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The application of allylic sulfoxide anions as vinyl anion equivalents. A general synthesis of allylic alcohols.
TotrehedronLotton uo. 16, pp 1305 - 1388, 1973.
P*r#ewn Pr8rn8. Printed in Grat Britain.
THE APPLICATIONOF ALLYLIC SULFOXIDEANIONS AS VINYL ANION EQUIVALENTS. A GENERAL SYNTHESISOF ALLYLIC ALCOHOLS. D. A. Evans,' 6. C. Andrews,T. T. Fujimoto,D. Wells ContributionNo. 3113 from the Departmentof Chemistry, Universityof California,Los Angeles, California90024 (Eooeivedin USA 26 Jonwqv 1973; reooivodin UK for ptbl1wti.a 12 Huoh 1973) Recentlywe reporteda general procedurefor the reversibleinterconversionof allylic sulfoxides and alcoholswith allylic rearrangement(e.g. IZz) and allud;dStothe possibleapplicaThe purpose of this tions of this transformationto a new synthesisof allylic alcohols. ’ comunication is to define the utility of sulfoxidestabilizedanions such as 4,as a synthon for the vinyl anion 5 in a new approach to the synthesisof allylic alcohols.
(MeOJP UR
WO”
2
5
J
0
R-X t
Ph
OH
f
5
The general condItIonsfor the alkylationof allylic sulfoxidesand for subsequenttransfotmationinto the rearrangedallylic alcoholsare describedbelow. AlQlation: (11.0 ml) . ..-.. _B....__To a cooled (-60') solutionof lithim diisopropylamide4
in 30 ml of
HO. 16
1386
dry THF under a nitrogen atmospherewas added 10 sum1 of the allylic sulphoxide&syringe. The resultingyellow anion5 was allowed to stir for 15 min and the alkyl halide (1-2 equiv) was then added in one portion. The temperaturewas raised to between -50' and -30' until the color of the anion was dissipated(see Table for specificconditions). The reactionwas quenched with saturatedNH4Cl solutionand extractedwith methylenechloride. Removal of the solvent affordedthe crude a-and y-alkylatedsulfoxides. Cleavage: The crude sulfoxide (10 mnol) was SIB-,.... .-. dissolvedin 10 ml of methanol and 20 nmol of freshly purifiedtrimethylphosphite6at room temperature. The rate of cleavagedepends upon the degree of u-substitution(a-dfsubstituted sulfoxidesrequire=1
hr, monosubstitutedsulfoxidesrequire=
12 hr). A saturatedaqueous
solutionof NaHC03 was added to the reactlon,and the desired allylic alcoholwas isolatedby chromatography(Florisll). The methanol-phosphfte solutionmay also be added directly to the alkylationmixture after quenchingthe allylic anion with alkylatingagent.
t u-
HO
0
1. base
Ph
SPh2.R-I 8
L
t
0 1. base
Ph-
SPh
2.WI
As illustratedabove, the anion derfved from cyclohexenylphenyl sulfoxide 5* may be readily alkylatedwith methyl iodide and the resultfngalkylatedderivative,7transformed1_1 &
(MeOH, (MeO)3P,1 hr) to 8 (R - CH3) in nearly quantitativeyield. In a similar fashion
cyclopentenylphenylsulfoxide9,affordedthe 3-substitutedcyclopentenolsLl_(R = CH3. C2H5, C3H5) in good yields.' The isolatedyields of these alcohols (Table)reflect the difficulties encounteredin purificationdue to dehydration. In the alkylationof the anions derived from both 6,and 9,only a-alkylationwas observed. As little as 2-3% of the y-alkylationproduct could have been detectedby mnr analysis. Alkylationof the acyclic allylic sulfoxides12,a,-c, with a variety of alkyl iodides afforded both the g- and I-alkylatedadducts &-s
and l+c-$ respectively,'the product ratio being
dependentupon the structureof both the alkyl halide and the sulfoxide(see Table). -In situ cleavage of the crude alkylationmixtures with methanol-trimethyl phosphiteaffordedthe trans-
1367
NO. 16
1
(YeO),P
5;
R,) R, = H
b R, = 3
R,,
CH,,
RI
= H
2
R, = CHI
disubstitutedallylfc alcohols~~~-,cand the correspondingy-alkylatedsulfoxides1%~
which
were readily Isolatedby chromatography(Florlsfl). As sunaaarlzed in the Table, the yields of allylic alcohols depend upon the extent of yalkylatlon. Attempts to alter the proportlonof I,3and lt by changingsolvent or introducing taetalion caaplexingagenii 0MEDA) were unsuccessful. In contrastto the high regfoselectfvity toward a-protonatfon and to a lesser extent towarda-alkylatlon,we have observed that the conjugate
bases of both 9 and 12a exhibit little site selectivityin addition reactionsto ..._1 both aldelwdesand ketones even at temperaturesas low as -100~. Table. Alkylation-Rearrangement of Allylic Sulfoxides . ..V-.-.. Sulfoxide 62 -798
E7
R-X CH31
AlkylationConditions a:y Ratio' -50°,
lhr
>>lO
b ROH' Yield,T 8
(99)
-40°, lhr
=lO
WO)
%I CH2=CHCH2Br
-40°, 3/4hr
>>lO
45 (75)
-50'. 1/2hr
>>lO
CH31
-35”,
1/2hr
5.6
74
C2H51 CH2-CHCH20r
-5O", 5hr
2.9
15a 60 ..,W_ { 49
Cl+31
E7
CH3I
12c7
C2H5' PC6Hl3I
-30'. lhr
1.3
-50'. lhr
>>lO
-3V, 4hr
6.7
-40°, 2hr
=lO
11
(
32 (73)
!!!j 85 ( 50 (561 15c -..." 70 (80)
a The I-allwlatfonproductswere isolatedand characterized.' The a,zyratios were detenafnad by mar. a Figures in parenthesisrefer to glc or nmr yields relativeto an interns1standard; other figures refer to isolatedyields based on startingsulphoxide.
13@@
HO. 16
There are several significantfeatures in this approach to the synthesisof allylic alcohols. It offers a new mathod of establishingcarbon-carbonbonds applicableto a wide varietyof structurallydfssimflarsystems. In addftion,the concertednature of the sulfoxide rearrangementresults fn the stereoselectiveformatfonof specificolefin geomatrics. The applicationof this approachto the synthesisof trisubstitutedolefins is discussedin the accompanying cawsunication." Acknarledaement.We wish to thank the U. S. Public Health Service,the NationalScience Foundatlon and the PetroleunResearchFund administeredby the knerican ChemicalSociety for their support of this research. References ..,."I-.,"_..,___ 1. Camille and Henry DreyfusTeacher-Scholarrecipient,1971-1976,A. P. Sloan Fellow, 19721974. 2. D. A. Evans, 6. C. Andrews, C. L. Sims, J. Amer. Chem. a., 3. D. A. Evans, 6. C. Andrews,a.,
93, 4956 (1971).
9_4, 3672 (1972).
4. Preparedby the additionof &-butyllithiunin hexane to a cooled (t 2 O") solutionof amine in THF. 5. The anions may also be formad by direct treatmantwith n-butyllithfun,however,byproducts (5-10X)result using this procedure,cf. K. K. Anderson,S. A. Yeager,&
&.
Chem., 28,
865 (1963). 6. Freshlydistilledfrom sodium metal. This purificationstep appears to be important. 7. Preparedfrom the correspondingsulfidewhich was oxidized accordingto the procedureof N. J. Leonard and C. R. Johnson,J. a.
m.,
22, 282 (1962).
8. Sulfoxide9 is unstabletoward moleculardistillationand was used without purification. 9. Satisfactoryspectra and elementalanalyseshave been obtained. 10. C. D. Broaddus,Accounts Chem. @.,
l_,231(1968),and referencescited therein.
11. D. A. Evans, G. C. Andrews,T. T. Fujimoto,D. Wells, Tetrahedron&&.,
0000 (1972).
P*r#ewn Pr8rn8. Printed in Grat Britain.
THE APPLICATIONOF ALLYLIC SULFOXIDEANIONS AS VINYL ANION EQUIVALENTS. A GENERAL SYNTHESISOF ALLYLIC ALCOHOLS. D. A. Evans,' 6. C. Andrews,T. T. Fujimoto,D. Wells ContributionNo. 3113 from the Departmentof Chemistry, Universityof California,Los Angeles, California90024 (Eooeivedin USA 26 Jonwqv 1973; reooivodin UK for ptbl1wti.a 12 Huoh 1973) Recentlywe reporteda general procedurefor the reversibleinterconversionof allylic sulfoxides and alcoholswith allylic rearrangement(e.g. IZz) and allud;dStothe possibleapplicaThe purpose of this tions of this transformationto a new synthesisof allylic alcohols. ’ comunication is to define the utility of sulfoxidestabilizedanions such as 4,as a synthon for the vinyl anion 5 in a new approach to the synthesisof allylic alcohols.
(MeOJP UR
WO”
2
5
J
0
R-X t
Ph
OH
f
5
The general condItIonsfor the alkylationof allylic sulfoxidesand for subsequenttransfotmationinto the rearrangedallylic alcoholsare describedbelow. AlQlation: (11.0 ml) . ..-.. _B....__To a cooled (-60') solutionof lithim diisopropylamide4
in 30 ml of
HO. 16
1386
dry THF under a nitrogen atmospherewas added 10 sum1 of the allylic sulphoxide&syringe. The resultingyellow anion5 was allowed to stir for 15 min and the alkyl halide (1-2 equiv) was then added in one portion. The temperaturewas raised to between -50' and -30' until the color of the anion was dissipated(see Table for specificconditions). The reactionwas quenched with saturatedNH4Cl solutionand extractedwith methylenechloride. Removal of the solvent affordedthe crude a-and y-alkylatedsulfoxides. Cleavage: The crude sulfoxide (10 mnol) was SIB-,.... .-. dissolvedin 10 ml of methanol and 20 nmol of freshly purifiedtrimethylphosphite6at room temperature. The rate of cleavagedepends upon the degree of u-substitution(a-dfsubstituted sulfoxidesrequire=1
hr, monosubstitutedsulfoxidesrequire=
12 hr). A saturatedaqueous
solutionof NaHC03 was added to the reactlon,and the desired allylic alcoholwas isolatedby chromatography(Florisll). The methanol-phosphfte solutionmay also be added directly to the alkylationmixture after quenchingthe allylic anion with alkylatingagent.
t u-
HO
0
1. base
Ph
SPh2.R-I 8
L
t
0 1. base
Ph-
SPh
2.WI
As illustratedabove, the anion derfved from cyclohexenylphenyl sulfoxide 5* may be readily alkylatedwith methyl iodide and the resultfngalkylatedderivative,7transformed1_1 &
(MeOH, (MeO)3P,1 hr) to 8 (R - CH3) in nearly quantitativeyield. In a similar fashion
cyclopentenylphenylsulfoxide9,affordedthe 3-substitutedcyclopentenolsLl_(R = CH3. C2H5, C3H5) in good yields.' The isolatedyields of these alcohols (Table)reflect the difficulties encounteredin purificationdue to dehydration. In the alkylationof the anions derived from both 6,and 9,only a-alkylationwas observed. As little as 2-3% of the y-alkylationproduct could have been detectedby mnr analysis. Alkylationof the acyclic allylic sulfoxides12,a,-c, with a variety of alkyl iodides afforded both the g- and I-alkylatedadducts &-s
and l+c-$ respectively,'the product ratio being
dependentupon the structureof both the alkyl halide and the sulfoxide(see Table). -In situ cleavage of the crude alkylationmixtures with methanol-trimethyl phosphiteaffordedthe trans-
1367
NO. 16
1
(YeO),P
5;
R,) R, = H
b R, = 3
R,,
CH,,
RI
= H
2
R, = CHI
disubstitutedallylfc alcohols~~~-,cand the correspondingy-alkylatedsulfoxides1%~
which
were readily Isolatedby chromatography(Florlsfl). As sunaaarlzed in the Table, the yields of allylic alcohols depend upon the extent of yalkylatlon. Attempts to alter the proportlonof I,3and lt by changingsolvent or introducing taetalion caaplexingagenii 0MEDA) were unsuccessful. In contrastto the high regfoselectfvity toward a-protonatfon and to a lesser extent towarda-alkylatlon,we have observed that the conjugate
bases of both 9 and 12a exhibit little site selectivityin addition reactionsto ..._1 both aldelwdesand ketones even at temperaturesas low as -100~. Table. Alkylation-Rearrangement of Allylic Sulfoxides . ..V-.-.. Sulfoxide 62 -798
E7
R-X CH31
AlkylationConditions a:y Ratio' -50°,
lhr
>>lO
b ROH' Yield,T 8
(99)
-40°, lhr
=lO
WO)
%I CH2=CHCH2Br
-40°, 3/4hr
>>lO
45 (75)
-50'. 1/2hr
>>lO
CH31
-35”,
1/2hr
5.6
74
C2H51 CH2-CHCH20r
-5O", 5hr
2.9
15a 60 ..,W_ { 49
Cl+31
E7
CH3I
12c7
C2H5' PC6Hl3I
-30'. lhr
1.3
-50'. lhr
>>lO
-3V, 4hr
6.7
-40°, 2hr
=lO
11
(
32 (73)
!!!j 85 ( 50 (561 15c -..." 70 (80)
a The I-allwlatfonproductswere isolatedand characterized.' The a,zyratios were detenafnad by mar. a Figures in parenthesisrefer to glc or nmr yields relativeto an interns1standard; other figures refer to isolatedyields based on startingsulphoxide.
13@@
HO. 16
There are several significantfeatures in this approach to the synthesisof allylic alcohols. It offers a new mathod of establishingcarbon-carbonbonds applicableto a wide varietyof structurallydfssimflarsystems. In addftion,the concertednature of the sulfoxide rearrangementresults fn the stereoselectiveformatfonof specificolefin geomatrics. The applicationof this approachto the synthesisof trisubstitutedolefins is discussedin the accompanying cawsunication." Acknarledaement.We wish to thank the U. S. Public Health Service,the NationalScience Foundatlon and the PetroleunResearchFund administeredby the knerican ChemicalSociety for their support of this research. References ..,."I-.,"_..,___ 1. Camille and Henry DreyfusTeacher-Scholarrecipient,1971-1976,A. P. Sloan Fellow, 19721974. 2. D. A. Evans, 6. C. Andrews, C. L. Sims, J. Amer. Chem. a., 3. D. A. Evans, 6. C. Andrews,a.,
93, 4956 (1971).
9_4, 3672 (1972).
4. Preparedby the additionof &-butyllithiunin hexane to a cooled (t 2 O") solutionof amine in THF. 5. The anions may also be formad by direct treatmantwith n-butyllithfun,however,byproducts (5-10X)result using this procedure,cf. K. K. Anderson,S. A. Yeager,&
&.
Chem., 28,
865 (1963). 6. Freshlydistilledfrom sodium metal. This purificationstep appears to be important. 7. Preparedfrom the correspondingsulfidewhich was oxidized accordingto the procedureof N. J. Leonard and C. R. Johnson,J. a.
m.,
22, 282 (1962).
8. Sulfoxide9 is unstabletoward moleculardistillationand was used without purification. 9. Satisfactoryspectra and elementalanalyseshave been obtained. 10. C. D. Broaddus,Accounts Chem. @.,
l_,231(1968),and referencescited therein.
11. D. A. Evans, G. C. Andrews,T. T. Fujimoto,D. Wells, Tetrahedron&&.,
0000 (1972).