Formation of Quaternary Stereogenic Centers by Wagner-Meerwein Rearrangement – Synthesis of Optically Active Cyclopentadienyl Complexes from Borneol and Fenchol Christian F¨arbera, Gotthelf Wolmersh¨auserb, and Helmut Sitzmannb a FB 18 der Universit¨at, M¨onchebergstraße 19, D-34109 Kassel, Germany b FB Chemie der TU, Erwin-Schr¨odinger-Straße 54, D-67663 Kaiserslautern, Germany Reprint requests to Prof. Dr. Helmut Sitzmann. Fax: +49-631-205-4676. E-mail: [email protected] Z. Naturforsch. 2009, 64b, 25 – 40; received September 24, 2008 Dedicated to Professor Otto J. Scherer on the occasion of his 75th birthday The development of optically active cyclopentadienyl complexes as enantioselective catalysts calls for simple synthetic procedures for cyclopentadienes with optically active alkyl substituents. While exo-bornyl chloride and exo-fenchyl bromide do not react or exclusively eliminate hydrogen halide with cyclopentadienylmetal compounds in ether solvents or ammonia, they undergo Wagner- Meerwein rearrangement and substitution with cyclopentadienylmagnesium chloride in toluene. The bornyl cation yields racemic exo-bornylcyclopentadiene and partially racemized isocamphyl- cyclopentadiene, but for the fenchyl cation no racemization pathway is available, and the main dia- stereomer among the lithium salts of the ensuing substituted cyclopentadienes can be isolated in 95 % diastereomeric purity by solvent extraction. This material with the IUPAC name lithium (2R)- 2,5,5-trimethylbicyclo[2.2.1]hept-2-ylcyclopentadienide carries an alkyl substituent having no trivial name so far. Exo-norbornylcyclopentadiene could be synthesized in high yield with a similar pro- cedure. The same protocol works with 1-bromoadamantane. The novel alkylcyclopentadienes have R been converted to ferrocenes and molybdenum complexes of the type [Cp Mo(CO)3CH3]. (2R)- 2,5,5-Trimethylbicyclo[2.2.1]hept-2-ylcyclopentadiene with an optical purity of 78 % ee (the optical purity of the starting material fenchol) was converted into an optically active titanocene dichloride and tested in the catalytic hydrogenation of 2-phenyl-1-butene. The hydrogenation product was ob- tained with 31 % ee, which compares favorably with results obtained with other group 4 metallocene dichlorides with one optically active alkyl substituent on each ring ligand. Facile procedures for the synthesis of the starting compounds exo-bornyl chloride and exo-fenchyl bromide based on the tosy- late method have been developed with a tosylate melt or with toluene serving as solvents. Key words: Bornyl Chloride, Fenchyl Bromide, Optical Activity, Enantioselective Hydrogenation, Titanocene Dichloride Introduction and linked bis(cyclopentadienyl) ligands for catalytic applications is often related to the work of Kagan on Catalytically active cyclopentadienyl complexes of menthyl- or neomenthylcyclopentadienide. The suc- early and late transition metals as well as lanthanides cess of this seminal paper is owed to the ease of the are available for a broad variety of synthetic reac- synthetic procedure, which converts readily available tions in organic chemistry. Examples are hydrogena- menthyl tosylate to neomenthylcyclopentadiene by nu- tion [1, 2], hydroboration, hydrosilylation, intramolec- cleophilic substitution with sodium cyclopentadienide ular hydroamination/cyclization [3], hydrophosphina- in 24 % yield [13]. tion, Diels-Alder cycloaddition reactions [4, 5], di- [6], Some odors of commercial interest like the cam- oligo- [7] and polymerization [8, 9] of olefins [10], car- phoraceous odor [14] or the odor of sandalwood [15] boalumination [11], and other transformations. There are associated with terpene derivatives, which have are many cyclopentadienyl ligands with optically ac- been synthesized in considerable variety without em- tive substituents known in the literature [12]. Never- ploying reactions of nucleophiles with terpene alco- theless, the design of optically active cyclopentadienyl hol derivatives. Chiral pool alcohols such as borneol 0932–0776 / 09 / 0100–0025 $ 06.00 c 2009 Verlag der Zeitschrift f¨ur Naturforschung, T¨ubingen · http://znaturforsch.com 26 C. F¨arber et al. · Quaternary Stereogenic Centers by Wagner-Meerwein Rearrangement or fenchol have been the object of mechanistic stud- enylmagnesium chloride and exo-bornyl chloride are ies and analytic work, but have not been used for the reacted in toluene suspension at rather high con- introduction of optically active alkyl groups by nucleo- centrations of at least 1 mol/L around r. t. Use of philic substitution on a preparative scale. We were at- cyclopentadienylmagnesium bromide leads to chlor- tracted by the perspective of optically active cyclopen- ide/bromide exchange, followed by elimination. Under tadienyl ligand syntheses offered by terpene cages. similar conditions endo-bornyl tosylate or endo-bornyl When starting this work, we certainly anticipated ex- chloride react with cyclopentadienylmagnesium chlo- perimental problems related to Wagner-Meerwein re- ride to substitution products as well, albeit very slowly. arrangements, but hoped to find a way to generate A more efficient procedure for the synthesis of exo- novel cyclopentadienyl ligands with optically active bornyl chloride appeared highly desirable, because substituents comparable in yield and number of steps we were unable to reproduce the 65 % yield given to the procedure of Kagan [13]. in lit. [21], and scale-up turned out unsuccessful in our hands as well. Since procedures involving hydro- Results and Discussion gen chloride formation would likely cause Wagner- Meerwein rearrangement reactions, we directed our at- Initial attempts at a nucleophilic substitution in tention towards the so-called “tosylate method” [22], bornyl tosylate with sodium cyclopentadienide failed which should allow for conversion of endo-bornyl to- to yield any detectable amount of substitution product sylate with alkali chlorides or magnesium chloride in in tetrahydrofuran, diethyl ether, dimethoxyethane, or acetone or ethereal solvents to the desired product by liquid ammonia. There was either no reaction, or (at el- an SN2 mechanism with inversion. We were unable evated temperatures) only elimination products could to find examples for the preparation of bicyclic alkyl be detected by GC-MS. Similar observations were halides like bornyl halides via the tosylate method in made when potassium or lithium cyclopentadienide or the literature, and experiments with different salts in cyclopentadienylmagnesium chloride were employed acetone, dimethoxyethane or tetrahydrofuran failed to under similar conditions in ethereal solvents, respec- accomplish the exchange of tosylate for chloride or tively. bromide. As alternative starting compounds endo-bornyl Magnesium dichloride tetrahydrofuran adduct (1 : 2) chloride, available by addition of hydrogen chloride could be used for the conversion of molten endo-bornyl to β-pinene in chloroform or petroleum ether [16 – tosylate to exo-bornyl chloride (1) in the absence of 18], albeit with significant fenchyl chloride contami- solvent: nation [19], and exo-bornyl chloride were taken into consideration. The most facile procedure given in the literature for the exo derivative is the selenium dioxide- catalyzed conversion of borneol with chlorotrimethyl- silane [20], but in our hands only the silyl ether of borneol could be distilled from the reaction mixture The exo-bornyl chloride obtained showed the same in almost quantitative yield. The procedure given by optical purity as the material prepared according to Marinetti [21] allowed us to prepare the desired exo- the literature procedure ([α]20 = 41.02◦; c = 17.3; bornyl chloride from endo-borneol with two equiv- Et2O [21]). alents of triphenylphosphane oxide in boiling tetra- The same method is also useful for the synthesis chloromethane. The bornene by-product could be re- of exo-bornyl bromide (2), if the bis(tetrahydrofuran) moved almost completely by repeated product subli- adduct of magnesium bromide is used. The bro- mation. mide obtained in 40 % yield is accompanied by elim- Experiments with cyclopentadienyllithium, -sodium ination products. The literature method uses bor- or -magnesium compounds were all unsuccessful. neol, bromomethane, triphenylphosphane, and 1,2,4- Only with cyclopentadienylmagnesium chloride in triazolidine-3,5-dione and promises a 75 % yield [23]. toluene exo-bornyl chloride gave a trace of a product Subsequent test reactions with 2 regarding nucleo- with the GC retention time and mass expected for a philic substitution with cyclopentadienylmagnesium substitution product. The desired substitution reaction bromide led to extensive elimination without forma- in our hands works reproducibly when cyclopentadi- tion of the desired substitution products. C. F¨arber et al. · Quaternary Stereogenic Centers by Wagner-Meerwein Rearrangement 27 Table 1. Crystal structure determination of complexes 3-Mo, 4-Mo, 7-Fe, and 11-Fe. 3-Mo 4-Mo 7-Fe 11-Fe Formula C19H24MoO3 C19H24MoO3 C30H38Fe C30H42Fe −1 Mr,gmol 396.32 396.32 454.45 458.49 Crystal size, mm3 0.60 × 0.40 × 0.20 0.50 × 0.50 × 0.42 0.52 × 0.10 × 0.02 0.44 × 0.16 × 0.08 Space group Pbca P212121 P1¯ P21 a, A˚ 14.2276(8) 10.1324(8) 7.2385(18) 7.3302(6) b, A˚ 12.6474(11) 11.7235(7) 11.127(3) 10.5777(8) c, A˚ 20.1795(12) 15.2964(9) 13.992(4) 15.5927(16) α, deg 90 90 84.75(4) 90 β, deg 90 90 89.48(3) 98.646(11) γ, deg 90 90 86.60(3) 90 V, A˚ 3 3631.1(4) 1817.0(2) 1120.2(5) 1195.27(18) Z 8422 T , K 293(2) 293(2) 193(2)