Organometallics 1995,14, 4899-4904
4899
Reactivity and Stereochemistry of /3-Heteroatom Elimination. A Detailed Study through a Palladium-Catalyzed Cyclization Reaction Model Guoxin Zhu and Xiyan Lu* Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, 354 Fenglin Lu, Shanghai 200032, China Received May 5, 1995@ The elimination of palladium and the @-leavinggroup of the organopalladium intermediate formed in a palladium(I1hatalyzed cyclization of 4'-heteroatom-2'-alkenyl 2-alkynoates leading to a-methylene-y-butyrolactones is sensitive to the leaving-group ability of the substituents # toI palladium. The reactivity order of @-eliminationfor different leaving groups was studied. The reaction of palladium chloride, palladium acetate, and palladium hydroxide elimination showed strict steric requirement requiring an antiperiplanar arrangement of palladium and the leaving group on the carbon @ to palladium.
Introduction /?-Elimination, as one of the most important reactions of (a-alkyllmetal compounds, involves interconversion of alkyl and olefin 1igands.l Formally, /?-elimination involves the cleavage of a bond on the carbon atom /? to the metal in an organometallic species t o produce an unsaturation, e.g.:
Scheme 1
P
/p-elimination
cood"io\
OAO'
The most common examples of /?-elimination are found in alkylmetals, where X = H, which have been explored extensively.2 Although the elimination of a /?-heteroatom with the metal is also apparently a general reaction, relatively fewer examples are known and the generality of this process is still limited.3-6 Recently, we reported a divalent palladium-catalyzed cyclization of 4'-heteroatom-2'-alkenyl2-alkynoatesstereoselectively affording a-methylene-y-butyrolactone derivatives. In this reaction, in order t o regenerate the catalytic species Pd(II), a heteroatom was introduced Abstract published in Advance ACS Abstracts, September 1,1995. (1)Collman, J. P.; Hegedus, L. S. Principles and Applications of Organotransition Metal Chemistry; University Science Books: Mill Valley, CA, 1987. Kochi, J. K. Organometallic Mechanism and Catalysis; Academic Press: New York, 1978.Yamamoto, A. Organotransition Metal Chemistry; Fundamental Concepts and Applications; John Wi1ey.k Sons: New York, 1986.Heck, R. F. Organotransition Metal Chemistry; Academic Press: New York, 1974. (2)Hegedus, L. S. In The Chemistry of the Metal-Carbon Bond; Hartley, F. R., Ed.; Wiley: Chichester, U.K., 1985; Vol. 2, p 401. Keinan, E.; Kumar, S.; Dangur, V.; Vaya, J. J.Am. Chem. SOC.1994, 116, 11151 and references cited therein. (3)Shiu, L.;Yu, C.; Wong, K.; Chen, B.; Cheng, W.; Yuan, T.; Luh, T. Organometallics 1993,12, 1018 and references cited therein. (4)Daves found that the acetoxy group was a good leaving group and the alkoxy group was a poor leaving group in their palladiumcatalyzed reaction: Cheng, J. C.-Y.; Daves, G. D., Jr. Organometallics 1986,5 , 1753. (5)For syn elimination of palladium and 8-hydroxyl, see: Hacksell, V.; Daves, G. D., Jr. Organometallics 1983,2, 772. Cheng, J. C.-Y.; Hacksell, V.; Daves, G. D., Jr. J.Org. Chem. 1986,51,3093. Backvall, J . E.;h e r m a r k , B.; Ljunggren, S. 0. J. Am. Chem. SOC.1979,101, 2411.For anti-periplanar elimination of palladium and the 8-acetoxy group, see: Daves, G. D., Jr. Acc. Chem. Res. 1990,23,201. (6)For nonstereospecific elimination of palladium and chloride, see: Henry, P. M. Acc. Chem. Res. 1973,6, 16. @
OAO'
into the 4'-position of the substrate. In the resulting cyclic intermediate by intramolecular carbon-carbon double bond insertion into a vinyl-palladium bond formed by halopalladation of the carbon-carbon triple bond, the heteroatom is located at the /?-positionof the palladium. Thus, this heteroatom directed the /?-elimination reaction to regenerate the catalytic species Pd(I1) affording /?-vinyl-substituted a-methylene-y-butyrolactones (Scheme l h 7 In this paper, we wish t o report the reactivity and stereochemistry of the elimination of palladium and the heteroatom /? to palladium using the Pd(I1)-catalyzed cyclization mentioned above as the model reaction.
Results and Discussion Reactivity of Elimination of Palladium and Different Heteroatoms /lto Palladium. In order to study the elimination of palladium and different leaving (7)(a) Lu, X.;Ma, S.; Ji, J.; Zhu, G.; Jiang, H. Pure Appl. Chem. 1994,66,1501.(b)Ma, S.;Lu, X. J.Chem. Soc., Chem. Commun. 1990, 733.Ma, S.;Lu, X. J. Org. Chem. 1991,56,5120. (c) Zhu, G.; Ma, S.; Lu, X. J. Chem. Res. (S)1993,366.Zhu, G.;Ma, S.; Lu, X. J. Chem. Res. (M) 1993, 2467. (d) Ma, S.;Lu, X. J. Organomet. Chem. 1993, 447, 305.
0276-733319512314-4899$09.00/00 1995 American Chemical Society
Zhu and Lu
4900 Organometallics, Vol. 14, No. 10, 1995
Table 1. Reactivity of Elimination of Palladium and Different Heteroatoms fl to Palladiuma
Scheme
i ,
E-2
OH
1
2-2
I I
time entry compd R L confignb cat.C (h) 8 Z A 1 3c Pr c1 E A 8 2 3C Pr C1 48 Z A 3 3B Pr OAc 48 E A 4 3B Pr OAc 48 Z B 5 3B Pr OAc 48 E B 6 3B Pr OAc 72 Z B 7 3A Pr OH E B 72 8 3A Pr OH 10 E A 9 3D H OMe 1Oe 3D H OMe E Ag 12
~
isolated yield f%) 4(Z:E)d 5 80 (44:56) 80 (27:73) 60(63:37) 75(45:55) 65(65:35) 75(47:53) 35(81:19) 19 50(37:63) 19 50(4D)f 60(4D'Y
Reaction conditions: Alkynoates (3)(1.0 mmol), catalyst (0.05 mmol), LiX (4.0 mmol), and HOAc (5 mL) at rt. Referring to the carbon-carbon double bond in the substrate (3). A = Pd(OAc)z, B = PdC12(PhCN)z.d All exocyclic double bonds of 4 and 5 were in 2-form, the ratios (referring to the carbon-carbon double bond of alkenyl at the P-position of lactone rings) were determined by 300 MHz lH NMR. e The substrate 3D was 4'-methoxyL2'-(E)butenyl2-butynoate. f The product 4D was (Z)-a-(chloroethylidene)P-vinyl-y-butyrolactone. g LiBr was used instead of LiCl in the reaction. The product 4 D was (2)-a-(bromoethy1idene)-P-vinyly-butyrolactone.
E-3C
E-3A
+OH
U
6 0 ' Z-3C
UReagents and conditions: (i) (a) EtMgBr, THF, (b) nPrCHO, (c) H30+,60%; (ii)LiAIH4,THF, reflux, 66%;(iii)PZ-
Ni (catalyst), Hz (1atm), rt, 90%; (iv) DCC, DMAP (catalyst), EtzO, -20 "C to rt, 52.5% for E-3A, 50% for Z-3A, (v) Pc13, EtzO, -20 to 0 "C; (vi) AczO, MeCN, CoClz (catalyst), 80 "C; 86% for E-3B; 63% for Z-3B.
groups in the above-mentioned cyclization reaction, the starting materials 4'-heteroatom-2'-(2)- or (E)-heptenyl 2-propynoates (3) were prepared according to Scheme 2. 2-Heptyne-1,4-diol (1)was obtained by alkynylation of butanal.* Catalytic hydrogenationg and LiAlH4 reductionloof compound 1 afforded (2)and (E)-a-heptene1,4-diol (2) with high stereoselectivities, respectively. The selective mono-esterification of the primary hydroxyl group of the diols 2 in the presence of DCC catalyzed by DMAP in ether afforded the esters 3A. 4'Acetoxy-substituted substrates 3B were obtained by subsequent acetylation of the hydroxyl group in compounds 3A. Chlorination of compounds 3A was realized by controlling the reaction temperature at -20 "C, which afforded 4'-chloro-substituted substrates 3C. Compound E-3D was synthesized by methylation of 4'hydroxyl-2'-(E)-butenyl 2-butynoate with Me1 in the presence of NaH. The cyclization of 4'-heteroatom-2'-heptenyl propynoates (3) occurred smoothly under the catalysis of palladium(I1) in HOAc at room temperature. The results were shown in Table 1. (8)Brandsma, L. Preparative Acetylenic Chemistry, 2nd ed.; Elsevier: Amsterdam, 1988;p 79. (9) Brown, C. A.; Ahuja, V. K. J.Chem. SOC.,Chem. Commun. 1973, 533. (IO)
Cowie, J. S.; Lander, P. D.; Landor, S. R. J.Chem. SOC.,Perkin Trans. 1 1973, 720.
When the leaving group in the substrates was a chloride (3C,Y = Cl), the cyclization proceeded quickly affording P-chloride elimination product as the sole cyclic product in good yield (entries 1 and 2, Table 1) without competitive P-hydride elimination. The exocyclic carbon-carbon double bond in the lactone product was believed to be in the Z-configuration by comparing the chemical shift of the vinylic protons of the exocyclic carbon-carbon double bond with its analogue^.^ The configuration of the carbon-carbon double bond at the /3-position of the lactone was determined by the lH NMR method. Irradiation of the signal at.2.09-2.02 ppm led t o the observation of two doublets of two groups of vinylic protons with coupling constants of 10.6 and 15.3 Hz, implying that the product was a mixture of two geometrical isomers with respect to the carbon-carbon double bond at the ,&position of lactone ring, the ratio of which was determined by IH NMR. For the acetate substrates (3B, Y = OAc), the cyclization reaction also occurred smoothly affording the P-acetoxy elimination product as the sole cyclic product under similar conditions, but the reaction was slower than the corresponding chloro-substituted substrates (entries 3-6, Table 1). Much slower reaction was found in case of hydroxyl substrates (3A, Y = OH). Besides the low reaction rate for hydroxyl substrates, the reaction was also less selective and two cyclic products 4 and 5 were isolated (entries 7 and 8, Table 1). Compound 5 was formed by P-hydride elimination in the last step. This result indicates that the reactivities of the ,&hydroxyl and P-hydride eliminations are comparable and the reaction gives rise to a mixture of products. From the results shown in Table 1,we could find that the elimination of palladium and a good leaving group (e.g. chloride, acetoxy4) was easier and faster than
&Heteroatom Elimination
Organometallics, Vol. 14, No. 10,1995 4901
Scheme 3"
t
a
41
the carbon-carbon double bond in the substrate could coordinate with the palladium before the intramolecular double bond insertion into vinylpalladium formed by halopalladation of the carbon-carbon triple bond (Scheme 3). There is no significant energy difference between these two coordination complexes (A t o D in Scheme 3), so this type of substrates would give different transition states and is not suitable to study the stereochemistry of @-eliminationin the next step. Stereochemistry of Elimination of Palladium and the Leaving Group fl to Palladium. Although the fact that syn-periplanar arrangement of palladium and p-hydride is required for the @-hydrideelimination reaction is well-known,1-2the studies on the stereochemistry of elimination of palladium and a heteroatom on the carbon B to palladium are rare. Daves reported that palladium acetate elimination required an antiperiplanar arrangement of palladium and the oxygen s ~ b s t i t u e n t . Nonstereospecific ~ elimination of palladium chloride was reported by Henry.6 On the basis of our previous studies, it occurs t o us that our cyclization reaction7 may be used as a model reaction t o study the stereochemistry of @-elimination. In the cyclization of 2-propynoates 3, both the re-face and si-face of the carbon-carbon double bond in the substrate could coordinate to vinylpalladium, which made the intermediate formed by intramolecular insertion variable. If the allylic double bond was fxed in a cyclic substrate, such as compound 611 (eq 31, after halopalladation of
Legend: (i) chloropalladation; (ii) intramolecular insertion.
@-hydrideelimination, while, for the hydroxyl group, its leaving-group ability was similar to that of a /%hydride. Thus, the ability of @-eliminationof different leaving groups at the @ position of palladium followed the order C1> OAc > OH = H. Daves found that in their (g1ycal)palladium system, alkoxy1 was a poor leaving group in palladium(I1) @-elimination reaction^.^ However, in our case, when the leaving group was changed to a methoxyl (entries 9 and 10, Table 11, the reaction also proceeded quickly to afford only one cyclic product through ,8-methoxy1 elimination, indicating that methoxyl group was a better leaving group than hydride. The results shown in Table 1 also imply that the configuration of the carbon-carbon double bond in substrates 3 had some influence on the cyclization, especially on the stereochemistry of @-elimination. Substrates with a 2-carbon-carbon double bond tended to give products with more 2-carbon-carbon double bond at the @-positionof the lactone; however, substrates with an E-carbon-carbon double bond gave the correspondingP-E-olefinproduct predominantly. These results indicate that the configuration of the carboncarbon double bond had some memory during the cyclization reaction. Such a memory effect increased when going from the chlorine substrates (3C) to the acetate substrates (3B)to the hydroxyl substrates (3A); that is, it increases with the covalency of the bond between palladium and the heteroatom (C1 < OAc < OH). On the other hand, both the re-face and si-face of
the carbon-carbon triple bond, the coordination of the carbon-carbon double bond with vinylpalladium species should only be in one direction due to the rigidity of the cyclohexenyl ring. Thus, a stereodefined new carbonpalladium bond generated by intramolecular carboncarbon double bond insertion could be quenched by B-elimination reaction, and the stereochemistry of @elimination could be deduced from the cyclic product formed in the reaction. Unfortunately, under the cyclization conditions, the reactions of both cis-6 and trans-6 (eq 3, Y = OAc or OH) were very slow and resulted in a complex mixture. So we failed t o obtain any useful information for the stereochemical study using cis-6 and trans-6. In our previous work,12we found that the diastereoselectivity in the intramolecular carbon-carbon double bond insertion step could be controlled by the substituents a t the 3- and 1'-positions of the cyclization precursors. For 2-butynoates (7), the substituent R a t the 1'-position could control the stereoselectivity in the step of the intramolecular insertion affording the cislactone (cis-8)(referring to P,y-substituents) as the sole cyclic product (eq 4). (11)Compounds 6 were prepared from 2-butynoic acid and the corresponding stereodefined cyclohexenols (Backvall, J. E.; Bystrom, S. E.; Nordberg, R. E. J. Org. Chen. 1984,49, 4619) in the presence of DCC and D W . (12) Ma, S.; Zhu, G.; Lu,X. J. Org. Chem. 1993, 58, 3692.
4902 Organometallics, Vol. 14,No. 10,1995
7
Zhu and Lu
ha
On the basis of such a stereoselectivity in the step of intramolecular carbon-carbon double bond insertion into the vinylpalladium bond, we chose stereodefined 2-butynoate 9 as the model compound to study the stereochemistry of @-heteroatomelimination. According to our previous results, halopalladation of the carboncarbon triple bond followed by stereoselective intramolecular carbon-carbon double bond insertion would generate a stereodefined cyclic intermediate (9A) with a newly formed a-carbon-palladium bond. Subsequent elimination of palladium and the leaving group would afford the lactone product with a 2-or E-double bond a t the @-positionof the lactone ring according to the steric requirement of the elimination (eq 5).
14b
14a
14C
Reagents and conditions: (i) NaH, DMSO, n-PrBr; (ii) (a)DIBAL-H, hexanePTHF, (b) CuC1; (iii) LiOAcBHzO, MnO2, p-benzoquinone, HOAc-H2O-hexane, Pd(0Ac)z (catalyst); (iv) NaOH (2M), MeOH; (v) LiCl, LiOAc2Hz0, p-benzoquinone, HOAc-hexane, Pd(0Ac)z (catalyst); (vi) KzCO3, MeOH; (vii) DCC, DMAP, CH2C12, -20 "C to rt, 52% for 14a, 77% for 14c; (viii) AczO, CoCl2 (catalyst), MeCN, 80 "C, 88%. a
9
9A
The stereodefined starting materials 14a-14c were synthesized according to the route shown in Scheme 4. E-(R*,RX)-4,7-DiacetOxy-5-decene (loll2and E-(R*,.R*)4-acetoxy-7-chloro-5-decene (W3were prepared by the methods reported by Backvall. Hydrolysis of 10 and 12 afforded the corresponding hydroxyl compounds 11 and 13, which were directly esterified with 2-butynoic acid affording 2-butynoates 14a and 14c in the presence of DCC catalyzed by DMAP. The acetoxy substrate 14b was prepared by acetylation of 14a in the presence of a catalytic amount of CoC12 (eq 6 ) .
Table 2. Stereochemistry of Elimination of Palladium and the Leaving Grow B to Palladium" leaving group entry
substrate
(Y)
1 2
14a 14b 14c
OH OAc c1
3
time (h) 60 60 3
isolated yield (%) ~ ~ ( E L Z ) ~16 23(>97:3) 91 (>97:3) 85 (>97:3)
51
a Reaction conditions: Alkynoates (14) (1.0mmol), catalyst (0.05 mmol), LiX (4.0 mmol), and HOAc (5 mL) at rt. Determined by 300 MHz 'H NMR spectra.
Scheme 5 (6)
The results of palladium(I1)-catalyzed cyclization of 14 were shown in Table 2. Under the catalysis of PdC12(PhCNh, cyclization of 14c occurred quickly giving the lactone 15 as the sole product. The relative configuration of the substituents at the @, y-positions was determined by comparing the lH NMR spectra with its analogs obtained in our previous w0rk;'2~~ the double bond of the alkenyl group at the P-position was believed to be in E-form based on the J value (J = 15 Hz) between the two vinylic protons. Under similar reaction conditions, the acetate substrate 14b also afforded the lactone 15 with E double bond of the alkenyl group at the P-position as the sole product. Although the cyclization of hydroxyl substrate 14a gave two cyclic products 15 and 16, the double bond of alkenyl group at the @-positionof the lactone product 15 was also in E-form. These results showed that the elimination of (13)Backvall, J. E.; Schink, H. E.; Renko, Z. D. J.Org. Chem. 1990, 55, 826.
palladium and the leaving groups, such as chloride, acetoxy, and hydroxyl, all occurred in a highly stereoselective way. The stereochemistry of j3-elimination can be deduced from the analysis based on Scheme 5. As we have discussed, the intramolecular carboncarbon double bond insertion into the vinylpalladium
/3-Heteroatom Elimination
bond formed by halopalladation of the carbon-carbon triple bond would generate the cyclic intermediate 17 with a newly formed stereodefined carbon-palladium bond. The latter gave the final organic product through elimination of palladium(I1) and the leaving group on the P-carbon of palladium. As illustrated in Scheme 5, anti-elimination of palladium and the leaving group would afford an E-carbon-carbon double bond of the alkenyl group a t the ,&position of the lactone, while a 2-carbon-carbon double bond which is stable under the cyclization condition7cwould result from syn-elimination. During our study, E-carbon-carbon double bond products were obtained as the sole products in all cases, implying that the elimination required the antiperiplanar arrangement for the palladium and the leaving group, such as chloride, acetoxy, and hydroxyl groups.
Organometallics, Vol. 14, No. 10, 1995 4903 113 (4.26), 109 (2.15), 95 (lOO.OO), 71 (39.811, 69 (77.611, 53 (36.65). HRMS: calcd for C10H1403, mle 182.0943; found, m l e 182.0940. l’-(R+)-Propyl-4‘-(R*)-hydroxyl-2-(E)-heptenyl 2-butynoate (14a)and l’-(R*).propyl-4’-(R*)-chloro-2’-(E)-hep. tenyl2-butynoate(14c)were synthesized similarly but using CHzClz instead of Et20 as solvent. l’-(R*)-Propyl-4‘-(R*).hydroxyl-2’-(E)-heptenyl 2-Butynoate (14a): oil; lH NMR (300 MHz, CDCl3) 5.75 (dd, J1= 5.9 Hz, JZ = 15 Hz, lH), 5.61 (dd, J1 = 6.8 Hz, JZ = 15 Hz,
1H),5.31(q,J=6.7Hz,1H),4.11(q,J=6.0Hz,1H),1.99(s,
3H), 1.90 (br, lH), 1.68-1.30 (m, 8H), 0.92 (t,J = 7.4 Hz, 6H); IR (neat) 3400,2960,2880,2250,1720,1470,1260,1070,970, 750 cm-1; MS m l e 221 (M+ - OH, 2.40), 191 (1.61),177 (4.36), 171 (0.28), 155 (8.95), 137 (15.551, 125 (13.38), 111(63.38), 67 (100.00). HRMS: calcd for Cl2HlsO2 (M+ - Et - HzO), m l e 191.1072; found, m l e 191.1054. l’-(R*)-Propyl-4’-(R*)~~o~~-(E)-heptenyl ZButynoate (14c): oil; ‘H NMR (300 MHz, CDCl3) 5.79 (dd, J1 = 7.7 Hz, Conclusions J 2 = 15.7 Hz, lH), 5.67 (dd, J1=6.2 Hz, Jz = 15 Hz, lH), 5.32 (q, J = 6.4 Hz, lH), 4.34 (m, lH), 1.99 (s, 3H), 1.80-1.57 (m, In summary, we have demonstrated the order of 4H), 1.44-1.33 (m, 4H), 0.93 (t, J = 7.4 Hz, 6H); IR (neat) leaving-group ability and the stereochemistry of j3-het2960,2860,2240,1715,1465,1250,1065,970,750cm-l; MS mle 221 (M+ - C1, 18.35), 205 (0.38, 203 (0.701, 193 (0.39, eroatom elimination in the cyclization reaction of 4‘191 (1.16), 175 (0.84), 173 (1.1441, 156 (0.741, 154 (3.51), 137 heteroatom-!2’-alkeny12-alkynoatesunder the catalysis (12.24), 121 (1.73), 95 (13.25), 67 (100.00). HRMS: calcd for of palladium(I1). When the substrate has a good leaving C14H2102, m l e 221.1542; found, m l e 221.1541. group (e.g. acetate, chlorine), an antiperiplanar arAcetylation of Allylic Hydroxyl Group. This was carrangement for palladium and the leaving group is ried out under the similar way reported in our previous required and no competitive ,%hydride elimination was paper.Ic observed; when the substituent a t the
