J. Org. Chem. 1983,48,464-469
464
sufficiently reliable to provide an additional method that should be used increasingly in conjunction with existing general procedures to assign the configuration of compounds similar to those described here. Experimental Section The compounds used in this study were prepared by literature methods. Optically active samples of the alcohols were prepared by resolution (3), reduction of the corresponding ketone using Cryptococcus macerans, or by enantioselective hydrolysis of the corresponding acetates using Rhizopus nigricam. The 'H NMR spectra (220 MHz) of the optically active samples were identical with authentic racemic materials. Specific rotations were determined by using a Perkin-Elmer 241MC polarimeter. The HPLC measurements were made by using an apparatus constructed from an Altex injector, an Altex pump Model llOA, a Gilson variable-wavelengthdetector, and a chiral 'Pirkle" column (Hi-Chrom reversible column) purchased from the Regis Chemical Co., Morton Grove, IL 60053. The column is (R)-N-(3,5-dinitrobenzoy1)phenylglycine ionically bonded to a y-aminopropyl-silanized silica The alcohols were converted to the corresponding acetates by acetic anhydride/pyridine by using standard techniques. Registry No. la (X = H; isomer l),1517-69-7; la (X = H; isomer 2), 1445-91-6; la (X = Ac; isomer l),16197-92-5;la (X = Ac; isomer 2), 16197-93-6;lb (X = H;isomer l ) , 1565-74-8;lb (X = H; isomer 2), 613-87-6; lb (X = Ac; isomer l),84275-44-5; lb (X = Ac; isomer 2), 83860-48-4; IC (X = H; isomer l), 22144-60-1;IC (X = H; isomer 2), 22135-49-5;lo (X = Ac; isomer I), 84194-64-9; IC (X = Ac; isomer 2), 84194-65-0; Id (X = H; isomer l ) ,14898-86-3;Id (X = H; isomer 2), 34857-28-8; Id (X = Ac; isomer l),84194-66-1; Id (X = Ac; isomer 2), 84194-67-2; le (X = H; isomer l),23439-91-0;le (X = H; isomer 2), 24867-90-1; le (X = Ac; isomer l), 23439-90-9; le (X = Ac; isomer 2), 84194-68-3;If (X = H; isomer l),10531-50-7;If (X = H; isomer 2), 340-06-7; If (X = Ac), 84194-69-4; lg (X = H; isomer l), 20698-91-3; lg (X = H; isomer 2), 21210-43-5; l g (X = Ac), 947-94-4; lh (X = H; isomer l),41822-67-7; lh (X = H; isomer 2), 5773-56-8 lh (X = Ac; isomer l),84194-70-7;li (X = H isomer
l),5928-66-5;li (X = H; isomer 2), 5928-67-6;li (X = Ac; isomer l),84275-456;li (X = Ac; isomer 2), 84275-46-7;lj (X = H; isomer l),84275-47-8; lj (X = H; isomer 2), 66768-23-8;l j (X = Ac; isomer l),84194-72-9; l j (X = Ac; isomer 2), 84194-73-0; l k (X = H), 4187-87-5; l k (X = Ac), 16169-88-3; 2a (X = H; isomer l), 42070-92-8;2a (X = H; isomer 2), 51154-54-2;2a (X = Ac; isomer l),84194-74-1;2a (X = Ac; isomer 2), 84194-75-2;2b (X = H), 6531-13-1; 2b (X = Ac), 19759-27-4;2~ (X = H), 3319-15-1;2~ (X = Ac), 945-89-1;2d (X = H; isomer l),1517-71-1;2d (X = H; isomer 2), 2516-69-0;2d (X = Ac; isomer l),84194-76-3;2d (X = Ac; isomer 2), 84194-77-4;3 (X = H; isomer l), 13448-81-2;3 (X = H; isomer 21, 13448-80-1;3 (X = Ac), 55012-78-7;4 (X = H; isomer l),42177-25-3;4 (X = H; isomer 2), 15914-84-8;4 (X = Ac; isomer l),16197-94-7;4 (X = Ac; isomer 2), 16197-95-8; 5 (X = H; isomer l),52193-85-8;5 (X = H; isomer 2), 27544-18-9; 5 (X = Ac; isomer l),84194-78-5;5 (X = Ac; isomer 2), 8419479-6; 6 (X = H; isomer l),84194-80-9;6 (X = H; isomer 2), 84194-81-0; 6 (X = Ac; isomer l),84194-82-1;6 (X = Ac; isomer 2), 8419483-2; 7 (x= HI, 420864-4;7 (x= AC), 22426-24-0;8 (x= H), 2309-47-9; 8 (X = Ac; isomer l),84194-84-3;8 (X = Ac; isomer 2), 84194-85-4; 9a (X = H), 6351-10-6;9a (X = Ac), 26452-982;9b (X = H; isomer l),84275-489; 9b (X = H; isomer 2), 57089-40-4;9b/9c (X = Ac), 58540-44-6; 9c (X = H), 17496-18-3; 9d (X = H; isomer 11, 24867-97-8; 9d (X = H; isomer 2), 57018-62-9; 9d (X = Ac), 54553-64-9;9e/9f (X = H), 5400-80-6; %/9f (X = Ac), 84194-86-5; 9g/9h (X = H), 67864-28-2;9g/9h (X = Ac), 84194-87-6;10a (X = H), 529-33-9; 10a (X = Ac), 21503-12-8; 10b (X = H; isomer l),38157-18-5; lob (X = H; isomer 2), 65941-81-3; 10b/10c (X = Ac), 84194-88-7;1Oc (X = H), 32281-70-2;10d (X = H; isomer l),24867-99-0;10d (X = H; isomer 2), 84275-49-0;10d (X = Ac), 84194-89-8;1Oe (X = H; isomer l),84275-50-3;1Oe (X = H; isomer 2), 84275-51-4;lb/lOf (X = Ac), 84194-90-1;10f (X = H; isomer l),79465-07-9;10f (X = H; isomer 2), 84275-52-5; log (X = H; isomer I), 84194-91-2;lOg (X = H; isomer 2), 84194-92-3;10g/10h (X = Ac), 84194-93-4; 10h (X = H; isomer l),84194-94-5; 10h (X = H; isomer 2), 84194-95-6;11 (X 5: H), 84194-96-7;11 (X = Ac), 84194-97-8;12 (X = H), 7508-20-5;12 (X = Ac), 84194-98-9; 13 (X = H; isomer l),79465-08-0; 13 (X = H isomer 2), 27549-85-5; 13 (X = Ac; isomer l), 84275-53-6; 13 (X = Ac; isomer 2), 65915-66-4.
Et hylaluminum Dichloride Catalyzed Ene Reactions of Aldehydes with Nonnucleophilic A1kenes Barry B. Snider* and Gary B. Phillips Department of Chemistry, Brandeis University, Waltham, Massachusetts 02254 Received July 13, 1982 Ethylaluminum dichloride, which is a strong Lewis acid and a proton scavenger, catalyzes the ene reactions of aliphatic aldehydes with nonnucleophilic alkenes. Higher aldehydes give good yields of ene adducts with terminal alkenes. Formaldehyde gives good yields of adducts with electron-deficient alkenes. This reaction hae been used for the synthesis of recifeiolide, ricinelaidic acid, and the insect pheromones (E,E)-8,10-dodecadienyl acetate and (E)-9,11-dodecadienyl acetate.
The ene reaction of carbonyl compounds with alkenes is a potentially valuable route to homoallylic a1cohols.l With reactive, i.e., electron deficient, aldehydes such as chloral or methyl glyoxylate,these reactions can be carried out thermally at 100-200 "C. Formaldehyde reacts with alkenes at 180 O C , with optimal yields often being obtained when acetic acid-acetic anhydride is the solvent.2 In the (1) (a) Hoffmann, H. M. R. Angew. Chem., Znt. Ed. Engl. 1969,8,556. (b) Snider, B. B. Acc. Chem. Res. 1980, 13, 426 and references cited therein.
presence of acid, aldehydes and alkenes undergo the Prins reaction3 Ene-type adducts have been obtained with Lewis acid catalysis from formaldehyde and alkenes which can give a tertiary carbenium (2) (a) Blomquist, A. T.; Passer, M.; Schollenberger, C. S.; Wolinsky, J. J. Am. Chem. SOC.1967, 79, 4972. (b) Blomquist, A. T.; Verdol, J.; Adami, C. L.; Wolinsky, J.; Phillips, D. D. Ibid. 1967, 79,4976. (c) Agami, C. Ann. Chim. (Paris) 1966,10,26. (d) Agami, C.;Prevost, C. C.R. Hebd. Seances Acad. Sci., Ser. C 1966,263, 163. (3) Adams, D. R.; Bhatnagar, S. P. Synthesis 1977,661 and references cited therein.
0 1983 American Chemical Society
J. Org. Chem., Vol. 48,No. 4, 1983 465
Ethylaluminum Dichloride Catalyzed Ene Reactions We have recently found that dimethylaluminum chloride (Me2A1C1) in equivalent or greater amounts is a useful catalyst for the ene reactions of aliphatic and aromatic aldehydes and leads to improved yields of ene adducts from f~rmaldehyde.~ Me2AlCl is a mild Lewis acid and a proton scavenger.6 A typical problem with Lewis acid catalyzed ene reactions of aldehydes is that the alcoholLewis acid complex produced in the reaction is susceptible to solvolysis and is a strong protic acid capable of protonating the double bond of the ene adduct or alkene. The alcohol-Me2A1C1 complex formed in the ene reaction decomposes rapidly to give methane and a nonbasic aluminum alkoxide which does not undergo these side react i o n (see ~ ~ eq ~ ~1). R
R
P
R
The methyl group of Me2AlClcan also act as a nucleophile.' The addition of a methyl group to formaldehyde is a problem only with the most nonnucleophilic alkenes. The addition of a methyl group to aldehydes other than formaldehyde is a significant side reaction with all but the most nucleophilic alkenes and precludes the use of monoand 1,2-disubstituted alkenes in Me2A1C1-catalyzedene reactions with these aldehyde^.^ We therefore chose to examine the reactions of formaldehyde and higher aldehydes with nonnucleophilic alkenes using ethylaluminum dichloride (EtA1Cl2)as a Lewis acid catalyst. EtAIClz is a stronger Lewis acid than Me2A1C1;the increased Lewis acidity results in a less nucleophilic but still basic alkyl group.
Results and Discussion Acetaldehyde. Treatment of terminal alkenes with acetaldehyde and Me2A1Clgives only 2-propanol and recovered alkene; the methyl group of Me2AlClis more nucleophilic than the alkene. Use of EtA1C12, a stronger Lewis acid with a less nucleophilic alkyl group, gives a moderate yield of ene adduct (see eq 2). Reaction of
la, R b, R c, R d, R e, R
= C,H,
= C,,H,,
= (CH,),CO,H = (CH,),OAc = (CH,),CO,H
OH
2a-d, R' = CH, e, R = C,H,,
1-hexene (la) with 2 equiv of acetaldehyde (as paraldehyde) and 2 equiv of EtAIClz for 6 min at 0 "C gives a 35%
yield of 4-octen-2-01(2a) as an 84:16 E-Z mixture. Since the volatility of l a prevents recovery of starting alkene, the reaction with 1-tetradecene (lb) was examined. Use of 1 equiv of acetaldehyde and 1 equiv of EtAlC12gives a 64% yield of recovered lb and a 28% yield of 2b as a 81:19 E-Z mixture. Use of 2 equiv of acetaldehyde and 2 equiv of EtAlC12gives a 56% yield of 2b, a 5% yield of recovered lb, and polymer. These reactions are very sensitive to reaction conditions. At longer reaction times (30 min) extensive polymer formation results. The most consistent results are obtained with EtAlC12in CH2C12solution. This reaction was used for a very short and efficient synthesis of recifeiolide, a macrolide isolated from the fungus Cephalosporium r e ~ i f e i . ~Reaction ,~ of 9-decenoic acid with 1equiv of acetaldehyde and 2.2 equiv of EtAlC12 for 1 h at 0 "C gives a 66% yield of 11-hydroxy-8-dodecenoic acid (2c) as a 4:l E-Z mixture. Similar mixtures, synthesized by much longer routes have been separated, and the E isomer has been lactonized to give recifeiolide.9a'Qb (E,E)-8,10-Dodecadien-l-yl acetate (3) is a major component of the female sex pheromone of the green budworm moth (Hedya rubeferena).1° The corresponding alcohol is the pheromone of the codling moth (Laspeyresia pomonella).l' Reaction of 9-decen-l-yl acetate ( l a ) with acetaldehyde (1.1 equiv) and EtAlC12 (2.2 equiv) for 1 h a t 0 "C gives 26% (87% based on recovered ld) of 2d as a 4.4:l E-Z mixture. Treatment of 2d with (o-nitropheny1)selenylcyanateand tri-n-butylphosphine gives the aryl selenide13which is oxidized with H202to the selenoxide which eliminated4to give an 82% yield of a 78:22 mixture of 3 and 4 (eq 3) which are separated by prepa-
3
(3)
-(CH2170*c
4
rative GC. Fragmentation of homoallylic selenoxides generally shows a preference for formation of a conjugated diene and an (E)-alkene.15 The moderate selectivity obtained here results from competing preference for formation of a terminal alkene.15 The selectivity is greater than that reported for the pyrolysis of 4-penten-2-yl acetate.16 Higher aldehydes are also suitable substrates. Reaction of 10-undecenoic acid (le) with 1 equiv of heptanal and (8) (a) Vesonder, R. F.; Stodola, F. H.; Wickerham, L. J.; Ellis, J. J.; Rohwedder, W. K. Can. J. Chem. 1971,49,2029. (b) Vesonder, R. F.; Stodola, F. H.; Rohwedder, W. K. Can. J. Biochem. 1972,50,363. (9)For previous syntheses see: (a) Carey, E. J.; Ulrich, P.; Fitzpatrick, J. M. J. Am. Chem. SOC. 1976,98,222. (b) Gerlach, H.; Oertle, K.; Thalmann, A. Helu. Chim. Acta 1976,59,755.(c) Narasaki, K.;Yamaguchi, M.; Mukaiyama, T. Chem. Lett. 1977, 959. (d) Utimoto, K.; Uchida, K.; Yamaya, M.; Nozaki, H. Tetrahedron Lett. 1977,3641. (e) Tsuji, J.; Yamakawa, T.; Mandai, T. Ibid. 1978,565. (0 Trost, B. M.; Verhoeven, T. R. J. Am. Chem. Sac. 1980,102, 4743. (9) Schreiber, S. J. Am. Chem. SOC. 1980.102.6163. (10)Frerot, B.;Priesner, E:; Gallois, M. Z. Naturjorsch., C: Biochem., Biophys., Biol. Virol. 1979,346,1248. (11)Roelofs, W.L.;Comeau, A.; Hill, A.; Milicevic, G. Science 1971, 174. 297.
- - - I
(4)(a) Blomquist, A. T.; Himics, R. J. J. Org. Chem. 1968,33,1156. (b) Addy, L.E.; Baker, J. W. J. Chem. SOC. 1953,4111.(c) Yang, N. C.; Yang,D.-D. H.; Ross, C. B. J. Am. Chem. SOC.1959,8I,133. (5)(a) Snider, B. B.; Rodini, D. J.; Kirk, T. C.; Cordova, R. J. Am. Chem. SOC.1982,104,555.(b) Snider, B. B.; Rodini, D. J. Tetrahedron Lett. 1980,21, 1815. (6)Snider, B. B.; Rodini, D. J.; Karras, M.; Kirk, T. C.; Deutsch, E. A.; Cordova, R.; Price, R. T. Tetrahedron 1981,37,3927. (7)Mole, T.; Jeffery, E. A. "Organoduminum Compounds"; Elsevier: Amsterdam, 1972.
(12)For previous syntheses see: (a) Reference 11. (b) Descoins, C.; Henrick, C. A. Tetrahedron Lett. 1972,2999. (c) Mori, K. Tetrahedron 1974,30,3807.(d) Samain, D.; Descoins, C.; Commercon, A. Synthesis 1978,388. (e) Bestmann, H. J.; Siiss, J.; Vostrowsky, 0. Tetrahedron Lett. 1978,3329. (f) Henrick, C. A. Tetrahedron 1977,33, 1845. (13)Grieco, P.A.; Gilman, S.; Nishizawa, M. J. Org. Chem. 1976,41, 1485. (14)Sharpless, K.B.; Young, M. W. J. Org. Chem. 1975,40,947. (15)Reich, H. J.; Shah, S. K. J. Am. Chem. SOC.1975,97,3250. (16)Emovon, E. U.; Maccoll, A. J. Chem. SOC.1964,227.
466 J. Org. Chem., Vol. 48, No. 4, 1983 2.2 equiv of EtAlC1, gives a 41% yield of a 4:l mixture of ricinelaidic acid and ricinoleic acid. Ricinoleic acid has been synthesized by much longer routes." Ricinelaidic acid has not been previously synthesized. A second equivalent of EtA1C12 is needed in the ene reactions of lc-e due to the presense of basic functional groups. The acid is converted to the dichloroaluminum carboxylate with loss of ethane. Similarly, alcohols (vide infra) are converted to dichloroaluminum alkoxides. Therefore, neither alcohols nor acids need to be protected in these reactions. Use of EtAlC12as a catalyst does not allow ene adduct to be obtained from acetaldehyde and cyclohexene or cis-4-octene and leads to lower yields of adduct than MezAIClfrom acetaldehyde and 2,3-dimethyl-2-buteneor 2-methyl-2-butene. All reactions with benzaldehyde and EtAlCl, were unsuccessful. Formaldehyde. H2C=O-Me&lC1reacta with all simple alkenes! The introduction of functionality into the alkene causes two problems. Most functional groups are more basic than formaldehyde so that a second equivalent of Lewis acid must be used, and the resulting functional group-Lewis acid complex is inductively electron withdrawing which decreases the nucleophilicity of the double bond. The reactions of 5-hexen-1-yl acetate (5b) are typical. The acetate group, which is more basic than formaldehyde, complexes to the first equivalent of Lewis acid. This complex is sufficiently electron withdrawing to reduce the nucleophility of the double bond toward formaldehyde beneath that of the methyl group of Me2A1C1. Treatment of 5b with 1 equiv of paraformaldehyde and 2 equiv of MezAICl gives no ene adduct and an 81% yield of recovered 5b. Use of 2 equiv of EtA1C12,a stronger Lewis acid with a less nucleophilic alkyl group, gives a 70% yield of 7-acetoxy-3-hepten-1-01as a 72~28E-Z mixture. 5-Hexen-1-01 (5a) reacts with alkylaluminum halides with loss of an alkane to give an alkoxyaluminum compound which has a weaker effect on the nucleophilicity of the double bond than the 5b-Lewis acid complex. Reaction of 5a with 1 equiv of paraformaldehyde and 2 equiv of Me&lCl gives a 32 % yield (63% based on recovered 5a) of 6a (eq 4) as a 8515 E-Z mixture. Use of 2 equiv of
5
6
a,n=3;R=H b, n = 3; R = Ac c , n = 8 ; R = Ac
I
EtAlC12 gives a 59% yield of 6a as a 69:31 E-Z mixture, but no 5a is recovered. The E-Z ratios of 6a obtained with Me2AlCland EtAlC12are typical of results obtained with terminal alkenes, formaldehyde, and these Lewis acid catalysts. A short synthesis of 9,ll-dodecadien-1-yl acetate (7), the female sex pheromone of the red-bollworm moth Oiparopsis c a ~ t a n e a , ' ~utilizes J~ this chemistry. Reaction of (17) (a) Crombie, L.; Jacklin, A. G. J. Chem. SOC.1955, 1740. (b) Bailey, A. S.; Kendall, V. G.; Lumb, P. B.; Smith, J. C.; Walker, C. H. Ibid. 1957,3027. (c) Gender, W. J.;Abrahams, C. B. J . Am. Chem. SOC.1958, 80, 4593.
(18) Nesbitt, B. F.; Beevor, P. S.; Cole, R.A.; Lester, R.; Poppi, R. G. J. Insect Physiol. 1975, 21, 1091.
Snider and Phillips Table I. Ene Reactions of CH,O.EtAICl, with cis- Alkenol Derivatives reactant v
I
C
H
z
I
o
y
% yield of R
y 1 : ; I . R
CHZW
8
9
3H
10 a,
n = 1, R = OH
b,n=l,R=OAc C, n = 2, R = OH d, n = 2, R = OAc e, n = 3, R = OH f , n = 3, R = OAc
g,n=3,R=H
43 59 63 64 50 81 75
9 / 1 0 ratio
1oo:o 1oo:o 80:20 82:18
67:33 69:31 44: 56
10-undecen-1-ylacetate (5c) with paraformaldehyde (1.1 equiv) and EtAlC12(2.2 equiv) gives a 72% yield of a 7822 E-Z mixture of 12-hydroxy-9-dodecen-1-yl acetate (6c; eq 4). Treatment with (0-nitropheny1)selenyl cyanate and tri-n-b~tylphosphinel~ followed by oxidation with H2O2l5 gives a 65% (from 5c) yield of 7 (eq 5) as a 78~22E-Z mixture, very similar to the naturally occurring mixture.Is The effect of electron withdrawal by the aluminum alkoxide and the acetate-EtA1C12 complex on the regiochemistry of addition of formaldehyde to 8 is shown in Table I. The major product results from formation of the carbenium ion furthest from the electron-withdrawing substituent. The absence of 10a and 10b may be due to the instability of allylic alkoxides and acetates to the reaction conditions. Although the inductive effect drops off with increasing chain length, it is still substantial for 8e and 8f as determined by comparison to the reference compound 8g, which shows preferential attack at the least hindered site to give the most stable carbenium ion. The formation of pure E adducts is a consequence of steric hindrance in the ene reaction of cis-alkenes. Reaction of 8c with only 1equiv of EtAlCl, gives results comparable to those shown in Table I. Reaction of 8d with only 1 equiv of EtAlC1, gives a 5 % yield of an 82:18 mixture of 9d and 9e. Thus the alkoxyaluminum dichloride formed from 8c functions as a Lewis acid while the acetate-ethylaluminum dichloride complex formed from 8d cannot. The A1 component of the female sex pheromone of the California red scale (13)20121 can be easily made by using an ene reaction with citronellyl acetate (11) as the key step. We reported the first synthesis of 13 using an ene reaction of 11 and methyl propiolate to attach the side chain. An attractive alternate involves reaction of 11 with paraformaldehyde to give 12a which could be coupled with an allyl moiety to give 13. Reaction of 11 with paraformaldehyde and 2 equiv of MezAIClgives a quantitative yield of 12a as a ca. 1:l mixture of diastereomers. Due to the nucleophilicity of the trisubstituted double bond, Me2AlCl is the Lewis acid of choice. Tosylation of 12a and dis(19) For previous syntheses see: (a) Nesbitt, B. F.; Beevor, P. S.; Cole, R. A.; Lester, R.; Poppi, R. G. Tetrahedron Lett. 1973, 4669. (b) Mori, K. Tetrahedron 1974 30, 3807. (c) Yasuda, A.; Tanaka, S.; Yamamoto, H.; Nozaki, H. Bull. Chem. SOC.Jpn. 1979,52, 1752. (d) Babler, J. H.; Martin, M. J. J. Org. Chem. 1977,42,1799. (e) Mandai, T.; Yasuda, H.; Kaito, M.; Tsuji, J.; Yamaoka, R.; Fukami, H. Tetrahedron 1979,35,309. (0 Wollenberg, R. H.; Perks, R. Tetrahedron Lett. 1979, 297. (g) Bestmann, H. J.; Suss, J.; Vostrowsky, 0. Ibid. 1979, 2467. (9) Babler, J.H.; Invergo, B. J. J. Org. Chem. 1979,44, 3723. (h) Cardillo, G.; Orena, M.; Porzi, G.; Sandri, S. Gazz. Chim. Ital. 1980, 110, 523. (20) Roelofs, W. L.; Gieselmann, M. J.; Card& A. M.; Tashiro, H.; Moreno, D. S.; Henrick, C. A.; Anderson, R.J. J . Chem. Ecol. 1978,4,211. (21) (a) Snider, B. B.; Rodini, D. J. Tetrahedron Lett. 1978,1399. (b) Anderson, R. J.;Adams, K. G.; Chinn, H. R.; Henrick, C. A. J. Org. Chem. 1980, 45, 2229.
Ethylaluminum Dichloride Catalyzed Ene Reactions
3 No1
11
r - a l l y l ntckel mdlde
12a, X = OH b, X = I
14
13
placement of the tosylate with sodium iodide in acetone gives 12b in 87% yield. Coupling of 12b with a-allylnickel iodide22 gives a complex mixture containing -25% of 13, -25% of 14 and numerous minor products. The structure of 13 was proven by spectral and chromatographic comparison with an au-
thentic sample. Reaction of the crude mixture with tetracyanoethylene in THF converted 14 to the polar DielsAlder adduct. Unfortunately, due to the presence of numerous minor impurities, this did not alleviate the problem of purification of 13. Reaction of 12b with a-allylnickel bromide converted 12b t o the corresponding bromide. Coupling of a-allylnickel halides with both allylic and saturated halides has been extensively studied.22The use of homoallylic halides has not been reported although reaction of a-methallylnickel bromide with cyclopropylcarbinyl bromide gives a 39% yield of 2-methyl-1,6-heptadiene.23 Elimination to the diene 14 is consistent with the radical chain mechanism which has been proposed.24 The minor produds may be derived from 14 via conversion to an allylic halide and coupling t o give a 1,5-diene.
Conclusion EtAIClzis a uniquely useful catalyst for the ene reaction of aldehydes with nonnucleophilic alkenes. T h e utility of this reaction has been demonstrated by the synthesis of the insect pheromones 3,7,and 13,recifeiolide, and ricinelaidic acid.
Experimental Section Me2AlClwas purchased from Texas Alkyls, Inc., as a 1.14 M solution in heptane. EtAlC12was purchased from the same source both neat and as a 1.54 M solution in heptane or from Alfa as a 1.5 M solution in hexane. Neat EtAlC12was diluted with CH2C12 to give a 3.8 M solution. CH2Clzwas distilled from CaHP Alkenes and paraformaldehyde were used without purification. 9-Decenoic acid, 9-decen-1-01, 10-undecen-1-01,cis-3-hexen-1-01,cis-4-hexen-1-01, and cis-5-octen-1-01were obtained from Bedoukian Research, Inc. Acetates were obtained from alcohols by treatment with acetic anhydridepyridine. 10-Undecenoic acid was obtained by Jones oxidation of 10-undecen-1-01. GC analyses were carried out on a 10 f t X 0.25 in. Carbowax 20M column at flow rates of 40-50 mL/min. Analyses were performed by Galbraith laboratories. General Procedure. The Lewis acid solution was added via syringe to a solution of the aldehyde and alkene in CH2C12in a flame-dried flask under nitrogen which was cooled in an ice bath. The reaction mixture was stirred at 0 OC for the specified time (22) Semmelhack, M.F. Org. React. 1972,19, 115-199. (23) Semmelhack, M.F. Ph.D. Thesis, Harvard University, 1967. (24) Hegedus, L. S.;Miller, L. L. J. Am. Chem. SOC.1975, 97, 459.
J. Org. Chem., Vol. 48, No. 4, 1983
467
and was quenched by dilution with ether followed by slow addition of water until gas evolution ceased. The solution was stirred until the precipitated alumina dissolves. The organic layer was separated, and the aqueous layer was washed twice with ether. The combined organic layers were washed with brine, dried (MgSO,), and evaporated in vacuo. Diols and hydroxy acids were isolated by extraction with CH2C12and dried (Na2S04). 4-Octen-2-01(2a).25 Reaction of 1-hexene (0.17 g, 2 mmol), paraldehyde (0.18 g, 4.2 mmol of acetaldehyde), and EtAIClz (1.1 mL of 3.8 M in CH2C12,4.2 mmol) in 6 mL of CH2C12at 0 "C for 6 min gave 252.3 mg of crude product. Flash chromatography on silica gel (2:l hexane-ether) of 234 mg of the crude product gave 83 mg (35%) of 2a an 84:16 E-2 mixture: 'H NMR (CCl,) d 5.1-5.6 (m, 2), 3.69 (tq, 0.16 X 1,J = 6, 6 Hz), 3.68 (tq, 0.84 X 1,J = 6, 6 Hz), 3.13 (s, 1,OH), 1.8-2.3 (m, 4), 1.38 (tq, 2, J = 7, 7 Hz), 1.13 (d, 0.16 X 3, J = 6 Hz), 1.12 (d, 0.84 X 3, J = 6 Hz), 0.89 (t, 3, J = 7 Hz); GC (140 "C) tR = 7.6 ( E ) ,8.6 (2) min. 4-Hexadecen-2-01(2b). Reaction of 1-tetradecene (lb; 0.39 g, 2.0 mmol), paraldehyde (0.09 g; 2.1 mmol of acetaldehyde), and in 6 mL of CH2C12 EtAlC12(0.58 mL of 3.8 M in CH2C12,2.2 "01) for 6 min gave 429 mg of crude product. Flash chromatography on silica gel (2:l hexane-ether) gave 248 mg (64%) of recovered lb and 130 mg (28%) of 2b as a 8k19 E-2 mixture: 'H NMR (CC,) 6 5.1-5.6 (m, 2), 3.70 (tq, 0.19 X 1,J = 6, 6 Hz), 3.68 (tq, 0.81 X 1, J = 6 , 6 Hz), 1.9-2.3 (m, 5 ) , 1.29 (br s, 18), 1.12 (d, 0.19 X 3, J = 6 H), 1.11 (d, 0.81 X 3, J = 6 Hz), 0.88 (t, 3, J = 6 Hz); GC (170 "C) t R = 73.7 (E),80.0 (2)min. Anal. Calcd for C16H32O: C, 79.93; H, 13.42. Found: C, 79.73; H, 13.55. Reaction of 1-tetradecene (0.39 g, 2.0 mmol), paraldehyde (0.18 g, 4.2 mmol of acetaldehyde), and EtAIClz (1.1mL of 3.8 M in CH2C12,4.1 mmol) in 6 mL of CH2C12for 6 min gave 489 mg of crude product. Purification of 487 mg as described above gave 266 mg (56%) of 2b as a 81:19 E-2 mixture and 140 mg of a nonpolar mixture of l b (
