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Formation of allenes by reaction of lithium diorganocuprates on propargylic acetates - a mechanistic approach
~atrahedron Letters No. 51, PP 4615 - 4618, 1975. PergamonPress. Printed in Great Bntaln.
Formation
of Allenes by Reactlon of Lithium Diorqanocuprates
on Propargylic
Acetates
J.L. Luche, E. Barreiro, C.E.R.M.O.,
Universite
- A Mechanistic
Approach1
J.M. Dollat and P. Crabbe" Screntifique
et Medicale,
38041 Grenoble, France (&calved m UK 30 October 1975; acceptedfor publloatlon6 November 1975)
In the past, we reported an efficient reactlon of lithium dlmethylcopper preparations
synthesis of substituted allenes by 2 acetates . Numerous other
with acetylenic
of allenes through the use of organometallic reagents (I;)on pro3-6 (2) have been reported . Besides the expected propadiene (z),
pargylic esters a non-alkylated
allene
(4) has sometimes
been isolated, the origin of which
remained obscure. As shown in the Table, the reaction appears to be general, applicable primary,
secondary and tertiary acetates of non-substituted
tuted propargylic
compounds.
One of the particular
that there seems to be no simple relationship ester and the ratio of alkylated
to
as well as substr-
facets of this reactron
is
between the structure of the
(3) and non-alkylated
(4) material.
The experimental reaction mechanism,
data listed in the Table induced us to re-examine the 2 since the free-radical approach mentioned earlier did not
account for all observations.
Instead, the results of some recent experiments
seem to imply the intervention allenic copper derlvatlve
of an organometallic
Reaction of lithium dlmethylcopper ditions
intermedlate
such as the
(2). on the acetate
(6) under the usual con-
(see Table), was followed by aced hydrolysis with 10% DBr in a D20
solution. Vapor phase chromatography 22% of deuterated
(V.P.C.) and mass spectrometry
indicated
(7a) and 78% of the methylated allene (&). Significantly, treatment of the acetate (2) with Li(CD3)2Cu followed by HCl hydrolysis afforded
allene
the trideuteromethyl
allene
in 79% and 21% yield respectively, in (7b) did not originate -
(e)
and the non-deuterated
thus establishing
from the organocuprate
4615
allene
(2)
that the entering hydrogen
reagent.
4616
NO. 51
TABLE
J!sters
R2CuL'" *
Hc~c-cH2aAc
HC5C-CH?411c
14ec
Cowsion
Allenes
in %b
3
4
not isolated
70
n-But
75
Ia2
n-Bu
-2
not isolated
80
I&CH=C=CBAm(75%)
H2CYXH?m(25%)
40
RucI#xHAm(x)%)
HZ-W)%)
Ph
50
PhcSC=wd100%)
Me
80
Me2C=C=CYAm(60%)
MeCWC=CHAm(traces)
Me
73
Me2C=C=CHPh(96%)
_(4%)
Me
93
bc
99
Me
85
Me
62
a. One equiv. ester add& into an ether soln. of n equlv. R2CuLi (n=1.2for R* R=nBu and Ph) cooled to -10' t-30'for R=nBu).After sis with sat. NH4C1, &a&on
stirring
with ether, the canpoundswsre xolatd.
estunationby V.P.C. (CarloErba Fractovap,4 m. 20% Card Bu+Jutyl ; Amamy
; Ph==yl.
d.Es~tedbymass
substitutedallenes could not be separatedby V.P.C.
; n=2 for
for 2 hrs. at same t9np., hydrolyb. Purificationard
20 M column, F.I.D.). c. -thy1
spectranetry,since these tri- and tetra-
4617
No. 51
An organometallic
intermediate
attack on the acetylene reasonable
precursor
of type
(S), formed by dimethylcopper
carbon and acetate expulsion, would constitute
for the allene
(7J). The intermediate
anion
a
(I) may lead to the
(8a) by alkyl migration from the copper to the sp2 carbon atom, while Its hydrolysis would produce the corresponding non-alkylated allene (2).
methyl-allene
Thus, direct distillation dimethylcopper
of the reaction mixture of the ester yielded
98% of alkylated
(a) with lithium
(8a) and only 2% of (7b) (the origin of the latter is attributed to traces of moisture In the medium). It 1s worth to emphasize that acid treatment (HCl, DBr) gave a higher proportion
before hydrolysis
allene
of allene
(7b) than hydrolysis with NH4Cl. Additionally, a longer reaction time increased the proportion of alkylated allene (&), by favouring alkyl migration
from the organometallic
of lithium dimethylcopper HCl hydrolysis,
afforded
to the ester 78% of
(a)
intermediate
(2). So, whereas addrtion
(a) for 2 hrs. at -lo', followed by 1.2N
and 22% of (z),
this ratio was modified
when the reaction time was (7b) respectively 2 hrs. at -lo', followed by 21 hrs. at room temperature. A higher yield of (8a) (98%) has been obtained under slightly different conditions. Conversely, the
to 91:9% of propadlenes
(&)
and
addition of cumene or a-methylstyrene,
as free radical scavengers,
: non-alkylated
reaction medium did not affect the alkylated It was also anticipated some light on its mechanism. formed on an optically
to the
allene ratio.
that the steric course of the reaction Hence, a lithium dimethylcopper
active propargylic
acetate.
should cast
reaction was per-
(S)-(-)-3-Hydroxy-1-octyne
acetate [aID -69.5' (2)7, obtained after esterification of the known (S)-(-) 8 , was treated with lithium dlmethylcopper under the usual conditions
alcohol
(at -10'). The allene of the Brewster-Lowe compound
-loo. Application (10) exhlblted a specific rotation [aID -9 rule leads to the (R)-(-) absolute configuration for
(lo). Hence the approach of the cuprate reagent and the formation of
the carbon-copper
bond seem to take place preferentially
with respect to the carbon-oxygen
was increased when the reaction was performed affording
the optically
active allene
at lower temperature
n073-7-1875
and 75-7-0141)
and the C.N.R.S.
or a cationicmechanism.
for GC-MS measurements.
(contracts
(F.R.A. n'478). E.B. is grateful
(Brazil) and J.M.D. to the C.N.R.S.
ships. Thanks are due to Mr. Bosso slons.
mechanism
: This work was supported by the D.G.R.S.T.
to the C.N.Pq. and S.A.R.S.A.
(-300), thus
(lo), showing [91D -18'1'. The above
results would appear to rule out a free-radical
Acknowledgements
in an anti-relatlonshlp
bond which is cleaved. This stereospecificity
(C.E.R.M.A.V.) and Mr. Nicotra
for fellow(C.P.N.G.)
We wish to thank Dr. A. Greene for stimulating
discus-
No. 51
4618
R2 I R-M + Rl-CsC-C-R3
I
OAc 4
3
2
1
1. No rearrangement Hydrolysis
Rearrangement
li.
I/ OAc
\
Rl-C&-R2
I c R2Cu0
R3
I
OAc +
LlCuR2
CsCH a, R = CH
6
b,R=CD: H nC5Hllv<-CsCH
+O=q~
0
ga, R = CH3
la, A = D
b, B = CD3
b,A=H LICU(CH~)~ ~
bAc 2
(S)-(-)
-10
(R)-(-)
References 1. 2. 3.
4. 5. 6. 7. 8. 9. 10.
Contrlbutlon No6 from the Laboratoxe de Chlmle Organique, C.E.R.M.O. For N05, see : P. CrabbB and A. Greene, Proceedings of the Intern. Confer. on Prostaglandlns, Raven Press, New York, In press. P. Rona and P. CrabbB, J. Amer. Chem. Sot., 90, 4733 (1968) ; ibld 3289 (1969). Inter alla : D.R. Taylor, Chem. Rev., 67, 317 (1967) ; G.H. Posner, Organic Reactions, 2, 1 (1972) ; J.F. Normant, Synthesis, 63 (1972) ; A.E. Jukes In Advances In Organometallx Chemistry, F.G.A. Stone and R. West (Edit.), Vol. 12, P. 215, Academic Press, New York (1974). J. Gore and M.L. Roumestant, Tetrahedron Letters, 891 (1970). L.I. Olsson, A. Claesson and C. Bogentoft, Acta Chum. Scandin., B28, 765 (1974). P. Vermeer, J. Mei3er and L. Brandsma, J. Royal Nertherl. Chem. Sot., 94/5, 112 (1975). The optical purity was shown to be higher than 95% by N.M.R. In the presence of Eu(tfaCam) ; see H.L. Goering, J.N. Fxkenberry, and G.S. Koermer J. Amer. Chem. Sot.; 2, 5913 (1971). J. Fried, C.H. Lin, M.M. Mehra, W.L. Kao and P. Dalven, Ann. N.Y. Acad. S&., 180, 38 (1971). G. Lowe, Chem. Comm., 411 (1965) , J.H. Brewster, In Topics in Stereochemistry N.L. Allinger and E.L. Eliel (Edit.), Vol. 2, p.1, InterSClenCe Publ., Ne: York (1967). All new compounds described in this Communlcatlon gave satxfactory I.R., N.M.R. and mass spectra. The rotations were taken at room temperature in CC14 solution for concentrations C=l.
Formation
of Allenes by Reactlon of Lithium Diorqanocuprates
on Propargylic
Acetates
J.L. Luche, E. Barreiro, C.E.R.M.O.,
Universite
- A Mechanistic
Approach1
J.M. Dollat and P. Crabbe" Screntifique
et Medicale,
38041 Grenoble, France (&calved m UK 30 October 1975; acceptedfor publloatlon6 November 1975)
In the past, we reported an efficient reactlon of lithium dlmethylcopper preparations
synthesis of substituted allenes by 2 acetates . Numerous other
with acetylenic
of allenes through the use of organometallic reagents (I;)on pro3-6 (2) have been reported . Besides the expected propadiene (z),
pargylic esters a non-alkylated
allene
(4) has sometimes
been isolated, the origin of which
remained obscure. As shown in the Table, the reaction appears to be general, applicable primary,
secondary and tertiary acetates of non-substituted
tuted propargylic
compounds.
One of the particular
that there seems to be no simple relationship ester and the ratio of alkylated
to
as well as substr-
facets of this reactron
is
between the structure of the
(3) and non-alkylated
(4) material.
The experimental reaction mechanism,
data listed in the Table induced us to re-examine the 2 since the free-radical approach mentioned earlier did not
account for all observations.
Instead, the results of some recent experiments
seem to imply the intervention allenic copper derlvatlve
of an organometallic
Reaction of lithium dlmethylcopper ditions
intermedlate
such as the
(2). on the acetate
(6) under the usual con-
(see Table), was followed by aced hydrolysis with 10% DBr in a D20
solution. Vapor phase chromatography 22% of deuterated
(V.P.C.) and mass spectrometry
indicated
(7a) and 78% of the methylated allene (&). Significantly, treatment of the acetate (2) with Li(CD3)2Cu followed by HCl hydrolysis afforded
allene
the trideuteromethyl
allene
in 79% and 21% yield respectively, in (7b) did not originate -
(e)
and the non-deuterated
thus establishing
from the organocuprate
4615
allene
(2)
that the entering hydrogen
reagent.
4616
NO. 51
TABLE
J!sters
R2CuL'" *
Hc~c-cH2aAc
HC5C-CH?411c
14ec
Cowsion
Allenes
in %b
3
4
not isolated
70
n-But
75
Ia2
n-Bu
-2
not isolated
80
I&CH=C=CBAm(75%)
H2CYXH?m(25%)
40
RucI#xHAm(x)%)
HZ-W)%)
Ph
50
PhcSC=wd100%)
Me
80
Me2C=C=CYAm(60%)
MeCWC=CHAm(traces)
Me
73
Me2C=C=CHPh(96%)
_(4%)
Me
93
bc
99
Me
85
Me
62
a. One equiv. ester add& into an ether soln. of n equlv. R2CuLi (n=1.2for R* R=nBu and Ph) cooled to -10' t-30'for R=nBu).After sis with sat. NH4C1, &a&on
stirring
with ether, the canpoundswsre xolatd.
estunationby V.P.C. (CarloErba Fractovap,4 m. 20% Card Bu+Jutyl ; Amamy
; Ph==yl.
d.Es~tedbymass
substitutedallenes could not be separatedby V.P.C.
; n=2 for
for 2 hrs. at same t9np., hydrolyb. Purificationard
20 M column, F.I.D.). c. -thy1
spectranetry,since these tri- and tetra-
4617
No. 51
An organometallic
intermediate
attack on the acetylene reasonable
precursor
of type
(S), formed by dimethylcopper
carbon and acetate expulsion, would constitute
for the allene
(7J). The intermediate
anion
a
(I) may lead to the
(8a) by alkyl migration from the copper to the sp2 carbon atom, while Its hydrolysis would produce the corresponding non-alkylated allene (2).
methyl-allene
Thus, direct distillation dimethylcopper
of the reaction mixture of the ester yielded
98% of alkylated
(a) with lithium
(8a) and only 2% of (7b) (the origin of the latter is attributed to traces of moisture In the medium). It 1s worth to emphasize that acid treatment (HCl, DBr) gave a higher proportion
before hydrolysis
allene
of allene
(7b) than hydrolysis with NH4Cl. Additionally, a longer reaction time increased the proportion of alkylated allene (&), by favouring alkyl migration
from the organometallic
of lithium dimethylcopper HCl hydrolysis,
afforded
to the ester 78% of
(a)
intermediate
(2). So, whereas addrtion
(a) for 2 hrs. at -lo', followed by 1.2N
and 22% of (z),
this ratio was modified
when the reaction time was (7b) respectively 2 hrs. at -lo', followed by 21 hrs. at room temperature. A higher yield of (8a) (98%) has been obtained under slightly different conditions. Conversely, the
to 91:9% of propadlenes
(&)
and
addition of cumene or a-methylstyrene,
as free radical scavengers,
: non-alkylated
reaction medium did not affect the alkylated It was also anticipated some light on its mechanism. formed on an optically
to the
allene ratio.
that the steric course of the reaction Hence, a lithium dimethylcopper
active propargylic
acetate.
should cast
reaction was per-
(S)-(-)-3-Hydroxy-1-octyne
acetate [aID -69.5' (2)7, obtained after esterification of the known (S)-(-) 8 , was treated with lithium dlmethylcopper under the usual conditions
alcohol
(at -10'). The allene of the Brewster-Lowe compound
-loo. Application (10) exhlblted a specific rotation [aID -9 rule leads to the (R)-(-) absolute configuration for
(lo). Hence the approach of the cuprate reagent and the formation of
the carbon-copper
bond seem to take place preferentially
with respect to the carbon-oxygen
was increased when the reaction was performed affording
the optically
active allene
at lower temperature
n073-7-1875
and 75-7-0141)
and the C.N.R.S.
or a cationicmechanism.
for GC-MS measurements.
(contracts
(F.R.A. n'478). E.B. is grateful
(Brazil) and J.M.D. to the C.N.R.S.
ships. Thanks are due to Mr. Bosso slons.
mechanism
: This work was supported by the D.G.R.S.T.
to the C.N.Pq. and S.A.R.S.A.
(-300), thus
(lo), showing [91D -18'1'. The above
results would appear to rule out a free-radical
Acknowledgements
in an anti-relatlonshlp
bond which is cleaved. This stereospecificity
(C.E.R.M.A.V.) and Mr. Nicotra
for fellow(C.P.N.G.)
We wish to thank Dr. A. Greene for stimulating
discus-
No. 51
4618
R2 I R-M + Rl-CsC-C-R3
I
OAc 4
3
2
1
1. No rearrangement Hydrolysis
Rearrangement
li.
I/ OAc
\
Rl-C&-R2
I c R2Cu0
R3
I
OAc +
LlCuR2
CsCH a, R = CH
6
b,R=CD: H nC5Hllv<-CsCH
+O=q~
0
ga, R = CH3
la, A = D
b, B = CD3
b,A=H LICU(CH~)~ ~
bAc 2
(S)-(-)
-10
(R)-(-)
References 1. 2. 3.
4. 5. 6. 7. 8. 9. 10.
Contrlbutlon No6 from the Laboratoxe de Chlmle Organique, C.E.R.M.O. For N05, see : P. CrabbB and A. Greene, Proceedings of the Intern. Confer. on Prostaglandlns, Raven Press, New York, In press. P. Rona and P. CrabbB, J. Amer. Chem. Sot., 90, 4733 (1968) ; ibld 3289 (1969). Inter alla : D.R. Taylor, Chem. Rev., 67, 317 (1967) ; G.H. Posner, Organic Reactions, 2, 1 (1972) ; J.F. Normant, Synthesis, 63 (1972) ; A.E. Jukes In Advances In Organometallx Chemistry, F.G.A. Stone and R. West (Edit.), Vol. 12, P. 215, Academic Press, New York (1974). J. Gore and M.L. Roumestant, Tetrahedron Letters, 891 (1970). L.I. Olsson, A. Claesson and C. Bogentoft, Acta Chum. Scandin., B28, 765 (1974). P. Vermeer, J. Mei3er and L. Brandsma, J. Royal Nertherl. Chem. Sot., 94/5, 112 (1975). The optical purity was shown to be higher than 95% by N.M.R. In the presence of Eu(tfaCam) ; see H.L. Goering, J.N. Fxkenberry, and G.S. Koermer J. Amer. Chem. Sot.; 2, 5913 (1971). J. Fried, C.H. Lin, M.M. Mehra, W.L. Kao and P. Dalven, Ann. N.Y. Acad. S&., 180, 38 (1971). G. Lowe, Chem. Comm., 411 (1965) , J.H. Brewster, In Topics in Stereochemistry N.L. Allinger and E.L. Eliel (Edit.), Vol. 2, p.1, InterSClenCe Publ., Ne: York (1967). All new compounds described in this Communlcatlon gave satxfactory I.R., N.M.R. and mass spectra. The rotations were taken at room temperature in CC14 solution for concentrations C=l.