture was stirred for 20 min, cooled to 78 C, and the appropriate aldimine (1.0
mmol) was added. After l-2 h at
and the mixture was taken up with
a saturated
Separation and analysis of the products
solution was added,
from organic phase were achieved by chromatographic and spectroscopic methods.

In case of
reactions, diethyl ether (5 ml) was used as solvent and
(1 was added prior to the addition of aldimines.
0.4
0.75-1.10 (6 H, m), 1.12-1.60 (6 H, m), 1.78 (3
H, d, J = 6 Hz), 1.70-2.10 (3 H, m), 2.42-3.02 (7 H, m), 5.48 (1 H, br d, J = 16
Hz), 5.68-6.15 (1 H, m). (neat) 3337, 3015, 2921, 1451, 1419, 1374, 1113, 974
cm -‘.
freshly distilled
a-Addition product 3 from and propylidene butylamine. Pale yellow oil,
(5% EtOAc in hexane).
m/z (W) 274 (11,
243 201 159 114 85 (65).
Anal. Calcd for
N, 4.86.
C, 61.48; H, 9.95; N, 5.12. Found: C, 61.38; H, 10.15;
y-Addition products 4 from 1 and propylidene butylamine. Mixture of erythro and
threo isomers (66 0.17 (8% EtOAc in hexane containing 0.5%
(CDCl,) 0.82 (6 H, t, J= 7.5 Hz), 0.89 (2.0 H, d, J= 7.2 Hz,
(1.0 H, d, J= 7.2 Hz, threo), 1.14-1.39 (6 H, m), 2.05-2.11 (2 H, m),
(1 H, m, NH), 2.44-2.52 (2 H, m, NCH,), 2.73-2.88 (6 H, m), 5.75 (0.66
H, d, J = 10
(0.34 H, d, J 10 Hz).
(neat) 3349, 2955, 2926, 1451,
1110, 880 cm-‘. m/z
274 (7, 114 (100). Anal. Calcd for
C, 61.48; H, 9.95; N, 5.12. Found: C, 61.30; H, 9.73; N, 5.04.
Pale yellow oil,
(CDCl,) 0.80-1.05 (6 H, m), 1.10-1.70 (8 H, m), 1.81 (3
H, d, J = 6 Hz), 1.72-2.10 (3 H, m), 2.20-3.20 (7 H, m), 5.50 (1 H, br d, J = 1 5
0.28
a-Addition product 5 from I and butylidene butylamine.
(5% EtOAc in hexane).
Hz), 6.00 (1 H, m).
(neat) 3334,
182 159
1374, 1275, 974 cm-‘. m/z
128 (100). Anal, Calcd for C,
288 (1,
62.66; H, 10.17; N, 4.87. Found: C, 62.34; H, 10.41; N, 4.76.
y-Addition products 6 from I and butylidene butylamine. Mixture of etythro and
threo isomers (70: 0.17 (8% EtOAc in hexane containing 0.5%
(CDCl,) 0.85 (6 H, t, J = 7 Hz), 0.93 (2.1 H, d, J = 6.6 Hz,
J= 6.6 Hz, threo), 1.18-1.43 (8 H, m), 2.08-2.16 (2 H, m), 2.29-2.32 (1 H, m),
(0.9 H, d,
2.49-2.59 (2 H, m), 2.78-2.91 (6 H, m), 5.82 (0.7 H, d, J = 9.6
(0.3 H, d,
J = 9.6 Hz).
(neat) 3370, 2955, 2926, 1457, 1110 cm-‘. m/z (W) 288 (4,
128 (100). Anal. Calcd for
C, 62.66; H, 10.17; N, 4.87. Found:
C, 62.68; H, 10.07; N, 4.79.
Pale yellow oil,
a-Addition product 7 from I and isopropylidene butylamine.
0.37 (5% EtOAc in hexane).
1.76 (3 H, d, J = 6 Hz), 1.70-2.38 (3 H, m), 2.42-3.00 (7 H, m), 5.45 (1 H, br d,
J = 15 Hz), 5.90 (1 H, m). (neat) 3333, 3015, 2953, 1457, 1419, 1374, 1113, 975
m/z 288 (1, 243 159 128 (100). Anal. Calcd for
C, 62.66; H, 10.17; N, 4.87. Found: C, 62.29; H, 10.17; N, 4.82.
Y-Addition products from 1 and isobutylidene butylamine. Mixture of
(CDCl,) 0.80-1.10 (9 H, m), 1.12-1.60 (5 H, m),
and threo isomers (60
(12 H, m), 1.12-1.50 (5 H, m), 1.72-2.38 (3 H, m),
d, J = 10 Hz,
1580, 1457, 1419, 1109, 911 cm-‘. m/z
0.1 (5% EtOAc in hexane).
(CDCl,) 0.70-1.00
(8 H, m), 5.80 (0.6 H,
(neat) 3490, 2954,
128 (100).
(0.4 H, d, J = 10 Hz, threo),
288 (75,
0.28 (5% EtOAc in
(CDCl,) 0.80 (3 H, t, J = 6 Hz), 1.00-1.56 (4 H, m), 1.78 (3 H, d,
a-Addition product 9 from I and benzylidene butylamine.
hexane).
J= 6 Hz), 1.72-2.10 (3 H, m), 2.39 (2 H, t, J= 7 Hz), 2.50-2.95 (4 H, m), 3.85 (1
H, s), 5.40 (1 H, br d, J= 16 Hz), 5.62-6.00 (1 H, m), 7.20-7.35 (5 H, m).
(neat) 3315, 3058, 2915, 1597, 1489, 1448, 1374, 755, 702
m/z
322 (35,

223
249
162 (100). Anal. Calcd for
C, 67.24; H, 8.46; N, 4.36.
Found: C, 66.90; H, 8.70; N, 4.18.
y-Addition products 10 from I and benzylidene
Mixture of erythro and
0.92 (0.45 H, d, J = 7
threo isomers (15
0.11 (5% EtOAc in hexane).
Hz,
(2.55 H, d, J 7 Hz, threo), 0.82 (3 H, t, J = 7 Hz), 1.18-1.39 (4
H, m), 1.74-1.79 (1 H, m), 2.00-2.14 (2 H, m), 2.28-2.43 (2 H, m), 2.54-3.07 (5 H,
m), 3.50 (0.15 H, d, J = 6
(0.85 H, d, J = 8 Hz), 5.71 (0.15 H, d, J = 10
(0.85 H, J = 10 Hz), 7.10-7.31 (5 H, m).
(neat) 3323, 3079, 2923,
162 (100). Anal. Calcd for
1598, 1488, 762, 702
m/z (W) 322 (30,
C, 67.24; H, 8.46; N, 4.36. Found: C, 67.58; H, 8.25; N, 4.04.
a-Addition product II from I and benzylidene benzenamine.
in hexane). 1.80 (3 d, J = 7 Hz), 1.70-2.30 (2 H, m),
0.22 (1% EtOAc
(4 H,
m), 4.48 (1 H, m), 4.83 (1 H, m), 5.35 (1 H, br d, J= 15 Hz), 5.92 (1 H, m),
6.42-6.70 (3 H, m),
2909,
(2 H, m), 7.20-7.60 (5 H, m).
701 cm-‘. m/z (W) 341 (16,
(neat) 3395, 3022,
266 182
159 (70). Anal. Calcd for
69.98; H, 6.95; N, 3.95.
y-Addition products I2 from and benzylidene benzenamine. Mixture of erythro
C, 70.34; H, 6.79; N, 4.10. Found: C,
and threo isomers (40
d, J = 7.5 Hz,
2.68-3.38 (5 H, m), 4.17 (1 H, br s, NH), 4.26 (0.4 H, d, J = 4.5
0.08 (1% EtOAc in hexane).
(1.8 Hz, d, J= 7.5 Hz, threo), 1.90-2.25 (2 H, m),
(0.6 H, d,
0.98 (1.2 H,
J = 8 Hz), 5.79 (0.4 H, d, J = 10
m), 6.80-7.00 (2 H, m),
(0.6 H, d, J 10 Hz), 6.27-6.55 (3 H ,
(5 H,
(neat) 3397, 3021, 2958, 2925,
1597, 1498, 868, 749, 701 cm-‘. m/z (W) 342 (2,
182 (100). Anal. Calcd
for
C, 70.34; H, 6.79; N, 4.10. Found: C, 69.96; H, 7.05; N, 4.07.
General procedure for hydrolysis of y-addition products 10 and 12 to give lactams 13
and
treated with
min. After the solvent was removed, the reddish residue was taken up with EtOAc
(10 and treated with a small amount of The mixture was filtered
through a short column of silica gel. The concentrated filtrate, showing no NMR
A solution of the y-addition product (0.4 mmol) in
(8
was
(0.48 in 1 of at room temperature for 30
resonance for olefinic proton, was dissolved in 5
of
A solution (2
= 4 1) of
(2.4 mmol) was added, and the
mixture was stirred at room temperature for 15 min. After addition of saturated
the mixture was extracted with
(1: 1). The organic phase
was thoroughly washed with saturated
(6-8 times), dried with anhydrous
concentrated and separated by chromatography to give the desired lactam
in 43-60% yield.
0.60 (3 H, d, J = 7.0 Hz), 0.83 (3 H, t, J = 7.3 H z),
1.14-1.44 (4 H, m), 2.14-2.48 (2 H, m), 2.51-3.76 (3 H, m), 4.58 (1 H, d,
Hz), 7.00-7.03 (2 H, m), 7.20-7.36 (3 H, m).
cm -‘.
(neat) 2957, 1687, 1600, 1452, 805
91 (100). 0.79 (3 H, t,
m/z
231
216
188
J = 7.1 Hz), 1.09 (3 H, d, J = 6.5 Hz), 1.14-1.44 (4 H, m), 2.14-2.46 (2 H, m),
2.50-3.75 (3 H, m), 4.06 (1 H, d, J= 5.9 Hz), 7.14-7.16 (2 H, m), 7.20-7.36 (3 H,
3029, 2963, 1697, 1584, 1489, 876, 748, 702
Anal. Calcd for
C, 77.88; H, 9.15; N, 6.05. Found: C, 77.62; H, 9.13; N, 6.24.
0.72 (3 H, d, J = 6.8 Hz), 2.40 (1 H, dd, J = 16.7, 11.5 Hz), 2.65 (1 H, dd, J = 16.7,
8.0 Hz), 2.76-2.91 (1 H, m), 5.12 (1 H, d, J= 7.8 Hz), 7.10-7.15 (2 H, m), 7.26-7.44
(8 H, m). Anal. Calcd for
C, 81.24; H, 6.82, N, 5.57. Found: C, 80.95;

224
H, d, J= 6 . 4
Hz). 7.10-7.15
1.24 (3
H, d, J = 5.6
Hz), 2.26-2.45 (2 H, m),
(2 H, m), 7.26-7.44 (8 H,
H, 6.88; N, 5.32.
2.88-2.95 (1 H, m), 4.68 (1
Acknowledgement
We thank the National Science Council (R.O.C.) for financial support.
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