Single-step stereoselective synthesis of (E)- and (Z)-allylamines from acetyl derivatives of Baylis-Hillman adducts

Article abstract of DOI:10.1055/s-2005-864822

Stereoselective synthesis of (E)- and (Z)-allylamines has been achieved in a single-step by treatment of the acetyl derivatives of Baylis-Hillman adducts with ammonium acetate in anhydrous methanol at room temperature. The reaction proceeded under neutral conditions to form the corresponding allylamines in high yields and stereoselectivity.

Full text of DOI:10.1055/s-2005-864822

1000
LETTER
Single-Step Stereoselective Synthesis of (E)- and (Z)-Allylamines from Acetyl
Derivatives of Baylis–Hillman Adducts1
Single-Step
S
tere
i
oselect
s
ive Synthe
w
sis of
(
E
)- and
(
Z
)
a
-Allylamin
n
es ath Das,* Gurram Mahender, Nikhil Chowdhury, Joydeep Banerjee
Organic Chemistry Division – I, Indian Institute of Chemical Technology, Hyderabad – 500 007, India
Fax +91(40)7160512; E-mail: biswanathdas@yahoo.com
Received 22 November 2004
NH4OC(O)H and NH4OAc in different solvents to opti-
Abstract: Stereoselective synthesis of (E)- and (Z)-allylamines has
been achieved in a single-step by treatment of the acetyl derivatives
of Baylis–Hillman adducts with ammonium acetate in anhydrous
methanol at room temperature. The reaction proceeded under neu-
mize the reaction conditions (Table 1). We examined an-
hydrous diethyl ether, anhydrous methanol and aqueous
methanol (containing 5% H2O) as solvents. The dissocia-
tral conditions to form the corresponding allylamines in high yields tion of NH4OAc in anhydrous diethyl ether has recently
been revealed7 and it was thus expected that this solvent
and stereoselectivity.
might also be useful for the preparation of allylamines.
However, in anhydrous diethyl ether the reaction did not
yield any product even after 12 hours. On the other hand,
in anhydrous methanol, both 1b and 2b gave the products
3b and 4b, respectively, with NH4OC(O)H as well as
NH4OAc, the yields of the products being much higher
with NH4OAc. In aqueous methanol the yields of 3b and
4b were somewhat low and the side products (3b¢ and 4b¢)
were also formed (Figure 1). Thus, it is evident that the
conversion of the acetyl derivatives of the Baylis–Hillman
adducts into allylamines is more facile with NH4OAc
using anhydrous methanol as solvent.
Key words: allylamine, Baylis–Hillman adduct, acetyl derivative,
NH4OAc, stereochemistry
The Baylis–Hillman reaction involves the coupling of ac-
tivated vinylic systems with electrophiles in the presence
of a tertiary amine (usually DABCO) as a catalyst.2 The
adducts of the reaction, 3-hydroxy-2-methylene-al-
kanoates 1 (derived from acrylate esters) and 3-hydroxy-
2-methylene-alkanenitriles 2 (derived from acrylonitrile)
have been employed for the stereoselective synthesis of
different multifunctional molecules.2b,3 In connection
with our work4 on the synthesis of trisubstituted alkenes
we have observed that the acetyl derivatives of these ad-
ducts can be utilized for the preparation of allylamines
(which are also b-aminoesters) and useful for the synthe-
sis of b-lactams, peptides, proteins and several other nat-
ural bioactive compounds.3b,5 The acetyl derivatives of the
Baylis–Hillman adducts, 1 and 2 on treatment with
NH4OAc in anhydrous methanol, afforded the corre-
sponding allylamines 3 and 4, respectively, in high yields
(Scheme 1). NH4OAc has recently been utilized6 by us as
a neutral catalyst for selective deprotection of aromatic
acetates.
Figure 1
In order to prepare a series of allylamines, acetyl com-
pounds 1 and 2 were treated with NH4OAc in anhydrous
methanol at room temperature for 4–6.5 hours (Table 2).8
Both electron-donating and electron-withdrawing groups
were present in the adducts. The reaction proceeded under
neutral conditions to form the allylamines in high yields.
It was observed that 3 was formed with E-configuration
while 4 was obtained with high Z-stereoselectivity. The
1H NMR spectra of the allylamines were used8 to establish
the structures and stereochemistries of the products4b and
the ratio of E- and Z-isomers was determined from the 1H
NMR spectra of the crude products. The spectral data of
the pure compounds were compared to those of the known
allylamines of similar system.3b Some reported relevant
1H NMR spectral values of trisubstituted alkenes were
also useful to determine the stereochemistries of the prod-
ucts.4b,9 In the 1H NMR spectrum of a trisubstituted alkene
b-vinylic proton cis and trans to the ester group is known
to resonate at d = 7.5 and 6.5 ppm, respectively, when R
is aryl.9a,b The same proton cis and trans to the ester group
Initially, 1b (R = 2-Cl-C6H4, EWG = -COOMe) and 2b
(R = 2-Cl-C6H4, EWG = -CN) were treated with
Scheme 1
SYNLETT 2005, No. 6, pp 1000–1002
0
6.
0
4.
2
0
0
5
Advanced online publication: 23.03.2005
DOI: 10.1055/s-2005-864822; Art ID: D34804ST
© Georg Thieme Verlag Stuttgart · New York

LETTER
Single-Step Stereoselective Synthesis of (E)- and (Z)-Allylamines
1001
Table 1 Treatment of 1b (R = 2-Cl-C6H4, EWG = -COOMe) and 2b (R = 2-Cl-C6H4, EWG = -CN) with NH4OC(O)H/NH4OAc in Different
Solventsa
Compound
NH4X
Solvent
Time (h)
Yield (%) of allylamine
Yield (%) of allylalcohol
1b
NH4OC(O)H
anhyd Et2O
anhyd MeOH
aq MeOH
12
4
4
0
76
62
0
0
9
2b
1b
NH4OC(O)H
NH4OAc
anhyd MeOH
aq MeOH
6
6
81
67
0
6
anhyd Et2O
anhyd MeOH
aq MeOH
12
4
4
0
94
91
0
0
5
2b
NH4OAc
anhyd MeOH
aq MeOH
6
6
92
81
0
6
a Compound 1b or 2b (1 equiv) was treated with NH4OC(O)H/NH4OAc (8 equiv) in the solvent (10 mL) at r.t.; allylamines were 3b and 4b
and allylalcohols were 3b¢ and 4b¢.
appears at d = 6.8 and 5.7, respectively, when R is Table 2 Preparation of Allylamines from Acetyl Derivatives of
Baylis–Hillman Adducts Using NH4OAc in Anhydrous Methanola
alkyl.9c,d Similarly, the b-vinylic proton cis and trans to
the nitrile group resonates at d = 7.4 and 6.8 ppm, respec-
tively, when R is aryl9h while the same proton cis and
trans to the nitrile group appears at d = 6.3 and 6.0 ppm,
Ally-
R
Time (h)
Isolated yield E:Z
lamine
(%)
1
respectively, when R is alkyl.9f These reported H NMR
3a
3b
3c
3d
3e
4a
4b
4c
4d
4e
C6H5
4
95
94
92
87
79
89
88
82
84
72
100:0
spectral data guided the characterization of E- and Z-iso-
mers of the products. The stereochemistries of the pre-
pared allylamines were also confirmed by NOESY
experiments. The 13C NMR spectra of some of the pre-
pared allylamines were also studied. Previously, some al-
lylamines were prepared10 from the acetyl derivatives of
Baylis–Hillman adducts in two steps by treatment of the
latter with NaN3 to form the corresponding allylazides,
which were subsequently reduced to amines by
Staudinger reaction using triphenyl phosphine and water.
2-Cl-C6H4
4-Cl-C6H4
3-NO2-C6H4
(CH3)2CH-CH2
C6H5
4
100:0
100:0
100:0
100:0
17:83
18:82
20:80
16:84
22:78
4
4.5
5
6
2-Cl-C6H4
4-Cl-C6H4
3-NO2-C6H4
(CH3)2CH-CH2
6
5.5
6.5
6.5
In the present reaction NH4OAc dissociates first to gener-
ate NH3 which being nucleophilic attacks the exocyclic
double bond of 1 or 2 and subsequent migration of the
double bond with concomitant loss of the -OAc group re-
sults in the formation of the allylamines 3 or 4, respective-
ly. The stereochemistry of the reaction can possibly be
explained3b by considering the transition state models A,
B and C (Figure 2). Model A is more favored than B when
EWG = -COOMe and E-products are thus formed exclu-
sively. On the other hand, model C is somewhat more
favored than A when EWG = -CN as -CN is linear and
hence Z-products are formed predominantly.
a The allylamines were characterized from their spectral (1H NMR
and MS) data.
(Z)-allylamines from activated Baylis–Hillman adducts
by treatment with NH4OAc in anhydrous methanol. The
operational simplicity, shorter reaction times (4–6.5 h),
availability of the inexpensive reagents, mild reaction
conditions and high yields as well as stereoselectivity of
the products are the great advantages of the present
method.
In conclusion, we have demonstrated a simple and
efficient process for stereoselective synthesis of (E)- and
Figure 2
Synlett 2005, No. 6, 1000–1002 © Thieme Stuttgart · New York

1002
B. Das et al.
LETTER
126.6, 52.0, 49.6. EIMS: m/z = 225, 227 [M+]. Anal. Calcd
for C11H12ClNO2 (%): C, 58.54; H, 5.32; N, 6.21. Found: C,
58.62; H, 5.29; N, 6.28.
Acknowledgment
The authors thank CSIR, New Delhi for financial assistance.
Compound 3d: IR (KBr): nmax = 3462, 1723, 1585, 1505
cm–1. 1H NMR (200 MHz, CDCl3): d = 8.40 (1 H, t, J = 2.0
Hz), 8.18 (1 H, dt, J = 8.0, 2.0 Hz), 7.82 (1 H, dt, J = 8.0, 2.0
Hz), 7.80 (1 H, s), 7.54 (1 H, t, J = 8.0 Hz), 3.83 (3 H, s), 3.54
(2 H, s). 13C NMR (50 MHz, CDCl3): d = 167.8, 148.3,
140.0, 136.4, 135.6, 129.6, 135.3, 124.3, 123.4, 52.2, 50.1.
MS (EI): m/z = 236 [M+]. Anal. Calcd for C11H12N2O4 (%):
C, 55.93; H, 5.08; N, 11.86. Found: C, 55.88; H, 5.01; N,
11.84.
References
(1) Part 56 in the series, ‘Studies on Novel Synthetic
Methodologies’. IICT Communication No. 050216
(2) (a) Baylis, A. B.; Hillman, M. E. D. German Patent 2155113,
1972; Chem. Abstr. 1972, 77, 34174q. (b) Basavaiah, D.;
Rao, A. J.; Satyanarayana, T. Chem. Rev. 2003, 103, 811;
and references cited therein.
Compound 3e: IR (KBr): nmax = 3440, 1732, 1560, 1522
cm–1. 1H NMR (200 MHz, CDCl3): d = 6.89 (1 H, t, J = 7.0
Hz), 3.64 (3 H, s), 3.08 (2 H, s), 2.09 (2 H, t, J = 7.0 Hz), 1.72
(1 H, m), 0.92 (6 H, d, J = 7.0 Hz). MS (EI): m/z = 171 [M+].
Anal. Calcd for C9H17NO2 (%): C, 63.17; H, 15.74; N, 12.96.
Found: C, 63.24; H, 15.81; N, 12.85.
Compound 4a: IR (KBr): nmax = 3453, 2354, 1620, 1532
cm–1. 1H NMR (200 MHz, CDCl3): d = 7.72–7.67 (2 H, m),
7.40–7.28 (3 H, m), 7.07 (1 H, s), 3.56 (2 H, s). 13C NMR (50
MHz, CDCl3): d = 137.2, 130.5, 129.9, 129.4, 128.6, 128.3,
126.2, 118.8, 116.5, 52.0. MS (EI): m/z = 158 [M+]. Anal.
Calcd for C10H10N (%): C, 83.33; H, 6.94; N, 19.44. Found:
C, 83.41; H, 6.88; N, 19.40.
Compound 4c: IR (KBr): nmax = 3442, 2352, 1522, 1485
cm–1. 1H NMR (200 MHz, CDCl3): d = 7.72 (2 H, d, J = 8.0
Hz), 7.43 (2 H, d, J = 8.0 Hz), 7.10 (1 H, s), 3.62 (2 H, s).
MS (EI): m/z = 192, 194 [M+]. Anal. Calcd for C10H9ClN2
(%): C, 62.34; H, 4.68; N, 14.55. Found: C, 62.41; H, 4.71;
N, 14.51.
(3) (a) Hoffmann, H. M. R.; Rabe, J. Angew. Chem., Int. Ed.
Engl. 1985, 24, 94. (b) Buchholz, R.; Hoffmann, H. M. R.
Helv. Chim. Acta 1991, 74, 1213.
(4) (a) Das, B.; Banerjee, J.; Ravindranath, N.; Venkataiah, B.
Tetrahedron Lett. 2004, 45, 2425. (b) Das, B.; Banerjee, J.;
Ravindranath, N. Tetrahedron 2004, 60, 8357. (c) Das, B.;
Banerjee, J.; Mahender, G.; Majhi, A. Org. Lett. 2004, 6,
3349. (d) Das, B.; Banerjee, J.; Majhi, A.; Mahender, G.
Tetrahedron Lett. 2004, 45, 9225.
(5) (a) Ma, J. Angew. Chem. Int. Ed. 2003, 42, 4290.
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2004, 6, 2507.
(6) Ramesh, C.; Mahender, G.; Ravindranath, N.; Das, B.
Tetrahedron 2003, 59, 1049.
(7) Tanemura, K.; Suzuki, T.; Nishida, Y.; Satsumabayashi, K.;
Horaguchi, T. Chem. Commun. 2004, 470.
(8) General Procedure for the Preparation of Allylamines.
To a solution of 1 or 2 (1 mmol) in anhyd MeOH (10 mL),
NH4OAc (8 equiv) was added in one portion under a
nitrogen atmosphere. The mixture was stirred at r.t. and
monitored by TLC. After completion, the solution was
concentrated and dissolved in CH2Cl2 (10 mL). The solution
was washed with brine (3 × 10 mL) followed by H2O (3 × 10
mL) and the combined aqueous washings extracted with
CH2Cl2 (3 × 10 mL). The total CH2Cl2 portion was
concentrated and subjected to column chromatography over
silica gel using EtOAc–hexane (1:4) as eluent to afford pure
allylamine (3 or 4). The spectroscopic and analytical data of
some representative allylamines (major product) are given
below.
(9) (a) Larson, G. L.; de Kaifer, C. F.; Seda, R.; Torres, L. E.;
Ramirez, J. R. J. Org. Chem. 1984, 49, 3385.
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S. J. Chem. Soc., Perkin Trans. 1 1984, 2501. (d) Tanaka,
K.; Yamagishi, N.; Tanikaga, R.; Kaji, A. Bull. Chem. Soc.
Jpn. 1979, 52, 3619. (e) Minami, I.; Yahara, M.; Shimizu, I.;
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403. (b) Patra, A.; Roy, A. K.; Batra, S.; Bhaduri, A. P.
Synlett 2002, 1819.
Compound 3b: IR (KBr): nmax = 3452, 1722, 1526, 1482
cm–1. 1H NMR (200 MHz, CDCl3): d = 7.92 (1 H, s), 7.46 (1
H, dd, J = 8.0, 2.0 Hz), 7.34 (1 H, dd, J = 8.0, 2.0 Hz), 7.22
(1 H, td, J = 8.0, 2.0 Hz), 7.12 (1 H, td, J = 8.0, 2.0 Hz), 3.74
(3 H, s), 3.10 (2 H, s). 13C NMR (50 MHz, CDCl3): d =
168.4, 139.7, 134.0, 133.5, 131.6, 131.2, 129.8, 129.4,
Synlett 2005, No. 6, 1000–1002 © Thieme Stuttgart · New York