Cross-condensation reactions of cycloalkanones with aldehydes and

Cross-condensation reactions of cycloalkanones with aldehydes and primary alcohols under the influence of zirconocene complexes. Tatsuya Nakano, Shinj...
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J. Org. Chem. 1987,52, 2239-2244 4.66 (d, J = 0.8 Hz, 2 H) in 36. Ethyl 2-Acetoxy-2-propen-1-yl-3,3-d2 Carbonate (48). 'H NMR spectral data were the same as those of 36 except for the following signals: 6 4.66 (s,2 H) in the place of the signals 6 5.11 (dt, J = 2.0, 0.8 Hz, 1 H), 5.03 (d, J = 2.0 Hz, 1 H), 4.66 (d, J = 0.8 Hz, 2 H) in 36. 1-Octen-2-yl benzoate (49): colorless liquid; bp 80 "C (0.3 mmHg); IR (neat) 1667,1732 cm-'; 'H NMR (CDC13)6 8-09(dm, J = 8.0 Hz, 2 H), 7.25-7.59 (m, 3 H), 4.86 (d, J = 1.5 Hz, 1 H),

2239

4.83 (d, J = 1.1Hz, 1 H), 2.34 (t, J = 7.1 Hz, 2 H), 1.16-1.74 (m, 8 H), 0.88 (t, J = 5.9 Hz,3 H); '% NMR (CDC1,) 6 164.5 (s), 156.8 (s), 133.2 (d), 129.9 (d), 129.4 (s), 128.4 (d), 101.2 (t),33.5 (t),31.6 (t),28.8 (t),26.6 (t),22.6 (t),14.0 (9);MS, m l z 232 (M+). Anal. Calcd for CI5HmO2:C, 77.55; H, 8.68. Found: C, 77.47; H, 8.70.

Acknowledgment. This work was partly supported by the Ministry of Education, Science and Culture (No. 61225012 and 61550634).

Cross-CondensationReactions of Cycloalkanones with Aldehydes and Primary Alcohols under the Influence of Zirconocene Complexes Tatsuya Nakano, Shinji Irifune, Shigetoshi Umano, Akihiro Inada, Yasutaka Ishii,* and Masaya Ogawa* Department of Applied Chemistry, Faculty of Engineering, Kansai University, Senriyama, Suita, Osaka 564, Japan Received June 2, 1986

Under the influence of zirconocene complex, Cp2ZrH2(1) or Cp,Zr(O-i-Pr), (9), cycloalkanones 2 condensed directly with aliphatic aldehydes 3 or primary alcohols 7 to form 2-alkylidenecycloalkanones4 or 2-alkyl-2cycloalken-1-ones 8, respectively, in fair to substantial yields. The selectivity of the cross-condensations was slightly improved by using 1 in combination with a metal salt such as NiC1,. Dihydrojasmone (13) was synthesized in 35% yield by one-step reaction from the commercially available 3-methylcyclopentanone (2e) with pentanol (7b) in the presence of 1 and NiC12.

Recently we reported that dicyclopentadienylzirconium dihydride, Cp2ZrH2(1), catalyzes the hydrogen-transfer reaction from alcohols to carbonyl compounds: Le., Meerwein-Ponndorf-Verley (MPV) type reduction of carbonyl compounds and Oppenauer (OPP) type oxidation of alcohols simultaneously proceeded under the influence ~ alcohols, which are of catalytic amount of 1 . l ~Primary difficult to be oxidized by the OPP method using aluminum alkoxides, were easily oxidized by 1 to the corresponding aldehydes.' Furthermore, diols involving both primary and secondary hydroxy groups were oxidized chemoselectivelyto the corresponding hydroxy aldehydes.2 In these reactions, the carbonyl compound having no ahydrogen such as benzophenone or benzaldehyde served as a good hydrogen acceptor, while acetone, considered to be a suitable hydrogen acceptor in the OPP oxidation, was inadequate owing to the aldol condensation of acetone itself. In the course of the study, it seemed of interest to investigate the cross-condensation between cycloalkanones and aldehydes, since the zirconocene dihydride 1was found to catalyze aldol condensation of ketones. Thus, cycloalkanones 2 were allowed to react with aliphatic aldehydes 3 under the influence of 1 to give cross aldol condensation products, 2-alkylidenecycloalkanones 4, in substantial yields with small amounts of self-condensates (eq 1). Despite the fact that primary alcohols 7 in the presence of a carbonyl compound lacking a-hydrogen were only converted to the corresponding aldehydes by 1, the same reaction of 7 employing cycloalkanones 2 as hydrogen acceptor in place of benzophenone or benzaldehyde gave

-C5-l 1 t NiClz

4a:n=2. R ~ = H b : n = 2 . W=CH3 C: n = 2 , R1=C3H7

d: n . 2 . R ~ = C ~ H B e:n=2.R1=C+Ii5 t : n = 2 .R ~ = c ~ H ~ ~ g : n = 2 , R':CH(CH& h : n = l . R1=C4Hg i : n =1. R1=C7H15 U

II

5a:n.Z b:n=l

6a: R1=CH3.R2=H b: R1=C3H7,R2=C2H5 C: R1=QHg,R2=C3H7 d: R'=C7H~~,R2"2&l13 e: R ~ = C ~ HR, *~=. Q H ~ ~

cross-condensation products 2-alkyl-2-cycloalken-1-ones 8 in fair yields (eq 2).

9

2a:n.Z b:n=l

0

7a:R3sCC3n7 b:R =C4H9 C: R3=C$-115 d: R3=CgH1g e: Ri=C&I31 f: R =CH(CH&

(1) Ishii, Y.; Nakano, T.;Inada, A.; Kishigami, Y.; Sakurai, K.; Ogawa, M. J. Org. Chem. 1986,51, 240. (2) Nakano, T.; Terada, T.; Ishii, Y.; Ogawa, M. Synthesis 1986,774.

0022-3263/87/1952-2239$01.50/0

+

0 1987 American Chemical Society

6 a : n = 2 , R3=C3H7 b : n = 2 . R3=C4H9 C:n=2. R3=C7Hi5 d: n = 2 , R3=CgHls a : n = 2 . R3=Ci5H3i f : n = 2 , R3=CH(CH3)2 g : n = 1 , R3=C4Hs h : n = l . R3=C7Hi5 i :n = 1, @=CsHls

2240 J. Org. Chem., Vol. 52, No. 11, 1987

Nakano et al.

Table I. Cross Aldol Condensation of Cyclohexanone (2a) with Various Aldehydes 3a-g Catalyzed by Cp2ZrH, ( 1 ) and NiCl2" product, yield ( % ) b 4c 6d run aldehyde 5aC 3a 3b

le

2 3f

3c 3d

4 5 68 7

3e 3f 3g

8

9

4a 32 (31) 4b 71 (71) 66 (62) 4c 73 (70) 4d 80 (73) 76 (71) 4e 74 (74) 4f 74 (68) 4g 75 (73)

37 (45) 9 (22) 10 (21) 8 (12) 8 (11)

6 (18) 9 (11)

9 (20) 13 (18)

6a 11 (14) 6 (14) 6b 12 (15) 6c 7 (12) 6 (14) 6d 4 (7) 6e 6 (13)

" A mixture of 2a (10 mmol) and 3 (10 mmol) was allowed to react under the influence of 1 (0.2 mmol) and NiClz (0.2 mmol) at 130 "C for 8 h. Determined by VPC. Based on the starting 2a. dBased on the starting 3. e 1,3,5-Trioxane (5 mmol) was used instead of formaldehyde 3a. f2,4,6-Trimethyl-1,3,5-trioxane (5 mmol) was used instead of acetaldehyde 3b. 99 (0.2 mmol) was used instead of 1.

Unsaturated cyclic ketones 4 and 8 prepared herein are useful intermediates in the synthesis of several natural Especially, 2-alkyl-2-cyclopenten-1-ones 8g-i are of interest as synthetic precursors of jasmones in the perfumery industry. Usually, these compounds, 4 and 8, are prepared by cyclization of dicarbonyl corn pound^^^^ or by rearrangement of a wide variety of cyclic ketone^.^^^

Results and Discussion (A) Zirconocene Complex Catalyzed Cross Aldol Condensation of Cycloalkanones with Aldehydes. An equimolar mixture of cyclohexanone (2a) with aliphatic aldehydes 3a-g was allowed to react under the influence of 1 and NiC12 (each 0.02 equiv) at 130 "C for 8 h without solvent, providing 2-alkylidenecyclohexanones4, which are useful precursors in the syntheses of several natural product^,^^^^ in about 3240% yields (Table I). The reaction of 2a with formaldehyde (3a) generated from 1,3,5-trioxanein the system took place with difficulty to form 2-methylidenecyclohexanone (44 in moderate yield (32%) (run 1). But acetaldehyde (3b) generated from 2,4,6-trimethyl-1,3,5-trioxane reacted easily with 2a, giving 2-ethylidenecyclohexanone (4b) in 66 % yield, and higher aldehydes 3c-g also condensed with 2a to give the corresponding condensation products 4c-g in 73-80% yields. In these reactions, the aldol condensation product of 2a, 2-(l-cyclohexenyl)cyclohexanone(5a), was formed in the range of 6-1370, except for the reaction of 2a with 1,3,5trioxane (run I),and aldol condensates 6a-e of aldehydes 3b-f were in 4-12% yields. In the reaction with 1,3,5trioxane, 5a was formed in 37 % yield. The stereochemistry of the cross-condensates 4b-g at the alkylidene site was identified as the E configuration by comparison of their spectral data with those of literature values." ~~

~~~

(3) (a) Harayama, T.; Cho, H.; Inubushi, Y. Tetrahedron Lett. 1975, 16, 2693. (b) Jung, M. E.; Pan, Y. G.; Rathke, M. W.; Sullivan, D. F.; Woodbury, R. P. J . Org. Chem. 1977, 42, 3961. (4) Fuhrhop, J.; Penzlin, G. ORGANIC S Y N T H E S I S , Concepts, Methods, Starting Materials; KlambbDruck GmbH.: West Berlin, 1983; p 247. (5) Yamashita, M.; Matsumiya, K.; Tanabe, M.; Suemitsu, R. Bull. Chem. SOC.Jpn. 1985,58, 407. (6) Conia, J. M.; Amice, P. Bull. Chirn. SOC.Fr. 1968, 3327. (7) Conrad, P. C.; Fuchs, P. L. J. Am. Chem. SOC.1978, 100, 346. (8) Cooper, G . K.; Dolby, L. J. Tetrahedron Lett. 1976, 17, 4675. (9) Kozikowski, A. P.; Stein, P. D. J. Am. Chem. SOC.1982,104,4023. (10) Buchi, G.; Coffen, D. L.; Kocsis, K.; Sonnet, P. E.; Ziegler, F. E. J . Am. Chem. SOC. 1966,88, 3099. (11)Crandall, J. K.; Arrington, J. P.; Hen, J. J . A m . Chern. SOC.1967, 89, 6208.

Table 11. Cross Aldol Condensation of Cyclohexanone (2a) with Octanal (3e) by Some Group IVA Metal Complexes and Lewis Acids" vield.* % run catalyst 4e' 5aC 6dd 1 1 71 18 13 2e 1 + NiC1, 74 9 4 3 9 68 33 27 4e 9 + NiC1, 68 17 14 5 Cp,Zr(H)Cl 66 23 27 6 Cp,ZrC12 39 60 35 7 CpzTiC1, 37 63 37 8 Cp2HfClZ 37 29 22 9 ZrC1, 10 90 70 10 TiC1, 12 88 66 11 AlC13 11 89 63 12 NiCl, 3 13 9 13 p-CH3C6H4S03H tr 38 45 " A mixture of 2a (10 mmol) and 3e (10 mmol) was allowed to react under the influence of catalyst (0.2 mmol) at 130 "C for 8 h. Determined by VPC. Based on the starting 2a. Based on the starting 3e. e NiClz (0.2 mmol) was added to 1 (0.2 mmol).

Table 111. Cross Aldol Condensation of Cycloalkanones 2a,b with Aldehydes 3d,e or loa-c Catalyzed by CpzZrHz( 1 ) and NiCl," run cycloalkanone aldehyde product yield,b % 1 47 2b 3d 4d 65 2 3e 4i 2c 48 3 4j 2d 70 4 4k 70 2a 10a 3 1 la 4 llb 86 10b 1oc 1IC 84 5 2b 69 1Oa 1 Id 6 7 lob 1 le 71 1oc 8 llf 67 "A mixture of 2 (10 mmol) and 3 or 10 (10 mmol) was allowed to react under the influence of 1 (0.2 mmol) and NiC1, (0.2 mmol) at 130 "C for 8 h. bIsolated yield. Based on the starting 2a-d.

Although self aldol condensations have been achieved by the acid- or base-catalyzed reaction of ketones and aldehydes, there are substantial difficulties in cross aldol condensations between carbonyl compounds having an a-hydrogen. In the literature, formaldehyde 3a condenses with 2a in acidic or basic media, giving 2-methylidenecyclohexanone (4a) in substantial yields,12but in general, direct cross aldol reaction of cycloalkanones with aliphatic aldehydes is difficult to complete. These condensation products are usually obtained through the addition of cycloalkanone enamines to aldehyde^.^^^'^ For example, 2-pentylidenecyclohexanone(4d) has been prepared in 40% yield from the condensation of cyclopentanone (2b) with N,N-dimethylformamide dimethyl acetal at 110 "C for 12 h followed by treatment with n-BuLi in THF at -30 to 0 "C.13 Therefore, the present direct cross aldol reaction of cycloalkanones with aldehydes is a very attractive route to prepare 2-alkylidenecycloalkanones4. In Table 11, catalytic activities of several group IVA ,~ complexes and Lewis (group 4 in 1985 n ~ t a t i o n ) metal acids for the condensation of 2a with 3e are summarized. Among the zirconium complexes examined, 1 exhibited the highest selectivity for the cross-condensation,followed by Cp,Zr(O-i-Pr)2 (9)15and Cp,Zr(H)Cl. The selectivity (12) Nielsen, A. T.; Houlihan, W. J. Org. React. 1968, 16, 1.

(13) Abdulla, R. F.; Fuhr, K. H. J. Org. Chem. 1978, 43, 4248. (14) Birkofer, L.; Kim, S. M.; Engels, H. D. Chem. Ber. 1962,95, 1495. (15) In a similar manner as the complex 1,' dicyclopentadienylzirconium diisopropoxide (9) also catalyzed the MPV-type reduction of carbonyl compounds and the OPP-type oxidation of alcohols in good yields.

J. Org. Chem., Vol. 52, No. 11, 1987 2241

Cross-Condensation of Cycloalkanones of the cross-condensation by Cp2Zr(H)C1was comparable

to that by 9. Cp2ZrClzand Cp2TiClz,however, showed poor selectivity for the cross-condensation. Lewis acids, ZrCl,, TiC14,and AlCl,, prompted the self-condensations of ketones and aldehydes rather than the cross aldol reaction. p-Toluenesulfonic acid catalyzed exclusively self aldol condensations of 2a and 3e to give condensates 5a and 2-hexyl-2-decenal(sd) in 38% and 45% yields, respectively (run 12). The addition of NiCl, to the system effected to depress the self-condensation of ketones and aldehydes, and the selectivity of the cross-condensation was slightly improved (run 2). Cross-condensations of cycloalkanones 2a-d with some aldehydes are shown in Table 111. Cyclopentanone (2b) reacted with 3e to afford 2octylidenecyclopentanone (4i) in 65% yield with the self-condensate of 2b, 2-(l-cyclopentenyl)cyclopentanone (5b) (25%). In the reaction of 2-methylcyclohexanone (2c) with 3e, the condensation occurred exclusively a t the a'position of 2c to form the corresponding alkylidene compound, 2-methyl-6-octylidenecyclohexanone (4j), in 48% yield. 4-Methylcyclohexanone (2d) gave 4-methyl-2octylidenecyclohexanone (4k) in 70% yield with the selfcondensate of 2d (16%), 4-methyl-2-(4-methyl-l-cyclohexeny1)cyclohexanone (5c). 0

41

4k 0

5c

On the other hand, the condensation of 2a with benzaldehyde (loa) or furfural (lob) having no a-hydrogen afforded exclusively bis condensation products, 2,2'-dibenzylidenecyclohexanone (1la) (70%) and 2,2'-difurfurylidenecyclohexanone(1l b ) (86%), respectively (eq 3). In both reactions, no mono condensation product was U

0

b: n. 2 ,

f:

R4=m

n = 1 , R4=CH=CHC&l5

formed. Similarly, cinnamaldehyde (1Oc) underwent facile bis condensation with 2a to give 2,2'-dicinnamylidenecyclohexanone (1IC)in 84% yield without formation of the

Table IV. Cross-Condensation of Cycloalkanones 2a,b with Primary Alcohols 7a-f Catalyzed by CpzZrHz(1) and NiCl,a run ketone alcohol product yield,b % 48 (42) 7a 8a 1 2a 48 (38) 2 7b 8b 48 (37) 3 7c 8C 4 7d 8d 42 (30) 7e 8e 25 (16) 5 40 (26) 6 7f 8f 7 2b 7b 8g 44 (37) 8h 42 (33) 8 7c 9 7d 8i 40 (28)

A mixture of 2 (10 mmol) and 7 (10 mmol) was allowed to react under the influence of 1 (0.2 mmol) and NiClz (0.2 mmol) at 150 "C for 8 h. *Determined by VPC. Based on the starting 2a or 2b. Parentheses show the yield in the absence of NiC12.

mono condensation product. Cyclopentanone (2b) also reacted with aldehydes loa-c under the same conditions as above to provide the corresponding bis condensation products lld-f in 67-71% yields (runs 6-8). (B) Zirconocene Complex Catalyzed Cross-Condensation of Cycloalkanones with Primary Alcohols. Cross-condensations of cycloalkanones 2a,b with various primary alcohols 7a-f are summarized in Table IV. An equimolar reaction of 2a with 7a under the influence of catalytic amount of 1 and NiC1, (each 0.02 equiv) at 150 "C without solvent afforded cross-condensation product 2-butyl-2-cyclohexen-1-one (8a) in 48% yield. Pentanol (7b), octanol (7c), and decanol (7d) also reacted with 2a to afford the corresponding 2-alkyl-2-cyclohexen-1-ones 8b-d in 42-48% yields, but the reaction with hexadecanol (7e) took place with some difficulty to form 2-hexadecyl-2-cyclohexen-1-one(8e) (25% yield) and self-condensate 5a (11%yield) (run 5). 2-Methyl-1-propanol (7f) condensed with 2a to give 2-isobutyl-2-cyclohexen-1-one (8f) in 40% yield. In these reactions except for run 5 , about half of the starting 2a was available to the condensation with 7 and another half of 2a served as hydrogen acceptor for the oxidation of alcohol to aldehyde and was recovered as cyclohexanol (12). Therefore, the self-condensation of 2a occurred to give trace amounts of 5a. However, in run 5 a small amount (17%) of self-condensate 5a was formed. Cyclopentanone (2b) reacted with primary alcohols 7b-d under the same conditions as above, affording 2-alkyl-2cyclopenten-1-ones 8g-i (40-44% yields) (runs 7-9) with small amounts (6-10%) of self-condensate of 2b, 241cyclopenteny1)cyclopentanone (5b). The catalytic activities of several metal complexes and metal salts for condensation of 2a with 7a are summarized in Table V. In a similar manner as the cross aldol condensation of cycloalkanones with aldehydes, zirconocene complexes 1 and 9 showed relatively good activity for the cross-condensations with alcohols (runs 2 and l l ) , but Cp2Zr(H)C1 gave cross-condensate Sa in poor yield. CpzZrClzafforded mainly self-condensate of 2a, instead of 8a. The addition of a metal salt such as NiClZ,PdC12, or CuC1, to the system slightly improved the selectivity of the cross-condensation of 2a with 7a (runs 2, 5 , and 6). Particularly, NiClz was effective for the depression of the self-condensation of 2a, although its apparent role is uncertain. Other nickel salts were also examined, but the selectivity was not so improved (runs 3 and 4). Several Lewis acids, AlCl,, TiC14,and ZrCl,, which gave 8a in poor yields (runs 7-91, seem to prompt the self-condensation of 2a rather than the cross-condensation. In order to clarify the effect of molar ratio of the starting ketone and alcohol, reaction temperature, and quantity of

2242 J. Org. Chem., Vol. 52, No. 11, 1987 Table V. Cross-Condensation of Cyclohexanone (2a) with Butanol (7a) by Some Group IVA Metal Complexes and Lewis Acidsa yield: 70 run catalyst additiveb gad 5ad 6de 1 1 none 37 9 4 2 NiCl, 48 2 tr 3 NiBr, 43 5 4 Ni(acac), 40 5 6 4 5 PdCIz 43 7 2 6 CUCl, 40 5 4 7 AIC13 10 40 17 TiCI, 12 38 16 8 9 ZrC1, 12 32 13 10 9 none 36 6 4 11 NiC12 46 4 1 12 Cp2Zr(H)C1 none 16 24 9 13 NiC1, 20 26 4 14 Cp2ZrC1, none 10 38 7 15 NiClz 10 40 3 16 Cp,TiCl, none tr 56 tr 17 NiCl, tr 61 tr

Q A mixture of 2a (10 mmol) and 7a (10 mmol) was allowed to react under the influence of catalyst (0.2 mmol) at 150 "C for 8 h. bMetal salt (0.2 mmol) was added. CDeterminedby VPC. dBased on the starting 2a. eBased on the starting 7a. Table VI. Cross-Condensation of Cyclohexanone (2a) with Butanol (7a) Catalyzed by Cp2ZrHz(1) and NiClz under Several Conditions" molar ratio 2a/7a, run mmol/mmol temp, "C 8a 12 othersc 1 10/10 24 (11) 27 (28) 3 (2) 130 48 (42) 49 (50) 2 lopa 150 2 (6) 3 10120 17 (13) 82 (85) 150 l(2) 14 (12) 14 (16) 19 (25) 4 20110 150 5d 10/10 150 39 (37) 61 (57) 8 (6) l o / 10 23 (13) 26 (26) 27 (32) 6 200

" A mixture of 2a (10 mmol) and 7a (10 mmol) was allowed to react under the influence of 1 (0.2 mmol) and NiClz (0.2 mmol) for 8 h. bDetermined by VPC. Based on starting 2a. Parentheses show the yield in the absence of NiClZ. CSelf-condensationproducts were included. 1 (0.4 mmol) was used.

catalyst, cyclohexanone 2a was allowed to react with butanol 7a in the presence of 1 and NiClz under several reaction conditions ( T a b l e VI). The cross-condensation could be achieved in 48% yield by using equimolar amounts of 2a and 7a at 150 "C for 8 h under the influence of 0.02 equiv each of 1 and NiC12. The reaction using excess 7a ( 7 a / 2 a = 2/11 gave principally cyclohexanol(l2) by MPV-type reduction of 2a. The same reaction with a contrary ratio ( 7 a / 2 a = 1/2), however, resulted in 8a in low yield (14%), even t h o u g h the yield of 8a was expected to increase.16 2-Alkylidenecycloalkanones4 and 2-alkyl-2-cycloalken1-ones 8 are of interest from the synthetic point of view, since these compounds are key intermediates for the synthesis of some natural products such as 2-methyl-2c y c l ~ h e x e n - l - o n edihydrojasmone ,~~ ( 13),l8 and dihydro(16)Unfortunately, a detailed mechanism for the cross-condensation reaction is still uncertain, but the reaction possibly proceeds through isomerization of the cross aldol condensates given by condensation of cycloalkanones with aldehydes generated in situ by the zirconocene complex catalyzed OPP-type oxidation of alcohols. The heating of 2butylidenecyclohexanone (4c) at 150 O C far 8 h in butanol under the influence of 1 led to 2-butyl-2-cyclohexen-2-one (sa) in about 50% yield, but not thoroughly. In the above reaction, no isomerization occurred in the absence of alcohol. (17)(a) Conia, J. M.; Craz, A. L. Bull. Chim. SOC.Fr. 1960,1934.(b) Stotter, P.L.; Hill, K. A. J.Org. Chem. 1973,38, 2576. (c) Taber, D.F. J . Org. Chem. 1976,41,2649.(d) Shimizu,I.; Tsuji, J. J. Am. Chem. SOC. 1982,104,5844.

Nakano et al.

jasmonate.lg For example, methyl dihydrojasmonate has been synthesized from 2-pentyl-2-cyclopenten-1-one (8g), which is prepared via lengthy steps from l-acetoxy-2,7octadiene derived from Pd-catalyzed telomerization of butadiene in acetic acid.20 Compound 13 has been prepared from 4h by a similar sequence of reactions as above.19 Abdulla13 has also prepared 13 from 2pentylidenecyclopentanone (4h) provided by addition of cyclopentanone enamine and pentanal (3d) followed by isomerization to 2-pentyl-2-cyclopenten-1-one (8g) and then methylation by CH3Li. B y the present zirconium-catalyzedcondensation, 13 was synthesized by one-step reaction f r o m the commercially available 3-methylcyclopentanone (2e) and 7b in 35 % yield, even though the regioisomer 14 was also formed in 8% yield (eq 4). 0

2e

n

13 U

Y 14

Experimental Section The melting points were determined on a Yanaco MP52032 apparatus and are uncorrected. The IR spectra were taken with a Jasco A202 spectrometer, and the 'H and 13C NMR spectra were recorded on a JEOL PMX-60 spectrometer and Hitachi R-90H with tetramethylsilane as an internal standard, respectively. The GLC analyses were performed on a Yanaco G1800 instrument with 3 m X 2.5 mm column packed with 5% Silicon OV-7 on Chromosorb W. Compounds were commercial grade, and solvents were used after dehydration with conventional methods. Preparation of CpzZrH2 (1) and CpzZr(O-i-Pr)2(9). Cp2ZrH2(1) and CpzZr(O-i-Pr)2(9) were prepared by a procedure similar to those described by Wailes.21~22 1: mp 304-305 O C (lit.21mp 305 "C); IR (KBr) 3100,1520,1300, 1020, 840, 740 cm-'. 9: IR (KBr) 3100, 1015, 840, 770 cm-'. Preparation of Cp2MClZ(M = Ti, Zr, Hf) and Cp2Zr(H)Cl. Cp2MClz(M = Ti, Zr, Hf) and CpzZr(H)C1 were prepared by a procedure described by Wailes22and by L a ~ p e r t , respectively. '~ CpzTiClz: IR (KBr) 3100, 1440, 1010, 830 cm-'. CpzZrC12: IR (KBr) 3070, 1440, 1010, 800 cm-'. Cp2HfC12: IR (KBr) 3110, 1440, 1020, 830 cm-'. CpzZr(H)Cl: IR (KBr) 3100, 1430, 1390, 1010, 820 cm-'. Analytical data of these complexes were in agreement with literature value^.^^^^^ General Method for Cross Aldol Condensation of Cycloalkanones 2a-d with Aldehydes 3a-g Catalyzed by CpzZrHz (1) and NiC12. A mixture of 1 (0.2 mmol), NiClz (0.2 mmol), 2 (10 mmol), and 3 (10 mmol) was placed into an autoclave (50 cm3) in an atmosphere of argon and heated with shaking a t 130 "C for 8 h. After removal of the catalyst by centrifugation and then (18) Hendrickson, J. B.; Palumbo, P. S.J.Org. Chem. 1985,50,2110. (19)Tsuji, J.; Kobayashi, Y.; Shimizu, I. Tetrahedron Lett. 1979,20,

39. (20)Tsuji, J.; Masaoka, K.; Takahashi, T.; Suzuki, A.;Miyaura, N. Bull. Chern. SOC.Jpn. 1977,50,2507. (21)Wailes, P. C.;Weigold, H. J . Organomet. Chem. 1970,24,405. (22)Wailes, P. C.;Weigold, H. J.Organomet. Chem. 1970,24,413. (23)Druce, P. M.;Kingston, B. M.; Spalding, T. R.; Lappert, M. F.; Srivastava, R. C. J. Chern. SOC.A 1969,2106. (24)Toda, F.;Oshima, T. 13C NMR Data Book; Sankyo: Tokyo, 1981; p 92.

Cross-Condensation of Cycloalkanones filtration, the products were isolated by distillation or by MPLC on silica gel (ethyl acetate/hexane = 1/5-10 eluent). Spectral data of each product were compared with those of authentic samples and literature va1ues.6J3,25,26 2-Methylidenecyclohexanone(4a): [M+] m / e 110; IR (NaCl) 3030,2930-2900,1660,1590,1450 cm-'; 'H NMR (CDCl3/Me,Si) 6 6.5-6.0 (m, 2 H), 2.4-1.5 (m, 8 H); 13CNMR (CDCl3/Me,Si) 6 199.4 (s), 145.1 (s), 122.6 (t), 41.2 (t), 31.7 (t), 27.7 (t), 24.6 (t). 2-Ethylidenecyclohexanone(4b): [M'] m / e 124; IR (NaC1) 3020,2900-2850,1670,1600,1450 cm-'; 'H NMR (CDCl,/Me,Si) 6 6.6 (t, 1H), 2.3-1.8 (m, 11 H); 13C NMR (CDC13/Me4Si)6 199.6 (s), 138.4 (s), 135.0 (d), 38.8 (t), 29.4 (t), 25.5 (t), 23.4 (t), 21.4 (q). 2-Butylidenecyclohexanone (4c): [M+] m / e 152; IR (NaC1) 2900, 2850, 1675, 1605 cm-'; 'H NMR (CDC13/Me4Si)6 6.70 (t, 1 H), 2.60-0.90 (m, 15 H); 13CNMR (CDCl,/Me,Si) 6 200.0 (s), 138.6 (d), 135.8 (s), 39.7 (t), 29.4 (t), 26.3 (t), 23.3 (t), 23.0 (t), 21.4 (t), 13.5 (q). 2-Pentylidenecyclohexanone (4d): [M'] m / e 166; IR (NaCl) 2900, 2850, 1680, 1600 cm-'; 'H NMR (CDCl,/Me,Si) 6 6.54 (t, 1 H), 2.66-0.90 (m, 17 H); 13C NMR (CDCl3/Me,Si) 6 200.2 (s), 139.1 (d), 135.8 (s), 39.9 (t), 29.6 (t),26.7 (t), 23.6 (t), 23.0 (t), 21.4 (t), 20.8 (t), 12.7 (9). 2-Octylidenecyclohexanone(4e): [M+] m / e 208; IR (NaCl) 2900,2840,1680,1610,1460,1140 cm-'; 'H NMR (CDCl,/Me,Si) 6 6.5 (t, 1 H), 2.7-1.2 (m, 20 H), 0.9 (t, 3 H); 13C NMR (CDCl,/Me,Si) 6 200.7 (s), 139.6 (d), 135.9 (s), 40.0 (t), 31.8 (t), 29.1 (t), 28.5 (t), 27.8 (t), 26.6 (t), 25.1 (t), 23.6 (t), 23.3 (t), 22.6 (t), 14.0 (q). 2-Decylidenecyclohexanone(4f): [M'] m / e 236; IR (NaC1) 2930, 2900, 2850, 1670, 1610, 1460, 1150 cm-'; 'H NMR (CDCl,/Me,Si) 6 6.62 (t, 1 H), 2.8-1.0 (m, 24 H), 0.9 (t, 3 H); 13C NMR (CDCl,/Me,Si) 6 202.2 (s), 140.8 (d), 136.0 (s), 40.4 (t), 32.2 (t), 29.4 (t), 28.9 (t), 28.2 (t), 27.9 (t), 26.6 (t), 25.2 (t), 23.8 (t), 23.6 (t), 23.0 (t), 22.6 (t),13.3 (q). 2-Isobutylidenecyclohexanone (4g): [M+] m / e 152; IR (NaCl) 3050-3020, 2920,2850,1670,1620,1450 cm-'; 'H NMR (CDCl,/Me,Si) 6 6.51 (t, 1 H), 3.20 (m, 1 H), 2.5-1.0 (m, 14 H); 13C NMR (CDCl3/Me,Si) 6 200.9 (s), 145.3 (d), 133.8 (s), 40.0 (t), 26.7 (t), 26.4 (d), 23.6 (t), 23.2 (t), 21.8 (9). 2-Pentylidenecyclopentanone(4h): [M+] m / e 152; IR (NaC1) 2900, 2820, 1680, 1610, 1460, 1295, 1130 cm-'; 'H NMR (CDCl,/Me,Si) 6 6.3 (t, 1 H), 2.7-1.7 (m, 12 H), 1.0 (t, 3 H); 13C NMR (CDCl,/Me,Si) 6 201.9 (s),140.3 (d), 135.8 (s), 40.0 (t), 29.7 (t), 26.4 (t), 23.6 (t), 23.2 (t), 21.8 (t), 14.0 (q). 2-Octylidenecyclopentanone (4i): [M+] m / e 194; IR (NaC1) 2950, 2850, 1660, 1630, 1450, 1310, 1130 cm-'; 'H NMR (CDCl,/Me,Si) 6 6.4 (t, 1 H), 2.6-1.8 (m, 18 H), 0.87 (t, 3 H); 13C NMR (CDCl,/Me,Si) 6 206.4 (s), 139.6 (d), 135.9 (s), 38.5 (t), 31.8 (t), 29.6 (t), 29.4 (t), 29.1 (t), 28.4 (t), 26.7 (t), 22.6 (t), 19.8 (t), 14.1 (q). Cross Aldol Condensation of Cyclohexanone (2a) w i t h Octanal (3e) Catalyzed by IVA Metal Complexes, Lewis Acids, o r p-Toluenesulfonic Acid. A mixture of catalyst (1 mmol), 2 (10mmol), and 3e (10 mmol) was placed into an autoclave (50 cm3) in an atmosphere of argon and heated with shaking a t 130 "C for 8 h. After removal of the catalyst by filtration, the filtrate was distilled in vacuo to give 5a. The residue was subjected to MPLC on silica gel (ethyl acetate/hexane = 1/5 eluent) to give 4e and 6d. In the case of p-toluenesulfonic acid catalyzed reaction, the reaction mixture was subjected to distillation and then MPLC on silica gel (ethyl acetate/hexane = 1/1 eluent) to give 5a and 6d. 2 4 1-Cyclohexenyl)cyclohexanone(5a): [M+] m / e 178; IR (NaCl) 2930,2850,1710,1440,1120 cm-'; 'H NMR (CDCl,/Me,Si) 6 5.5 (t, 1 H), 1.3-0.4 (m, 17 H); 13CNMR (CDCl3/Me,Si) 6 211.1 (s), 135.8 (s), 120.8 (d), 42.1 (d), 33.1 (t), 31.9 (t), 27.3 (t), 27.0 (25) Andrieux, J.; Barton, D. H. R.; Path, H. J. Chem. SOC.,Perkin Trans. 1 1977, 359. (26) Chuit, C.; Corriu, R. J. P.; Reye, C. Synthesis 1983, 294. (27) In this paper the periodic group notation is in accord with recent

actions by IUPAC and ACS nomenclature committees. A and B notation is eliminated because of wide confusion. Groups IA and IIA become groups 1and 2. The d-transition elements comprise groups 3 through 12, and the p-block elements comprise groups 13 through 18. (Note that the former Roman number designation is preserved in the last digit of the new numbering: e.g., I11 3 and 13.)

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J. Org. Chem., Vol. 52, No. 11, 1987

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(t), 25.3 (t), 24.9 (t), 22.8 (t), 22.4 (t). %-Hexyl-%-decenal(6d):[M'] m l e 238; IR (NaCl) 2930,2850, 1700,1445,1120 cm-'; 'H NMR (CDC13/Me4Si)6 9.5 (9, 1 H), 6.2 (t, 1 H), 2.9-1.5 (m, 22 H), 1.0 (t, 3 H), 0.9 (t, 3 H); 13C NMR (CDC13/Me4Si)6 193.5 (d), 153.5 (s), 142.8 (d), 44.4 (t), 31.7 (t), 29.3 (t), 29.0 (t), 28.8 (t), 28.6 (t), 28.2 (t), 26.3 (t), 22.8 (t), 22.6 (t), 20.7 (t), 13.9 (q), 13.7 (9). 2-(l-Cyclopentyl)cyclopentanone (5b): [M+] m / e 150; IR (NaC1) 2930,2850,1700,1445,1120 cm-'; 'H NMR (CDCl,/Me,Si) 6 6.2 (t, 1 H), 1.9-0.7 (m, 13 H); 13C NMR (CDCl,/Me,Si) 6 206.5 (s), 158.0 (s), 127.8 (d), 49.6 (d), 34.2 (t), 32.4 (t), 29.5 (t), 27.0 (t), 25.3 (t), 20.1 (t). 2-Methyl-6-octylidenecyclohexanone(4j): [M'] m / e 222; IR (NaCl) 2950, 2850, 1680, 1600, 1450, 1140 cm-'; 'H NMR (CDCl,/Me,Si) 6 6.3 (t, 1 H), 2.9-1.2 (m, 19 H), 1.0 (d, 3 H), 0.8 (t, 3 H); 13C NMR (CDC13/Me4Si)6 204.1 (s), 140.0 (d), 135.2 (s), 40.0 (t), 32.0 (d), 29.0 (t), 28.5 (t), 27.9 (t), 26.5 (t), 25.0 (t), 24.0 (t), 23.3 (t), 22.6 (t), 14.0 (q), 12.3 (q). 4-Methyl-2-octylidenecyclohexanone (4k): [M'] m / e 222; IR (NaCl) 2950, 2850, 1690, 1620, 1460, 1160 cm-'; 'H NMR (CDCl,/Me,Si) 6 6.4 (t, 1 H), 2.6-1.0 (m, 19 H), 0.8 (t, 3 H), 0.7 (d, 3 H); 13CNMR (CDCl3/Me,Si) 201.1 (s), 139.0 (d), 136.1 (s), 40.0 (t), 32.2 (d), 29.0 (t), 28.5 (t), 28.1 (t), 26.6 (t), 25.4 (t), 24.0 (t), 23.3 (t), 22.6 (t), 13.8 (q), 10.4 (q). 4-Methyl-2-(4-methyl-l-cyclohexenyl)cyclohexanone (512): [M+] m / e 206; IR (NaCl) 2950,2850,1680,1450,1100cm-'; 'H NMR (CDC13/Me4Si)6 5.4 (t, 1 H), 2.2-1.2 (m, 15 H), 1.0 (t, 3 H), 0.9 (t, 3 H); 13C NMR (CDCl,/Me,Si) 6 210.1 (s), 135.6 (s), 122.7 (d), 57.3 (d), 41.5 (t), 40.0 (t), 35.6 (d), 33.9 (t), 32.0 (t), 31.0 (t), 28.2 (t), 26.9 (t), 21.6 (q), 21.4 (9). General Method f o r Cross-Condensation of Cycloalkanones 2a,b w i t h a,&Unsaturated Aldehydes loa-c Catalyzed by Cp,ZrHz (1)and NiCl,. A mixture of 1 (0.2 mmol), NiCl, (0.2 mmol), 2 (10 mmol), and 10 (20 mmol) was placed into an autoclave (50 cm3) in an atmosphere of argon and heated with shaking a t 130 "C for 10 h. After removal of the catalyst by centrifugation and then filtration, the product was purified by recrystallization from hexane. Spectral data of each product were compared with those of authentic samples and literature values.'4* 2,6-Dibenzylidenecyclohexanone ( l l a ) : mp 116-117 "C (lit.26mp 115-117 "C); [M'] m / e 274; IR (KBr) 3050,2900,1690, 162&1600,1440,1250,1180 cm-'; 'H NMR (CDCl,/Me,Si) 6 7.60 (m, 10 H), 7.31-7.05 (5, 2 H), 2.9-2.7 (t, 4 H), 1.75 (m, 2 H); 13C NMR (CDCl3/Me,Si) 6 189.7 (s), 136.6 (s), 136.0 (d), 135.8 (d), 130.2 (d), 128.4 (d), 128.2 (s), 28.4 (t) 23.0 (t). 2,6-Difurfurylidenecyclohexanone(Ilb): [M+] m / e 254; IR (KBr) 3000-2850,1670,1590,1450,1280-1120,1010 cm-'; 'H NMR (CDCl3/Me,Si) 6 7.7-6.2 (m, 8 H), 3.2-2.4 (m, 6 H); 13C NMR (CDCl,/Me,Si) 6 190.2 (s), 154.7 (s), 146.3 (s), 133.2 (d), 119.9 (d), 115.9 (d), 112.4 (d), 23.1 (t), 22.4 (t). 2,6-Dicinnamylidenecyclohexanone(1IC): [M+] m / e 326; IR (KBr) 3050,2900,1690,1620-1600,1440,1250,1180cm-'; 'H NMR (CDCl,/Me,Si) 6 7.7-6.6 (m, 16 H), 3.3-2.2 (m, 6 H); 13C NMR (CDCl,/Me,Si) 6 188.7 (s), 140.6 (s), 136.7 (d), 136.2 (d), 135.2 (d), 128.6 (d), 128.3 (d), 127.0 (d), 123.6 (s), 27.9 (t), 21.6

(t). 2,5-Dibenzylidenecyclopentanone(1 Id): [M'] m / e 260; IR (KBr) 3100,2900, 1670,1600, 1460, 1260, 1150 cm-'; 'H NMR (CDCl,/Me,Si) 6 7.7-7.0 (m, 12 H), 3.7-2.9 (m, 4 H); 13C NMR (CDCl3/Me4Si)6 213.0 (s), 137.1 (s), 135.6 (d), 133.6 (d), 130.5 (d), 129.1 (d), 128.6 (s), 26.5 (t). 2,5-Difurfurylidenecyclopentanone(1le): [M'] m / e 240; IR (KBr) 3030,2860,1680,1600,1450,1290-1110,1010cm-'; 'H NMR (CDC13/Me4Si) 6 7.7-6.3 (m, 8 H), 3.3-2.7 (m, 4 H); 13C NMR (CDCl3/Me,Si) 6 195.0 (s), 152.6 (s), 144.9 (s), 135.7 (d), 119.6 (d), 115.7 (d), 112.5 (d), 25.7 (t). 2,5-Dicinnamylidenecyclopentanone (1If): [M'] m / e 312; IR (KBr) 3100,2900,1670,1600,1470,1250,1150 cm-'; 'H NMR (CDCl,/Me,Si) 6 7.7-6.7 (m, 16 H), 3.1-2.7 (m, 4 H); I3C NMR (CDCl3/Me4Si) 6 194.6 (s), 141.0 (s), 139.6 (d), 136.4 (d), 132.4 (d), 128.8 (d), 128.6 (d), 127.0 (d), 124.5 (s), 25.7 (t). General Method f o r Cross-Condensation of Cycloalkanones 2a,b w i t h P r i m a r y Alcohols 7a-f Catalyzed by Cp,ZrHz (1) a n d NiC12. A mixture of 1 (0.2 mmol), NiC1, (0.2 mmol), 2 (10 mmol), and 7 (10 mmol) was placed into an autoclave (50 cm3) in an atmosphere of argon and heated with shaking a t

J. Org. Chem. 1987,52, 2244-2248

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27.1 (t),26.8 (t), 23.4 (t), 22.7 (t),20.1 (t),14.0(9). 150 "C for 8 h. After removal of the catalyst by centrifugation 2-Decyl-2-cyclopenten-1-one (8i): [M+] m / e 222;IR (NaCl) and then filtration, the product was isolated by distillation or by 3000,2880,1720,1650,1470-1450,1400,1300-1120 cm-'; 'H NMR MPLC on silica gel (ethyl acetate or chloroform/hexane = 1/5-10 (CDC13/Me4Si)6 6.53(t, 1 H),2.6 (t, 2 H), 2.0(m, 2 H), 1.9-0.9 eluent). Spectral data of each product were compared with those 6 200.2(s), 142.6(d), 138.1 of authentic samples and literature ~ a l u e s . 6 ~ ~ ~ ~ ~ (m, ~ 21 ~ H); ~ ~13C ~ NMR ~ ~ (CDCl,/Me,Si) ~ 2-Butyl-2-cyclohexen-1-one (sa): [M+] m / e 152;IR (NaCl) (s), 41.2 (t), 31.6 (t), 29.8(t),28.7(t),27.4(t),24.5 (t),23.8 (t), 22.6 (t),21.2(t),20.9 (t), 20.1 (t), 12.6(q). 2900,2850,1700,1610 cm-'; 'H NMR (CDC13/Me4Si)6 6.40(t, Cross-Condensationof 3-M~thylcyclopentanone(2e) with 1 H), 2.40-0.70 (m, 15 H); 13C NMR (CDC13/Me4Si)6 200.8(s), Pentanol(7b) Catalyzed by CpzZrH2(1) and NiC12. A mixture 138.8(d), 136.1(s),40.0(t), 29.9(t),26.8(t),23.7(t), 23.5(t),21.9 of 1 (0.2mmol), NiC12 (0.2mmol), 2e (10mmol), and 7b (10mmol) (t), 13.9 (q). was placed into an autoclave (50 cm3) in an atmosphere of argon 2-Pentyl-2-cyclohexen-1-one (8b): [M+] m / e 166;IR (NaCl) and heated with shaking a t 150 "C for 8h. After removal of the 2900,2800,1700,1610 cm-'; 'H NMR (CDC13/Me4Si)6 6.34(t, catalyst by filtration, the reaction mixture was subjected ta MPLC 1 H), 2.40.66'(m,17 H); 13C NMR (CDC13/Me4Si)6 201.1 (s), on silica gel (benzene/hexane 5 2/1eluent) to give dihydrojas139.4(d), 136.6(s),40.2(t),29.9(t),26.9 (t),23.8(t),23.5(t),22.6 mone (13) and its regioisomer 14. (t),21.7 (t), 13.1 (q). Dihydrojasmone (13): [M+] m / e 166;IR (NaCl) 3000,1680, 2-Octyl-2-cyclohexen-1-one(8c): [M+] m / e 208 IR (NaCl) 1650,1370,1060 cm-'; 'H NMR (CDC13/Me4Si)6 2.7-2.0(m, 9 3000,2900,2850,1700,1640 cm-'; lH NMR (CDC13/Me4Si)6 6.1 H), 1.8-1.1(m, 6 H), 0.87 (t, 3 H)[lit.182.6-1.9(m, 6 H), 2.05(s, (t, 1 H), 2.2-1.0(m, 20 H), 0.8 (t, 3 H); 13C NMR (CDC13/Me4Si) 3 H), 1.6-1.0(m, 6 H), 0.85 (t, 3 H)]; 13C NMR (CDCl,/Me4Si) 6 203.8(s), 143.1(d), 137.2(s),40.6(t),30.1 (t), 29.6 (t),29.0(t), 6 206.6(s), 167.6(s), 140.3(s), 37.6(t), 34.7(t),32.1(t),28.4(t), 27.0 (t), 26.4 (t), 23.6 (t), 22.6 (t), 22.3 (t), 20.6 (t), 13.8 (q). 27.3 (t), 24.5 (t),19.9 (q), 14.1 (9). 2-Decyl-2-cyclohexen-1-one (8d): [M'] m / e 236;IR (NaCl) 4-Methyl-2-pentyl-2-cyclopenten-l-one (14): [M+]m / e 166; 3030-2900,2860,1700,1620 cm-'; 'H NMR (CDC13/Me4Si)6 6.0 IR (NaC1) 3000, 1680, 1650, 1400, 1020 cm-'; 'H NMR (t, 1 H), 2.7-1.1(m, 24 H), 0.8 (t,3 H); 13C NMR (CDC13/Me4Si) (CDC13/Me4Si)6 5.2(d, 1 H), 2.9-1.8(m, 11 H), 1.2(d, 3 H), 0.9 6 206.1(s), 144.2(d), 137.1(s),41.7(t), 31.2(t),30.1(t), 29.8(t), (t, 3 H); 13C NMR (CDC1,/Me4Si) 6 206.0(s), 146.7(d), 138.0(s), 29.0(t), 27.8(t),27.0 (t), 26.2(t), 23.8(t), 22.4 (t),22.0 (t),20.4 40.2(t),35.1(d), 32.3 (t),28.4(t),27.2(t), 25.1 (t), 15.4(q), 14.1 (t), 12.1 (4). 2-Hexadecyl-2-cyclohexen-1-one (8e): [M'] m / e 320;IR (9). (NaCl) 3050-2920,2860,1710,1640 cm-'; 'H Nh4R (CDC13/Me4Si) 2a, 108-94-1; 2b, 120-92-3; 2c, Registry No. 1, 12116-83-5; 6 6.5(t, 1H), 2.84.7(m, 39 H);13C NMR (CDCl,/Me,Si) 6 209.1 583-60-8; 2d, 589-92-4; 2e, 1757-42-2; 3a, 110-88-3; 3b, 75-07-0; (s), 146.8(d), 138.8(s),41.2(t), 34.6(t), 30.7(t), 29.7(t), 28.9(t), 3c, 123-72-8; 3d, 110-62-3; 3e, 124-13-0; 3f, 112-31-2; 3g, 78-84-2; 27.5 (t),26.6(t), 25.2(t),24.6 (t),23.2(t), 22.9 (t),22.6 (t), 22.4 4a, 3045-98-5; 4b, 1122-25-4; 4c, 7153-14-2; 4d, 25677-40-1; 4e, (t), 22.1 (t), 21.4 (t), 21.1 (t),20.7 (t), 19.7 (t), 10.5 (9). 72927-86-7; 4f, 107799-61-1; 4g, 43108-69-6; 4h, 16424-35-4; 4i, 2-Isobutyl-2-cyclohexen-1-one (80: [M+]m / e 152;IR (NaC1) 40564-16-7; 4j, 107799-65-5; 4k, 107799-66-6; 5a, 1502-22-3; 5b, 3020-2980,2890,2850,1705,1660 cm-'; 'H NMR (CDCl,/Me,Si) 7027-34-1; 5c, 13705-82-3; 6a, 4170-30-3; 6b, 645-62-5; 6c, 6 5.7 (t, 1 H), 3.1 (m, 1 H), 2.8 (d, 2 H), 2.2-1.1(m, 12 H); 13C 34880-43-8; 6d, 13893-39-5; 6e,25234-33-7; 7a, 71-36-3; 7b, 71-41-0; NMR (CDC13/Me4Si)6 211.6(s),144.4(d),140.6(s),43.2(t),30.7 7e, 36653-82-4; 7f, 78-83-1; 8a, 7c, 111-87-5; 7d, 112-30-1; (d), 29.7(t), 24.2 (t),22.7 (t), 14.1(9). 34737-39-8; 8b, 25435-63-6; 8c, 52914-72-4; 8d, 107799-62-2; 8e, 2-Pentyl-2-cyclopenten-1-one (8g): [M+] m / e 152;IR (NaC1) 107799-63-3; 8f, 107799-64-4; 8g, 25564-22-1; 8h, 54625-13-7; 8i, 2950,2865,1718,1645,1470,1370,1300-1120 cm-'; 'H NMR 64351-95-7; 9,78091-186; loa, 100-52-7; lob, 9801-1; lOc, 104-55-2; (CDC13/Me4Si)6 6.2(t, 1 H), 2.8-1.9(m, 12 H), 0.9(t, 3 H); 13C l l a , 897-78-9; l l b , 893-00-5; l l c , 18977-40-7; l l d , 895-80-7; lle, NMR (CDC13/Me4Si)6 206.1(s),147.4(d), 137.8(s), 38.8(t),31.4 1026-78-4; 1 If, 21856-78-0; 13, 1128-08-1; 14, 75359-55-6; NiC12, (t),29.4 (t), 27.2 (t), 23.6 (t),19.9 (t),14.1 (9). 771854-9;Cp2Zr(H)Cl,37342-97-5; Cp2ZrC12,1291-32-3; CpZTiCl2, 2-Octyl-2-cyclopenten-l-one (8h): [M+]m / e 194;IR (NaCl) 1271-19-8; Cp2HfC12,12116-66-4; ZrCl,, 10026-11-6; TiC14,75502950,2870,1720,1650,1470,1380,1300-1140 cm-'; 'H NMR 45-0;AlCl,, 7446-70-0;4-H3CC6H4SO3H,104-15-4;NiBr2, (CDCl3/Me,Si) 6 6.42(t, 1 H), 2.57(t, 2 H), 2.07 (m, 2 H), 1.87 13462-88-9; Ni(acac)2,3264-82-2; PdC12, 7647-10-1; CuC12, 7447(t, 2 H),1.33 (m, 12 H), 0.9 (t, 3 H); 13C NMR (CDC1,/Me4Si) 39-4;2,4,6-trimethyl-1,3,5-trioxane, 123-63-7. 6 195.1(s), 139.3(d), 137.5(SI, 39.7(t),29.7(t),29.4(t),28.9(t),

Different Enzymatic Reactions of an Enantiomeric Pair: Simultaneous Dual Kinetic Resolution of a Keto Ester by Bakers' Yeast Dee

W. Brooks,*la Michael Wi1son,lb and Michael Webblb

Pharmaceutical Products Division, Abbott Laboratories, Abbott Park, Illinois 60064, and Department of Chemistry, Purdue University, West Lafayette, Indiana 47907 Received December 18, 1986

An example of different enzymatic reactions of an enantiomeric pair involving a simultaneous dual kinetic resolution by two different enzymes in bakers' yeast on a racemic synthetic substrate is described. The 1R,5S enantiomer of methyl (*)-3-oxo-7,7-(ethylenedioxy)bicyclo[3.3.0]octane-2-carboxylate(1) is converted by a dehydrogenase enzyme present in bakers' yeast to methyl (+)-(lR,2R,3S,5S)-3-hydroxy-7,7-(ethylenedioxy)bicyclo[3.3.0]octane-2-carboxylate(4) and the 1S,5R enantiomer of 1 is converted to 7,7-(ethy1enedioxy)bicyclo[3.3.O]octan-3-one (5) by a process that likely involves ester hydrolysis by an esterase and subaequent decarboxylation of a proposed intermediate /3-keto acid.

The applications of enzymes t o effect selective transformations of synthetic substrates is a useful method to

provide optically pure intermediates for synthesis.2 Microorganisms may be simply viewed by an organic chemist

0022-3263/87/ 1952-2244$01.50/0 0 1987 American Chemical Society