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Zinc chloride induced cycloaddition of allyl chlorides to alkynes: A new cyclopentene synthesis
Tetrahedron Letters Vol. 21, pp 577 - 580 @Pergnmon Press Ltd. 1980. Printed in Great Britain
ZINC CHLOBIDE INDUCED CYCLOADDITIOE OF ALLYL CELOBIDES TC AIKYEES: A EEW CYCLOPEETEBE SYETIiESIS
Allen
Milled and Michael Moore
Department of Chemistry, The diversity, Dundee, DDl 4HN, Scotland
suMMmY
Zinc chloride catalyses both cycloaddition and simple addition of sllylic chlorides to slkynes. The former reaction csn lead to good yields of 4-chloro-cyclopentenes, and constitutes a new cyclopentene synthesis.
[4+2]-Cycloaddition(Diels Alder reaction) end [3+2]-cycloaddition(1,3-dipole reaction) processes using neutral reactants have long had an important place in the synthesis of .&cyclic and heterocyclic compounds. By contrast, polar cycloadditionsleading to fivemembered rings, as in equation
(11, were
led by Hoffmsnn2 and by Noyori.3
almost mown'
until the pioneering work of groups
Their efforts have resulted in the development of
conditions favourable to [3+2]- end [3+4]-cycloadditionreactions, notably those baaed on oxy-ally1 cations,
>--_(
+
9
c
fire recently, others have shown that simple Lewis acid-ally1 halide interactions csn 4,5 or of [3+2]produce intermediates capable of [3+4]-cycloadditionto 1,3-dienes, cycloadditionto slkenes.5
Our previous interest in heterogeneous Lewis acid catalysis6
577
578
also led us to the view that such cmditions might lead to cycloaddition. We now report that anhydrous zinc chloride c5n induce [3+2]-cycloedditionto -es,
thu5 providing a new route
to substituted cyclopentenes,8s shown for the general c8se in equation (2).
vFL
n”’
+-=- -
---
(2)
our procedure is extremely simple, and involves the gradual addition of * 8~1allylic chloride, 1, to a stirred mixture of an alkyne, 2, (1 mol. equiv.), and zinc
Experimentally
chloride in 1,2-dichloroeth811e.~ Sometimes cooling is advisable during the addition, and, after this is complete, the mixture is stirred at 20°C, for the times shown in the Table. The catalyst is then removed by filtration, and the product(s) isolated by conventional methods,usually chromatographic. Our results (see Table) show that cycloedditionis observable with a reng chlorides, .I, and aUome5.2.
of allylic
The efficiency of cycloadditionis quite variable, and this is
Largely due to ccrmpetition between cycloeddition (equation (2)), and simple additicm (equati.01 (3)),to the sJ.kyne. Cycloadditionis favoured with phenyl acetylenes, aad when two possible regioisauers mey be formed, only ane is observed.
The regiochemistryof the cycloedditionproducts is not miquely established by the u~iualspectroscopicmethod5 of analysis. Chemical ccnfirmationWBB achieved by ozonolysis (Zn-HOAc work-up), 55 shown in equation (4) for the cycloadduct,5, of phenyl acetylene with
579
l-chloro-3-methylbut-2-ene.The n.m.r.
an a-f)-unsaturatedsXehy&
of the al&&y&
ozanolysis product,
$, clearly reveals
structure, and allows rejection of 5 es a possible cycloaddition
product. TABLE: Yields of cycloadductsa and of 1.4~dienesb from zinc chloride catalysed sllyl chloride-alkynereactions.
cl
R’
ALWL
a
CHLoRIrE
+
J_
R’-Z-R4
F
-E2.
m
(h)
% CYCLOADDUCrJ
72
0
0
+=Ms, R4=Ph
6
50
28
Rl=Pb, R2=H
$=Me, R4=Ph
3.5
33
7
R&R&&
#=H, R4=Ph
2
36
48
11 I,
R3=&, R4=Ph
3
78
0
II 11
R&u
4
57
0
II 11
R3=R4,ph
2
75
0
11 It
Rs=Rb,Et
6
21
42
1, 11
R3=H, R4=!Bu
12
<5
1, 11
R3=CCQEt, R4=Ph
72
0
R1=R2=H
R3=Ii,R4=Ph
R1=Me, R2=H
9 R4=Ph
0
appropriate microanalytical and spectroscopic data has been obtained for new structures.
b
$ 1.3DIENESA
trans-1-chloro-1.4~dienes. mixtures of -cis-l-chloro- and _
+P CL
Me,pyU
Ph
t
Ph---_+I
-
Me
3
In conclusion, this work describes the first [3+2]-cycloadditionto an alkyne,* and provides a one pot route to cyclopentenesnot readily prepared by available methods. The synthetic prospects end mschsnistic aspects
of these reactions are being investigated.
References
1.
Polar cycloadditionswere first reviewed by R.R. Schmidt, Angew. Chem. Internat. E&I., 1973, _&
212.
Cycloadditions of the [3+2] or [3+4] typs form a minor part of this
review. 2.
Reviewed in H.M.R. Hoffmann, Angew. Chem. Inteznat. Edn., 1973,x,
819. For more
recent work, see H.M.R. Hoffmsnn and R. Chidgey, Tetrahedron Letters, 1978, 85; D.I. Rawson, B.K. Carpenter, andH.M.R. Hoffmann, J. Amer. Chem. Sot., 1979,&l_, 1786. 3. Y. Hayakawa, K. Yokoyame, and R. Noyori, J. Amer. Chem. Sot., 1978,a.
1791.
work by the same group is reviewedby R. Noyori, Act. Chem. Res., 1979,g,
Other
61.
4.
H. Sakurai, A. Shirshata, end A. Hosomi, Annew. Chem. Internat. Edn., 1979, 2,
5.
N. Shimizu and Y. Tsuno, Chem. titters, 1979, 103.
6.
J.A. Miller, Tetrshedron Letters, 1975, 2959; J.A. Miller end M.J. Nunn,
163.
J.C.S. Perkin I, 1976, 416. 7.
Other non-polar aprotic solvents are also suitable, although rates are generally lower.
8.
For snother attempt, see A.P. Cowling and J. Mann. J.C.S. Chem. Conmn.,1978, 1006. (Received in UK JO November 1979)
ZINC CHLOBIDE INDUCED CYCLOADDITIOE OF ALLYL CELOBIDES TC AIKYEES: A EEW CYCLOPEETEBE SYETIiESIS
Allen
Milled and Michael Moore
Department of Chemistry, The diversity, Dundee, DDl 4HN, Scotland
suMMmY
Zinc chloride catalyses both cycloaddition and simple addition of sllylic chlorides to slkynes. The former reaction csn lead to good yields of 4-chloro-cyclopentenes, and constitutes a new cyclopentene synthesis.
[4+2]-Cycloaddition(Diels Alder reaction) end [3+2]-cycloaddition(1,3-dipole reaction) processes using neutral reactants have long had an important place in the synthesis of .&cyclic and heterocyclic compounds. By contrast, polar cycloadditionsleading to fivemembered rings, as in equation
(11, were
led by Hoffmsnn2 and by Noyori.3
almost mown'
until the pioneering work of groups
Their efforts have resulted in the development of
conditions favourable to [3+2]- end [3+4]-cycloadditionreactions, notably those baaed on oxy-ally1 cations,
>--_(
+
9
c
fire recently, others have shown that simple Lewis acid-ally1 halide interactions csn 4,5 or of [3+2]produce intermediates capable of [3+4]-cycloadditionto 1,3-dienes, cycloadditionto slkenes.5
Our previous interest in heterogeneous Lewis acid catalysis6
577
578
also led us to the view that such cmditions might lead to cycloaddition. We now report that anhydrous zinc chloride c5n induce [3+2]-cycloedditionto -es,
thu5 providing a new route
to substituted cyclopentenes,8s shown for the general c8se in equation (2).
vFL
n”’
+-=- -
---
(2)
our procedure is extremely simple, and involves the gradual addition of * 8~1allylic chloride, 1, to a stirred mixture of an alkyne, 2, (1 mol. equiv.), and zinc
Experimentally
chloride in 1,2-dichloroeth811e.~ Sometimes cooling is advisable during the addition, and, after this is complete, the mixture is stirred at 20°C, for the times shown in the Table. The catalyst is then removed by filtration, and the product(s) isolated by conventional methods,usually chromatographic. Our results (see Table) show that cycloedditionis observable with a reng chlorides, .I, and aUome5.2.
of allylic
The efficiency of cycloadditionis quite variable, and this is
Largely due to ccrmpetition between cycloeddition (equation (2)), and simple additicm (equati.01 (3)),to the sJ.kyne. Cycloadditionis favoured with phenyl acetylenes, aad when two possible regioisauers mey be formed, only ane is observed.
The regiochemistryof the cycloedditionproducts is not miquely established by the u~iualspectroscopicmethod5 of analysis. Chemical ccnfirmationWBB achieved by ozonolysis (Zn-HOAc work-up), 55 shown in equation (4) for the cycloadduct,5, of phenyl acetylene with
579
l-chloro-3-methylbut-2-ene.The n.m.r.
an a-f)-unsaturatedsXehy&
of the al&&y&
ozanolysis product,
$, clearly reveals
structure, and allows rejection of 5 es a possible cycloaddition
product. TABLE: Yields of cycloadductsa and of 1.4~dienesb from zinc chloride catalysed sllyl chloride-alkynereactions.
cl
R’
ALWL
a
CHLoRIrE
+
J_
R’-Z-R4
F
-E2.
m
(h)
% CYCLOADDUCrJ
72
0
0
+=Ms, R4=Ph
6
50
28
Rl=Pb, R2=H
$=Me, R4=Ph
3.5
33
7
R&R&&
#=H, R4=Ph
2
36
48
11 I,
R3=&, R4=Ph
3
78
0
II 11
R&u
4
57
0
II 11
R3=R4,ph
2
75
0
11 It
Rs=Rb,Et
6
21
42
1, 11
R3=H, R4=!Bu
12
<5
1, 11
R3=CCQEt, R4=Ph
72
0
R1=R2=H
R3=Ii,R4=Ph
R1=Me, R2=H
9 R4=Ph
0
appropriate microanalytical and spectroscopic data has been obtained for new structures.
b
$ 1.3DIENESA
trans-1-chloro-1.4~dienes. mixtures of -cis-l-chloro- and _
+P CL
Me,pyU
Ph
t
Ph---_+I
-
Me
3
In conclusion, this work describes the first [3+2]-cycloadditionto an alkyne,* and provides a one pot route to cyclopentenesnot readily prepared by available methods. The synthetic prospects end mschsnistic aspects
of these reactions are being investigated.
References
1.
Polar cycloadditionswere first reviewed by R.R. Schmidt, Angew. Chem. Internat. E&I., 1973, _&
212.
Cycloadditions of the [3+2] or [3+4] typs form a minor part of this
review. 2.
Reviewed in H.M.R. Hoffmann, Angew. Chem. Inteznat. Edn., 1973,x,
819. For more
recent work, see H.M.R. Hoffmsnn and R. Chidgey, Tetrahedron Letters, 1978, 85; D.I. Rawson, B.K. Carpenter, andH.M.R. Hoffmann, J. Amer. Chem. Sot., 1979,&l_, 1786. 3. Y. Hayakawa, K. Yokoyame, and R. Noyori, J. Amer. Chem. Sot., 1978,a.
1791.
work by the same group is reviewedby R. Noyori, Act. Chem. Res., 1979,g,
Other
61.
4.
H. Sakurai, A. Shirshata, end A. Hosomi, Annew. Chem. Internat. Edn., 1979, 2,
5.
N. Shimizu and Y. Tsuno, Chem. titters, 1979, 103.
6.
J.A. Miller, Tetrshedron Letters, 1975, 2959; J.A. Miller end M.J. Nunn,
163.
J.C.S. Perkin I, 1976, 416. 7.
Other non-polar aprotic solvents are also suitable, although rates are generally lower.
8.
For snother attempt, see A.P. Cowling and J. Mann. J.C.S. Chem. Conmn.,1978, 1006. (Received in UK JO November 1979)