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Copper-catalysed reactions of grignard reagents with epoxides and oxetane.
Tetrahedron Letters No. 17, pp 1503 - 1506. 0 Pergamon Press Ltd. 1979. Printed in Great Britain.
COPPER-CATALYSED
Fadila
Chanh HUYNH, E.R.
REACTIONS
12 du C.N.R.S.,
24, rue Lhomond,
OF GRIGNARD
DERGUINI-BOUMECHAL Laboratoire
REAGENTS
WITH EPOXIDES
and Gerard
AND OXETANE.
LINSTRUMELLE
de Chimie de 1'Ecole Normale
Supkieure
75231 Paris Cedex 05.
ABSTRACT : The coppm-ca&Lqbed mageti pmceedn
The nucleophilic
usedmethod reagents
of epoxides by organometallic reagents is a frequently 1 of new carbon-carbon u bonds . The utilisation of Grignard is a well established route 2,3 ; however it has been limited in scope due to compearising
from either
These different
Ke now report which proceeds (1 equiv.) equiv.)
ring opening
for the generation
ting reactions reagent.
mechanistic
the efficient
the Lewis acidity pathways
copper-catalysed
in tetrahydrofuran the copper
representative
required
oxide
(1.5 equiv.)
salt, in the same conditions
Grignard
Benzylmagnesium not
chloride
Thus, when cyclohexene
and copper iodide (0.15 6 at 0" for 2 hr, trans-2-phenyl-cyclohexanol was obtained in 82%
2a was formed along with side products
hexene
or the basicity of the organometallic 4 have been investigated _ 5 reaction of Grignard reagents with epoxides
in high yield under very mild conditions.
was treated with phenylmagnesium
yield. Without
Several
by Gtignahd
hing opening 06 epoxiden and uxetane in good yield undek r&d conditionb.
reagents
chloride
for the efficient
oxide in tetrahydrofuran
pure trans-2-benzyl-cyclohexanol
and unchanged
(2 hr at O"), less than 3% of alcohol
starting
listed in table
material
1 led to similar
was found to be more reactive
ring opening
of the epoxides
at 0' without
copper
catalysis
was
; thus, when treated with cyclo-
salt, this reagent
RMgX \ 0.l (1)
1
results.
and copper
in 90% yield.
0
(40%).
2
gave, within
2 hr,
1504 Table
No. 17
: Reaction of Grignard reagents
1
in THF after 2 hr ar 0' PRODUCT
(1.5 equiv.) with cyclohexene
oxide
(1 equiv.)
:
R
X
Yield a (%) 10 % Cu I without
with
catalyst
2a -2b
Cl
82b
3
A!-C4R9
Cl
5$-
6
-2c
CH3-C=CH2
Br
88
4od
-2d
(CH3)2C=CH-CH2
Cl
86e,f
86'
_2e
'gHgCH2
Cl
40
86h
Y5
a yield of distilled
product
iodo-cyclohexanol.
calculated
' 10% of cyclohexanone
with lithium
cuprates,
temperature,
alcohol -2c was obtained f
- 300 8b. cyclohexanol Grignard
By using
see ref.7.
epoxides
epoxides
towards
Grignard
propylene
oxide
(1 equiv.)
(0.15 equiv.)
yield. Without
However,
reagents
Containing
6% of trans-2-
: This side product was also observed
copI>er salt, after 6 hr at 0' and 1 hr at room e This reaction was carried out at
iodide, predominant
formation
of trans-2-iodo-
by using 3 equiv. of copper bromide,
and 3 equiv. of
and ethylene
g
h
see ref. 8b.
see ref. 9.
oxide are more reactive
and are less dependent
upon
was treated with butyl magnesium
copper
chloride
than disubstituted
catalysis.
Thus, when
(1.5 equiv.)
and copper
for 2 hr at O", it gave pure heptan-2-01
in the same conditions,
; however after 8 hr at room temperature,
reaction
b
in 80% yield.
in tetrahynrofuran
catalyst,
oxide.
formed
67% of alcohol _2d were obtained.
Monosubstituted
bromide
were
d Without
1.5 equiv. of copper
was observed.
reagent,
from cyclohexene
the yield was only 26% because
in 93% of incomplete
alcohol ?c was formed in 86% yield. ll,l2,13
The less strained
cyclic ether, oxetane 2, has lower reactivity
The ring cleavage benzene
of this compound by Grignard reagents has been reported 11 for several hours . However, when treated at room temperature
hydrofuran
with
These catalytic oxetane
10% of copper iodide,
processes
by Grignard
represent
reagents.
it gave the alcohols
a useful procedure
than epoxides by refluxing
in
for 20 hr in tetra-
_6 in acceptable
for the ring opening
yields.
of epoxides
and
No. 17
1505 R2
R2
R1 Mgx w
cu (1)
OH
f!
3 Table
2 :
hydrofuran
Reaction
of Grignard
after 2 hr at 0"
PRODUCT
reagents
(1.5 equiv.)
with epoxides
R1
R2
4a -
'gH5
_4b
'gH5
4c _
n-C4"9
CH
_4d
_n-c4E+
H
4e _
CH3-?=CH2
4f _
'gHgCH2
CH
X
3
H
CH CH
3
3
Cl
81b
75c
Cl
93
26e
Cl
88b
55d
Br
90
90
91
95
from epoxide _3. e Without copper
alcohol -4c was obtained
b
1 equiv. of Grignard salt, after
Reaction
of Grignard a iodide :
of 10% of copper PRODUCT
R
A
reagents
X
6a _
“-C4Hg
_Gb
'gH5
-6c
CH2=CH-CH
_6d
(CH3)2C=CH-CH2d
2
was
in 86% yield.
cu (1)
OH
5
:
reagent
1 hr at 0" and 8 hr at
RMgX
0
3
catalyst 80
0 Table
(8) without
95
Cl
3
Yielda 10% CuBr
Cl
Yield of distilled product calculated c d used. see ref. 10. see ref. 3. room temperature,
in tetra-
:
with
a
_3 (1 equiv.)
6 (1 equiv.)
with oxetane
(3 equiv.)
in the presence
Solvent
Yield b(%)
Cl
ether
75c
Br
THF
52
Br
ether
50
Cl
THF
5oeef
s 'Ebeaddition of the reagent to the oxide was carried out at-BOand the reaction mixture was allowed to warm to room temperature and maintained at +20° for 20 hr unless otherwise noted. Distilled yield bzsed onGrignard reagent. Identity was confirmed by comparison with an authentic sample.e Without copper iodide, after 90 hr at 0'. 10%fof n-heptanol were formed. d See ref. 8. This reaction was carried out at 0" for 20 hr. 3%-of 4-4-dimethyl-5kxenolwere also formed. Without copper salt, after 12 hr at O', a mixture (15:85) of gd and 4-4-dimethyl-5-hexenol was obtained in 75% yield.
b
No. 17 TYPICAL
PROCEDURE
FOR THE RING OPENING
OF EPOXIDES.
14 Trans-2-phenyl-cyclohexanol : To 430 mg (2.3 mm011 of copper iodide in anhydrous THF chloride were added dropwise at -30". (10 ml), 23 mm01 (2.25N in THF) of phenylmagnesium After 5 mm at -3O", 1.47g (15 mmol) of cyclohexene oxide were added. The mixture was allowed to warm to O" and maintained at this temperature for 2 hr. Work-up in the usual manner and distillation gave 2,16 g 482%) of trans-2-phenyl-cyclohexanol a, b.p. 102-1030/0.5 mm ; m.p. 57-58O (from pentane) . TYPICAL PROCEDURE FOR THE RING OPENING OF OXETANE 5. To 164 mg (0.862 mm011 of copper iodide 14 and 2 g (34mmol) of oxetane inanhydrous ether (15 ml), 8.62 mm01 (1.98N in ether) of c-butylmagnesium chloride were added dropwise at -30". The reaction mixture was allowed to warm to room temperature and stirring was maintained for 20 hr. Then, the mixture was hydrolysed with saturated ammonium chloride, extracted with ether and the combined extracts dried and evaporated. Distillation gave 750 mg (75%) of _n-heptanol.
REFERENCES 1. R.E. PARKER and N.S. ISAACS, Chem. Rev., 59, 737 (1959). 2. M.S. KHARASH and 0. REINMUTH, Grignard reactions of nonmetallic substances, Prentice Hall Inc., New-York, 1954. 3. VOGEL'S, Textbook of pratical organic chemistry, Longman, London-and New-York, Fourth edition, 1978, p. 367 ; E.E. DREGER, Org. Syn., ~011. vol. 1,Second Ed., 1947. P. 306 4. R.C. HUSTON and H.E. TIEFENTHAL, J. Org. Chem., 5, 673 (1951) ; A. SCHAAP and J.F. ARENS, Rec. Travaux Chim. Pays Bas, 87, 1249 (1968). with epoxides is often used : however excess of 5. The reaction of lithium dialkylcuprates cuprate is usually required : For a recent report, see : R.D. ACKER, Tetrahedron lett. 3407 (1977) and references therein. 1810 (1950) ; R.W. HERR, D.M. 6. E.R. ALEXANDER and A. MUDRACK, J. Amer. Chem. Sot., ", WIELAND and C.R. JOHNSON, J. Amer. Chem. Sot., 92, 3814 (1970). 7. C.R. JOHNSON, R.W. HERR and D.M. WIELAND, J. Org. Chem., 38, 4263 (1973). of allylic Grignard reagents 8. Under copper catalysed conditions, regioselective alkylatzn occurs at the primary carbon atom : a) F. DERGUINI-BOUMECHAL, R. LORNE and G. LINSTRUMELLE, Tetrahedron Lett., 1181 (lY77) ; b) G. LINSTRUMELLE, R. LORNE and H.P. DANG, Tetrahedron Lett., 4069 (1978). 9. M. MOREAU, R. QUAGLIARO, R. LONGEPAY and J. DREUX, Bull. Sot. Chim,1362 (1969). rn __.H.E. RAMSDEN, A.E. BALINT, W.R. WHITFORD, J.J. WALBURN and R. CSERR, J. Org. Chem, 22, 1202 (1957). 11.~. SEA&ES, J. Amer. Chem. Sot., 13, 124 (1951). 12.T. CUVIGNY and H. NORMANT, C.R. Acad. SC., 254, 316 (1962) ; H. NORMANT, C.R. Acad. SC., 240, 440 (1955). 13.~. MILLON and G. LINSTRUMELLE, Tetrahedron LeE, 1095 (1976). 14. G. LINsTRUMELLE, J.K. KRIEGER and G.M. WHITESIDES, Org. Syn., 55, 103 (1976).
(Received
in UK 21 February
1979)
COPPER-CATALYSED
Fadila
Chanh HUYNH, E.R.
REACTIONS
12 du C.N.R.S.,
24, rue Lhomond,
OF GRIGNARD
DERGUINI-BOUMECHAL Laboratoire
REAGENTS
WITH EPOXIDES
and Gerard
AND OXETANE.
LINSTRUMELLE
de Chimie de 1'Ecole Normale
Supkieure
75231 Paris Cedex 05.
ABSTRACT : The coppm-ca&Lqbed mageti pmceedn
The nucleophilic
usedmethod reagents
of epoxides by organometallic reagents is a frequently 1 of new carbon-carbon u bonds . The utilisation of Grignard is a well established route 2,3 ; however it has been limited in scope due to compearising
from either
These different
Ke now report which proceeds (1 equiv.) equiv.)
ring opening
for the generation
ting reactions reagent.
mechanistic
the efficient
the Lewis acidity pathways
copper-catalysed
in tetrahydrofuran the copper
representative
required
oxide
(1.5 equiv.)
salt, in the same conditions
Grignard
Benzylmagnesium not
chloride
Thus, when cyclohexene
and copper iodide (0.15 6 at 0" for 2 hr, trans-2-phenyl-cyclohexanol was obtained in 82%
2a was formed along with side products
hexene
or the basicity of the organometallic 4 have been investigated _ 5 reaction of Grignard reagents with epoxides
in high yield under very mild conditions.
was treated with phenylmagnesium
yield. Without
Several
by Gtignahd
hing opening 06 epoxiden and uxetane in good yield undek r&d conditionb.
reagents
chloride
for the efficient
oxide in tetrahydrofuran
pure trans-2-benzyl-cyclohexanol
and unchanged
(2 hr at O"), less than 3% of alcohol
starting
listed in table
material
1 led to similar
was found to be more reactive
ring opening
of the epoxides
at 0' without
copper
catalysis
was
; thus, when treated with cyclo-
salt, this reagent
RMgX \ 0.l (1)
1
results.
and copper
in 90% yield.
0
(40%).
2
gave, within
2 hr,
1504 Table
No. 17
: Reaction of Grignard reagents
1
in THF after 2 hr ar 0' PRODUCT
(1.5 equiv.) with cyclohexene
oxide
(1 equiv.)
:
R
X
Yield a (%) 10 % Cu I without
with
catalyst
2a -2b
Cl
82b
3
A!-C4R9
Cl
5$-
6
-2c
CH3-C=CH2
Br
88
4od
-2d
(CH3)2C=CH-CH2
Cl
86e,f
86'
_2e
'gHgCH2
Cl
40
86h
Y5
a yield of distilled
product
iodo-cyclohexanol.
calculated
' 10% of cyclohexanone
with lithium
cuprates,
temperature,
alcohol -2c was obtained f
- 300 8b. cyclohexanol Grignard
By using
see ref.7.
epoxides
epoxides
towards
Grignard
propylene
oxide
(1 equiv.)
(0.15 equiv.)
yield. Without
However,
reagents
Containing
6% of trans-2-
: This side product was also observed
copI>er salt, after 6 hr at 0' and 1 hr at room e This reaction was carried out at
iodide, predominant
formation
of trans-2-iodo-
by using 3 equiv. of copper bromide,
and 3 equiv. of
and ethylene
g
h
see ref. 8b.
see ref. 9.
oxide are more reactive
and are less dependent
upon
was treated with butyl magnesium
copper
chloride
than disubstituted
catalysis.
Thus, when
(1.5 equiv.)
and copper
for 2 hr at O", it gave pure heptan-2-01
in the same conditions,
; however after 8 hr at room temperature,
reaction
b
in 80% yield.
in tetrahynrofuran
catalyst,
oxide.
formed
67% of alcohol _2d were obtained.
Monosubstituted
bromide
were
d Without
1.5 equiv. of copper
was observed.
reagent,
from cyclohexene
the yield was only 26% because
in 93% of incomplete
alcohol ?c was formed in 86% yield. ll,l2,13
The less strained
cyclic ether, oxetane 2, has lower reactivity
The ring cleavage benzene
of this compound by Grignard reagents has been reported 11 for several hours . However, when treated at room temperature
hydrofuran
with
These catalytic oxetane
10% of copper iodide,
processes
by Grignard
represent
reagents.
it gave the alcohols
a useful procedure
than epoxides by refluxing
in
for 20 hr in tetra-
_6 in acceptable
for the ring opening
yields.
of epoxides
and
No. 17
1505 R2
R2
R1 Mgx w
cu (1)
OH
f!
3 Table
2 :
hydrofuran
Reaction
of Grignard
after 2 hr at 0"
PRODUCT
reagents
(1.5 equiv.)
with epoxides
R1
R2
4a -
'gH5
_4b
'gH5
4c _
n-C4"9
CH
_4d
_n-c4E+
H
4e _
CH3-?=CH2
4f _
'gHgCH2
CH
X
3
H
CH CH
3
3
Cl
81b
75c
Cl
93
26e
Cl
88b
55d
Br
90
90
91
95
from epoxide _3. e Without copper
alcohol -4c was obtained
b
1 equiv. of Grignard salt, after
Reaction
of Grignard a iodide :
of 10% of copper PRODUCT
R
A
reagents
X
6a _
“-C4Hg
_Gb
'gH5
-6c
CH2=CH-CH
_6d
(CH3)2C=CH-CH2d
2
was
in 86% yield.
cu (1)
OH
5
:
reagent
1 hr at 0" and 8 hr at
RMgX
0
3
catalyst 80
0 Table
(8) without
95
Cl
3
Yielda 10% CuBr
Cl
Yield of distilled product calculated c d used. see ref. 10. see ref. 3. room temperature,
in tetra-
:
with
a
_3 (1 equiv.)
6 (1 equiv.)
with oxetane
(3 equiv.)
in the presence
Solvent
Yield b(%)
Cl
ether
75c
Br
THF
52
Br
ether
50
Cl
THF
5oeef
s 'Ebeaddition of the reagent to the oxide was carried out at-BOand the reaction mixture was allowed to warm to room temperature and maintained at +20° for 20 hr unless otherwise noted. Distilled yield bzsed onGrignard reagent. Identity was confirmed by comparison with an authentic sample.e Without copper iodide, after 90 hr at 0'. 10%fof n-heptanol were formed. d See ref. 8. This reaction was carried out at 0" for 20 hr. 3%-of 4-4-dimethyl-5kxenolwere also formed. Without copper salt, after 12 hr at O', a mixture (15:85) of gd and 4-4-dimethyl-5-hexenol was obtained in 75% yield.
b
No. 17 TYPICAL
PROCEDURE
FOR THE RING OPENING
OF EPOXIDES.
14 Trans-2-phenyl-cyclohexanol : To 430 mg (2.3 mm011 of copper iodide in anhydrous THF chloride were added dropwise at -30". (10 ml), 23 mm01 (2.25N in THF) of phenylmagnesium After 5 mm at -3O", 1.47g (15 mmol) of cyclohexene oxide were added. The mixture was allowed to warm to O" and maintained at this temperature for 2 hr. Work-up in the usual manner and distillation gave 2,16 g 482%) of trans-2-phenyl-cyclohexanol a, b.p. 102-1030/0.5 mm ; m.p. 57-58O (from pentane) . TYPICAL PROCEDURE FOR THE RING OPENING OF OXETANE 5. To 164 mg (0.862 mm011 of copper iodide 14 and 2 g (34mmol) of oxetane inanhydrous ether (15 ml), 8.62 mm01 (1.98N in ether) of c-butylmagnesium chloride were added dropwise at -30". The reaction mixture was allowed to warm to room temperature and stirring was maintained for 20 hr. Then, the mixture was hydrolysed with saturated ammonium chloride, extracted with ether and the combined extracts dried and evaporated. Distillation gave 750 mg (75%) of _n-heptanol.
REFERENCES 1. R.E. PARKER and N.S. ISAACS, Chem. Rev., 59, 737 (1959). 2. M.S. KHARASH and 0. REINMUTH, Grignard reactions of nonmetallic substances, Prentice Hall Inc., New-York, 1954. 3. VOGEL'S, Textbook of pratical organic chemistry, Longman, London-and New-York, Fourth edition, 1978, p. 367 ; E.E. DREGER, Org. Syn., ~011. vol. 1,Second Ed., 1947. P. 306 4. R.C. HUSTON and H.E. TIEFENTHAL, J. Org. Chem., 5, 673 (1951) ; A. SCHAAP and J.F. ARENS, Rec. Travaux Chim. Pays Bas, 87, 1249 (1968). with epoxides is often used : however excess of 5. The reaction of lithium dialkylcuprates cuprate is usually required : For a recent report, see : R.D. ACKER, Tetrahedron lett. 3407 (1977) and references therein. 1810 (1950) ; R.W. HERR, D.M. 6. E.R. ALEXANDER and A. MUDRACK, J. Amer. Chem. Sot., ", WIELAND and C.R. JOHNSON, J. Amer. Chem. Sot., 92, 3814 (1970). 7. C.R. JOHNSON, R.W. HERR and D.M. WIELAND, J. Org. Chem., 38, 4263 (1973). of allylic Grignard reagents 8. Under copper catalysed conditions, regioselective alkylatzn occurs at the primary carbon atom : a) F. DERGUINI-BOUMECHAL, R. LORNE and G. LINSTRUMELLE, Tetrahedron Lett., 1181 (lY77) ; b) G. LINSTRUMELLE, R. LORNE and H.P. DANG, Tetrahedron Lett., 4069 (1978). 9. M. MOREAU, R. QUAGLIARO, R. LONGEPAY and J. DREUX, Bull. Sot. Chim,1362 (1969). rn __.H.E. RAMSDEN, A.E. BALINT, W.R. WHITFORD, J.J. WALBURN and R. CSERR, J. Org. Chem, 22, 1202 (1957). 11.~. SEA&ES, J. Amer. Chem. Sot., 13, 124 (1951). 12.T. CUVIGNY and H. NORMANT, C.R. Acad. SC., 254, 316 (1962) ; H. NORMANT, C.R. Acad. SC., 240, 440 (1955). 13.~. MILLON and G. LINSTRUMELLE, Tetrahedron LeE, 1095 (1976). 14. G. LINsTRUMELLE, J.K. KRIEGER and G.M. WHITESIDES, Org. Syn., 55, 103 (1976).
(Received
in UK 21 February
1979)