J. Org. C h e m . 1990,55, 975-984 American Cancer Society Institutional Research Grant No. IN-l47F, Maryland Cancer Program/University of Maryland. Registry No. (Z)-ld-7e, 124267-35-2;(E)-ld-7e,124267-36-3; 2a, 22117-97-1;2b, 23074-59-1; 2d-5b, 124267-27-2;(Z)-2d-7e, 124267-33-0;(E)-2d-7e, 124267-34-1;3, 124267-24-9;4b, 124267-25-0;5a, 121590-82-7; 5b, 124267-26-1; 5c, 89998-56-1; (Z)-6a, 121590-83-8;(E)-6a, 75283-44-2;(Z)-6b, 121590-84-9; (E)-6b, 121590-89-4;( Z ) - ~ C121590-85-0; , (E)-~c, 121590-90-7; (Z)-6e, 121590-86-1;(E)-6e, 121590-91-8;(Z)-6f, 121590-87-2; (E)-6f, 111303-28-7;(Z)-6g, 124267-28-3;(E)-6g, 124267-29-4; (Z)-6h, 121590-88-3;(E)-6h, 121590-92-9;(Z)-7a, 29179-04-2; (E)-7a,29179-03-1; (Z)-7e, 124267-31-8; (E)-7e, 124267-32-9; (Z)-8a, 124267-37-4;(E)-8a, 124267-38-5;(Z)-8c, 124267-39-6;(E)&, 124267-40-9;(2)-8d, 124267-41-0;(E)-8d, 124267-42-1;(Z)-8e,
975
124267-43-2;(E)-8e, 124267-44-3;(Z)-8f, 124267-45-4;(Z)-8g, 124267-46-5;( E ) - 8 g , 124267-47-6;13a, 124267-49-8;13d, 124267-50-1;14a, 124267-51-2;14d, 124267-52-3; TMSC=CH, 1066-54-2;Me2CuLi, 15681-48-8;MeCu(CN)Li, 41753-78-0; Me2Cu(CN)Li2, 80473-70-7;EtCu(CN)MgBr, 124267-54-5; Et,Cu(CN)(MgBr),, 121589-72-8; i-Pr,Cu(CN)(MgCl),, 12158974-0;Bu2CuLi, 24406-16-4;Bu,Cu(CN)(MgBr),, 124267-55-6; Bu2Cu(CN)Li2,80473-69-4;t-Bu2CuLi, 23402-75-7;t-Bu2CuPh2CuMgBr,58938-91-3; Ph2CuMgBr.MeZs, (CN)Li2,87263-84-1; 124267-57-8;Ph,Cu(CN)(MgBr),, 121589-76-2;Ph2Cu(CN)Li2, 80473-66-1; (CH,=CH),CuMgBr.Me,S, 124267-59-0;(CH2=CH),Cu(CN)(MgBr),, 113153-17-6;(CH2=CH)2Cu(CN)Li2, 80473-65-0;PhSLi, 2973-86-6;3-(1,3-butadienyl)-2-methyl-2cyclopenten-1-one 2,4-dinitrophenylhydrazone,124267-30-7; 3(1,3-butadienyl)-2-methyl-2-cyclohexen-l-one 2,4-dinitrophenylhydrazone, 124267-48-7.
Preparation of Allylic Acetates from Simple Alkenes by Palladium(I1)-Catalyzed Acetoxylation Sverker Hansson,t Andreas Heumann,*J Tobias Rein,? and Bjorn Akermark*y+ Department of Organic Chemistry, Royal Institute of Technology, S-100 44 Stockholm, Sweden, and Facult; de St.-J6rome-ESIPSOI, U A 126, F 13397 Marseille Ceden 13, France Received J u l y 21, 1989
The scope and limitations of palladium-catalyzed allylic acetoxylation of alkenes has been investigated, using benzoquinone-manganese dioxide as the reoxidation system. Unsubstituted cycloalkenes gave good to excellent yields of allylic acetates. Total yields were also good for many substituted cycloalkenes and for linear alkenes, but these substrates generally gave several isomeric acetates. The exploratory mechanistic studies show that the acetoxylation can proceed via both 1,2-acetoxypalladation and ~~~-allylpalladium complex formation. The keen balance between these processes depends on the structure of the alkene.
Introduction Allylic acetates have become important intermediates in organic synthesis, in particular after it was realized that metal-catalyzed replacement of the acetoxy group by nucleophiles is a facile and efficient reacti0n.l Allylic acetates are usually prepared from the corresponding allylic alcohols, but a number of routes which lead directly from alkenes have been devised. Most of these involve peroxides2 and/or a variety of metal salts.3 Due to several factors, such as the necessity for stoichiometric amounts of metal reagents and lack of generality, these reactions have not been used extensively in organic synthesis. We have recently shown that simple cycloalkenes may be efficiently and selectively converted into allylic acetates, using palladium acetate as catalyst in combination with an oxidation system consisting of benzoquinone and manganese dioxide (Scheme I).4 In this paper we report on an examination of the scope of this reaction and also on the results of an exploratory study of its mechanism.
Results and Discussion In order t o examine t h e generality of palladium-catalyzed allylic acetoxylation we have studied a range of olefins (Tables I and 11). The reactions were performed in acetic acid solution, using 5% palladium acetate as catalyst, ca. 20% benzoquinone as cooxidant, and 110-200% manganese dioxide as oxidant. For a few alkenes, other ratios between substrate and catalyst were also Royal Institute of Technology.
* Facult6 de St.-Jerome-ESIPSOI. 0022-3263/90/1955-0975$02.50/0
Scheme I
1
n=l
2 n=2 3 n=3
4 n=4 5 n=6 6 n=8
studied. The reaction temperature was generally 60 "C, but temperatures as low as room temperature were also used in some cases. With the exception of cyclooctene, the unsubstituted cycloalkenes gave good yields of allylic acetates (Table I). This is also true for most of the substituted cycloalkenes (Table 11) and for the two linear alkenes that were studied, (E)-3-hexene and (E)-5-decene (Table I). There are considerable differences in reactivity among the substrates. Cyclopentene, cyclohexene, cycloheptene, and (E)-cyclododecene all reacted within 50 h or less a t 60 "C to give good yields of allylic acetates (Table I, entries 1, 2, 4, and 7). In contrast, (2)-cyclooctene and (2)(1) (a) Tsuji, J. Organic Synthesis with Palladium Compounds; Springer Verlag: Heidelberg, 1980. (b) Trost, B.M.; Verhoeven, T. R. In Comprehensive Organometallic Chemistry; Wilkinson, G., Ed.; Pergamon: Oxford, 1982; Vol. 8, pp 799-938. (c) Heck, R. F. Palladium Reagents in Organic Syntheses; Academic Press: New York, 1985. (d) Magid, R. M. Tetrahedron 1980, 36,1901-1930. (2) Rawlinson, D.J.; Sosnovsky, G.Synthesis 1972, 1-28. (3)For reviews, see: (a) Muzart, J. Bull. SOC.Chim. Fr. 1986,65-77. (b) Rawlinson, D.J.; Sosqovsky, G.Synthesis 1973, 567-603. (4) (a) Heumann, A.; Akermark, B. Angew. Chem., Int. J d . Engl. 1984,23,453-454. (b) Heumann, A.; Hansson, S.; Rein, T.; Akermark, B. Org. Synth.. in press.
1990 American Chemical Society
976 J . Org. Chem., Vol. 55, No. 3, 1990
Hansson et al. Scheme I11
Scheme I1 R-
RL
R
R R = CH3 R = C3H7
-.
8 R=CH3
IO R=C3H7
PdClp
cyclodecene reacted very slowly, the latter requiring 12 days a t 60 "C for ca. 90% conversion (Table I, entries 5 and 6). T h e reasons for the striking differences in reactivity are not clear. It is tempting to suggest that conformational factors in the intermediate q2-complexes (or possibly q3-allylcomplexes) of the 8 and 10-membered ring substrates are the cause.5 Also the reactivities of the desired allylic acetates are of importance, and low yields were in many cases correlated with further oxidation to diacetates. In this context it is interesting to compare cyclooctene and cyclodecene. Cyclooctene gave only 35% optimized yield of the allylic acetate after 90 h a t 60 "C, while cyclodecene, although the reaction was not complete even after 1 2 days, gave essentially quantitative yield of allylic acetate, based on consumed cycloalkene (Table I, entries 5 and 6). T h e major byproducts in the oxidation of cyclooctene were diacetates, suggesting that in this particular case the primary product is about as reactive as the starting material. T h e configuration around the double bond, E or 2, is important, b u t its influence has only been studied fortuitously. Commercial cyclododecene, which was used in our oxidation reactions, contains ca. 60% E and 30% 2 isomer, the remainder being mainly cyclododecane. After about 80% conversion (43 h a t 60 "C), 93% of the (E)cyclododecene and only 67% of the 2 isomer have been consumed.6 This is probably the result of an interplay between factors such as intrinsic reactivity of E and 2 double bonds, coordinating ability, and conformational factors. T h e relative importance of these factors has to be studied separately. An observation, that was not anticipated, is that cyclowere very reactive pentene and cis-bicyclo[3.3.0]oct-2-ene substrates, while indene reacted very sluggishly? (Table I, entry 1; Table 11, entries 2 and 3). T h e two linear alkenes (E)-3-hexene and (E)-5-decene both reacted a t a rate comparable to that of the cycloalkenes. A 1:l mixture of two acetates was formed in both cases (Scheme 11; table I, entries 9 and 10). The products from (E)-3-hexene were identified as 8 and 9, but with those from (EI-Bdecene the assignments as 10 and 11 are tentative. In these reactions it was noted that although benzoquinone is generally necessary for a smooth oxidation it also slows down the rate. T h e reason is probably competition between the alkene and benzoquinone for palladium(I1). Thus, the rate of reaction of (E1-3-hexene in the presence of 200% benzoquinone is much lower than that obtained with the combination of 20% benzoquinone and 120% manganese dioxide. With alkenes such as cyclo(5) Still, W. C.; Galinker, I. Tetrahedron 1981, 37, 3981-3996. (6) The product was the E isomer exclusively. ( 7 ) The 17~-allyl complex 61 is readily formed8 and smoothly reacts to give the allylic acetate 17. However, control experiments showed that 17 is slowly consumed under the conditions for catalytic acetoxylation.
61
17
OAc
(8) Nakasuji, K.; Yamaguchi, M.; Murata, I.; Tatsumi, K.; Nakamura, A. Organometallics 1984, 3, 1257-1260.
PdCl
Scheme IV
hexene, which probably coordinate more efficiently to palladium(II), the effects of the benzoquinone concentration on the rate were smaller. Since one important factor is the coordinating power of the alkenes, it seemed probable that polyenes would be more reactive than the corresponding monoenes. In ac(vide infra), (E,E,E)cordance, (E,2)-1,5-~yclodecadiene 1,5,9-cyclododecatriene (Table I, entry 8) and (E,E)-1,5dimethyl-l,5-~yclooctadiene (Table 11, entry 13) all reacted considerably faster than their monounsaturated analogues. This is also true for 1,4-~yclohexadienes,as shown by earlier studies (e.g. Scheme III).g In addition to more efficient coordination, the introduction of additional double bonds may lead to dramatic changes in the mechanism. This is illustrated by the acetoxylation of (E,Z)-1,5-cyclodecadiene, which gives 33 as the major product (Scheme IV).l0 The mechanism for this rather unexpected transformation is probably Cope rearrangement to divinylcyclohexane," followed by 1,2acetoxypalladation, cyclization, and @-eliminationof palladium hydride.12 The striking difference between the reactions of (2,2)-1,5-dimethyl-1,5-cyclooctadiene and (E,Z)1,5-cyclodecadiene could be due partly to the difference in configuration of the double bonds. Comparison of the results from oxidation of (E$$)-cyclododecatriene and its E&,Z isomer also suggests a difference: the E,E,Eisomer gave one single product 7, while the E$,Z isomer gave a mixture of a t least three products, none of which is 7.13 The influence of substituents on the reactions of cycloalkenes was also studied. T h e reaction rates of alkylsubstituted cycloalkenes were comparable t o those of the parent compounds, and the total yields were generally good. One exception is 1-methylcyclopentene, which gave only 25% optimized yield of a mixture of the four monoacetates 12-15 (Table 11, entry 1). This result illustrates the major problem with the reactions of the substituted cycloalkenes, the formation of several isomeric products. 1-Methylcyclohexene gave a far better yield of acetates, and the selectivity is also better since two major products, 18 and 19, are formed, accompanied by trace amounts of two other unidentified products (Table 11, entry 4).14 (9) (a) Soderberg, B. C. Ph.D. Thesis, Royal Iqstitute of Technology, Stockholm, Sweden, 1987. (b) SBderberg, B. C.; Akermark, B.; Hall, S. S. J. Org. Chern. 1988,53, 2929-2937. (10) Major component (52%) in a mixture of at least six products. (11)Overman, L. E. Angew. Chern., Int. Ed. Engl. 1984,23,579-586. (12) (a) Heumann, A.; Reglier, M.; Waegell, B. Angew. Chem., Int. Ed. Engl. 1979,18,866-867. (b) Antonsson, T.; Heumann, A.; Moberg, C. J. Chern. SOC., Chern. Comrnun. 1986, 518-520. (13) Hansson, ,S., unpublished results. (14) 2-Methyl~denecyclohexanol can be detected in the product from hydrolysis of the crude acetate mixture, which indicates that the corresponding acetate is one of the primary products.
J . Org. Chem., Vol. 55, No. 3, 1990 977
Palladium (11)-Catalyzed Acetoxylation
Table I. Oxidation of Unsubstituted Cycloalkenes and Linear Alkenes w i t h Pd(OAc)2/Benzoquinone/Mn02in Acetic Acid" converisolated products yield, 90 temp, "C time, h sion, %* entry substrate
1
2
3
4
5
6
7
8
0 0
50
16
Q/""
95c
66
1
CYoAc
60
50
95
25
16
-
75
-
82%
2
77
2
36%
0
60
28
98
73
Q
60
90
60
35
c3
60
300
93
78
0
60
43
77
72 W
72
40
6O
A
c
60
85
7 9
m
72
60
>80e,g
-
9
8
68
95
L
t
10
74
&
11
" 5 % Pd(OAc)2, 20% benzoquinone, 110-200% MnOz in acetic acid (0.4 M in alkene). *For the substrates in this table, conversion is defined as allylic acetate/(allylic acetate substrate). Determined by NMR. d0.5% Pd(OAc),, 10% benzoquinone. e GLC yield. 'The substrate was a mixture of approximately 60% E isomer and 30% 2 isomer, the remaining 10% being mainly cyclododecane. SA 1:l mixture of regioisomers.
+
A phenyl substituent, such as in 1-phenylcyclohexene, has no major influence on the product pattern, which is similar to t h a t from 1-methylcyclohexene, but rate and yield go down (Table 11, entry 7 ) . An alkoxycarbonyl substituent seems to have a similar influence, as indicated by a comparison between 4-methylcyclohexene and methyl 3-cyclohexenecarboxylate (Table 11, entries 6 and 8). 3Cyclohexenecarbonitrile and 3-cyclohexenyl methyl ketone appear to be totally unreactive, suggesting that a nitrile or acyl substituent inhibits the acetoxylation, perhaps by competing for coordination sites on palladium (Table 11, entries 9 and 10). The position of the substituent does not appear to have any major influence on the rates and yields, since 3- and 4-methylcyclohexene both give high yields of a mixture of three major regioisomeric acetates, 19-21, from 3-methylcyclohexene and 20-22 from 4-methylcyclohexene (Table 11, entries 5 and 6). The compound 21 is a 1:l mixture of trans and cis isomers, indicating a complete lack of face selectivity in the acetoxylation. We were not able to determine the trans:cis ratio for 20. Since 20 and 21 are probably interconvertible under the reaction
conditions,'lJ5 20 is also likely to be a 1:ltrans:cis mixture. In contrast, the trans:& ratio for 22 is 52:6. If the double bond is exocyclic, this can have a major influence on the catalytic acetoxylation, and methylenecyclohexane gave a complex mixture of products (Table 11, entry 11). In contrast, ethylidenecyclohexane reacted to give three products 27-29 (Table 11, entry 12). In order to understand these puzzling differences, and also be able to control the product distribution from the substituted cycloalkenes, it is necessary to understand more about the mechanism of acetoxylation.
Mechanism There are two reasonable pathways for the palladiumcatalyzed allylic acetoxylation of alkenes: (i) 1,2-acetoxypalladation, followed by p-elimination of palladium hydride, and (ii) initial transformation of the alkene into a q3-allyl complex, followed by nucleophilic attack of (15) Henry, P. M. Acc. Chem. Res. 1973, 6,16-24.
978 J . Org. Chem., Vol. 55, No. 3, 1990
Hansson et al.
Table 11. Oxidation of Substituted Alkenes with Pd(OAc)2/Benzoquinone/Mn02 in Acetic Acid"
entry
1
2
substrate
tema. "C
0
40
time,-h
48
conversion, %
95
12
0
isolated vield. %
products
14
13
15
H
50
30
98
76
H
Ac
16
60
3
72
(yJ
20
