- Email: [email protected]
One pot synthesis of 2-vinyl-1-azadienes and divinylketones
Tetrahedron Letters,Vo1.30,No.40,pp Printed in Great Britain
5493-5496,1989
0040-4039,'89 $3.00 + -00 Perqamon Press plc
ONE POT SYNTHESIS OF 2=VINYIrl-AZADIENES
AND DIVINYLKETONES.
Jose Barluenga =,Isabel Merino and Francisco Palacios. Departamento
de Qufmica OrganometBlica.
Facultad de Quimica. Universidad
de Oviedo. 33071 Oviedo.
Spain. SUMMARY:Preparationof2=vinyl=l=azadienesand pazene, triphenyl@rop=2=ynyl)phosphonium Divinylketones
represent
1,4~pentadien-3~onesfromN~phenyl~triphenyl~~~~phos~
bromide and aldehydes is described.
synthetically attractive building blocks for cyclopentanoid
natural products,
through the Nazarov reaction 2.They have been extensively used not only as dienophiles
in the Diels-Alder
reaction 3,but also in the Robinson annellation4. materials in the development
On the other hand , l-azadienes
of a wide variety of methods for the construction
are very versatile starting of p -antibiotics
5 and six
membered heterocycles 6 Previously, several procedures
of synthesis of divinyl ketones have been reported ‘8, however the
preparation of such compounds is far from simple *.Moreover the preparation of the (I- p-unsaturated
imines
from amines and carbonyl compounds, specially in the case of ketones, only yields good results in very specific cases 9 and it generally leads to Michael additionlO. In this context we have recently studied the [2+ 21 cycloaddition
reaction of acetylene acid esters with
phosphonium ylides and the related isoelectronic xs=phospazenes **aswell as their ability as starting materials in the preparation
of 2=aza=1,3=dienes I2and phosphorilated
of h “=phosphazenes as intermediates 2-vinyl=l=aza=1,3=dienes
p-enamines 13.Continuing
our interest in the use
in organic synthesis, we describe a very easy one- pot preparation
and 1,4=pentadien=3-ones
from comercially
N=phenyl=P,P,P=x *=phosphazenes 1, propargyltriphenylphosphonium Thus, triphenyl(prop=2ynyl)phosphonium rature for 36-40 h leading to the phosphonium
available
starting
reagents
of
14, as
bromide 2 and aldehydes.
bromide 2 reacts with x5-phosphazenes I51 at room tempeylide 3, in a similar way to that described for other acetylenic
compounds ll. Subsequent treatment of 3, without its isolation, with aldehydes (l-24 h, see table) affords the corresponding
p-enamino phosphonium
salts l64 in excellent yields. Compounds 4 were characterized
on the
basis of their spectroscopic data 17.For instance, the enaminic =CH of 4a give a ‘H resonance at 6 = 4.85 ppm (‘J, = 14.1 Hz) and a 13Cresonance at 6 = 61.4 ppm(‘J, = 117.9 Hz) as well resolved doublets, while the vicinal coupling constant
(“J,,= 15.8 Hz) between the vinylic protons reveals the E configuration
5493
.
5494
Ph,P =
NPh
NPh
NHPh
R’CH=O
mle
Rl &
of phosphonium
Compound
CPPW-
salts 4
RI
Reaction
Solvent
TW
m.p.(?IJb
Yield (W
Time(hP 4a
w5
14
CH,C4
25
157-158(d)
93
4b 4c
p-CH,_C,H, o-NO&H,
16 10
CH,CN CH,C4
60 25
69-70(d) 191-193(d)
86 88
4d
2-Fury1
20
CH,CN
60
210-212(d)
79
4e
H
1
CHC4
25
217-218(d)
95
4f
CI-JCH,
24
CH,Cl,
40
146-147(d)
68
’ Addition of aldehydes to the crude reaction mixture from 1 and 2 b From ethylacetate-CH,C1, Metallation
of compounds 4 with butyllithium
leads to 2-vinyl-1-aza-1,3-dienes
followed by addition of aldehydes and aqueous work-up
61s,isolated by means of a short chromatography
This result parallels that reported for the C-alkylation of p-enamino compounds 6 with 2N H,SO,affords prepared from phosphonium
the corresponding
colummwith ether as eluent.
A“-phosphazenes 13.Acid hydrolysis of
divinyl ketones 7 19.These derivatives 7 can be also
salts 4 and aldehydes when the reaction was quenched with 2N H,SO,,
5495
NPh
NHPh
i: BuLi, -7O”C, ii: R2CH = 0, -70°C to ZS’C, THF; iii: H,O; iv: H,O+
It is noteworthy that the preparation and purification
of the phosphonium
these salts 4, after evaporation
of divinylic ketimines 6 and ketones 7 does not require the isolation
salts 4. Improved overall yields are obtained in one pot reaction when
of the solvent, are directly metallated in THF with subsequent
addition of
aldehydes and aqueous or acid work-up, respectively.
Table of 2-vinyl-1-aza-13-dienes Compound
6 and 1.6pentadien-3-ones
7 prepared
RI
R2
m.p.(“Q
Yield( %p
6a
CP,
w,
97-98
86(84)
6b
o-NO&H,
C,H,
109-110
6c
C,H,CH= CH
6d
C,H, 2-Fury1
W81) oil(R, = 0.8)c 78(75)
C,H,CH = CH
oil(R, = 0.9p
6e
H
C&f,
oil(R, = 0.7)5 85(82)
72(70)
7a
(3-4
W
105106
88(X2)
7b
o-NO&H,
Cp,
92-93
84(79)
C,H, 2-Fury1
C,H,CH = CH
oil(R, = 0.8)0 79(7S)
C,H,CH=CH
oil(R,=0.9)c
7c 7d
74(71)
a From hexane “Yields from phosphonium =Silica gel, ether
salts 4. Yields given in parenthesis refer to the one-pot process from 1 and 2
5496
REFERENCES LA. Paquette, Top. Curr Chem. 1984,1,119.
l.- B.M. Trost, Chem. Sot. Rev. 1982,11,141.
M. Rarniah,
Synthesis, 1984,529. 2.- N.I. Nazarov, 1.1. Zaretskaya, Zh. Obshch. Khun, 1957,27, 693. G. Ohloff, K.H.Schulte, E. Demole, Helv. Chim. Acta, 1971,54,2913. 3.. G. Desimoni, G. Tacconi, Chem. Rev., 1975,75,651.
G. Desimoni, G. Tacconi, A. Barco, C.P. Pollini
in “Natural Products Synthesis through Pericyclic Reactions”. Am. Chem. Sot., Washintong
1983. E.
Ciganek, 0%. React., 1984,32, 1. 4.- M.E. Yung, Tetrahedron, 1976,32,3.
R.E. Gawley, Synthesis, 1976,.777.
5.- D.A. Evans, J.M. Williams, Tetrahedron Lett., 1988,29,5065.
J. Lasarte, C. Palomo, J.P. Picard, J.
Dunogues, J.M. Aizpurua, J. Chem. Sot. Chem. Comm., 1989,72. 6.- D.L. Boyer, S.M. Weinreb in “Hetero Diels-Alder
Methodology in Organic Synthesis”, Academic
Press, San Diego, 1987, p. 239. 7.- J. Barluenga, F. Aznar, M.P.Cabal, C.Vald&, Tetrahedron Left., 1989,30, 1413. 8.- M.R. Peel, C.R. Johnson, Tetrahedron Lett., 1986,27,5947
and references therein cited.
9.- SK. Malholra, D.F. Hookley, F. Johnson, J. Am. Chem. Sot., 1967,89,2794. lo.- M. S. Gibson in “The Chemistry of Amino Group”, Ed. S. Patai, J. Willey, London,l968, ll.- J. Barluenga, F. Upez,
p. 63.
F. Palacios,J. Chem. Sot. Chem. Comm., 1986,1574. J. Barluenga, F. Lopez,
F. Palacios, F. S&nchez, Tetrahedron Lett, 1988,29,381. 12.- J. Barluenga, M. Ferrero, F. Palacios, 13.- J. Barluenga, F. Upez,
Tetrahedron Lett, 1988,29, 4863.
F. Palacios, F.H. Cano, M. C. Foces,J. Chem. Sot. Perkin Trans.& 1988,
2329. 14.- Reagents 1 and 2 are available from Aldrich. lS.- E.E. Schweiser, C.S. Kim, C.S. Labau, W.P. Murray, J. Chem. Sot. Chem. Comm., 1973,7. 16.- Due to the imine-enamine tautomer 5 (l&19%);
equilibrium,
crude compounds 4 contain a small proportion
the tautomers ratio was determinated
of the iminic
by )‘I’-NMR (&= 16.5 ppm for 4a *and
s = 24.1 ppm for 5a, 83: 17). 17.- Spectral data for 4a: ~~(300 MHz, CDCL,): 48S(d,lH,27,,= 6.8-7.8S(m,ArH),
&.O(d,lH, ‘J,,= 15.8,CH=),
‘J,= 117.9,C-l), 119.7(d,?lE=7.0,C-3),
14.1,CH=), 6.l(d,lH
ST,,,,=15.8, CH=),
10.4(s, lH,NH); &, (75 MHz, CDCI,): 61.4(d,
122.6-148.3(CArom
(120 MHz, CDCU: 16.5 ppm. MS (70 ev): m/z=481
+ C-4), 161.0(d,T_ = 11.6,C-2); 6,
(M+-HBr).
18.- Spectral data for 6a: &,(300 MHz, CDC4): 6.76(d,lH, ‘J,, = 16.5,CH =), 6.91-7.6(m,ArH 7.58(d,lH, V,,,,,=16S,CH=); MS(70 ev): m/z=309
6, (75 MHz, CDC4): 120.8-150,7(CArom
1.5.8,CH=), 7.25-7.60(m,ArH),
lS.X,CH=); S, (75 MHz, CDCQ: (CArom + C-2 + C-4), 143(C-1 + C-5), 188(C-3)
ppm; MS(70 ev)m/z =234 (M+). (Received
ppm;
CM+).
19.- Spectral data for 7a: s,,(300 MHz, CDCA): 7.12(d,lH;J,,= 7.64(d,lH,?I,,=
+ CH =),
+ CH=),162.8(C-3)
in
UK 28 July
1989)
5493-5496,1989
0040-4039,'89 $3.00 + -00 Perqamon Press plc
ONE POT SYNTHESIS OF 2=VINYIrl-AZADIENES
AND DIVINYLKETONES.
Jose Barluenga =,Isabel Merino and Francisco Palacios. Departamento
de Qufmica OrganometBlica.
Facultad de Quimica. Universidad
de Oviedo. 33071 Oviedo.
Spain. SUMMARY:Preparationof2=vinyl=l=azadienesand pazene, triphenyl@rop=2=ynyl)phosphonium Divinylketones
represent
1,4~pentadien-3~onesfromN~phenyl~triphenyl~~~~phos~
bromide and aldehydes is described.
synthetically attractive building blocks for cyclopentanoid
natural products,
through the Nazarov reaction 2.They have been extensively used not only as dienophiles
in the Diels-Alder
reaction 3,but also in the Robinson annellation4. materials in the development
On the other hand , l-azadienes
of a wide variety of methods for the construction
are very versatile starting of p -antibiotics
5 and six
membered heterocycles 6 Previously, several procedures
of synthesis of divinyl ketones have been reported ‘8, however the
preparation of such compounds is far from simple *.Moreover the preparation of the (I- p-unsaturated
imines
from amines and carbonyl compounds, specially in the case of ketones, only yields good results in very specific cases 9 and it generally leads to Michael additionlO. In this context we have recently studied the [2+ 21 cycloaddition
reaction of acetylene acid esters with
phosphonium ylides and the related isoelectronic xs=phospazenes **aswell as their ability as starting materials in the preparation
of 2=aza=1,3=dienes I2and phosphorilated
of h “=phosphazenes as intermediates 2-vinyl=l=aza=1,3=dienes
p-enamines 13.Continuing
our interest in the use
in organic synthesis, we describe a very easy one- pot preparation
and 1,4=pentadien=3-ones
from comercially
N=phenyl=P,P,P=x *=phosphazenes 1, propargyltriphenylphosphonium Thus, triphenyl(prop=2ynyl)phosphonium rature for 36-40 h leading to the phosphonium
available
starting
reagents
of
14, as
bromide 2 and aldehydes.
bromide 2 reacts with x5-phosphazenes I51 at room tempeylide 3, in a similar way to that described for other acetylenic
compounds ll. Subsequent treatment of 3, without its isolation, with aldehydes (l-24 h, see table) affords the corresponding
p-enamino phosphonium
salts l64 in excellent yields. Compounds 4 were characterized
on the
basis of their spectroscopic data 17.For instance, the enaminic =CH of 4a give a ‘H resonance at 6 = 4.85 ppm (‘J, = 14.1 Hz) and a 13Cresonance at 6 = 61.4 ppm(‘J, = 117.9 Hz) as well resolved doublets, while the vicinal coupling constant
(“J,,= 15.8 Hz) between the vinylic protons reveals the E configuration
5493
.
5494
Ph,P =
NPh
NPh
NHPh
R’CH=O
mle
Rl &
of phosphonium
Compound
CPPW-
salts 4
RI
Reaction
Solvent
TW
m.p.(?IJb
Yield (W
Time(hP 4a
w5
14
CH,C4
25
157-158(d)
93
4b 4c
p-CH,_C,H, o-NO&H,
16 10
CH,CN CH,C4
60 25
69-70(d) 191-193(d)
86 88
4d
2-Fury1
20
CH,CN
60
210-212(d)
79
4e
H
1
CHC4
25
217-218(d)
95
4f
CI-JCH,
24
CH,Cl,
40
146-147(d)
68
’ Addition of aldehydes to the crude reaction mixture from 1 and 2 b From ethylacetate-CH,C1, Metallation
of compounds 4 with butyllithium
leads to 2-vinyl-1-aza-1,3-dienes
followed by addition of aldehydes and aqueous work-up
61s,isolated by means of a short chromatography
This result parallels that reported for the C-alkylation of p-enamino compounds 6 with 2N H,SO,affords prepared from phosphonium
the corresponding
colummwith ether as eluent.
A“-phosphazenes 13.Acid hydrolysis of
divinyl ketones 7 19.These derivatives 7 can be also
salts 4 and aldehydes when the reaction was quenched with 2N H,SO,,
5495
NPh
NHPh
i: BuLi, -7O”C, ii: R2CH = 0, -70°C to ZS’C, THF; iii: H,O; iv: H,O+
It is noteworthy that the preparation and purification
of the phosphonium
these salts 4, after evaporation
of divinylic ketimines 6 and ketones 7 does not require the isolation
salts 4. Improved overall yields are obtained in one pot reaction when
of the solvent, are directly metallated in THF with subsequent
addition of
aldehydes and aqueous or acid work-up, respectively.
Table of 2-vinyl-1-aza-13-dienes Compound
6 and 1.6pentadien-3-ones
7 prepared
RI
R2
m.p.(“Q
Yield( %p
6a
CP,
w,
97-98
86(84)
6b
o-NO&H,
C,H,
109-110
6c
C,H,CH= CH
6d
C,H, 2-Fury1
W81) oil(R, = 0.8)c 78(75)
C,H,CH = CH
oil(R, = 0.9p
6e
H
C&f,
oil(R, = 0.7)5 85(82)
72(70)
7a
(3-4
W
105106
88(X2)
7b
o-NO&H,
Cp,
92-93
84(79)
C,H, 2-Fury1
C,H,CH = CH
oil(R, = 0.8)0 79(7S)
C,H,CH=CH
oil(R,=0.9)c
7c 7d
74(71)
a From hexane “Yields from phosphonium =Silica gel, ether
salts 4. Yields given in parenthesis refer to the one-pot process from 1 and 2
5496
REFERENCES LA. Paquette, Top. Curr Chem. 1984,1,119.
l.- B.M. Trost, Chem. Sot. Rev. 1982,11,141.
M. Rarniah,
Synthesis, 1984,529. 2.- N.I. Nazarov, 1.1. Zaretskaya, Zh. Obshch. Khun, 1957,27, 693. G. Ohloff, K.H.Schulte, E. Demole, Helv. Chim. Acta, 1971,54,2913. 3.. G. Desimoni, G. Tacconi, Chem. Rev., 1975,75,651.
G. Desimoni, G. Tacconi, A. Barco, C.P. Pollini
in “Natural Products Synthesis through Pericyclic Reactions”. Am. Chem. Sot., Washintong
1983. E.
Ciganek, 0%. React., 1984,32, 1. 4.- M.E. Yung, Tetrahedron, 1976,32,3.
R.E. Gawley, Synthesis, 1976,.777.
5.- D.A. Evans, J.M. Williams, Tetrahedron Lett., 1988,29,5065.
J. Lasarte, C. Palomo, J.P. Picard, J.
Dunogues, J.M. Aizpurua, J. Chem. Sot. Chem. Comm., 1989,72. 6.- D.L. Boyer, S.M. Weinreb in “Hetero Diels-Alder
Methodology in Organic Synthesis”, Academic
Press, San Diego, 1987, p. 239. 7.- J. Barluenga, F. Aznar, M.P.Cabal, C.Vald&, Tetrahedron Left., 1989,30, 1413. 8.- M.R. Peel, C.R. Johnson, Tetrahedron Lett., 1986,27,5947
and references therein cited.
9.- SK. Malholra, D.F. Hookley, F. Johnson, J. Am. Chem. Sot., 1967,89,2794. lo.- M. S. Gibson in “The Chemistry of Amino Group”, Ed. S. Patai, J. Willey, London,l968, ll.- J. Barluenga, F. Upez,
p. 63.
F. Palacios,J. Chem. Sot. Chem. Comm., 1986,1574. J. Barluenga, F. Lopez,
F. Palacios, F. S&nchez, Tetrahedron Lett, 1988,29,381. 12.- J. Barluenga, M. Ferrero, F. Palacios, 13.- J. Barluenga, F. Upez,
Tetrahedron Lett, 1988,29, 4863.
F. Palacios, F.H. Cano, M. C. Foces,J. Chem. Sot. Perkin Trans.& 1988,
2329. 14.- Reagents 1 and 2 are available from Aldrich. lS.- E.E. Schweiser, C.S. Kim, C.S. Labau, W.P. Murray, J. Chem. Sot. Chem. Comm., 1973,7. 16.- Due to the imine-enamine tautomer 5 (l&19%);
equilibrium,
crude compounds 4 contain a small proportion
the tautomers ratio was determinated
of the iminic
by )‘I’-NMR (&= 16.5 ppm for 4a *and
s = 24.1 ppm for 5a, 83: 17). 17.- Spectral data for 4a: ~~(300 MHz, CDCL,): 48S(d,lH,27,,= 6.8-7.8S(m,ArH),
&.O(d,lH, ‘J,,= 15.8,CH=),
‘J,= 117.9,C-l), 119.7(d,?lE=7.0,C-3),
14.1,CH=), 6.l(d,lH
ST,,,,=15.8, CH=),
10.4(s, lH,NH); &, (75 MHz, CDCI,): 61.4(d,
122.6-148.3(CArom
(120 MHz, CDCU: 16.5 ppm. MS (70 ev): m/z=481
+ C-4), 161.0(d,T_ = 11.6,C-2); 6,
(M+-HBr).
18.- Spectral data for 6a: &,(300 MHz, CDC4): 6.76(d,lH, ‘J,, = 16.5,CH =), 6.91-7.6(m,ArH 7.58(d,lH, V,,,,,=16S,CH=); MS(70 ev): m/z=309
6, (75 MHz, CDC4): 120.8-150,7(CArom
1.5.8,CH=), 7.25-7.60(m,ArH),
lS.X,CH=); S, (75 MHz, CDCQ: (CArom + C-2 + C-4), 143(C-1 + C-5), 188(C-3)
ppm; MS(70 ev)m/z =234 (M+). (Received
ppm;
CM+).
19.- Spectral data for 7a: s,,(300 MHz, CDCA): 7.12(d,lH;J,,= 7.64(d,lH,?I,,=
+ CH =),
+ CH=),162.8(C-3)
in
UK 28 July
1989)