J . Am. Chem. SOC.1994,116, 6130-6141
6130
Allylbarium Reagents: Unprecedented Regio- and Stereoselective Allylation Reactions of Carbonyl Compounds Akira Yanagisawa, Shigeki Habaue, Katsutaka Yasue, and Hisashi Yamamoto. Contributionfrom the School of Engineering, Nagoya University, Chikusa, Nagoya 464-01, Japan Received February 1 , 1994'
Abstract: The first direct preparation of allylbarium reagents by reaction of in situ generated reactive barium with various allylic chlorides and their new and unexpected selective allylation reactions with carbonyl compounds are disclosed. Highly reactive barium was readily prepared by the reduction of barium iodide with 2 equiv of lithium biphenylide in dry T H F at room temperature. Avariety of carbonyl compounds reacted with barium reagents generated from ( E ) - or (2)-allylic chlorides in T H F at -78 OC. All reactions resulted in high yields with remarkable a-selectivities not only with aldehydes but also with ketones. The double bond geometry of the starting allylic chloride was completely retained in each case. Stereochemically homogeneous ( E ) - and (Z)-@,y-unsaturated carboxylic acids were easily prepared in good yields by highly a-selective carboxylation of allylic barium reagents with carbon dioxide. A selective Michael addition reaction with a,p-unsaturated cycloalkanone was also achieved using an allylbarium reagent. Treatment of 2-cyclopentenone (1 equiv) with allylbarium chloride (2 equiv) in T H F at -78 OC for 20 min afforded 3-allylcyclopentanonein 94% yield with a 1,4/1,2 ratio of >99/1. Furthermore, the in situ generated barium enolate was efficiently trapped with various kinds of electrophiles (Me2C=CHCHzBr, "CsHllCHO, and CHsCOCl). Introduction
Scheme 1 OH
An allylmetal is one of the most useful reagents for the formation of carbon4arbon bonds.' Although a large number of allylic organometallics have been developed for selective allylation reactions, the allylic organometalliccompoundsof heavier alkaline earth metals have found little application in organic synthesis. Indeed, they do not offer any particular advantages over simple Grignard reagents.2 We have been interested in using barium and strontium reagents with the anticipation that such species should exhibit stereochemical stabilities different from that of the ordinary magnesium reagent.' Reported herein are the first direct preparation of allylbarium reagents by reaction of in situ generated reactive barium with a variety of allylic chlorides4 and
*Abstract published in Aduance ACS Abstracts, June 1, 1994. (1) Reviews: (a) Courtois, G.; Miginiac, L. J. Organomet. Chem. 1974, 69, 1. (b) Biellmann, J. F.; Ducep, J. B. Org. React. 1982, 27, 1. (c) Roush, W. R. In Comprehensiue Organic Synthesis; Trost, B. M., Fleming, I., Heathcock, C. H., Eds.; Pergamon Press: Oxford, U.K., 1991; Vol. 2, p 1. (d) Yamamoto, Y.; Asao, N. Chem. Rev. 1993, 93, 2207. Reviews of allylic Grignard reagents: (e) Benkeser,R. A. Synthesis 1971,347. (0 Niitzel, K. In Houben- Weyl: Methoden der Organischen Chemie; Miiller, E., Eds.; Thieme Verlag: Stuttgart, Germany, 1973; Vo1.13/2a, p 88. See also: (g) Wakefield, B. J. Organolithium Methods; Academic Press: London, 1988. (h) Schlosser, M. Pure Appl. Chem. 1988, 60, 1627. (2) Reviews: (a) Ioffe,S. T.;Nesmeyanov, A. N. The OrganicCompounds of Magnesium, Beryllium. Calcium, Strontium anddarium; North-Holland: Amsterdam, 1967. (b) Niitzel, K. In Houben- Weyl: Methoden der Orgunischen Chemie; Miiller, E., Eds.;ThiemeVerlag: Stuttgart, Germany, 1973; Vo1.13/2a, p 529. (c) Gowenlock, B. G.; Lindsell, W. E. In Journal of Organometallic Chemistry Library 3, Organometallic Chemistry Reviews;
Seyferth, D., Davis, A. G., Fischer, E. O., Normant, J. F., Reutov, 0. A., Eds.; Elsevier: Amsterdam, 1977; p 1. (d) Lindsell, W. E. In Comprehensiue Organometallic Chemistry; Wilkinson,G., Stone, F. G.A., Abel, E. W., Eds; Pergamon Press: Oxford, U.K., 1982;Vol. 1,Chapter 4, p 223. (e) Wakefield, B. J. In Comprehensiue Organometallic Chemistry;Wilkinson,G., Stone, F. G.A., Abel, E. W., Eds; Pergamon Press: Oxford,U.K., 1982;Vol. 7, Chapter 44. (3) Yanagisawa, A.; Habaue, S.; Yamamoto, H. J. Am. Chem. Soc. 1991, 113, 5893. (4) Allylbarium has, as yet, been prepared only by transmetalation with diallylmercury" or tetraallyltinsb in THF. ( 5 ) (a) West, P.; Wdville, M. C.Ger. Offen. 2,132,955, 1972. (b) West, P.; Wdville, M. C. US. Pat. 3,766,281, 1973.
their new and unexpected selective allylation reactions with carbonyl compounds (Scheme 1).6
Results and Discussion Preparation of Allylic Barium Reagents. Highly reactive barium was readily prepared by the reduction of barium iodide with 2 equiv of lithium biphenylide' in dry T H F at room temperature for 30 min (eq 1). The dark brown suspension thus obtained was exposed to an allylicchloride at -78 OC. A slightly exothermic reaction took place immediately to give a dark red solution* of allylic barium that could be used directly (eq 2). Ba12
+
2Li+[Ph-Ph]7
-
THF 25 'C,30 min
Ba*
(1)
Stereochemical Stability of AUylic Barium Reagents. In the realm of stereoselectivity one great challenge that had not previously been met was the preparation of stereochemically homogeneous alkali and alkaline-earth allylmetals directly from (6) A preliminary communication of this work has been published: Yanagisawa, A.; Habaue, S.; Yamamoto, H. J. Am. Chem. Soc. 1991,113, 8955. (7) Highly reactive calcium was prepared by the lithium biphenylide reduction of CaBrl or CaI2, see: Wu, T.-C.; Xiong, H.; Rieke, R. D. J. Org.
Chem. 1990,55, 5045.
(8) Sometimesa dark red suspension is obtained which can be used without difficulty.
0002-~a63194/ 1516-6130$04.50/0 0 1994 American Chemical Society
J . Am. Chem. SOC.,Vol. 116, No. 14, 1994 6131
Allylbarium Reagents and Selective Allylation
ua=
~
-+*
"22
lEQlz
-
r
i
4E or 42
3
1) M ' _. v
2) MeQH
v
-L
v
I
+/
I
SE or 52
~
6
40160
I
30fl
1 64%
- I I -I I I I I 0/100 I I -100 -90 -80 -70 -60 -50 -40 -30 -20 -10
I
0
10
temperature ("C) Mg; 0:from lE, u: from 12 Ba; 0:from lE, a: from 1Z (sly = 60/40-71/29) (dv=91/9-98/1) Li; 0:f" w., +:from tz (WY = 95/5-98/1)
-100 -90 -80 -70 -60 -50 -40 -30 -20 -10 temperature ("C)
Mg;o:from4E, .:from42 (WY = 21/79-37/63) Lk o:from4E, +:from42 (Ury = 78/22-92/8)
0
10
Ba; O:from4E, .:from42 (Ury= 86/14-9416)
F i g w 1. Temperature dependence of the E/Z ratio of the allylic metals (Li, Mg, and Ba) derived from geranyl chloride (14E/Z > 99/1) and neryl chloride (1Z; E/Z < 1/99). Numbers refer to combined yields of the products 2 and 3.
Figure 2. Temperature dependence of the E/Z ratio of the allylic metals (Li, Mg,and Ba) derived from (E)-2-docenyl chloride (46, E/Z > 99/ 1 ) and (Z)-2-dccenylchloride(42;E / Z = 2/98). Numbemrefer tocombined yields of the products 5 and 6.
allylic halides? This is not a simple problem, since y-substituted allylmetals, crotylmagnesium bromide, for example, are known to isomerize rapidly between the Z and E isomers even at low temperature.10 Our interest in the structural aspects of these species has led us to undertake a careful investigation of these well-known organometallics. Our initial assumption was that stereoisomerization of the allylmetal was due to the rapid isomerization through metallotropic rearrangements that were temperature dependent. Thus, a ?substituted allylic chloride was transformed to the corresponding barium reagent at -78-0 OC in 25 OC intervals. The mixture was stirred for 30min at each temperature" and quenched with methanol. The rate of isomerization was measured by analyzing a mixture of E and Z hydrocarbons (eq 3).
(the temperature of the system and the choice of metal) and three consequences (the E/Z ratio of the olefins produced, the yield (%), and the orly ratio of the protonation products). Although there was no remarkable E/Z selectivity obtained by protonation of magnesium derivatives above -60 OC, extremely high stereoretention was observed below -95 Oca3In contrast, the double bond geometry of the allylic barium compounds was retained even at -50 OC,a temperature higher than that for the corresponding lithium compounds. The superiority of barium reagent is thus apparent for stereoselectivity. It should be further noted that the yields of the derived olefins were sufficiently high for practical purposes.
1) Ba*/THF
2) MeOH -78-O'C *
" pa R2
R
I
p
H
+
"'F (3) R~ H
EIZ ratio
The results with geranyl- and nerylbarium compounds are shown in Figure 1. Similarly, magnesium12 and lithium derivat i v e ~ were ' ~ prepared and quenched as above. The implications of Figure 1 are apparent. There are two experimental variables (9) Wardell,J. L. In ComprehensiueOrganometallic Chemistry;Wilkinson, G., Stone, F. G,A., Abel, E. W., Eds; Pergamon Press: Oxford, U.K., 1982; Vol. 1, Chapter 2. (10) Hutchinson, D. A.; Beck, K. R.; Benkeser, R. A.; Grutzner, J. B. J . Am. Chem. SOC.1973, 95, 7075. (1 1) A digital thermometer (Model HH81, OMEGA Engineering, Inc.) was used to measure the internal reaction temmratures. (12) The corresponding allylic Grignard &gents were generated using Rieke-Ma.13 (13) $urns, T.P.; Rieke, R. D. J. Org. Chem. 1987,52, 3674. (14) Prepared using lithium biphenylidel5 or lithium 4,4'-di-?ert-butylbiphenylide (LDBB).'6 (15) (a) Holy, N. L. Chem. Rev. 1974.74, 243. (b) Cohen, T.; Bhupathy, M. Acc. Chem. Res. 1989, 22, 152. (16) (a) Freeman, P. K.; Hutchinson, L. L. J. Org, Chem. 1980,45,1924. (b) Cohen,T.; Jeong, I.; Mudryk, B.; Bhupathy, M.; Awad, M. M. A. J. Org. Chem. 1990, 55, 1528.
The temperature dependence of the E/Z ratio of 2-decenylmetals was also investigated, and the results are summarized in Figure 2. In contrast to the disubstituted allylmetals, a significant isomerization rate enhancement was observed for these monosubstituted allylmetals and rapid stereoisomerization of magnesiumderivatives was observed even at -100 O C . 3 Although the cause of this enhancement was not immediately apparent, it does rather than magnesium or indicate that barium at below -70 lithium should be chosen for the effective generation of configurationally homogeneous monosubstituted allylmetals.
Metal Effectson the a/r Selectivityin the Reactions of Various Ceranylmetals with Benzaldehyde. The versatility of stereochemically homogeneous mono- and disubstituted allylmetals in synthesis is noteworthy, as is their complementary relationship to other key functional groups. Thus, we examined the metal effects on the a/y selectivity in the reactions of various geranylmetals with benzaldehyde (Table 1). It is well established that the allylic magnesium or calcium reagent gives the y-substituted product predominantly(entries 3 and 4) and the allylation with the lithium reagent is less selective (entry 1). In marked contrast, however, the barium reagent reacted with remarkable or-selectivity (or/7 = 92/8) and retention of configuration of the starting halide (E/Z = 98/2, entry 6). Geranylcerium reagent
6132 J. Am. Chem. SOC.,Vol. 116, No.14, I994
Table 1. Reactions of Various Geranylmetals with Benzaldehyde
7a (a-product)
entry ld
2' 3 4 5
6
I 8
M* Li+[Ph-Ph]* K+[Ph-Ph]+ Mg Ca Sr IBa Cd Ce
8a (PProdUCt)
combined yield, K a/yC a-product, E / Z c 36 41/53 >99/1 35 61/33 9812 99 4/99 IO 12/88 9812 89 54/46 9113 90 9218 98/21 39 45/55 9113 52 12/28 >99/1
a Unless otherwise specified, the reaction was carried out by using geranyl chloride, reactive metal, and benzaldehyde (2, 2, and 1 equiv, respectively)at-I8 OC for 30min. Isolated yield. Determined by GLC analysis. Geranyl chloride,lithium biphenylide,and benzaldehyde (2.5, 5.6, and 1 quiv, rcspectively) were used. * Geranyl chloride, potassium biphenylide, and benzaldehyde (1.2,2.9, and 1 equiv, respectively) were used. 1Prepared by reduction of CubPBu, with lithium naphthal~nide.'~
also showed a moderate a-selectivity (a/y= 72/28, entry 8).17 The extraordinary a-selectivity and stereospecificity of the carbonyl addition of barium reagent provide an unprecedented route to homoallylic alcohols.
a-Selectiveand Stereospecific Allylation of Carbonyl CompoundswithAllylic BarimReagentsPreparedfromVariousAllylc Chlorides. We investigated the generality of the a-selective allylation using allylic barium reagents. Table 2 summarizes the results obtained for the reactions of a variety of carbonyl compounds with barium reagents generated from primary (E)and (2')-allylic chlorides in T H F at -78 OC. Some characteristic features of the reaction are as follows: (1) All reactions resulted in high yields with remarkable a-selectivities not only with aldehydes but also with ketones. (2) The double bond geometry of the starting allylic chloride was completely retained in each case. (3) In the reaction with an a,&unsaturated aldehyde, 1,2addition proceeded preferentially (entry 3). (4) (Z)-y-Monosubstituted allylbarium showed relatively low a-selectivities in reactions with carbonyl compounds (entries 6-9 and 13). However, condensationswith bulky carbonyl compounds 2,2,4,4tetramethyl-3-pentanoneand n-hexanoyltrimethylsilaneproduced (5) The alkyl the a-product exclusively (entries 10 and 1 substituent at the &position of allylic barium had no effect on the regioselectivity (entries 23 and 25). (6) Existence of a triple bond or benzyl ether group in the allylic barium reagent had no effect on its preparation or the course of the reaction (entries 24 and 25). 12-Hydroxysqualene (1l), an important intermediate of squalenebiosynthesis,19was readily prepared by this new allylation reaction. Treatment of (E,E)-famesal(lO) with theallylic barium reagent 9 derived from (E,E)-farnesyl chloride in T H F at -95 OC afforded 11 almost exclusively in 75% yield (eq 4L20
10
9
< -95 'C
11,755
(17) Highly stereocontrolled a-selective allylation using allylceriums has k e n reported by Cohen, see: Guo. B.-S.;Doubleday, W.; Cohen, T. J. Am.
Chem. Soc. 1987,109,4710. (18) (a) Yanagbawa, A,; Habaue, S.;Yamamoto, H.J. Org. Chem. 1989, 54,5198. (b) Yanagisawa, A.; Habaue, S.; Yamamoto, H. Terrahedron 1992, 48, 1969. (19) Private communication from Professor T. Nishino, Kyoto University. (20) The y-isomer of 11 was obtained as a minor product (7% yield).
Yunugisuwu ef 01. Next, we turned our attention to secondary allylic barium compounds. It is more difficult to control regie and stereochemistries of secondary alkali and alkaline-earth allylmetals than those of the corresponding primary allylmetals because of their rapid stereoisomerization. Results of allylation of carbonyl compounds with allylic barium reagents prepared from various secondary allylic chlorides are shown in Table 3. Reaction of benzaldehyde with allylic barium reagents generated from 3-chloro-1-buteneat -78 OCgavea4060mixtureofthea-product and y-product in 98% yield (entry 2). At lower temperature (-95 "C),a slight increase of a-selectivity was observed (a/y= 50/50, entry 3). Existenceof two methyl groupsat the y-position of the secondary allylic chloride proved effective for obtaining a higher regioselectivity (a/y = 56/44, entry 4). The highest a-selectivity (a/y = 91/9) was gained using 2-chloro-4,8dimethylnona-3,7-diene,which possesses a long alkyl chain at the y-position (entry 5). A similar regioselectivity (a/y= 92/8) was observed in the condensation of the same barium reagent with acetone, and thedouble bond geometry of thestarting allylic chloride was completely retained throughout the reaction (E/Z > 99/1, entry 6). Figure 3 provides a graphical interpretation of the reaction pathway of primary allylic barium reagents with carbonyl compounds. Selective formation of the E isomer of a-product F from (E)-allylicchlorideA is readily accounted for by theoxidative addition of barium metal to halide A to generate a primary allylic barium compound (A C), followed by its condensation at the F). Since stereoia-carbon with a carbonyl compound (C somerization of the barium reagent (C D E) does not occur a t -78 OC,no Z isomer of the a-product H is formed from (E)allylic chloride A at this temperature. Similarly, the formation of the Z isomer of a-product H from (2')-allylic chloride B proceeds by the pathway B E H. Minor y-product G may arise from C or E via a six-membered cyclic transition structure. On the other hand, the secondary allylic barium reagent seems to isomerize rapidly between the a-and y-isomers even at low temperature. Existenceofa longalkylsubstituent at theyposition is requisite to stop such metallotropic rearrangement. At present the reason is not clear why an allylic barium compound m c t s selectively at the a-carbon with a carbonyl compound; however, the unusually long barium-carbon bond (2.76-2.88 A)21 might prevent the formation of a six-membered cyclic transition structure leading to the y-product. A fourmembered cyclic structure including B a - C and C - 0 bonds is one of the possible transition-state models for the a-selective allylation.
-
- --
--
Regioselectiveand Stereospecific Synthesis of B,y-Unsaturated Carboxylic Acids Using Allylbariums. @,y-Unsaturated carboxylic acids and their derivatives are valuable synthetic intermediates of various natural products. Two typical multistep processes for the synthesis of &y-unsaturated acids, (1) Knoevenagel reaction/isomerization with baseZZand (2) allylic ~yanide/hydrolysis,2~ are those most commonly used. Other new methods have been however, most of these suffer from the problem of E/Z stereoselectivity. One straightforward way to obtain @,y-unsaturated acids is by the carboxylation of (21) Kaupp, M.; Schleyer, P. v. R. J. Am. Chem. Soc. 1992, 114, 491. (22) (a) Caspi, E.; Varma, K. R. J. Org. Chem. 1968, 33, 2181. (b) Maercker, A.; Streit, W. Chem. Ber. 1976, 109, 2064. (c)kikolajczak, K. L.; Smith, C. R., Jr. J. Org. Chem. 1978,43,4762. (d) Grob, C. A.; Waldncr, A. Helu. Chim. Acru 1979, 62, 1854. (e) Ragoussis, N.Tetrahedron Leu. 1987, 28, 93. (23) (a) Katagiri, T.; Agata, A.; Takabe, K.; Tanaka, J. Bull. Chem. Soc. Jpn. 1976,49,3715. (b) Hirai, H.; Matsui, M. Agric. Biol. Chem. 1976,40, 169. (c)Garbers,C.F.;Beukes,M.S.;Ehlers,C.;McKenzie,M. J. Terrahedron Lett. 1978,77. (d) Hoye, T. R.; Kurth, M. J. J. Org, Chem. 1978,43,3693. (e) Gasselin, P.; Roueapac, F. C. R.Seunces Acud. Scl., Ser. 2 1982,295,469. (f) Mori, K.; Funaki, Y. Tetruhedron 1985, 41, 2369. (24) Ene reaction of diethyl oxomalonate: (a) Salomon, M. F.; Pardo, S. N.; Salomon, R. G. J. Am. Chem. Soc. 1980,102,2473. (b) Salomon, M. F.; Pardo, S.N.; Salomon, R. G. J. Am. Chem. Soc. 1984, 106, 3797. (25) ~-Vinyl-Bpropiolactone/organocopper reagent: Kawashima, M.; Sato, T.; Fujisawa, T. Bull. Chem. Soc. Jpn. 1988,61, 3255.
Allylbarium Reagents and Selective Allylation
J. Am. Chem. SOC.,Vol. 116, No. 14, 1994 6133
Table 2. Regio- and StereoselectiveAllylation of Carbonyl Compounds with Allylic Barium Reagents Prepared from Primary Allylic Chlorideso
R'wa
1) Ba* 2)R3COR2
HO R3
THF
R2
-78 "
entry
allylic chlorideb r
f
RbK + J.
R' Rz 8 (7-product)
R2
carbonyl compound a
+
7 (a-product)
(E)-"C~H~SCH=CHCH~C~ PhCHO "C~HI~CHO (E)-PhCH-CHCHO cyclohexanone PhCOCH3 r a PhCHO (Z)-"C~H,~CH=CHCHZC~ "C~HIICHO cyclohexanone 'PrCO'Pr BuCO'Bu "C5HllCOSiMe3 "C~H~ICHO
1 2 3 4 5 6 7 8 9 10 11 12
R3 OH
R'#Rd
products
combined yield, %c
al r d
a-product, EIZd
80 82 73e 95 94 98 75 89 99 99 89 65
9713 9812 9416 991 1 9614 73/27 86/14 75/25 82/18 >99/1 991 1 83/17
>99/ 1 9713 9812 991 1 991 1 2/98 2/98 2/98 2/98 99/1 991 1 2/98 99/ 1
9713
>99/1
+ 86 7d + 8d 7e + 8e 7f + 8f 7g + 8g 7h + 8h 71 + 8i 7j + 8j 7b
7c + 8c
+
7k 8k 7h+8V n + 81
+ 8m + 8a
13 14 15 16 17 18 19 20 21 22 23 24
"C5H I iCHO PhCHO "CsHiiCHO cyclohexanone PhCOCHs PhCHO "C~H~ICHO cyclohexanone PhCOCH3 "C~HIICHO cyclohexanone PhCHO
7m
+ 8s + 8t 7u + 8u 7v + 8v 7w + 8w
56 90 90 98 96 89 73 98 84 64 92 98
25
C2H5CHO
7x + 8x
74
7a
7n + 8n 70 + 80 7P + 8P 79 + 8cl 7r + 8r 7s 7t
0 Allylation was carried out by using an allylic chloride, reactive barium, and carbonyl compound (2, 2, and 1 equiv, respectively) at -78 O C for 30 min. Stereochemicallypure (>99%) allylic chlorides were used. Isolated yield. Determined by GLC analysis. e The 1,4-adductwas also obtained in 14% yield. The intermediate a-hydroxysilanes were desilylated with "BuNF in DMF.'*
*
an allylmetal. In the substituted allylic series, the reaction usually occurs at the more sterically hindered terminus.la A stereospecific route for the synthesis of homogeranic acid and homoneric acid by carboxylation of the lithiated allylic sulfone has also been reported.28 We anticipated that carboxylation of allylic barium would show a-selectivity without loss of the double bond geometry. Actually, treatment of excess carbon dioxide with allylic barium reagent resulted in a-carboxylation, whereas y-carboxylation occurred with allylic magnesium reagentla (Scheme 2). Some results of carboxylation of allylic bariums are summarized in Table 4,29 and the characteristic features of the reaction are as follows: (1) Allylic barium reagents generated from a variety of y-mono- and y-disubstituted allyl chlorides showed high a-selectivities without exception. (2) The double-bond geometry of the allylbarium was completely retained in each case. (3) The alkyl substituent a t the @-positionof allylic barium had no effect on the regioselectivity. In conclusion, this is one of the most straightforward and practical methods to date for regioselective (26) Transition-metal-catalyzed carbonylation: (a) Alper, H.; Amer, I. J. Mol. Curd. 1989,54, L33. (b) Garlaschelli, L.; Marchionna, M.; Iapalucci, M. C.; Longoni, G. J. Orgunomet. Chem. 1989,378,457. (c) Satyanarayana, N.;Alper, H.;Amer, I. Orgummerullics 1990,9,284.(d) Imada,Y.;Shibata, 0.; Murahashi, S.-I. J. Orgunomct. Chem. 1993,451, 183. For synthesis of the &-punsaturatedester: (e) (Review) Murahashi, %I.; Imada, Y. J. Synth. Org. Chcm., Jpn. 1991,49,919 and references cited therein. ( f ) Murahashi, S A ; Imada,Y.;Taniguchi, Y.; Higashiura, S . J. Org. Chem. 1993.58, 1538. (g) Okano, T.; Okabe, N.;Kiji, J. Bull. Chem. Soc. Jpn. 1992,65, 2589. (27) Review: (a) Colvin, E. W. In Comprehensive Organic Chemistry; Barton, D. H.R., Ollis, W.D., Eds.; Pergamon: Oxford, U.K.,1979; Vol. 2, p 620. The BBchi-WBest rearrangement is a useful method for synthesis of &y-unsaturated amides: (b) BBchi, G.; Cushman, M.; WBest, H. J. Am. Chem. Soc. 1914,96, 5563. (28) Gosselin, P.; Maignan, C.; Rouessac, F. Synthesis 1984, 876. (29) Yanagisawa, A.; Yasue, K.; Yamamoto, H. Synlert 1992, 593.
1
3.
Ba*
Ba*
-78 'C
Figure 3. Reaction pathway of primary allylic barium reagents with carbonyl compounds. and stereospecific synthesis of @,y-unsaturatedcarboxylic acids using allylmetals. Selective Michael Addition Reactions of Allylbarium with a@Umaturated Cycloalkanones. The conjugate addition of an allylic anion to an a,@-enone is an extremely useful process for the introduction of a @-functionalizedsubstituent.30 However, allylic copper reagents are unstable and d o not always give satisfactory (30)Reviews: (a) Posner, G. H. Org.Reucr. 1972,19,1. (b) Comprehensive Orgunic Synthesis; Trost, B. M., Fleming, I., Semmelhack, M. F., Eds.; Pergamon Press: Oxford, U.K.,1991; Vol. 4, p 1-268. (c) Perlmutter, P. ConjuguteAddition Reactions in OrgunicSynthesis;Pergamon Press: Oxford, U.K.,1992. (d) Lipshutz, B. H.; Sengupta, S . Org. React. 1992, 41, 135.
Yanagisawa et al.
6134 J. Am. Chem. SOC.,Vol. 116, No.14, 1994 Table 3. Allylation of Carbonyl Compounds with Allylic Barium Reagents Prepared from Secondary Allylic Chlorideso HO R3 R3 OH 1) Ba* 2)R3COR4 R'+R~ R4+Me Rz Me Rz Me R' R2 12 (a-product) 13 (y-product)
Scheme 3
b
+
entry
allylic chloride
; -'7" 3 4
y-ya
carbonyl compound
T,'c
pmducts combined yield,
PhMO PhCHO
o 13. + 11. 9 8 I& + I t . -9s it. + it.
PhCHO
-78
PhCHO
ma
FtlCFiO CHlCOCH,
lab
+
lab
THF, -78 'C
sb d4
98 98 9s
uwo
81
Ea44
6amo
laa
+
lac
71
916
1Sd
+ lad
70
WE'
0 Unless otherwise specified, allylation was carried out by using an allylic chloride, reactive barium, and carbonyl compound (2, 2, and 1 equiv, respectively) at -78 OC for 30 min. b Isolated yield. C Determined by GLC analysis. Stereochemically pure ( E / Z > 99/ 1) allylic chloride was used. e The E/Zratio of the a-product was >99/1.
Scheme 2
TIP. -78 'C
1
7 -carboxylation
L
a -carboxylation
Table 4. Regie and Stereaselective Carboxylation of Allylic Bariums' ~
enty
allylic chloride'
~~
a-pmduct
combined yield, %e
4
22
a--p.edusS
Eli
O Allylation was camed out using an allylicchloride (1 equiv), reactive barium (1 equiv), and carbon dioxide (excess) at -78 O C for 30 min. b Stereochemicallypure (>99%) allylicchloride was used. Isolated yield. d Determined by GLC analysis after conversion to the methyl ester.
r e s ~ l t s . 3 ~In 1977, Hosomi and Sakurai reported the smooth
reaction of allylsilane with an a,&enone preferentially in a conjugate mode in the presence of titaniumchloride as an activator of the enone, leading to a &e-enone by simple p r o t o n ~ l y s i s . ~ ~ (31) (a) House, H. 0.;Fischer, W. F., Jr. J. Org. Chem. 1969,34, 3615. (b) Daviaud, G.; Miginiac, P. Tetrahedron Lett. 1973,3345. (c) House, H. 0.; Sayer, T.S.B.; Yau, C:-C. J . Org. Chem. 1978,43,2153. (d) House, H. 0.; Wilkins, J. M. J. Org. Chem. 1978,43,2443.(e) Yamamoto, Y.; Yatagai, H.; Maruyama, K. J. Am. Chem. Soc. 1981, 103, 1969. (f) Luche, J. L.; Pttrier, C.; Gemal, A. L.; Zikra, N. J. Org. Chem. 1982,47,3805. (9) Corey, E. J.;Boaz,N. W. TetrahedronLett. 1985,26,6019.Reccntexcellentsolutions to this problem: (h) Lipshutz, B. H.; Ellsworth,E. L.; Dimock, S.H.; Smith, R. A. J. J. Am. Chem. Soc. 1990,112,4404. (i) Liphutz, B. H.; Ung, C.; Elworthy, T. R.; Reuter, D. C. Tetrahedron Lett. 1990,31,4539. 0)Stack, D. E.; Dawson, B. T.;Rieke, R. D. J. Am. Chem. Soc. 1991,113,4672. (k) Stack,D.E.;Dawson,B.T.;Rieke,R.D. J. Am. Chem.Soc. 1992,114,5110. (I) Stack, D. E.; Klein, W.R.; Rieke, R.D. Tetrahedron Lett. 1993,34,3063.
2-Cyclopentenone D THF, -78 'C
22 (LCadd~kt) 21 (1.2-adduct) entry Id 2' 3 4
M* Li+[Ph-Ph]' K+[Ph-Ph] Mg Ca
-5
r
*
Table 5. Reaction of Various Allylmetals with 2-Cyclopentenond
M*
-78
J
~
MI&(
-78
L
I H2C=CHCH2BaCI
6
IBa
combined yield, %b 79 38 81 65 63 94
1,4/ 1,2' 99/ 1 and 98/2, respectively, by GLC analysis after conversion to the methyl ester with diazomethane in ether: TLC R10.27 (1:l ethyl acetate/hexane); bp 106 OC (0.4 Torr); IR (neat) 3650-2380,2969,2923,2854,1713,1437,1416,1300,1225,1154,1109,
939,831 cm-l; IH NMR (200 MHz, CDC13)6 1.60 (s,3 H, CH3), 1.65 (s, 3 H, CH3), 1.68 (s, 3 H, CH3). 2.07 (m, 4 H, 2 CHI), 3.10 (d, 2 H, J = 7.0 Hz, CH2), 5.05-5.13 (m,1 H,vinyl), 5.31 (t, 1 H, J = 7.0 Hz, vinyl), 10.2-1 1.4 (br, 1 H,C02H); 13C NMR (50 MHz, CDClp) 6 15.9, 17.3, 25.3, 26.1, 33.2, 39.3, 115.1, 123.9, 131.5, 139.5, 178.8; MS (EI, 70 eV) m/z (relative intensity) 167 (3.36, M+ - 15), 149 (7.49, 139 (46) Rouessac, A.; Rouessac, F.;Zamarlik, H. Tetrahedron Lett. 1981, 22, 2641.
J. Am. Chem. SOC.,Vol. 116, No. 14, 1994 6139 (17.87), 122 (9.1 l), 69 (62.75); MS (FAB) m/z 183 (M+
+ 1). Anal.
Calcd for C11Hl802: C, 72.49; H,9.95. Found: C, 72.51; H, 10.20. Procedure for Luge-Scale Cvboxylrtion of Gemylbarlum Reagent. An oven-dried, three-necked round-bottomed 300-mL flask, equipped witha Tefloncoated magneticstirring bar, was flushedwith argon. Freshly cut lithium (210 mg,30.3 mmol) and biphenyl (4.7 g, 30.5 mmol)were placed into the apparatus and covered with dry THF (80 mL), and the mixture was stirred for 2 h at room temperature. In a separate ovendried, thrce-necked round-bottomed 500-mL flask, equippedwith a Tefloncoated magnetic stirring bar and a 100-mLdropping funnel, was placed anhydrous BaI2 (6.0 g, 15.3 mmol) under an argon atmosphere; this was covered with dry THF (80 mL) and stirred for 5 min at room temperature. To the resulting yellowish solution of BaI2 in THF was added at room temperature a solution of the lithium biphenylide through a stainless steel cannula under an argon stream; the reaction mixture was stirred for 1 h at room temperature. To the resulting dark brown suspension of active barium in THF was added dropwise over 20 min a solution of geranyl chloride (1.19 g, 6.87 mmol) in THF (40 mL) from the 100-mL droppingfunnel at -78 OC, and the mixture was stirred at this temperature for 30 min. An excess of dry ice (ca. 10 g) was added at -78 OC and stirring continued for 10 min. The reaction mixture was quenched with 1 N HCI (40 mL) at -78 OC, warmed to room temperature, and poured into a mixture of H2O (200 mL) and EtOAc (200 mL). After vigorous shaking, the organic layer was separated and washed with 1 N sodium thiosulfate solution (200 mL). The two aqueous layers were combined, acidified (pH
