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Easy oxidation of organozinc compounds to alcohols
Tetrahedron Letters, Vol.36, No. 18, pp. 3157-3160,1995
Pergamon
ElsevierScienceLtd Printedin GreatBritain 0040-4039/95$9.50+0.00 0040-4039(95)00500-5
Easy Oxidation of Organozinc Compounds to Alcohols
Fabrice Chemla and Jean Normant
Laboratoire de Chimie des OrganoEltments, assoei6 au CNRS, Universit6 P. et M. Curie, Tour 44-45, BP 183 - 4 pl. Jussiea - 75252 PARIS
Abstract : Primaryand secondaryorganozinccompoundscan b¢ readilyoxidizedby dry air (slow absorption)in THF to give, withoutany reductiveworkup,primaryand secondaryalcoholsin good to excellentyields.
The oxidation of organometallic compounds into alcohols is a well-documented reaction. When molecular oxygen is used as oxidant, organometallic peroxides are obtained1-4. These peroxides can be reduced into alcoxides t-4 or be used as "foreign" reagents to oxidize other organometallic compounds5. The mechanism of these reactions was proposed to be as follows 6 :
02 R--M
•
O/M
R--O--O--M
H20 •
2 R-O-M
~
2 ROH
Scheme 1 When M=Zn, excellent yields of hydroperoxides have been obtained by slow addition of RZnX or R2Zn to a cold (-100°C) solution of oxygen in various solvents, followed by warming up7. Also, pure diethylzinc peroxide has been reduced in 94% yield by diethylzinc8. However combination of both redox systems in the same flask raises many problems, and Abraham8 reported that exposure of an ethereal solution of Bu2Zn to dry air yielded 78.5% n-butanol and 18.5% n-butyl hydroperoxide after two weeks; t-butanol was obtained from tBu2Zn in 80% yield after 4 weeks. The only case where oxidation-reduction operates efficiently is reported by Czernecki9 with a more reactive crotylzinc derivative. A 97% yield of alcohols axe obtained (primary 29% Z, 32% E and secondary 39%).
3157
3158
In the reduction step (Scheme 1) the organometallic peroxide behaves as an electrophile, and for this reason was named "oxenoid", by analogy with carbenoids 5h. We thought that in order to accelerate the reduction of the peroxide, two ways were possible : first, an increase in the solvent polarity should enhance the nucleophilic nature of the organozinc species toward the electrophilic oxenoid; secondly, the reaction should be favoured by a low concentration in peroxide. In a typical experiment, the organozinc compound was allowed to react with air overnight in THF (in a 1M to 0.2M range) in the presence of HMPA (one equivalent) in a flask topped by a drying tube fitted with CaC12. Two different methods for the preparation of organozinc species were used : insertion of a zinc atom into the carbon-halogen bond, by reaction with activated zinc powder (Zn*) as described by Knoche110, and transmetallation of organolithium (in ether) or Grignard reagents (in THF) with ZnBr2, 1M in TI-IF. After acidic work-up, the yields were evaluated by 1H NMR with an internal standard (methyl phenyl sulfone). The results are summarized in Table 1: Table 1. Oxidation of Organozinc species to Alcohols. Entry
Organozinc source
Product
Yield of alcohol
1
n-Oct-I + Zn* (5 eq.)
n-Oct-OH
65 %
2
n-Oct-Li + ZnBr2 (1 eq.)
n-OCt-OH
54 %
3
n-Hept-Li + ZnBr2 (0.5 eq.)
n-Hept-OH
98 %
4
n-Hept-Li + ZnBr'2 (0.3 eq.)
n-Hept-OH
72 %
5
Cyclohexyl-I + Zn* (5 eq.)
Cyclohexanol
81%
6
Cyclohexyl-I + Zn* (1 eq.)
Cyclohexanol
56 % (a)
7
Cyclohexyl-I + Zn* (5 eq.)
Cyclohexanol
63 % (b)
8
Cyclohexyl-MgBr + ZnBr'2 (1 eq.)
Cyclohexanol
93 %
9
Cyclohexyl-MgBr + ZnBr'2 (1 eq.) + Zn* (2 eq.)
Cyclohexanol
92 %
10
Benzyl bromide + Zn* (5 eq.)
Benzyl alcohol
75 % (c)
Notes :
(a) Starting material (32 %) was recovered.(b) Without HMPA. (c) Less than 15 % diphenyl-l,2-ethanewas
observed. As one can see from the Table, the yields were good to excellent for primary and secondary alkyl zinc halides. The use of dialkylzinc instead of an alkylzinc halide increased the yield (entries 2 and 3). The yield was slightly improved in the presence of magnesium bromide (entries 5 and 8) but the presence of activated zinc had no action (entries 8 and 9). The importance of the HMPA is emphazised by the comparison of entries 5 and 7. Benzylic zinc halide underwent also oxidation with good yield (entry 10), but this type of compounds
3159
are known to be very sensitive toward oxidation 11. The small amount of coupling product (diphenyl-1,2ethane) is an indication of the non-radical character of the oxidation reaction, in opposition to the observations of Razuvaev 12 in the case of diphenylzinc. By contrast, we were unable to observe any oxidation product from the reaction of vinylic zinc halides or divinylzinc species under various conditions. However, in the case of phenylzinc bromide, 20% of phenol could be isolated. From a synthetic point of wiew, this oxidation could be coupled with the already describedl3 tandem carbozincation-chlorination-alkylation of vinyllithium species, to yield ~/-ethylenic secondary alcohols, as shown on Scheme 2 :
nCsH1(/~--%,Li
+
~....,.fMgBr
1) PhSO2CI THF 2) 2 nBuLi
nCsH11~ ~
°ZnBr2 Et20 ZnBu \nC4H9
nCsH1//~ 1 K tm ~k m2 HMPA Dry air
nCsH11~_~H (k \
"nC4H9 1
Scheme 2 In a four step-one pot procedure, the secondary alcohol 1 was obtained in 40% isolated yield as a 1:1 mixture of two diastereomers. In summary, the slow delivery of dilute dry oxygen is a key factor for the efficient oxidation of organozinc compounds to zinc alcoxides. The reduction step of the peroxide is thus favoured (particularly for R2Zn derivatives) much more efficiently than with an excess of active Zn0 or any other reducing agent. Since various zinc derivatives are available by carbozincationl3,14, this route should find large applications due to its simplicity. References
I. 2. 3.
Sosnovsky, G.; Brown, J.H. Chem. Rev. 1966, 66, 529. Razuvaev, G.A.; Brilkina, T.G. Russ. Chem. Rev. 1976, 45, 1135. Brindley, P.B.: Organometallic peroxides. In The Chemistry of Peroxides; Patai, S. Ed.; Wiley &
4.
Sons: New York, 1983; pp 807-828. a) Oxidation of organolithium compounds : Sch611kopf,U.: Lithium-organische Verbindungen. In Methoden der Organischen Chemie (Houben-Weyl); MUller, E. Ed; Georg Thieme Verlag: Stuttgart, 1970; Vol 13/1, pp 170-172. b) Oxidation of organomagnesium compounds : Ntitzel, K.: Organo-magnesium Verbindungen. In Methoden der Organischen Chemic (Houben-Weyl); MUller, E. Ed; Georg Thieme Verlag: Stuttgart, 1973; Vol 13/2a, pp 234-244 c) Oxidation of organozinc compounds : Niitzel, K.: Organo-zinc Verbindungen. In Methoden der Organischen Chemie (Houben-Weyl); MUller, E. Ed; Georg Thieme Verlag: Stuttgart, 1973; Vol 13/2a, pp
3160
5.
6. 7. 8. 9. 10. 11. 12.
13. 14.
700-706 d) Oxidation of organocadmium compounds : Natzel, K.: Organo-eadmium Verbindungen. In Methoden der Organischen Chemie (Houben-Weyl); Mailer, E. Ed; Georg Thieme Verlag: Stuttgart, 1973; Vol 13/2a, pp 908-915 e) Oxidation of alkylmetals: Geibel, K.; Hofmann, H.; Kropf, H.; Thiem, J.: Alkohole. In Methoden der Organischen Chemie (HoubenWeyl); Mailer, E.; Bayer, O. Eds; Georg Thieme Verlag: Stuttgart, 1979; Vol 6/la, pp 217-223. f) Oxidation of arylmetals: Wedemeyer, K-F.: Phenole. In Methoden der Organischen Chemie (Houben-Weyl); Mailer, E. Ed; Georg Thieme Verlag: Stuttgart, 1976; Vol 6/lc, pp 141-146. On the use of organolithium peroxides in organometallic oxidation, see : a) Chang, H.S.; Edward, J.T. Can. J. Chem. 1939, 41, 1603. b) Nilsson, M.; Norin, T. Acta Chem. Scand. 1963, 17, 1157. c) Panek, E.J.; Kaiser, L.R.; Whitesides, G.M.J. Am. Chem. Soc. 1977, 99, 3708. d) Neumann, H.; Seebach, D. Chem. Ber. 1978, 111, 2785. e) Kemp, M.S.; Burden, R.S.; Loeffler, R.S.T.J. Chem. Soc., Perkin Trans. ! 1983, 2267. f) Julia, M.; Saint-Jalmes, V.P.; Verpeaux, J.N. Synlett 1993, 233. g) Chemla, F.; Julia, M.; Uguen, D. Bull. Soc. Chim. Fr. 1994, 131, 639. h) Boche, G.; Bosold, F.; Lohrenz, J.C.W. Angew. Chem. Int. Ed. Engl. 1994, 33, 1161. On the use of organomagnesium peroxides in organometallic oxidation, see : i) Lawesson, S.O.; Yang, N.C.J. Am. Chem. Soc. 1959, 81, 4230. Hock, H.; Kropf, H.; Ernst, F. Angew. Chem. 1959, 71,541. Davies, A.G.; Roberts, B.P.J. Chem. Soc. Ser. B 1968, 1074. Hock, H.; Ernst, F. Chem. Ber. 1959, 92, 2716. Seyferth, H.E.; Henkel, J.; Rieche, A. Angew. Chem. 1965, 12, 1074. Abraham, M.H.J. Chem. Soc. 1960, 4130. Czernecki, S.Georgoulis, C.; Gross, B.; Pr6vost, C. C. r. Acad. Sci., Ser. C 1968, 266, 1617. Knochel, P.; Singer, R.D. Chem. Rev. 1993, 93, 2117. Berk, S.C.; Yeh, M.C.P.; Jeong, N.; Knochel, P. Organometallics 1990, 9, 3053. Razuvaev, G.A.; Galiulina, R.F.; Petukhov, G.G.; Likhovidova, N.V.J. Gen. Chem. USSR 1963, 33, 3358. Galiulina, R.F.; Druzhkov, O.N.; Petukhov, G.G.; Razuvaev, G.A.J. Gen. Chem. USSR 1965, 35, 1168. Chemla, F.; Marek, I4 Normant, J.F. Synlett 1993, 665. Meyer, C.; Marek, I.; Courtemanche, G.; Normant, J.F.J. Org. Chem. 1995, 60, 863.; Lorthiois, E.; Marek, I.; Meyer, C.; Normant, J.F. Tetrahedron Lett. 1995, 36, 1263; Vaupel, A.; Knochel, P. Tetrahedron Lett. 1994, 35, 8349 and ref. cit.
(Received in France 6 March 1995; accepted 17 March 1995)
Pergamon
ElsevierScienceLtd Printedin GreatBritain 0040-4039/95$9.50+0.00 0040-4039(95)00500-5
Easy Oxidation of Organozinc Compounds to Alcohols
Fabrice Chemla and Jean Normant
Laboratoire de Chimie des OrganoEltments, assoei6 au CNRS, Universit6 P. et M. Curie, Tour 44-45, BP 183 - 4 pl. Jussiea - 75252 PARIS
Abstract : Primaryand secondaryorganozinccompoundscan b¢ readilyoxidizedby dry air (slow absorption)in THF to give, withoutany reductiveworkup,primaryand secondaryalcoholsin good to excellentyields.
The oxidation of organometallic compounds into alcohols is a well-documented reaction. When molecular oxygen is used as oxidant, organometallic peroxides are obtained1-4. These peroxides can be reduced into alcoxides t-4 or be used as "foreign" reagents to oxidize other organometallic compounds5. The mechanism of these reactions was proposed to be as follows 6 :
02 R--M
•
O/M
R--O--O--M
H20 •
2 R-O-M
~
2 ROH
Scheme 1 When M=Zn, excellent yields of hydroperoxides have been obtained by slow addition of RZnX or R2Zn to a cold (-100°C) solution of oxygen in various solvents, followed by warming up7. Also, pure diethylzinc peroxide has been reduced in 94% yield by diethylzinc8. However combination of both redox systems in the same flask raises many problems, and Abraham8 reported that exposure of an ethereal solution of Bu2Zn to dry air yielded 78.5% n-butanol and 18.5% n-butyl hydroperoxide after two weeks; t-butanol was obtained from tBu2Zn in 80% yield after 4 weeks. The only case where oxidation-reduction operates efficiently is reported by Czernecki9 with a more reactive crotylzinc derivative. A 97% yield of alcohols axe obtained (primary 29% Z, 32% E and secondary 39%).
3157
3158
In the reduction step (Scheme 1) the organometallic peroxide behaves as an electrophile, and for this reason was named "oxenoid", by analogy with carbenoids 5h. We thought that in order to accelerate the reduction of the peroxide, two ways were possible : first, an increase in the solvent polarity should enhance the nucleophilic nature of the organozinc species toward the electrophilic oxenoid; secondly, the reaction should be favoured by a low concentration in peroxide. In a typical experiment, the organozinc compound was allowed to react with air overnight in THF (in a 1M to 0.2M range) in the presence of HMPA (one equivalent) in a flask topped by a drying tube fitted with CaC12. Two different methods for the preparation of organozinc species were used : insertion of a zinc atom into the carbon-halogen bond, by reaction with activated zinc powder (Zn*) as described by Knoche110, and transmetallation of organolithium (in ether) or Grignard reagents (in THF) with ZnBr2, 1M in TI-IF. After acidic work-up, the yields were evaluated by 1H NMR with an internal standard (methyl phenyl sulfone). The results are summarized in Table 1: Table 1. Oxidation of Organozinc species to Alcohols. Entry
Organozinc source
Product
Yield of alcohol
1
n-Oct-I + Zn* (5 eq.)
n-Oct-OH
65 %
2
n-Oct-Li + ZnBr2 (1 eq.)
n-OCt-OH
54 %
3
n-Hept-Li + ZnBr2 (0.5 eq.)
n-Hept-OH
98 %
4
n-Hept-Li + ZnBr'2 (0.3 eq.)
n-Hept-OH
72 %
5
Cyclohexyl-I + Zn* (5 eq.)
Cyclohexanol
81%
6
Cyclohexyl-I + Zn* (1 eq.)
Cyclohexanol
56 % (a)
7
Cyclohexyl-I + Zn* (5 eq.)
Cyclohexanol
63 % (b)
8
Cyclohexyl-MgBr + ZnBr'2 (1 eq.)
Cyclohexanol
93 %
9
Cyclohexyl-MgBr + ZnBr'2 (1 eq.) + Zn* (2 eq.)
Cyclohexanol
92 %
10
Benzyl bromide + Zn* (5 eq.)
Benzyl alcohol
75 % (c)
Notes :
(a) Starting material (32 %) was recovered.(b) Without HMPA. (c) Less than 15 % diphenyl-l,2-ethanewas
observed. As one can see from the Table, the yields were good to excellent for primary and secondary alkyl zinc halides. The use of dialkylzinc instead of an alkylzinc halide increased the yield (entries 2 and 3). The yield was slightly improved in the presence of magnesium bromide (entries 5 and 8) but the presence of activated zinc had no action (entries 8 and 9). The importance of the HMPA is emphazised by the comparison of entries 5 and 7. Benzylic zinc halide underwent also oxidation with good yield (entry 10), but this type of compounds
3159
are known to be very sensitive toward oxidation 11. The small amount of coupling product (diphenyl-1,2ethane) is an indication of the non-radical character of the oxidation reaction, in opposition to the observations of Razuvaev 12 in the case of diphenylzinc. By contrast, we were unable to observe any oxidation product from the reaction of vinylic zinc halides or divinylzinc species under various conditions. However, in the case of phenylzinc bromide, 20% of phenol could be isolated. From a synthetic point of wiew, this oxidation could be coupled with the already describedl3 tandem carbozincation-chlorination-alkylation of vinyllithium species, to yield ~/-ethylenic secondary alcohols, as shown on Scheme 2 :
nCsH1(/~--%,Li
+
~....,.fMgBr
1) PhSO2CI THF 2) 2 nBuLi
nCsH11~ ~
°ZnBr2 Et20 ZnBu \nC4H9
nCsH1//~ 1 K tm ~k m2 HMPA Dry air
nCsH11~_~H (k \
"nC4H9 1
Scheme 2 In a four step-one pot procedure, the secondary alcohol 1 was obtained in 40% isolated yield as a 1:1 mixture of two diastereomers. In summary, the slow delivery of dilute dry oxygen is a key factor for the efficient oxidation of organozinc compounds to zinc alcoxides. The reduction step of the peroxide is thus favoured (particularly for R2Zn derivatives) much more efficiently than with an excess of active Zn0 or any other reducing agent. Since various zinc derivatives are available by carbozincationl3,14, this route should find large applications due to its simplicity. References
I. 2. 3.
Sosnovsky, G.; Brown, J.H. Chem. Rev. 1966, 66, 529. Razuvaev, G.A.; Brilkina, T.G. Russ. Chem. Rev. 1976, 45, 1135. Brindley, P.B.: Organometallic peroxides. In The Chemistry of Peroxides; Patai, S. Ed.; Wiley &
4.
Sons: New York, 1983; pp 807-828. a) Oxidation of organolithium compounds : Sch611kopf,U.: Lithium-organische Verbindungen. In Methoden der Organischen Chemie (Houben-Weyl); MUller, E. Ed; Georg Thieme Verlag: Stuttgart, 1970; Vol 13/1, pp 170-172. b) Oxidation of organomagnesium compounds : Ntitzel, K.: Organo-magnesium Verbindungen. In Methoden der Organischen Chemic (Houben-Weyl); MUller, E. Ed; Georg Thieme Verlag: Stuttgart, 1973; Vol 13/2a, pp 234-244 c) Oxidation of organozinc compounds : Niitzel, K.: Organo-zinc Verbindungen. In Methoden der Organischen Chemie (Houben-Weyl); MUller, E. Ed; Georg Thieme Verlag: Stuttgart, 1973; Vol 13/2a, pp
3160
5.
6. 7. 8. 9. 10. 11. 12.
13. 14.
700-706 d) Oxidation of organocadmium compounds : Natzel, K.: Organo-eadmium Verbindungen. In Methoden der Organischen Chemie (Houben-Weyl); Mailer, E. Ed; Georg Thieme Verlag: Stuttgart, 1973; Vol 13/2a, pp 908-915 e) Oxidation of alkylmetals: Geibel, K.; Hofmann, H.; Kropf, H.; Thiem, J.: Alkohole. In Methoden der Organischen Chemie (HoubenWeyl); Mailer, E.; Bayer, O. Eds; Georg Thieme Verlag: Stuttgart, 1979; Vol 6/la, pp 217-223. f) Oxidation of arylmetals: Wedemeyer, K-F.: Phenole. In Methoden der Organischen Chemie (Houben-Weyl); Mailer, E. Ed; Georg Thieme Verlag: Stuttgart, 1976; Vol 6/lc, pp 141-146. On the use of organolithium peroxides in organometallic oxidation, see : a) Chang, H.S.; Edward, J.T. Can. J. Chem. 1939, 41, 1603. b) Nilsson, M.; Norin, T. Acta Chem. Scand. 1963, 17, 1157. c) Panek, E.J.; Kaiser, L.R.; Whitesides, G.M.J. Am. Chem. Soc. 1977, 99, 3708. d) Neumann, H.; Seebach, D. Chem. Ber. 1978, 111, 2785. e) Kemp, M.S.; Burden, R.S.; Loeffler, R.S.T.J. Chem. Soc., Perkin Trans. ! 1983, 2267. f) Julia, M.; Saint-Jalmes, V.P.; Verpeaux, J.N. Synlett 1993, 233. g) Chemla, F.; Julia, M.; Uguen, D. Bull. Soc. Chim. Fr. 1994, 131, 639. h) Boche, G.; Bosold, F.; Lohrenz, J.C.W. Angew. Chem. Int. Ed. Engl. 1994, 33, 1161. On the use of organomagnesium peroxides in organometallic oxidation, see : i) Lawesson, S.O.; Yang, N.C.J. Am. Chem. Soc. 1959, 81, 4230. Hock, H.; Kropf, H.; Ernst, F. Angew. Chem. 1959, 71,541. Davies, A.G.; Roberts, B.P.J. Chem. Soc. Ser. B 1968, 1074. Hock, H.; Ernst, F. Chem. Ber. 1959, 92, 2716. Seyferth, H.E.; Henkel, J.; Rieche, A. Angew. Chem. 1965, 12, 1074. Abraham, M.H.J. Chem. Soc. 1960, 4130. Czernecki, S.Georgoulis, C.; Gross, B.; Pr6vost, C. C. r. Acad. Sci., Ser. C 1968, 266, 1617. Knochel, P.; Singer, R.D. Chem. Rev. 1993, 93, 2117. Berk, S.C.; Yeh, M.C.P.; Jeong, N.; Knochel, P. Organometallics 1990, 9, 3053. Razuvaev, G.A.; Galiulina, R.F.; Petukhov, G.G.; Likhovidova, N.V.J. Gen. Chem. USSR 1963, 33, 3358. Galiulina, R.F.; Druzhkov, O.N.; Petukhov, G.G.; Razuvaev, G.A.J. Gen. Chem. USSR 1965, 35, 1168. Chemla, F.; Marek, I4 Normant, J.F. Synlett 1993, 665. Meyer, C.; Marek, I.; Courtemanche, G.; Normant, J.F.J. Org. Chem. 1995, 60, 863.; Lorthiois, E.; Marek, I.; Meyer, C.; Normant, J.F. Tetrahedron Lett. 1995, 36, 1263; Vaupel, A.; Knochel, P. Tetrahedron Lett. 1994, 35, 8349 and ref. cit.
(Received in France 6 March 1995; accepted 17 March 1995)