Cyclomagnesation of Dienes Catalyzed by a Chiral Ansa-Zirconocene 1

Cyclomagnesation of dienes catalyzed by a chiral ansa-zirconocene 1

Sandra Martin 2, Hans-Herbert Brintzinger * Faklliliitfiir Chemie. Unil'enitiit Konstan:. D-78457 Komtan:. Germam'

Dedicated to the memory of Profe~sor Mark E. vor pin

Abstract

The biphenyl-bridged. chiral zirconocene complex rac-2.2' -biphenyl-bis( 3.4-dimethylcyclopentadienyl Izirconium dichloride catalyzes the reaction of 1.6- and 1,7 -dienes with excess dibutyl magnesium to bis( butyl-magnesio-methyl '-substituted cycloalkanederivatives. Analogous reactions occur with butyl magnesium chloride and with heteroatom-t.:Ontaining dienes. The preference of 1.6-dienes for trans-fusedcyclizatioo products and that of 1,7-dienes for cis-fusion at ambient and for trans-fusion at elevated temperatures is similar to that observed before for unsubstituted zirconocene complexes. The R-enantiomer of the biphenyl-bridged zirconocene complex gives Irans-fused cyclization products with an optical purity of only 15 ± 1% ee. The stereochemistry of ihese cyclomagnesalion reactions is explained in terms of the relative fates of mutually competing cyclization and transmetalation steps.

Keywords: Ansa-zirconocene; Catalysis; Diene cyclomapesation

1. Introduction reactions 111-161. a mechanism for this catalytic cycle was proposed, which involves the formation of zircooacyclic Since the discovery by Vol' pin and coworkers that metal intermediates and their transmetalation with excess alkyl lacyclic compounds are formed from low-valent group IV magnesium reagent 120 J. metallocenes with unsaturated substrate molecules [I], the X;-./ • R,Mg 1C,H,):bCJ, xr--('"'-'9R (l) formation of metallacyclic intermediates by reductive !::Oll ~ 2-10mol% ~!\IgR piing reactions has become an effective tool for the construc Dependmg on the diene and alkyl magnesium reagents and tion of carbo- and heterocyclic ring structures [2-6]. Early on the reaction conditions. these cyclizations occur with dif studies concerned primarily the stoichiometric cyclization of ferent stereochemistry: the (C H )!ZICl!-catalyzed cyclo enynes and dienes r7-15] . Molecular mechanics and density 5 s magnesation of I ,6-heptadiene with mOOtyl magnesium gave functional methods were used by Taber and coworkers [ 16 J to predict the relative stabilities of alternative zirconacyclic predominantly the trans-fused diastereomer [19.20]. while products and to rationalize the stereoselectivity of the cycli 1.7 -octadiene was cyclized either to the cis or the trans prod zation step. uct, depending on the reaction conditions. Theseobservations More recently, zirconocene dichloride was found to cata were explained by Waymouth and coworkers on the ba... is of lyze the cyclization of non-conjugated dienes in the presence kinetic and thermodynamic preferences arising from different of dialkyl magnesium, Le. their conversion to cyc\oalkanes rates of the zirconacycle formation and transmetalation steps with two alkyl-magnesium-methyl substituents (Eq. (I» [ 20 J. The relative rates of traDsmetaJation for alternative [ 17-19). On the basis of the corresponding stoichiometric intermediates were also considered to be crucial for the enan tioselectivity of asymmetric cyclomagnesations with the '" Corresponding author. Tel.: +49-7531-882629; fax: +49-7531·8&3 dUral ethylene-bridged bis( tetrahydroindenyl) zirconium 137. complex <:n(thindhZrCl! 121). I ansa-Metallocene derivatives part XLII. For part XLI see: H.R.H. We have tried to obtain further cines to the factors which Dannau, M.H. Prosenc. U. Rief, F. S<:haper. H.H. Brintzinger.J. Organomet. control the diastereoselectivity and enantioselectivity in zir Chern., in press. conium-catalyzed cyclomagnesatioos of non-conjugated 'Present addres~': Departamento de Quimica Organica. FJ.cultad de Ciencias Quimicas, Univelliidad Nacional de Cordoba. Ciudad Uni ~ersitaria dienes by investigating the reactions of 1.6- and 1.7-dienes CC 61, SUe. 16.5016 Cordoba. Argentina. with n-Bu~Mg or n-BuMgCI in the presence of catalytic 190

The organic layer was separated and the water layer \\ashed three times with 20 ml portiol1s of ether. The combined organic layers were washed with saturated solutions of

NaHCO.1 and NaCI and dried over anhydrous MgSO~. Yields and isomer ratios were detennincd by gas chromatography (GC), using toluene as internal standard. The identity of each product was confinncd by GC w-injection with an authentic

sample and by the following I.1C NMR data (all in CDCl.1). cis-l,2-Dimetbylcyclohexane (2A) [27], S 15.95. 23.58, 31.32, 34.24; trans-I,2-dimethylcyclohexane (28) [27]. S 20.37,26.93,35.89,39.38; trans-I,2-dimethylcyclopentane (3B) r28). S18.89,23.40, 35.03,42.67; trans-I.2-dimethyl J·O-TBDMS-cyclopentane (48) [191. S 18.10. 20.56, 22.38,26.35,35.48,66.82; N-tert-butyl-rrans-3,4-dimethyl pyrrolidine (5B) (cf. Ref. (29]). S 19.06, 20.56.42.12, Fig. I. Structure of 2.2' -biphenyl-bis( 3.4-dimethylcyclopentadienyl )zir 59.42, 62.45; I, I-dimethyl-trans-3.4-dimethyl-l-silacyclo conium dichloride (1 l. as determined by X-ray diffraction [22); the R pentane (68) [30], 6 - 1.11, - 3.52. 21.89. 18.58; enantiomer is represented; hydrogen atoms are omitted for clarity. spiro ( (rrans-3,4-dimethylcyc\opentane )-1.9' -fluorene] (7B) [20], S 17.87,43.82,49.26,55.18, 119.62, 122.76, 126.64, amounts of the chiral biphenyl-bridged zirconocene 127.5,138.89,156.oI. biph(CsH2Me2 )ZrC11 (1) [22], the geometry of which is less affected by confonnational fluctuations than that of ethylene-bridged zirconocene derivatives [23,24] and hence 2.2. Asymmetric cyclizations more suited for stereochemical model considerations (Fig. 1). The R-enantinmer of 1 was obtained by an asymmetlic transformation procedure (31]; an optical purity of > 95% ee was determined by I H NMR analysis of its (S)-I-phenyl 2. Experimental I-propanol derivative. With this catalyst, cyclomagnesations of 1.6-heptadiene and 1,7-octadiene were conducted and the All work involvir,g air- or moisture-sensitive compounds products collected as described above. The enantiomeric was carried out under an atmosphere of Ar or N1, using excess of the trans isomer was determined by GC with the standard Schlenk or glovebox techniques. NMR spectra were capillary cyc\odextrin column mentioned above. recorded on Bruker AC 250 MHz. WM 250 MHz or DRX 600 MHz spectrometers. Chemical shifts are reported in ppm with the solvent as the internal standard. Gas chromato 3. Results and discussion graphic (Ge) analyses were perfonned on a Perkin-Elmer 8320 GC with a FID detector using a Machery and Nagel SE Treatment of 1.7-octadiene with n-Bu~Mg ( 1.5 equiv.) or capillary column (25 m, 0.25 mm ID) and a 25 m capillary with n-BuMgCI (3 equiv.) in the presence of complex 1 column with heptakis( 6-0-methyl-2,3-di-O-pentyl )-/3- (8 mol. %) in ether l!t room temperature yields, after hydro cyclodextrin as a stationary phase for enantiomer analyses. lysis, mostly cis-I,2-dimethylcyclohexane (2A), together Under N2 atmosphere, diethyl ether was distilled from Na WIth 10-20% of the trans isomer 28 (Eq. (2), Table I). metal/benzophenone. toluene from Na metal. 1.7 -Octadiene. Deuterolysis of the cyclization products with DCI/D~O \,6-heptadiene and diallyl-dimethylsilan were purchased affords 1,2-bis{ deuteriomethyl)cyclohexane in 92% yield. from Adrich; 9,9-diallylfluorene [20]. 4-tert-butyldimethyl This documents the complete formation of dimagnesated siloxy-I,6-heptadiene [251 and N-tert-butyldiallylamine reaction products. i.e. of useful synthons for a wide range of {26] were prepared as described in the literature. further functionalization reactions.

R ,....#' 1(6 mol'!.) x:(M9 NH,CI X • n.BLIMgR -- 1.1. Zirconium-caraly:.ed cyclomagllesation (represelltativl! ~ EI,O MgR HI> x:(. x~ procedure) R=n-Bu.CI 2A·7A 28-78 (2) In a glovebox. 60 mg (0.12 mmol) of complex 1 [221. placed in a 50 ml Schlenk tube, was suspended in 13 ml The stereochemistry of the cyc1omagnesation of l,7-octa diethyl ether. After addition of 2.25 ml (3 equiv., 4.5 mmol) diene is found to be quite sensitive to the reaction tempera of a 2 M solution of n-BuMgCI in ether, the reaction mixture ture: The cis product 2A predominates when the cyclization was stirred for 5 min. Then 0.58 ml (1.50 mmol) of 1.7- is carried out in ether or toluene at room temperature. At octadiene was added. The solution was stirred for 48 h, and H)(tC in toluene, however. the trans diastereomer 2B is the then quenched with a saturated aqueous solution of NH"CL dominant product. Cyclization of 1,6-heptadienes. on the 191

Table I Zilconiurn-calalyzed cydornagnesalion of 1.6- and 1.7-dienes .•

SubslIate Alkyl- Solvent Temperature Pr,;,duct' Yield Ci.s:/rans magnesium (0C) (%) f".1tiu' c:: n-BuMgCI EI.O 25 ex 2A 94 90:10 c: n-Bu2Mg I:~O 25 ex 2A 89 80:20 ~ n-BuMgCI toluene 100 ex 29 91 9:91

~ n-BuMgCI E~O 25 d.. 38 91 9:91

n-Bu Mg 25 38 85 12:88 ~ 2 Etp d ..

,/ TBDMSO~ n-BuMgCI EI,O 25 TBDMSO-(l .. 48 80 20:80

~~ n-BuMgCI EI20 25 r:l... 58 85 30:70 ,.J ;Si~ n-BuMgCI E~O 25 ;sO: 68 86 14:86 ~ n-BuMgCI EllO 25 go: 78 87 8:92 .• Reactions with 8 rnoL% of I and 1.5 equiv. n-Bu,Mg or 3 equiv. n-BuMgCL • Workup with NH"CIIH,O. 'ByGC. other hand, yields predominantly the Irans products 3B-7B lion to cis- or tram-fused metallacyeles ( lOA and 1GB) and even at room temperature. The stereochemistry of all of these relatively slow transmetalations with n-BuMgX, the second reactions is similar to that observed before for reactions cat of which frees the respective cyelomagnesation products alyzed by unsubstituted (C~H5hZrCl! [17-20]. Like other from the Zr center and completes the catalytic cycle by re zirconocene complexes, complex I is also able to cydo generating the instable dibutylzirconocene species 8 magnesate heptadiene substrates containing different hetero (Scheme I ). Previous observations on stoichiometric reac atoms, as shown in entries 6-8 of Table I. tion systems r 10-16) as well as the effects. of changing reac We have funhertested the enantioselectivity of the reaction tion temperatures and reagent concentrations on the observed of I ,6-heptadiene with n-BuMgCl in the presence of8 mol. Ck diastereoselectivities [201 indicate that for l.6-dienes trans of enantiopure (R)-I [31] in ether. After hydrolysis, a 91 Ck fusion is favored in kinetic as well as thermodynamic terms yield of trans-I,2-dimethylcyclopentane was obtained with while fOf 1,7-dienes cis-fusion is faster, but trans-fusion still an optical purity of only 14% ee. The cyclization of 1.7- favored thennodynamically. octadiene with n-BuMgCI and with (RH as a catalyst in OUf observation that very similar product distributions toluene at 100°C, followed by hydrolysis, afforded a 911k arise with the chirally substituted, biphenyl-bridged complex yield of trans-I,2-dimethylcyc1ohexane with a similarly low I as with unsubstituted (C,Hs) ~ZrC11 shows that the stereo eeof 16%. chemical course of the cyclization catalysis - including the Our experimental results can be incorporated into the relative rale of the l,·ansl::.:talalion sleps- is hardly affected mechanistic analysis proposed by Waymouth and coworkers by the ligand geometry of the zU'conocene compiex. Inter [20), which involves the formation of dibutylzirconocene actions within the alternative bicyclic zirconium diolefin che (8) from the zirconocene dichloride and n-BuMgR (R = CI. lates 9A and 9B and their respective cis- and trans-fused n-butyl), its decomposition [32] under formation of alter metallacyc1ic products lOA and lOB thus appear to dominate native diene chelates (9A and 98). their reversible cyeliza- over any interdctions involving the ligand framework with 192

~ ~ Cpl~O:> - Cp"2Zr X = Cp"2Zr X = CPI2Z(,':CX '/-I' ~""..I 10A 9A 10B E~ ~;} fEt l .. Et ~.. ~ \ '-- x r~ Et ~ ?"-' t MgR Et MgR l Et (9R ~Et R, ~\::o CP'2Z~ ( c~S:, 11A "\ 8 Et 11B

NH4CI NH.CI

\ ..... H2O H2O ~ ?:'MgR 12A >:'MgR 12B 28·78 A1ternativ~ ~ ~ Scheme I. catalytic cyclt leading to cis-fused and trans-fused cyclomagnesation products 12A and 128. respectively. regard to the stereochemical course d the cyclization (7J E. Negisbi. T. Takahashi. Acc. Chern. Res. 27 ( 1994) 124. reaction. [8J E. Negishi. SJ. Holmes. J.M. Tour. J.A. Miller. 1. Am. Chern. Soc. 107 (1985) 2568. Entirely in line with this lack of influence of the ligand [91 E. Negishi. F.E. Cederbaum. T. Takahashi. Tetrahedron Lelt. 27 framework on the stereochemical course of the diolefin cycli (1986) 2829. zation is the very low enantiomer excess obtained from [ 10 J E. Negishi. SJ. Holmes. J.M. Tour. J.A. Miller. F.E. Cederbaum. D.R. cyclomagnesations catalyzed by the enantiopure complex R Swanson. T. Takahasbi. J. Am. Cbem. Soc. III (1989) 3336. I. Ourrcsults thus support the notion [20.21] that the metal [111 D.R. Swanson. CJ. Rousset. E. Negishi. T. Takahashi. T. Seki. M. lacyclic intennediates lOA and lOB are in a relatively fast. Saburi. Y. Uchida. 1. Org. Chern. 54 (1989) 3521. [12J W.A. Nugent. D.L. Thorn. R.L. Harlow. J. Am. Cbem. Soc. 109 reversible equilibrium with each other. which is only mini ( 1987) 2788. mally affected by the zirconocene structure. Useful enantio [ \3 J T.V. RajanBabu. W.A. Nugent. D.E Taber. PJ. Fagan. J. Am. Chern. selectivities. as observed by Mori and coworkers [21]. are Soc. 110 (1988) 7128. thus to be expected only if the transmetalation step is ster [14J W.A. Nugent. D.F. Taber. J. Am. Chern. Soc. III (1989) 6435. eoselectively accelerated by interactions of additional sub [ lSI C,J. Rousset. D.R. Swanson. F. Lamaty. E. Negisbi. Tetrahedron Lett. 30 (1989) 5105. stituents at the zirconacyclc with the chiralligand framework. [161 D.F. Taber. J.P. Louey. Y. Wang. W.A. Nugent. D.A. Dixon. R.L. Further studies are aimed at a more detailed molecular Harlow. J. Am. Chern. Soc. 116 (1994) 9457. mechanics analysis of crucial sterlc interactions in these reac [17J K.S. Knigbt. R.M. Waymoulb. 1. Am. Chern. Soc. 113 (1991) 6268; tion systems and at an exploration of the possibility to OrganCJmelallics 13 (1994) 2575. improve enantioselectivities for this type of catalysis by engi [18) D.B. Millward. RM. Waymouth. Organometallics 16 (1997) 1153. neering the rate-limiting transmetalation step in such a way [19J U. Wiscbmeyer. K.S. Knight. RM. Waymouth. Tetrahedron Lett. 33 i\992) 7735. that one of the product enantiomers is released from the Zr 1201 KS. Knight. D. Wang. R.M. Way mouth. J. Ziller. J. Am. Chern. Soc. reaction center faster than its counterpart. 116 (1994) 1845. 1211 Y. Yamaura. M. Hyakulake. M. Mori.J. Am. Chern. Soc. 119 (1997) 7615. Acknowledgements [22J M.E. Huttenloch. 1. Diebold. U. Rief. H.H. Brintzinger. Financial support of this work by a DAAD stipend is grate Organometallics II (1992) 3600. 123) .\. Scbafer. E. Karl. L. Zsolnai. G. Huttner. H.H. Brintzinger. 1. fully acknowledged. Crganomet. Chtlll. 328 (\ 987) 87. 1241 F. Piemonlesi. 1. Camurali. L. Resconi. D. Balboni. A. Sironi. M. Referenc:es Moret. R. Zeigler. N. Piccolrovazzi. Organollletallics 4 (\ 995) 1256. 1251 S.K. Cbaudhary. O. Hernandez. Tetrahedron Lett. ( 1979) 99. [I] M.E. VoJ'pin. VA. Dubovitski. OV. Nogina. D.N. Kursanov. Dokl. 126 J Y. Negi. S. Harada. O. Ishizuka. J. Polym. Sci .. Part A 5 (1967) 1951. Akad. Nauk. SSSR 151 (1963) 1100. [27J T. MUller. 1. Chern. Phys. 37 ( 1962) 1167. ! 2 J S.L. Bucbwald. R.B. Nielsen. Cbem. Rev. 88 ( 1988) 1047. [28J B. William. T. Nurmi. P. Jeffrey. W. Wei. J. Am. Chern. Soc. 10 [3J P.A. Wender. F.E. McOonald.J. Am. Chem. Soc. 112 (1990) 4956. (1987) 2442. [4J G. Angel. E. Negishi. 1. Am. Chern. Soc. 113 (\991) 7424. [29 J G. Pandey. G. Reddy. G. Kumaraswamy. Tetrahedron 50 ( 1994) 8185. (5J M. Akita. H. Yasuda. H. Yamamoto. A. Nakamura. Polybedron 10 [30J J.-t. Boucher. S. Yadon. A. Tomas. B. Viossat. D. Mansuy. (1991) I. Tetrahedron Lett. 37 ( 1996) 3113. 16J M.Mori. N. Uesaka. F. Saitoh.M.Shibasaki.J.Org.Chem. 59 (1994) [311 M. Ringwald. H.H. Brintzinger. manuscript in preparation. 5643. 1321 V.K. Dioumaev. IF. Harrod.Organometallics 16 (1997) 1452.