Catalytic Enantioselective Hydrogenation of 1,1-Disubstituted Alkenes

Organometallics 1995,14, 4865-4878

4865

Catalytic Enantioselective Hydrogenation of 1,l-DisubstitutedAlkenes with Optically Active Titanocene and Zirconocene Complexes Containing either Identical or Different Ligands Leo A. Paquette,” Mark R. Sivik,laEugene I. Bzowej,lb and Kenetha J. StantonlC Evans Chemical Laboratories, The Ohio State University, Columbus, Ohio 43210 Received April 18, 1995@ The synthesis of a variety of nonbridged optically active C2- and C1-symmetric titanocenes and zirconocenes is reported together with a detailed investigation of the ability of these complexes to effect the catalytic asymmetric hydrogenation of 2-phenyl-1-butene and 24anaphthyl)-1-butene. The respective dihydro products are shown to be produced with enantiomeric excesses ranging from 4% to 69%. The absolute configuration of these 2-arylbutanes was noted to be sensitive to the three-dimensional characteristics of the particular bicyclo-fused ligand involved. For a series of verbenone-related metallocenes, an increase in the size of a substituent positioned a and syn to the metal center was found to be unfavorable for stereoinduction. This phenomenon has been rationalized in transition state terms, with the alkene approaching laterally to engage in hydrogen atom transfer. The three-dimensional stereochemical model advanced in explanation of the observed catalytic selectivity underscores the development of steric biases during olefin coordination to the reactive metal hydride intermediate. Optically active titanocene and zirconocene complexes are in increasing demand as a direct result of their ability to effect asymmetric homogeneous catalytic reactions of various typesa2J The classical means for generating chirality in these systems involves the elaboration of a stereogenic metal enter.^^^ However, the considerable difficulty associated with the preparation of nonracemic 1 and related molecules severely

1

3

2

c;

CI

4

5

reduces their serviceability. Alternatively, one or both @Abstractpublished in Advance ACS Abstracts, October 1, 1995. (1)(a) National Needs Fellow, 1989-1990; Amoco Foundation Fellow, 1991.(b) NSERC (Canada) Postdoctoral Fellow, 1994-1995. (c) University Fellow, 1991-1992. (2)Duthaler, R. 0.; Hafner, A. Chem. Rev. 1992,92,807. (3)Halterman, R. L. Chem. Rev. 1992,92,965. (4)(a)Moi’se, C.; Leblanc, J.-C.; Tirouflet, J. Tetrahedron Lett. 1974, 1723.(b) Morse, C.; Leblanc, J.-C.; Tirouflet, J. J.A m . Chem. SOC.1976, 97,6272. (5)(a) Brunner, H. Acc. Chem. Res. 1979,12,250.(b) Brunner, H. Adv. Organomet. Chem. 1980,18,151.

cyclopentadienyl ligands may be chiral. The earliest members of this class were made available by attaching a single chiral auxiliary such as menthyl to one of the rings as in 2.6 Subsequently, enantiomerically pure complexes derived by fusing cyclopentadiene rings to naturally occurring terpenes, e.g. 3, made their appearan~e.’,~In the past several years, these metallocenes have been joined by bridged bis(cyclopentadieny1)complexes typified by 49 and others constructed of C2symmetric annulated cyclopentadienes such as 5.l0 Ellis et al. have itemized several of the possible complications associated with the preparation of belted metallocenes related to 4.11 These include predominant or exclusive formation of Umeso”isomers with loss of chirality,12formation of diastereomeric complexes other than the desired Cz-symmetric species,13J4and related (6)Cesarotti, E.; Kagan, H. B.; Goddard, R.; Kriiger, C. J . Organomet. Chem. 1978,162,297. (7)(a)Halterman, R. L.; Vollhardt, K. P. C. Tetrahedron Lett. 1986, 27, 1461.(b) Halterman, R. L.; Vollhardt, K. P. C. Organometallics 1988,7,883. (8)(a) McLaughlin, M. L.; McKinney, J. A.; Paquette, L. A. Tetrahedron Lett. 1986,27, 5595. (b) Paquette, L. A,; McKinney, J. A.; McLaughlin, M. L.; Rheingold, A. L. Tetrahedron Lett. 1986,27,5599. (c) Paquette, L. A.; Moriarty, K. J.; McKinney, J . A,; Rogers, R. D. Organometallics 1989,8, 1707.(d) Paquette, L. A.; Moriarty, K. J.; Rogers, R. D. Organometallics 1989,8,1506.(e) Moriarty, K.J.; Rogers, R. D.; Paquette, L. A. Organometallics 1989,8,1512.(0 Sivik, M. R.; Rogers, R. D.; Paquette, L. A. J . Organomet. Chem. 1990,397, 177. (E) Rogers, R. D.; Sivik, M. R.; Paquette, L. A. J. Organomet. Chem. 1393,250,125. (9) (a) Gibis, K.-L.; Helmchen, G.; Huttner, G.; Zsolnai, L. J. Organomet. Chem. 1993,445, 181. (b) Chen, Z.;Halterman, R. L. Svnlett 1990.103.(c) Chen. Z.:Eriks, K.; Halterman, R. L. Organoketallics 1991,IO,3449. (10)Halterman, R. L.;Vollhardt, K. P. C.; Welker, M. E.; Blaser, D.; Boese, R. J.Am. Chem. SOC.1987,109,8105. (11)Ellis, W. W.; Hollis, T. IC;Odenkirk, W.; Whelan, J.; Ostrander, R.; Rheingold, A. L.; Bosnich, B. Organometallics 1993,12,4391. (12)Bandy, J . A,; Green, M. L. H.; Gardiner, I. M.; Prout, K. J. Chem. SOC.,Dalton Trans. 1991,2207. (13)Burk, M. J.; Colletti, S. L.; Halterman, R. L. Organometallics 1991, 10, 2998.

0276-733319512314-4865$09.00/00 1995 American Chemical Society

Paquette et al.

4866 Organometallics, Vol. 14, No. 10, 1995 ~hen0mena.l~ Notwithstanding, chiral ansa-titanocenes and zirconocenes possessing a bridge at the 1-and 1'positionsl6 are highly effective catalysts in enantioselective s y n t h e s i ~ , including ~ ~ - ~ ~ ~stereoselective ZieglerNatta p o l y m e r i z a t i ~ n . ~ ~ J ~ ~ ~ ~ ~ The utilization of Cz-symmetric annulated cyclopentadienyl ligands has been highly touted because they are homotopic and metal complexation to either equivalent nface affords only a single diastereomer, e.g., 6." While this is true, C1-symmetric l,2-disubstituted cyclopentadienyl ligands should not be downgraded. The diastereotopic nature of their two faces offers the possibility that diastereomeric mixtures of complexes will result. However, one face of the anion can often be engaged in reaction in advance of the other by virtue of steric control8 or by proper modulation of monomerdimer equilibria involving lithium ionsz1 and reaction temperature.22 Furthermore, net inversion of n-facial selectivity can be readily achieved by silylation on the less hindered surface followed by electrophilic attack with inversion of configurati~n.~~ Accordingly, the number of chiral catalysts available from a C1-symmetric cyclopentadiene can be more than double that capable of being produced by Cz-symmetric systems,22b thus providing improved opportunity for assessing those transition states operational in asymmetric reactions and their stereodifferentiatingrelationship to the ligands involved.

Results Selection of Olefinic Substrates. The pioneering studies of Cesarotti and KaganZ4served to define the enantioselective hydrogenation of 2-phenyl-1-butene (8Iz5 as the benchmark process for evaluating the

6

7

asymmetric inducing ability of cyclopentadienyl-derived metallocenes. The absolute configurations of both enan~

~~~

(14) Hollis, T. K.; Rheingold, A. L.; Robinson, N. P.; Whelan, J.; Bosnich, B. Organometallics 1992, 11, 2812.

(15)Rheingold, A. L.; Robinson, N. P.; Whelan, J.; Bosnich, B. Organometallics 1992, 11, 1869. (16) Brintzinger, H. H. In Transition Metals and Organometallics as Catalysts for Olefin Polymerization; Kaminsky, W., Sinn, H., Eds.; Springer-Verlag: Berlin, Heidelberg, 1988. (17) (a)Collins, S.; Kuntz, B. A.; Hong, Y. J . Org. Chem. 1989, 54, 4154. (b) Collins, S.; Hong, Y.; Taylor, N. J. Organometallics 1990,9, 2695. (c) Collins, S.; Hong, Y.; Ramachandran, R.; Taylor, N. J. Organometallics 1991, 10, 2349. (18)(a) Grossman, R. B.; Doyle, R. A.; Buchwald, S. L. Organometallics 1991, 10, 1501.(b) Grossman, R. B.; Davis, W. M.; Buchwald, S. L. J. Am. Chem. Soc. 1991, 113, 2321. (c) Willoughby, C. A.; Buchwald, S. L. J.Am. Chem. Soc. 1992,114,7562. (d) Broene, R. D.; Buchwald, S. L. J . Am. Chem. Soc. 1993, 115, 12569. (e) Lee, N. E.; Buchwald, S. L. J.Am. Chem. Soc. 1994,116,5985. (0Willoughby, C. A.; Buchwald, S. L. J . Am. Chem. Soc. 1994,116, 11703. (19) (a)Waymouth, R.; Pino, P. J.Am. Chem. SOC.1990,112,4911. (b) Coates, G. W.; Waymouth, R. M. J. A m . Chem. Soc. 1991,113,6270. (20) For selected recent citations, see: (a) Ewen, J. A.; Jones, R. L.; Razavi, A.; Ferrara, J . D. J. Am. Chem. SOC.1988, 110, 6255. (b) Collins, S.; Gauthier, W. J.; Holden, D. A.; Kuntz, B. A.; Taylor, N. J.; Ward, D. G. Organometallics 1991, 10, 2061. (21) (a) Paquette, L. A.; Bauer, W.; Sivik, M. R.; Biihl, M.; Feigel, M.; Schleyer, P. v. R. J . Am. Chem. Soc. 1990, 112, 8776. (b) Bauer, W.; O'Doherty, G . A.; Schleyer, P. v. R.; Paquette, L. A. J. Am. Chem. Soc. 1991,113,7093. (cf Bauer, W.; Sivik,M. R.; Friedrich, D.; Schleyer, P. v. R.; Paquette, L. A. Organometallics 1992,11,4178. (d) Paquette, L. A.; Sivik, M. R.; Bauer, W.; Schleyer, P. v. R. Organometallics 1994, 13, 4919.

tiomers of 2-phenylbutane are consequently firmly established. The S isomer has been reported to exhibit a maximum optical rotation ([a];') of f22.7 (c 1.0, ethanol),26 and this value has served as a point of reference in the present study. The higher naphthalene analogue 7 has also been examined in order to assess the extent t o which a somewhat greater disparity in the relative size of the substituents flanking the double bond would impact on enantioselection. In addition to a larger steric differentiation between the geminal substituents, this substrate offers an additional aromatic ring for possible n-directing capabilities and greater hindrance to rotation about the u bond connecting the naphthyl ring system to the olefinic centersz7 Acquisition of the nonracemic dihydro form of 7, uiz. 2-(a-naphthyl)butane (8),was originally reported by Menicagli and co-workers.28 Beginning with optically active 24a-naphthyl)propionic acid, they were able to demonstrate that the enantiomer has the S configuration. Enantiomeric purity was not achieved, and the optical rotation of the completely homogeneous antipode was projected to be [a1i5+25.4 (neat). Since the survey nature of this investigation was not projected to provide quantities of 8 adequate for optical assay in undiluted form, we initially set out to develop an enzymatic route to this hydrocarbon for the purpose of defining a broader range of usable [ab values. The application of Kazlauskas' procedurez9to racemic ester 12 provided alcohol 14 of only 24% ee as determined by Mosher ester analysis30(Scheme 1). Following reductive removal of the hydroxyl group, (-1-8 was obtained. This sample exhibited [a]:' -6.6 (neat) or [a]:' -1.4 (c 2.3, ethanol). On this basis, the maximum rotation for neat and solution samples of 8 would be -27.2 and -5.7, respectively. These data were considered to be inconsistent with Menicagli's reports, the discrepancy perhaps arising because of the low optical purity of our sample and the large extrapolation involved. An alternative means for producing 8 by enzymatic means was therefore pursued. In an adaptation of the method of Bloch,3l ester 16 was hydrolyzed at pH 7.3 with horse liver esterase (Scheme 2). After 30 h, optically active acid 17 was isolated in 32% yield, exhibited a rotation of -133.6 in CHzClz, and was tentatively assigned the R configuration by analogy to

+

(22) (a) Paquette, L. A.; Moriarty, K. J.; Meunier, P.; Gautheron, B.; Sornay, C.; Rogers, R. D.; Rheingold, A. L. Organometallics 1989, 8, 2159. (b)Sornay, C.; Meunier, P.; Gautheron, B.; ODoherty, G. A.; Paquette, L. A. Organometallics 1991, 10, 2082. (23) Paquette, L. A.; Sivik, M. R. Organometallics 1992, 11, 3503. (24) (a)Cesarotti, E.; Ugo, R.; Kagan, H. B. Angew. Chem., Int. Ed. Engl. 1979,18,779. (b) Cesarotti, E.; Ugo, R.; Vitiello, R. J.Mol. Catal. 1981, 12, 63. (2.5) Lardicci, L.; Menicagli, R.; Salvadori, P. Guzz. Chim. Ital. 1968, 98, 738. (26) Craig, J. C.; Pereira, W. E., Jr.; Halpern, B.; Westley, J. W. Tetrahedron 1971,27, 1173. (27) Anderson, J . E.; Hazelhurst, C. J . J . Chem. Soc., Chem. Commun. 1980, 1188. (28) (a) Menicagli, R.; Lardicci, L.; Botteghi, C. Chem. Ind. 1974, 920. (b) Menicagli, R.; Piccolo, 0.; Lardicci, L.; Wis, M. L. Tetrahedron 1979,35, 1301. (c) Piccolo, 0.;Menicagli, R.; Lardicci, L. Tetrahedron 1979,35, 1751. (d) Menicagli, R.; Piccolo, 0. J. Org. Chem. 1980,45, 2581. (29)Kazlauskas, R. J. Org. Synth. 1992, 70, 60. (30) (a) Dale, J. A.; Dull, D. L.; Mosher, H. S. J. Org. Chem. 1969, 34, 2543. (b) Dale, J. A.; Mosher, H. S. J . Am. Chem. Soc. 1973, 95, 512. (31) Ahmar, M.; Girard, C.; Bloch, R. Tetrahedron Lett. 1989, 30, 7053.

Hydrogenation of 1,l-Disubstituted Alkenes

Organometallics, Vol. 14, No. 10,1995 4867

Scheme 1

Chart 1

4

$OH

0

-

10

m-

19

20

21

22

24

25

-

C

d

12

11

ent-20

e

13

14

H

H

HCH3

OTs

& -Qb I

23

4

(fl14-1-8

15

LDA (> 2 equiv), THF, HMPA, 0 "C; CH3CH21. LiAIH4, THF,

A. CHa(CH&C(O)CI, Et3N, ether, 0 OC. *Bovine pancreas acetone powder, pH 7 phosphate bufler, ether; 1 N NaOH dropwise to maintain pH 7.2. e TsCl,py, CH2CI2,0 OC. 'Li(B(CH2CH3)]H,THF.

26

27

29

ent-29

28

Scheme 2 0

- & a

16

17

H3

b-d

(W4-8 0.5 M NaOH dropwise to maintain pH 7.3. LiAIH4,THF, 0 "C. TsCI, py, CH2C12,0 OC --f rt. dLi(B(CH2CH3))H,THF. a Horse liver esterase, pH 7 phosphate buffer, THF;

earlier results.31 Lithium aluminum hydride reduction of 17 produced an alcohol determined to have an optical purity of 87.3% after Mosher ester analysis.30 The subsequent conversion to 8 gave material that displayed an [a]: of -22.2' (neat) or -4.38 in ethanol solution. Correction for the existing level of enantiomeric excess increases these values to -25.4 (neat) and -5.01 (ethanol), thus confirming Menicagli's configurational assignment and maximum rotation. The Choice of Chiral Complexes. The optically active titanocene complexes that were evaluated as asymmetric hydrogenation catalysts are compiled in Chart 1. The syntheses of 18,8d19,8c,20,8e ent-20,8f26,6 28Fd and 2gEehave been previously described. The

30

remainder are new, and the details of their preparation are provided in the Experimental Section. Note that dichlorides 26 and 27 are diastereomerically related. This feature is made possible because of the readiness with which unnatural (1R,5R)-(+)-verbenone ( 3 1 ) is available by the oxidation of (1R)-(+)-a-~inene.~~ The series ent-20-22 was prepared in an effort to assess the consequences of increased steric bulk by the pair of "inside" substituents on hydrogenation enantioselectivity. The titanocenes 21 and 22 were accessed in a manner paralleling that developed for ent-20 (Scheme 3). Following addition of the appropriate homocuprate to 31, ketones 32 were individually treated with vinylmagnesium bromide at 0 'C. Addition occurred stereoselectively under steric control of the apical methyl group to give 33b,c exclusively. Following dehydration with activated basic alu-mina (activity I) and dibromocarbene addition under phase transfer conditions, recourse was made to the Skattebal rearrangement33 for the purpose of annulating the cyclopentadiene ring onto the pinane framework as in 36. The lithium cyclopentadienides 37 were smoothly transformed into (32) Sivik, M. R.; Stanton, K. J.; Paquette, L. A. Org. Synth. 1996,

72,57.

(33) (a) Skattebel, L.Tetrahedron 1967,23,1107.(b)Butler, D. N.; Gupta, I. Can. J. Chem. 1978,56,80.( c ) Charumilind, P.; Paquette, L. A. J.Am. Chem. SOC.1984, 106, 8225.

Paquette et al.

4868 Organometallics, Vol. 14, No. 10, 1995

Table 1. Enantioselective Hydrogenation of 6 with "itanocene Complexes" expt no. complex T,'Clcocatalyst [a]:' (CZH~OH) % ee

Scheme 3

31

1 2 3 4 5 6 7

32

8 33

9 10 11 12 13 14

34

f

35

18 19 20 ent-20 21 22 23 24 25 26 27 28 29 ent-29

-2Oln-BuLi -2Oln-BuLi -ZOln-BuLi -2Oln-BuLi -2Oln -BuLi -2Oln -BuLi -2Oln-BuLi -2Oln-BuLi -2Oln -BuLi -2Oln-BuLi -2Oln-BuLi -2Oln-BuLi -2Oln-BuLi -2Oln-BuLi

-2.11 -7.88 -10.1 $15.5 +2.8 $7.4 f3.8 -7.6 -2.3 +6.2 +1.5 -0.75 -3.64 +5.67

9 35 44 69 12 33 17 33 10 27 7 4 17 25

"All reactions were performed in toluene under 20 psi of hydrogen according to method A. The chemical yields were quantitative.

36

37 a, R = CH3; b, R = CH(CH3)2; C, R = CsH5 a CHaLi, CUI, Me3SiCI or RMgCI, CuBr*SMe2,HMAP or DMAP, THF, -78 "C. CH2=CHMgBr,THF, 0 "C. Basic Ai2O3,150 "C, 0.5 Torr. dCHBr3,50% NaOH, TEBA, ethanol, CH2C12. "CH3Li, ether, 0 OC. 'n-BuLi, ether-hexanes, 0 "C. TiCI3, DME, -78 "C to reflux; conc HCI, air.

*

Chart 2

4 38

40

39

41

the stereochemically homogeneous titanocenes by conventional means. The structural features of the catalysts span a substantial range: (a) symmetrical dimers in which both chiral ligands are constituted of bridged cyclopentadienyl units; (b) complexes which feature two chiral cyclopentadienyl units of different type; (c) titanocenes whose chirality is dictated by one ligand only, with the other being constituted of the parent Cp or of the isodicyclopentadiene unit with coordination t o its exo face. By comparison, a much smaller group of zirconocenes was examined (Chart 2). All are of the Cz-symmetric dimer type. The first two (38,39)have been described previously.8c-e Asymmetric Hydrogenation Studies. The first series of reductions to be investigated involved 2-phenyl-

l-butene (6) and the titanocene dichlorides depicted in Chart 1. Typically, the hydrogenations were carried out on 2-4 mmol of olefin substrate in the presence of 0.020.04 mmol of catalyst, and -0.2-0.4 mmol of cocatalyst. The use of Red-Al for activation, in the manner originally reported by C e ~ a r o t t i was , ~ ~ briefly examined. However, the Brintzinger protocoP4 involving the use of an alkyllithium proved to be more serviceable and was adopted throughout this investigation. The results are compiled in Table 1. Several relevant conclusions can be drawn from these data. In general, complexes that are Cz-symmetric deliver 2-phenylbutane at higher levels of optical purity than do C1-symmetriccomplexes. Experiments 2-4 and 6 are particularly noteworthy. Similar conclusions were arrived at by Vollhardt.lo Of additional interest is the fact that the chirality induced by these titanocenes, which are substituted with alkyl groups on the pair of carbon atoms directly linked to the cyclopentadienyl ligands, have the capacity for inducing a higher level of enantioselection than their counterparts with hydrogens in these positions. The comparisons of 18 versus ent-20 and of 28 with 29 are exemplary. Within the pinane subfamily of catalysts, ent-20 gave rise to the highest level of asymmetric induction observed (69%). The isopropyl (21) and phenyl homologs (22) seemingly have become too sterically congested and consequently limit facial discrimination as the alkene approaches. Although an upper limit of steric feasibility can be exceeded, advantages normally accrue to catalysts which carry structurally larger ligands. For example, C1-symmetric complexes such as 23 and 24, which feature an isodicyclopentadienyl component, produce 2-phenylbutane in a more optically enriched state than comparable structures, e.g., 28, 29, and ent-29, having only a cyclopentadienyl ring. As expected,35 the catalytic activity of the chiral zirconocenes 38-41 was considerably lower than the titanium compounds. While the experiments defined in Table 1 were standardized to a temperature of -20 "C, a reaction time of 48 h, and a hydrogen pressure of 20 psi in order to achieve complete reaction, 38-41 proved unreactive under these conditions. Reduction did occur slowly at +20 "C and 40 psi (Table 2). (34)Smith, J. A.; Brintzinger, H. H. J.Orgunomet. Chem. 1981,218, 159. (35)Cuenca, T.;Flores, J. C.; Royo, P. J. Orgunomet. Chem. 1993, 462, 191.


Organometallics, Vol. 14, No. 10, 1995 4869

Table 2. Asymmetric Hydrogenation of 6 with Zirconocene Complexesa expt no.

complex

15

38 39

16 17 18

40 41

reacn time, days

T, Wcocatalyst

P, psi

% conversion

config of product

% eeb

7 4 10 32

2Oln-BuLi 2Oln-BuLi 2Oln-BuLi 20/CH3Li

40 20 40 40

'99 49 > 99 > 99

S R R R

15 4 53 4

Method D was followed. The optical rotations were performed in 95% ethanol.

Table 3. Enantioselective Hydrogenation Results for 7 (Method B) expt no. 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36

complex

19 ent-20 ent-20 ent-20 ent-20 23 23 25 25 26 26 ent-29 ent-29 30

30 30

38 40

T, "C/cocatalystb

P, psi % conversion A. Titanocene Catalysts

22/CH3Li 29 96 > 99 -18lCH3Li 28 100 22/CH3Li 28 1 98 22/CH3LiC 2 2ln -BuLiC 39.5 100 221CH3Li 26 100 -30 to -15/n-BuLi 28 97 22/CH3Li 20 '99 22ln-BuLi 20 93 22/n-BuLiC 29 100 221n-BuLid 29 22 100 22/CH3Li 27 100 22/n-BuLi 26 -78KH3Li 28 100 22/CH3Lie 28 100 100 22ln-BuLif 29 B. Zirconocene Catalysts (Method D) 2Oln-BuLi 40 17 2Oln-BuLi 40 44

config of product

% eea

R S S S S S S R R S S S S S S S

16 61 53 50 53 28 32 2 8 61 60 17 25 15 13 16

S R

9 14

a The optical rotations were determined either on neat samples or in 95% ethanol solution. The reactions were performed in toluene solvent except where noted. Hexane was the reaction medium; expt 23 required 96 h to go to completion. The reaction time was 163 h. e Reduction was complete in 15 min. f Reduction was complete in 30 min.

Reaction times of 4-32 days were necessary. No parallel trend in enantioselection was seen relative to the titanocene analogues. While 38 (15% ee) was more effective than 18 (9% ee), 39 (4% ee) was substantially inferior to 19 (35% ee). Notwithstanding these differences, the higher reactivity of titanium catyalysts provides greater utility for this class of compounds than the zirconocenes for enantioselective hydrogenation. In general, enantioselectivity increases for the naphthyl olefin 7 relative to 6 in the examples studied (Table 3). A comparison of experiments 7 and 25 involving 23 as catalyst revealed that the level of chiral induction increases from 17% to 32% ee. The selectivity normally increased with decreasing temperature, although little effect was observed in a number of cases. A dependence on cocatalyst was also noted. In general, recourse t o methyllithium increased the reactivity of the hydrogenation system relative t o when n-butyllithium was present. A companion effect often observed was a decrease in asymmetric inducing ability with methyllithium. This phenomenon is clearly evident upon inspection inter alia of experiments 22123, 26/27,301 31,and 33134. The reactivity of dimethyltitanocene 30 was greatly elevated relative to the dichlorides. Quite unexpectedly, however,35 the use of a cocatalyst was required to achieve reduction. Both alkyllithiums are effective, with n-butyllithium delivering product of modestly higher ee than that exhibited by methyllithium as usual. Solvent effects were briefly examined with ent-20 as the probe precatalyst. In this instance, the activity of the hydrogenation system was found t o be significantly increased in hexane relative to toluene. In the first of these solvents, 7 was completely reduced in approximately 1 h at 22 "C (expt 22). An increase in the

reaction time to 40 h or more was necessary to reach the same point when toluene was the medium (expt 21). The percent ee in the naphthylbutane was very similar in the two cases (53 vs 50%). In our estimation, this solvent effect will prove to be a general phenomenon. Discussion X-ray crystallographic analyses of several of the nonbridged metallocene systems utilized in this study have been detailed earlier. In the solid state, the CZsymmetric titanocene ent-20af and zirconocene 3g8" adopt three-dimensional characteristics featuring in common a significant out-of-plane tilting of the coordinating five-membered rings. However, they differ widely in the mutual orientation of their ligands. Their distinctive conformational arrangements, which range from synclinal for the Ti example to distal for the Zr complex, are not considered to be of fundamental significance since open metallocenes are recognized t o possess low-energy torsional potentials such that rotation about the central metal in either direction is virtually unimpeded.36 Crystal packing forces are likely responsible for the observed conformational features. Relevantly, the "freezing-out" of a bent metallocene rotamer in solution has only recently been observed in chiral nonbridged bis(indeny1) complexes of special design.37 It has been postulated that reductions of the type examined here involving 2 equiv of n-butyllithium (36)Doman, T. N.; Hollis, T. K.; Bosnich, B. J.Am. Chem. Soc. 1996, 117, 1352.

(37) Erker, G.; Aulbach, M.; Knickmeier, M.; Wingbermiihle, D.; Krtiger, C.; Nolte, M.; Werner, S. J.Am. Chem. Soc. 1993,115,4590.

4870 Organometallics, Vol. 14,No. 10,1995 Scheme 4

A

proceed with the conversion of a Ti(IV) to a Ti(II1) intermediate via ,&hydride e l i m i n a t i ~ n The . ~ ~result~~~ ing titanocene hydride then assumedly serves as the catalytic species involved in the hydrogen transfer process. If this mechanistic profile holds for the present hydrogenation conditions, then the variations in asymmetric induction which accompany the change in aryl substitution in the alkene are not adequately accommodated if the complex adopts that conformation in which the ligands are distal (Scheme 4; the tilting of the ligands about the Ti is not accentuated). Before an analysis is carried out, it must be recognized that the observed enantioselectivity may be a direct consequence of the kinetics of complexation of the alkene if the subsequent insertion step is facile. Alternatively, the distribution of dihydro enantiomers may be the product of a preequilibrium involving diastereomeric complexes if the insertion step is more energy demanding. All of this is further complicated if the insertion step itself is reversible. We have no information on any of these options. Nonetheless, adaptation of the Lauher-Hoffmann theoretical analysis40 for the maximization of metal hydride HOMO/olefin LUMO overlap, as pioneered by Buchwald for related c o m p l e x e ~ , lto ,~~ our transition state models has several implications. The spatial orientation of the valence orbitals at the metal are so directed that incorporation of the olefin very likely occurs laterally as shown in B and C. Once in the chiral cleft, the alkene becomes subject to hydride transfer from the metal. Reductive cleavage of the titaniumcarbon bond ensues. The issue of the extent to which B and C may be formed is, of course, related directly to the steric factors present in the ligands and the bulk of those substituents present on the double bond. A reasonable sensitivity to spatial demands can be anticipated. Transition state B is destined to lead to dihydro product of the S configuration, while passage via C will (38)(a) Bercaw, J. E.; Brintzinger, H. H. J.Am. Chem. SOC.1969, 91, 7301. (b)Bercaw, J. E.; Marvich, R. H.; Bell, L. G.; Brintzinger, H. H. J.Am. Chem. SOC.1972,94, 1219. (39) Berk, S. C.; Kreutzer, K. A.; Buchwald, S . L. J.Am. Chem. SOC. 1991, 113,5093. (40) Lauher, J. W.; Hoffmann, R. J.Am. Chem. SOC.1976,98,1729.

Puquette et al.

give rise to the R enantiomer. The experimental facts are that 6 and 7 are converted by ent-20 predominantly into the respective (S)-Zarylbutane. From among the C2-symmetric titanocenes, ent-20 delivers reduction product in the highest percent enantiomeric excess (69% for 6 , 61% for 7 ; expts 4, 20). Notably, the verbenonederived ligand in ent-20 projects only a methyl substituent in that direction syn to the metal center. The higher homologs 21 and 22, which have isopropyl and phenyl groups located at the same interior sites, are clearly less effective asymmetric catalysts (expts 5,6). Our working model must take account of these facts. Other trends are evident. Although pinane derivative 18 lacks comparable substituents a to the Cp ring and is consequently less able to transfer chirality, sufficient recognition is achieved between the catalyst and olefin to induce product stereochemistry that is opposite to that realized in the preceding reductions (expt 1). Transition state C may gain greater kinetic importance when these methyl subsituents are lacking. The CIsymmetric complexes 23, 24, and 27-30 are only modestly effective at enantioselective hydrogenation (expts 7,8,11-14,24,25,30-34). The related complex 26 has proven generally more effective toward both alkenes (expts 10,28,29). The consequences of varying the alkene structure on substrate stereoselectivity are also reflected in the data compiled in Tables 1 and 3. For the titanocenes 19 and ent-20, a decrease in the observed enantiomeric excess materializes when progressing from 6 to 7 . For precatalysts 26 and ent-29, the percent ee’s remained essentially constant for both olefins. In contrast, the behavior of 23 and 26 is distinguished by an increased ee for the a-naphthyl derivative. The geometric features present in B, although in conformance with the requirement that S dihydro product be formed, are not fully accommodating of the experimental facts. If the assumption is made that the aryl substituent in the alkene assumes a local conformation which maintains conjugative overlap with the neighboring olefinic center until the hydrogen atom is transferred from the metal, then the a-naphthyl group would need to be positioned as in B and be energetically disadvantaged because of its enforced proximity to the ethyl substituent. This steric interaction need not develop in C because the a-naphthyl subunit is no longer oriented proximal to the verbenone ligands. In addition, the methano bridge experiences less steric compression in C due to its proximity to the ethyl group of the olefin as compared to B where a methano/aryl interaction operates. This balance of forces should facilitate preferred passage via C, a conclusion at odds with its role as precursor to R dihydro product. On the other hand, much of the close contact in B is skirted if the verbenone-derived ligands are oriented in a more gauchelike arrangement (Scheme 5). According t o this model, the initial nonparallel approach of the olefin will be governed predominantly by those nonbonded interactions that develop in the region labeled as a circled X. As the complexation process advances and the olefin approaches even further, a second interaction designated as a circled Y gains importance. The Cp wedge must be at its widest point a t this stage of reaction in order to assimilate the alkene properly. The degree of tilting becomes so substantial that mutual compression of the ligands must not become excessive.


Scheme 6

Ar


possibility would lead to an erosion in the proportion of S enantiomer ultimately formed.

HZ

E

I

Me

H

F

0

The stacked arrangements proposed in D and F minimize complications of this type. Notwithstanding, the methano bridge closest to C-1 of the olefin could also exert an effect, indicated by a circled Z, the extent of which will depend, of course, upon the structural features of the complex. According to Scheme 5 , the phenyl group in 6 should prefer to approach the titanocene hydride as in D since steric interaction circled X will be less when CzH5 is projected close to the R substituent. This compressional advantage will be somewhat offset as reaction progresses and steric compression in the circled Y corridor begins to exert itself. Evidently, however, when R is methyl, the reaction coordinate along D and E is significantly more favored and the S dihydro product dominates appreciably. As the R group increases in size from methyl to phenyl and isopropyl, the relative differences in energy between diastereomeric transition states D E and E/G are lessened because the steric bulk of R offsets the difference in size between the aryl and ethyl substituents of the alkene within the molecular cavity. Thus, the enantioselectivity decreases. This phenomenon would be expected t o be particularly significant if a preequilibrium is established and olefin insertion becomes kinetically retarded as the cavity is more densely crowded. When this steric control element by an R group is not present as in the case in 18, the dominant steric interaction may involve the methano bridge and be of type circled Z. In such a case, the involvement of F and G should be favored and formation of the R antipode would be anticipated. Indeed, this enantiomer is dominant in the product, although only t o a modest level. The possibility remains open that 18 may actually prefer to be oriented as in B and C since repulsive interactions involving the R group are now minimal. Progression through C also leads t o the R enantiomer. The small dropoff in enantioselectivity that surfaces during the reduction of 7 as compared to 6 by ent-20 may equally well stem from nonbonded interactions operational in the circled Z sector when the a-naphthyl group is involved. The necessity of maintaining conjugative overlap could be responsible for destabilization as in H and consequential greater involvement of I. This

I

0 I

Titanocene 26 was among the most effective catalysts for the enantioselective hydrogenation of 7. The demonstrated kinetic preference for formation of S-(+)-8 conforms to operation of the transition state trajectories defined as J and/or K. When Ar is a-naphthyl, the

x9 4L

reduction in steric compression available in J and K significantly overshadows that attainable in either L or M. The reduced bulk of the phenyl group in 6 is sufficient to bring transition state models L and M into closely competitive operation versus J and K. Although complete understanding of these phenomena must await further study, it is already clear that the orientation of the R groups in D-G relative to the H-Ti---HzC=CRR plane is critical to the energy differences separating the two diastereomeric complexes. Despite the longer bond lengths present in the zirconocenes, there exists a reasonable parallel with the titanocenes. For example, 40, which has verbenone-like ligands enantiomeric to those present in ent-20, reduces 6 to (R)-a-phenylbutane with an enantioselectivity


Puquette et al.

0.91 (t, J = 7.7 Hz, 3 H), 0.86 (t,J = 7.3 Hz, 3 H); 13C NMR (75 MHz, CDC13) 173.7,137.8,133.9,132.5,128.8,127.0,125.8, 125.30, 125.27, 123.5, 123.0, 67.8, 40.0, 33.9, 26.9, 25.3, 22.0, 13.5, 11.7 ppm; HRMS m l z (M+)calcd for C19H2402 284.1776, obsd 284.1780. Enzymatic Hydrolysis of 12. Ester 12 (8.80 g, 30.9 mmol), ether (100 mL), and pH 7.0 phosphate buffer solution (100 mL) were combined at rt. The pH was adjusted to 7.2 with a few drops of 1 N NaOH solution. Addition of bovine pancreas acetone powder (5.45 g, Sigma) followed by slow addition of 1.0 N NaOH solution (16.1 mL) by means of a 40 syringe pump connected to a pH controller in order to maintain the pH at 7.2 f 0.05 afforded a mixture of ester 13 and alcohol Experimental Section 14. Separation afforded 3.87 g (91%) of 13 and 2.94 g (90%) of alcohol 14; [a];' = -9.7 (c 4.0, CHC13). Mosher ester General. All reactions were carried out under an inert analysis indicated this material to be of 24.1% ee. atmosphere of argon unless otherwise indicated. Glassware (-)-(2S)-2-(a-Naphthyl)butyl p-Toluenesulfonate (15). was generally oven-dried or flame-dried in vacuo and purged Alcohol 14 (2.70 g, 13.5 mmol), CHzClz (75 mL), and pyridine well with argon. Dichloromethane was distilled from CaHz (50 mL) were combined in a flask. The solution was cooled to under nitrogen or argon prior to use. Benzene, hexanes, 0 "C, and p-toluenesulfonyl chloride (2.83 g, 14.8 mmol) was diethyl ether, toluene, and tetrahydrofuran were distilled from added. After 1h at 0 "C, the mixture was stirred at rt for 10 sodiumhenzophenone prior to use. DMF, HMPA, and pyridine h, poured into 200 mL of ether, and washed with 2 M HzS04 were distilled from CaHz and stored over molecular sieves until the aqueous phases were acidic. The organic layer was under argon. Reactions were monitored by thin-layer chrowashed with saturated NaHC03 solution (100 mL), dried, matography (TLC) or gas chromatography. Flash column filtered, and concentrated to afford a near colorless oil which chromatography was performed using Kieselgel60 (230-400 solidified on standing. There was obtained 3.59 g (75%) of 15 AST Mesh) silica gel or basic alumina (Brockmann 1, standard as a white solid, mp 65-68 "C: IR (neat, cm-'1 1355, 1188, grade, Aldrich). lH and 13C NMR spectra were recorded 1174, 950, 775; lH NMR (300 MHz, CDCl3) 6 7.95 (m, 1 H), predominantly on Bruker 80, 250, and/or Bruker 300 MHz 7.85 (m, 1H), 7.73 (d, J = 8.1 Hz, 1 H), 7.60(d, J = 8.3Hz, 2 instruments. The high-resolution mass spectra were obtained H), 7.47 (dd, J = 6.3, 3.3 Hz, 2 HI, 7.39 (t, J = 7.5 Hz, 1 H), at The Ohio State University Campus Chemical Instrumenta7.25 (d, J = 6.9 Hz, 1HI, 7.18 (d, J = 8.1 Hz, 2 H), 4.25 (dm, tion Center. Elemental analyses were performed a t the J = 9.8, 7.3 Hz, 2 HI, 3.77 (t, J = 8.1 Hz, 1 H), 2.39 (s, 3 H), Scandinavian Microanalytical Laboratory, Herlev, Denmark. 2.05 (dm, J = 8.5, 6.6 Hz, 1 H), 1.84 (dm, J = 7.2, 1.3 Hz, 1 (f)-2-(~-Naphthyl)butanol (11). nButyllithium (95.7 H), 0.84 (t,J = 7.4 Hz, 3 H); 13CNMR (75 MHz, CDC13) 144.4, mL, 2.5 M in hexanes, 0.25 mol) was added to diisopropylamine 135.9, 134.0, 132.8, 132.1, 129.6, 129.0, 127.7, 127.4, 126.1, (24.21 g, 0.24 mol) in 300 mL of THF at 0 "C. A solution of 125.5, 125.3, 123.9, 122.6, 73.4, 40.4, 24.6, 21.5, 11.5 ppm; 1-a-naphthylaceticacid (9) (20.00 g, 0.11 mol) in 30 mL of THF HRMS m / z (M+)calcd for C21H~203S354.1290, obsd 354.1288; was introduced followed by addition of HMPA (21.87 g, 0.122 [a]:' = -21.5 (c 4.0, ether). mol). The red solution was stirred for 25 min before ethyl (-)-(2R)-2-(a-Naphthyl)butane(8). A cooled (0 ' C) iodide (50.26 g, 0.32 mol) was introduced. The solution was solution of tosylate 15 (2.50 g, 7.03 mmol) and THF (50 mL) warmed to rt (room temperature) and quenched with 10%HCl was treated with lithium triethylborohydride (10.6 mL, 1.0 M solution (200 mL) 30 min later. Extraction with petroleum in THF, 10.6 mmol). The reaction mixture was stirred for 60 ether (3 x 150 mL), washing with brine, and drying afforded min a t 0 "C and at rt for 10 h, at which point saturated NH434.0 g of unpurified ester 10. C1 solution (50 mL) was introduced. Extraction with ether (3 The above material was dissolved in 100 mL of THF and x 25 mL), drying, and concentration afforded 8 (0.63 g, 48%) added slowly to a slurry of lithium aluminum hydride (6.02 g, after chromatography on silica gel (elution with pentane) as 0.16 mol) in 500 mL of THF at 0 "C. After addition was a colorless oil: 'H NMR (300 MHz, CDC13) 6 8.27 (d, J = 8.1 complete, the slurry was heated to reflux for 10 h, cooled to 0 Hz, 1 H), 7.98 (dd, J = 7.2, 1.9 Hz, 1H), 7.83 (d, J = 8.0 Hz, "C, and quenched with saturated sodium potassium tartrate 1 H), 7.49-7.66 (m, 4 HI, 3.65 (m, J = 6.8 Hz, 1H), 1.99 (dm, solution. Extraction with ether (3 x 200 mL) and drying J = 7.3, 0.8 Hz, 1 H), 1.88 (m, J = 7.4 Hz, 1 HI, 1.51 (d, J = afforded alcohol 11 as a colorless oil (12.26 g, 57% based on 6.8 Hz, 3 H), 1.07 (t, J = 7.4 Hz, 3 H); 13C NMR (75 MHz, 11): IR (neat, cm-l) 3375,1035,795,780;'H NMR (300 MHz, CDC13) 143.7, 134.0, 131.8, 128.9, 126.2, 125.6 (2 C), 125.2, CDC13) 6 8.19 (d, J = 7.6 Hz, 1 H), 7.89 (dd, J = 7.4, 2.9 Hz, 123.2, 122.4, 35.3, 30.6, 21.2, 12.2 ppm; [a]:' = -6.55 (neat); 1 H), 7.77 (d, J = 8.1 Hz, 1 HI, 7.47-7.58 (m, 3 H), 7.40 (dd, [a];' = -1.37 (c 2.3, ethanol). J = 7.2, 1.1Hz, 1H), 3.90 (d, J = 3.2 Hz, 1H), 3.88 (d, J = 3.2 Methyl 2-(a-Naphthyl)butanoate(16). A flame-dried Hz, 1 H), 3.68 (m, J = 8.0 Hz, 1 H), 1.91 (dm, J = 44.1, 7.9 three-necked 250 mL flask was charged with distilled diisoHz, 2 H), 1.65 (br s, 1 H), 0.92 (t, J = 7.4 Hz, 3 H); 13C NMR propylamine (3.85 mL, 27.5 mmol) and THF (40 mL). To the (75 MHz, CDCl3) 138.4,134.0,132.7,128.9,126.9,125.9,125.4, cooled solution (-78 "C) was added dropwise n-butyllithium 123.5,123.1,66.7,43.6,25.1, 11.9ppm;HRMSm/z(Mf)calcd (21.2 mL, 27.5 mmol, 1.3 M). After 3 h, a solution of racemic for C14H160 200.1201, obsd 200.1204. Anal. Calcd for methyl (a-naphthyllacetate (5 g, 25 mmol) in THF (20 mL) C14H160: C, 83.96; H, 8.05. Found: C, 83.86; H, 8.20. was introduced via cannula followed 1.5 h later with HMPA 2-(a-Naphthyl)butylPentanoate (12). Alcohol 11 (5.80 (4.8 mL, 27.5 mmol) and 15 min later with ethyl iodide (2.5 g, 29.0 mmol) was combined with ether (150 mL) and triethymL, 31.3 mmol). The bright yellow solution, which was lamine (3.22 g, 31.9 mmol). The cooled (0 "C) solution was allowed to warm to ambient temperature overnight, was treated with valeryl chloride (3.85 g, 31.9 mmol). After being quenched by the addition of water and extracted with ether. stirred for 1h at 0 "C,the reaction mixture was warmed to rt Purification of the concentrate by chromatography on silica and quenched after an additional 1h with saturated NaHCO3 gel (elution with 10% ethyl acetate in hexanes) afforded 16 solution (100 mL). Extraction with ether (3 x 100 mL), drying, (5.25 g, 92%) as a colorless oil: 'H NMR (80 MHz, CDC13) 6 and concentration afforded ester 12 (8.10 g, 98%): IR (neat, 8.06-8.20 (m, 1 H), 7.70-7.91 (m, 2 H), 7.40-7.56 (m, 4 H), cm-l) 1740,1732, 1464, 1260, 1175, 778; IH NMR (300 MHz, 4.29 (dd, J = 8.0, 6.8 Hz, 1 H), 3.63 (s, 3 H), 1.76-2.60 (m, 2 CDC13) 6 8.19 (d, J = 8.4 Hz, 1 H), 7.88 (d, J = 9.4 Hz, 1 H), 7.76(d,J=8.0Hz,lH),7.40-7.57(m,4H),4.39(m,J=6.9H), 0.96 (t,J = 7.3 Hz, 3 H). Enzymatic Hydrolysis of 16. A three-necked flask was Hz, 2 H), 3.86 (m, J = 6.3 Hz, 1H), 2.24 (t,J = 7.3 Hz, 2 H), charged with 16 (5.23 g, 22.91 mmol) and horse liver esterase 1.96 (dm, J = 34.9, 7.4 Hz, 2 H), 1.51 (m, 2 H), 1.24 (m, 2 H),

closely approaching that exhibited by ent-20 (expts 4, 17)but antipodal to it.


Organometallics, Vol.14, No. 10,1995 4873

(4.6g, Sigma; acetone powder). Water (200mL) was added, The above salt (315mg, 1.62mmol) was dissolved in 15 mL and the mixture was mechanically stirred as 0.5 M NaOH (17.2 of THF and added to a cold (-78 "C) solution of (exomL, 8.6 mmol, 0.38eq) was added via syringe pump at such a isodicyclopentadieny1)trichlorotitanium(463 mg, 1.62 mmol) via cannula. The reaction mixture was maintained at -78 "C rate as to maintain the pH at or below 7.3. After 30 h, all of for 3 h and allowed to warm to room temperature. After 24 the base had been consumed and the mixture was filtered h, the solvent was removed in vacuo leaving a green-brown through Celite. The Celite was washed well with water, and solid, which was recrystallized from toluene at -20 "C to afford the aqueous filtrate was extracted with ether, acidified with 23 (483mg,68%), mp 240.0-241.4"C (toluene): 'H NMR (300 2 N HCl, and re-extracted with three portions of CH2Cl2 (75 MHz, CDC13) 6 6.34(t,J = 2.8 Hz, 1 H), 6.32 (d, J = 2.5 Hz, mL). After drying and solvent evaporation in uucuo, the 2 H), 6.11 (br s, 1 H), 5.93 (t,J = 2.4Hz, 2 H), 3.35 (br s, 2 H), residue was purified by chromatography on silica gel (elution 2.80 (t, J = 5.2 Hz, 1 H), 2.54 (ddd, J = 11.9,10.5,6.3Hz, 1 with 20% ethyl acetate in hexanes) to give 17 (650mg, 35%) H),2.08(d,J=10.5Hz,1H),1.87(dd,J=10.4,2.6Hz,2H), as a colorless oil: lH NMR (80 MHz, CDC13) 6 8.02-8.23 (m, 1.67 (t, J = 5.3 Hz, 1 H), 1.47(br t, J = 9.4Hz, 2 H), 1.42 (s, 1 H), 7.69-7.98(m, 2 H), 7.30-7.68(m, 4 H), 4.31 (t, J = 4.7 3 H), 1.40 (9, 3 H), 1.28 (8,3 H), 1.10(dd, J = 7.6,2.2 Hz, 2 Hz, 1 H), 1.75-2.52 (m, 2 H), 0.98(t,J = 4.7Hz, 3 H); [a]i2= H), 0.44 (s,3 H); 13CNMR (75MHz, CDCg) 149.9,147.2,145.7, -133.6 (c 3.3,CHzC12, unpurified). 143.3,126.6,118.1,117.8, 109.9,107.1,107.0,54.3,48.1,45.3, (-)-(2R)-2-(a-Naphthyl)butane (8).A cooled (0 "C) solu41.4,41.3,40.6,30.9,23.0,28.1,28.0,27.6,24.3ppm; HRMS tion of (-)-(R)-17 (607mg, 2.83 mmol) in THF (25 mL) was m l z (M+ - C1) calcd for C24H30ClTi401.1516,obsd 401.1525; treated with LiAlH4 (320mg, 8.5 mmol) with vigorous stirring [a];' -60.0 (c 0.05, CHC13). Anal. Calcd for C24H30C12Ti: C, overnight. After recooling of the gray mixture to 0 "C and 65.92;H, 6.91. Found: C, 65,92;H, 7.01. careful quenching with dilute HCl, the reaction mixture was extracted with ether (3 x 50 mL). The dried concentrate was (-)-(~6-[azo-Isodi~yclopentadienyll)(~~-( 1~,7~)-1,10,10purified by chromatography on silica gel (elution with 20% trimethyltricycl0[5.2.1.02~~]deca-3,S-dien-2-yl)dc~o~tiethyl acetate in hexanes) yielding the R alcohol (525mg, 92%) tanium (24). (exo-Isodicyclopentadienyl)trichlorotitani~m~~ as a colorless oil. This material exhibited [a]F = -39.1 (c (316mg, 1.11 mmol) and 50 mL of THF were placed in a 100 mL round-bottomed flask equipped with a side arm. The 3.3,ethanol). Mosher ester analysis indicated the alcohol to solution was cooled to -78 "C, and to it was added camphorbe of 87.3% ee. cyclopentadienide lithium salt" (200mg, 1.11 mmol) dissolved A solution of the above alcohol (959mg, 4.79mmol) in CH2in THF (20mL) via cannula. One hour later, the dry ice bath Cl2 (30mL) and pyridine (18mL) was cooled to 0 "C. Freshly was removed and the mixture was stirred for 2 days, filtered recrystallizedp-toluenesulfonyl chloride (1.1g, 5.75"01) was through Celite, and concentrated to leave a red oil, which added, and the solution was stirred under an atmosphere of crystallized from toluene-pentane to give 24 (152mg, 36%) argon for 4 h at 0 "C and then at ambient temperature for an as a red powder, mp 183-184 "C (toluene): lH NMR (300 additional 36 h. The reaction mixture was poured into ether MHz, CDC13) 6 6.36 (m, 2 H), 6.22 (m, 2 HI, 6.14(t, J = 2.8 (200mL) and washed with H2S04 solution (1.8M) until the Hz, 1 H), 5.99(t, J = 2.8 Hz, 1 H), 3.31 (br s, 2 H), 2.76 (d, J washings were acidic. The organic layer was then washed =4.3Hz,lH),2.05-1.5O(seriesofm,8H), 1.24(s,3H),1.10 with NaHC03 solution, dried, and evaporated to yield a near (~~,J=~.~,~,~HZ,~H),O.~~(S,~H),O.~~ colorless oil, which was purified by filtration through silica (75MHz, CDC13) 125.5,124.2,112.8,108.0,107.6,70.1,54.2, gel (elution with 10% ethyl acetate in hexanes) to give the 51.5,47.7,41.6,41.5,32.4,28.2,28.0,25.5,21.1,19.9,12.9 tosylate as a colorless oil (1.59g, 94%) with spectral properties ppm; HRMS mlz (M+- C1) calcd for C23H28ClTi 387.1359,obsd identical to those reported above. This compound exhibited 387.1365;[a];' -175.4 (c 0.12,toluene). an [a]i2= -82.2 (c 1.35,CHC13). The tosylate (1.562g, 4.41mmol) was dissolved in THF (30 (+)-(~~-Neomenthyl~~lopentadienyl)(~~-[exo-(lS,8S)mL) in a dry flask under argon. To the ice-cooled solution was 7,7,9,9-tetramethyltricyclo[6.1.1.02+T-deca-3,S-dien-2-yll)dichlorotitanium (26). An isomeric mixture of neomenthadded lithium triethylborohydride (6.6mL, 6.6 mmol, 1 M) dropwise with vigorous stirring. Stirring was maintained for ylcyclopentadienes (22.40g, 0.110mol) was placed in a three21 h, the reaction mixture was recooled to 0 "C, and saturated necked 500 mL round-bottomed flask fitted with two septa, NH4Cl solution was added slowly with stirring. Dilution with condenser, and gas inlet. The hydrocarbon mixture was ether and twofold washing with saturated NH&l solution, once degassed and dissolved in hexane (100mL) and ether (150mL) under argon. The solution was cooled to 0 "C while nwith NaHC03 solution, and once with brine followed by drying butyllithium (43.8mL, 2.5M in hexane, 0.110mol) was added and concentration in uucuo provided a light yellow oil, purification of which by chromatography on silica gel (elution with via syringe. A white precipitate formed as the mixture thickened. One hour later, the ice bath was removed and the hexanes) provided 8 (724mg, 89%) as a colorless oil: [ali2= flask swirled a few times. After 6 h at 25 "C, the mixture was -22.2 (neat); [a]? = -4.38 (c 1.05,ethanol). (-)-(~5-[exo-Isodicyclopentadienyll)(~6-[exo-(lS,8S)-filtered through a Schlenk filter stick under argon. Washing of the white solid twice with hexane (20 mL) and vacuum 7,7,9,9-tetramethyl-tricyclo[6.1.1.02~~ldeca-3,S-dien-2-yll )drying for 6 h afforded the lithium salt (13.62g, 59%) as a dichlorotitanium (23). Optically pure (-)-(lS,8S)-tetramoisture- and air-sensitive solid. methyltricyclo[6.1.1.02~61deca-2,5-diene (36a)(3.00g, 15.9"01) Neomenthylcyclopentadienyllithium (6.83g, 32 mmol) was was placed in a 250 mL three-necked round-bottomed flask taken up in 50 mL of THF, and this solution was added fitted with gas inlet, septum, and condenser, dissolved in 30 dropwise via cannula to a solution of chlorotrimethylsilane mL each of ether and hexane, cooled to 0 "C, and treated with (7.06g, 65 mmol) in 350 mL of THF at 0 "C. The reaction n-butyllithium (13.3mL, 1.2 M in hexane, 15.9 mmol) via mixture was stirred for 1 h, kept at 25 "C for 10 h, and poured syringe. A white solid formed as the mixture was warmed to into a mixture of saturated NaCl solution (100mL) and ether 25 "C. The flask was fitted with an apparatus to filter air(200mL). The separated aqueous phase was extracted with sensitive solids 10 h later. The solid, collected under inert gas, ether (3 x 100 mL), and the ethereal layers were dried, filtered, was washed with hexane (15 mL) and vacuum dried t o give and concentrated to leave a light yellow oil, which was 2.80g (91%)of lithium salt 37a as a moisture- and air-sensitive redissolved in twice its volume of hexane and passed through solid: lH NMR (400MHz, 0.35 M, THF-de) 6 5.43 (dd, J = a 2-in. pad of silica gel (elution with hexane) to give, after 2.6,2.6 Hz, 1 H), 5.30 (dd, J = 2.6,2.6Hz, 1 H), 5.22 (dd, J = concentration, 8.00 g (89%) of the silane as a colorless oil: IR 2.6,2.6 Hz, 1 H), 2.50 (ddd, J = 8.5, 5.6,5.6 Hz, 1 H), 2.44 (neat, cm-l) 2962,2945,2880,2850,1254,989,870,840,817; (dd,J=5.6,5.6Hz,lH),l.69(dd,J=5.6,5.6Hz,lH),1.58 lH NMR (300MHz, CDC13)6 6.62(br s, 1 H),6.40(br s, 1 H), (d, J = 8.5 Hz, 1 H), 1:31 (s, 3 H),1.18 (s, 6 H), 0.52(9, 3 H); 6.21(d,J=l.lHz,lH),3.15(brd,J=4.2Hz,2H),1.82(br 6Li NMR (93MHz, 0.35 M,THF-de) 6 -7.74;13C NMR (100 MHz, 0.35M, THF-de) 124.5,121.2,98.7,98.5,98.0,57.3,46.1,s, 1 H), 1.78(br d, J = 1.8Hz, 2 H), 1.55 (br t, J = 13.0Hz, 3 H), 1.24(dt, J = 12.7,5.0Hz, 2 H), 1.06(br m, 1 H), 0.92 (d, 45.4,38.2,35.0,34.3,35.0,29.8,29.0,26.0 ppm.

4874 Organometallics, Vol. 14,No. 10,1995

Paquette et al.

prior to drying and concentration. (+)-(lR,5R)-7,7,9,9-Tetramethylbicyclo[3.1.1lheptan-2-one(32a) was obtained as a light yellow oil, (24.22g, 97%). The spectral data were identical to those of the enantiomer; [a];' +49 (c 0.7,ethanol). In a 300 mL three-necked round-bottomed flask fitted with condenser, addition funnel, and gas inlet were placed magnesium turnings (1.46g, 60.2 mmol) and 100 mL of tetrahydrofuran. In the addition funnel was placed vinyl bromide (8.37 g, 5.52 mL, 78.3mmol) and 20 mL of THF. Carefully, a small amount of this solution was added t o the magnesium while leaving a green-brown oil, Kugelrohr distillation of which simultaneously heating the mixture to initiate the reaction. (110-130 "C, 4 x Torr) yielded the complex as a yellowAfter a slight change in color, the heat was removed and the orange syrup (4.96g, 48%) which crystallized into a solid mass final portion of halide solution was added dropwise as the on standing, mp 53-55 "C: 'H NMR (300MHz, CDCl3) 6 7.23 reaction mixture continued t o reflux. Once addition was (q, J = 2.2Hz, 1 H), 7.00 (dt, J = 3.3,2.2 Hz, 1 H), 6.93 (9, J completed, the mixture was stirred until all of the magnesium = 2.2Hz, 1 H), 6.77 (9, J = 3.2Hz, 1 H), 3.55 (br d, J = 3.4 metal was consumed (approximately 2 h), cooled t o 0 "C, and Hz, 1 H), 2.12 (dq, J = 16.2,2.5 Hz, 1 H), 1.90 (br m, 2 H), treated with a solution of the above ketone (5.00 g, 30.1mmol) 1.69(brm,1H),1.19-1.41(m,4H),1.01(d,J=6.2Hz,3H),in 20 mL of THF dropwise over 20 min. The reaction mixture 0.91(d,J=6.2Hz,3H),0.83(dd,J=l7.1,6.2Hz,lH),0.74was stirred at 0 "C for 1h and at rt for 6 h. Saturated NH&1 (d, J = 6.2Hz, 3 H); 13CNMR (75MHz, CDC13) 148.4,125.0, solution (200mL) was slowly added, the layers were separated, 123.6,123.4,122.7,49.9,39.9,39.7,35.2,29.6,28.2,24.5,22.6, and the aqueous phase was extracted with ether (3 x 150 mL). 22.0,20.6ppm; HRMS m l z (M+)calcd for C15H23CLjTi 323.062, The combined organic fractions were dried, filtered, and obsd 323.0582;[a];' f87.5 (c 0.3,CHC13). Anal. Calcd for concentrated to give a light yellow oil, which was purified by C15H23C13Ti: C, 50.38;H, 6.48. Found: C, 50.83;H, 6.60. chromatography (silica gel, elution with 10% ethyl acetate in Lithium ero-(1S,8S)-7,7,9,9-tetramethyltricyclo[6.l.l.O~~6l-petroleum ether) t o give 4.90g (84%) of (-)-(lR,2S,5R)-4,4,6,6deca-3,5-dienide (37a) (217mg, 1.12mmol) was dissolved in tetramethyl-2-vinylbicyclo[3.1.l]heptan-2-ol(33a) as colorless 15 mL of THF and added dropwise via cannula to a cold (-78 crystals, mp 62.5-63.5 "C (from ethyl acetate): IR (CHC13, "C) solution of (neomenthylcyclopentadieny1)trichlorotitanium cm-l) 3593,1468,995,936; 'H NMR (300MHz, CDC13) 6 6.05 (400mg, 1.12mmol) in 35 mL of THF. The brick red solution (dd, J = 16.3,10.6 Hz, 1 H), 5.20 (dd, J = 16.3,1.0Hz, 1 H), was stirred for 2 h at -78 "C and for 24 h at 25 "C prior to 5.0l(dd,J=9.7,1.0Hz,lH),2.15(dt,J=6.3,1.5Hz,1H), concentration to leave a green-brown solid. The solid was 1.95(dd,J=15.7,5.3Hz,2H),l.84(t,J=4.9Hz,lH),1.58 dissolved in toluene (5 mL) from which crystals of 26 formed (t, J = 5.1 Hz, 1 H), 1.52(s, 1 H), 1.30 (s, 3 H), 1.26(s, 3 H), at -20 "C (330 mg, 58%), mp 110-113 "C): 'H NMR (300 1.20(d, J = 11.1 Hz, 1 H), 1.09(s, 3 H), 0.95(s, 3 H); I3C NMR MHz, CDC13) 6 6.73(q, J = 2.2Hz, 1 H), 6.31-6.38(m, 4 H), (75MHz, CDC13) 146.4,111.1,77.2,53.4,52.5,45.8,40.0,33.7, 6.19(q, J = 2.3 Hz, 1 H), 5.99 (t,J = 2.3 Hz, 1 H), 3.54 (br d, 31.9,30.7,29.3,27.0,26.2 ppm; HRMS m l z (M+) calcd for J=3.3Hz,lH),2.84(t,J=5.2Hz,lH),2.55(ddd,J=l1.8,C&220 194.1671,obsd 194.1671;[a]:' -1.3 (c 3.9,CHC13). 10.6,6.3 Hz, 1 H), 2.17(dt, J = 13.7,4.0 Hz, 1 H), 2.02 (d, J Anal. Calcd for C13H220: C, 80.35;H, 11.41. Found: C, 80.58; = 10.5 Hz, 1 H), 1.91(m, J = 6.8 Hz, 1 H), 1.81 (m, 1 H), 1.67 H, 11.41. (t, J = 1.1 Hz, 1 H), 1.62 (br d, J = 8.9Hz, 1 H), 1.41 ( 8 , 6 H), This allylic alcohol (3.10g, 16.0mmol) and alumina (100g, 1.29(s, 3 H), 1.26(m, 3 H), 0.99 (d, J = 6.4Hz, 3 H), 0.98 (m, activity I) were combined in a one-necked round-bottomed 2 H), 0.88 (d, J = 6.4Hz, 3 H), 0.72 (d, J = 6.4Hz, 3 H), 0.45 flask. The alumina was evenly coated, and the solid mixture (s,3 H); I3C NMR (75MHz, CDCl3) 149.7,143.9,141.0,126.4, was allowed to stand for 3 h. The flask containing the solid 121.0,119.1,117.4,115.8,112.9,111.1,54.4,50.1,45.3,45.3, mixture was connected to a receiver for bulb-to-bulb distillation 40.6,39.4,38.2,35.6,31.0,30.0,29.9,29.2,28.4,27.7,24.7, and slowly heated under vacuum (0.5 mmHg). The product 24.4,22.8,22.3,20.8 ppm; HRMS m l z (M+ - C1) calcd for was collected in the receiver a t -78 "C. After 1 h of heating C2~H42Cl~~Ti 473.2455, obsd 473.2455; [a];' -150 (c 0.2, at 150 "C, the distillation was stopped. The product was CHC13). Anal. Calcd for C29H42C12Ti: C, 68.37;H, 8.31. passed through a short column of silica gel (elution with 1% Found: C, 68.36;H, 8.29. ether (~S-Neomenthylcyclopentadienyl)(~s-[e~o-(lR,8R~- in pentane) t o give (-)-(lS,fiR)-4,4,6,6-tetramethy1-2vinylbicyclo[3.1.1lhept-2-ene (34a) as a near colorless oil (1.16 7,7,9,9-tetramethyl-tricycl0[6.1.1 .Oasl-deca-3,6-dien-2-yll)g, 41%): IR (neat, cm-') 1625,1474,1383,1367,990,894,853; dichlorotitanium (27). Copper iodide (28.53g, 0.150mmol, 'H NMR (300MHz, CDC13) 6 6.37(dd, J = 10.8,6.6Hz, 1 H), purified by complexation to potassium iodide)41was placed in 5.26 (8,1 H), 5.09 (d, J = 17.4Hz, 1 H), 4.91 (d, J = 9.7 Hz, 1000 mL flame-dried three-necked round-bottomed flask a 1 H), 2.54(t, J = 5.1 Hz, 1 H), 2.26 (m, 1 HI, 1.70(dt, J = 3.8, equipped with an addition funnel, gas inlet, septum, and stir 2.0Hz, 1 H), 1.38 (d, J = 9.2Hz, 1 H), 1.29 ( 6 , 3 H), 1.04(s, 3 bar. The near white solid was slurried in 300 mL of ether, H), 0.97(s,3 H), 0.96(s,3 H); I3CNMR (75MHz, CDC13) 144.3, and the flask was placed in an ice bath. Methyllithium (200 138.5,139.0,110.6,54.0,41.72,41.70,38.9,31.2,30.2,27.9, mL, 1.5M in ether, 0.30mmol) was gradually introduced over 26.2,24.6 ppm; HRMS m l z (M+) calcd for C13H20 176.1565, 30 min. The mixture turned bright yellow and then became obsd 176.1569;[a];' -19.5 (c 7.5,hexane). Anal. Calcd for colorless at the equivalence point (2equiv of CH3Li to 1 equiv C13H20: C, 88.57;H, 11.43. Found: C, 88.57;H, 11.55. of CUI). Fifteen minutes later, a solution of (lR)-(+)-verbenone (22.50g, 0.150 mol), chlorotrimethylsilane (32.54g, 0.300 To diene 34a from above (7.40g, 0.042mol) in 100 mL of mmol), and 50 mL of ether was added over 30 min. The dichloromethane was added bromoform (15.91g, 0.063mol), mixture was stirred for 2 h at 0 "C and monitored by TLC. benzyltriethylammonium chloride (0.25g, 0.91mmol), and 0.5 After complete reaction, saturated NH4C1 solution (150mL) mL of ethanol. The mechanically stirred mixture was cooled was gradually introduced. The ice bath was removed, and the in a n ice bath and treated slowly with 21 mL of 50% sodium mixture was stirred for 30 min at rt. Concentrated ammonium hydroxide solution. Once addition was complete, the twohydroxide solution (50mL) was added, and the mixture was phase system was stirred for 24 h at rt and poured into a stirred until all of the copper salts dissolved. The blue mixture separatory funnel. The separated aqueous layer was diluted was poured into a separatory funnel, the separated aqueous with 100 mL of water and extracted with dichloromethane (3 layer was extracted with ether, and the combined organic x 200 mL). The combined organic fractions were dried, phases were washed with water (100mL) and brine (100mL) filtered, and concentrated to leave a brown oil, which was passed through a 2-in. pad of silica gel (elution with hexane) (41)Kauffman, G . B.;Fang,L.Y.Inorg. Synth. l9SS,22, 101. and concentrated at 25 "C t o give 35a as a light yellow oil.

J = 6.5Hz, 6 H), 0.85 (d, J = 6.2Hz, 3 H), -0.07 ( 8 , 9 H); I3C NMR (75MHz, CDCl3) 147.8,134.9,135.0,129.4,51.0,48.1, 43.0,38.3,36.1,30.5,27.1,27.1,23.1,21.5,21.5,-1.9 ppm; HRMS mlz (M+)calcd for C18H32Si 276.2273,obsd 276.2272; [a];' +19.3 (c 4.5,hexane). The silane mixture (8.00 g, 28.9 mmol) was degassed, dissolved in 35 mL of toluene, and added to a cold (-78 "C) solution of titanium tetrachloride (5.49g, 28.9 mmol) and 150 mL of toluene. After 2 h at -78 "C, the mixture was warmed to r t and stirred for 10 h. The solvent was removed in vacuo

Hydrogenation of 1,l-DisubstitutedAlkenes

Organometallics,Vol. 14, No. 10, 1995 4875

The material was placed in a 1000 mL round-bottomed flask gray-tan slurry to turn bright yellow-orange. After 15 min, a equipped with a side arm and dissolved in 500 mL of solution of 31 (15.0 g, 0.10 mol) and chlorotrimethylsilane anhydrous ether. The flask was cooled in an ice bath at which (21.70 g, 0.20 mol) in 150 mL of tetrahydrofuran was added slowly over 1 h. The mixture was stirred at -78 "C for 4 h time methyllithium (115.0 mL, 1.5 M in ether, 0.172 mol) was before it was allowed to warm to rt and then quenched by the slowly introduced via syringe. The light yellow-green solution slow addition of saturated NH&l solution (200 mL) and, 2 h was allowed to stir at rt for 24 h after addition was complete later, 75 mL of concentrated NH4OH solution. The mixture and added to 1000 mL of icelsalt water via cannula. The separated aqueous phase was extracted three times with ether was allowed to stir until the aqueous layer was blue. After separation and extraction of the aqueous phase with ether (4 (200 mL), and the combined organic layers were dried, filtered, and concentrated at rt t o give a yellow-orange oil, purification x 200 mL), the combined organic layers were washed with 1 of which on a short column of silica gel (elution with pentane) N HC1 (3 x 100 mL), water (100 mL), and brine (100 mL), gave 5.01 g (62%based on recovered 34a)of pure cyclopentaprior to drying and concentration to give a light yellow oil, diene 36a as a faint yellow oil. Spectral data are identical purification of which on silica gel (elution with 10% ethyl acetate in petroleum ether) afforded 14.77 g (75%)of 32b as a with those reported earlier for the enantiomer;se [a];' -22.2 colorless oil: IR (neat, cm-l) 1720, 1473, 1396, 1375, 1270; 'H (c 8.0, hexane). NMR (300 MHz, CDC13) 6 2.43 (m, 2 H), 2.33 (m, 1 H), 2.15 Lithium salt 37a of this cyclopentadiene (217 mg, 1.12 (d, J = 19.6 Hz, 1 H), 2.04 (t, J = 5.0 Hz, 1 H), 1.69 (m, J = mmol), prepared in the manner described above, was taken 6.8 Hz, 1 H), 1.58 (d, J = 8.8 Hz, 1H), 1.29 ( 8 , 3 H), 0.93 (s, 3 up in 20 mL of THF and added to a solution of (neomenthylH),0.88(~,3H),0.79(d,J=6.8Hz,3H),0.66(d,J=6.8Hz, cyclopentadieny1)trichlorotitanium(400 mg, 1.12 mmol) in 30 3 H); 13CNMR(62.5 MHz, CDCl3) 214.0,57.6,50.7,48.2,40.5, mL of THF at -78 "C via cannula. After 2 h, the dry ice bath 36.3, 27.4, 25.6, 23.3, 18.4, 17.3, 16.2 ppm; HRMS m l z (M+) was removed and the mixture was allowed to stir at 25 "C for calcd for C13H220 194.1671, obsd 194.1669; [a];' +25.7 (c 3.6, 24 h, concentrated, and redissolved in dichloromethane (ca. ethanol). Anal. Calcd for C13H220: C, 80.36; H, 11.41. 50 mL). This solution was filtered through a Celite pad, and Found: C, 80.17; H, 11.41. the filtrate was concentrated. Sublimation (170-175 "C, 5 x Torr) of a portion of the solid and crystallization of the (+)-( 1R,2S,4S,5R)-4-Isopropyl-4,6,6-trimethyl-2-vinylremaining material from toluene at -20 "C afforded 353 mg tricyclo[3.1.1]heptan-2-ol(33b).Magnesium turnings (3.65 (62%)of 27 as a fluffy green microcrystalline solid, mp 201g, 0.150 mol) were placed into a 1000 mL three-necked round202 "C (toluene): 'H NMR (300 MHz, CDC13) 6 6.77 (9, J = bottomed flask fitted with a condenser, gas inlet, addition 2.1 Hz, 1 H), 6.56 (q, J = 3.0 Hz, 1 H), 6.41 (t,J = 2.3 Hz, 1 funnel, and septum. THF (300 mL) was added, and the H), 6.31 (q, J = 2.8 Hz, 1 H), 6.08-6.12 (m, 3 H), 3.55 (br d, J magnesium was activated by addition of a few drops of ethyl =3 .O Hz, 1 H), 2.85 (t, J = 5.2 Hz, 1 H), 2.53 (ddd, J = 11.8, bromide. A solution of vinyl bromide (16.86g, 0.158 mol) and 10.6, 6.3 Hz, 1 H), 2.15 (dd, J = 9.6, 4.1 Hz, 1 H), 2.03 (d, J = THF (50 mL) was slowly introduced into the slurry. Once all 10.6 Hz, 1H), 1.93 (m, J = 4.2 Hz, 1 H), 1.82 (br m, 1 H), 1.63 of the magnesium had dissolved, the solution was cooled t o 0 (dd, J = 11.4, 6.1 Hz, 1 H), 1.56 (d, J = 24.2 Hz, 1 H), 1.40 (9, "C. Ketone 32b (14.75 g, 0.075 mol) in 50 mL of THF was 3 H), 1.37 (9, 3 H), 1.30 (s, 3 H), 1.28 (m, 3 H), 0.98 (d, J = 6.1 slowly added, and the mixture was stirred at 0 "C for 2 h and Hz, 3 H), 0.97 (m, 2 H), 0.88 (d, J = 6.4 Hz, 3 H), 0.70 (d, J = at rt for an additional 6 h before it was carefully neutralized 6.2 Hz, 3 H), 0.43 (s, 3 H); 13C NMR (75 MHz, CDC13) 152.0, with saturated NH&l solution (200 mL). The layers were 141.3, 141.0, 126.5, 120.9, 117.4, 117.0, 116.6, 113.5, 111.4, separated, and the aqueous phase was extracted with ether 54.5, 49.9, 45.4, 45.3, 40.2, 39.3, 38.4, 35.5, 30.8, 30.1, 29.9, (4 x 125 mL). The combined organic layers were dried and 29.2, 28.5, 27.6, 24.6, 24.3, 22.8, 22.3, 20.7 ppm; HRMS m l z concentrated t o leave a n orange oil. TLC analysis indicated (M+ - C1) calcd for C29H4237C146Ti 473.2471, obsd 473.2467; the presence of two nearly superimposable compounds, with [a];' +356.1 (c 0.1, CHC13). Anal. Calcd for C2sH42C12Ti: C, 33b consisting of 52% (ca. 8.75 g) of the product mixture as 68.37; H, 8.31. Found: C, 68.33; H, 8.33. determined by lH NMR. Data for 33b: IR (neat, cm-') 3422, 1417, 1369, 993; 'H NMR (300 MHz, CDC13) 6 6.04 (dd, J = (-)-(tl5-Cyclopentadienyl)(tl5-[e~o-(1S,8S~-7,7,9,9-tet17.3, 10.4 Hz, 1 H), 5.19 (dd, J = 17.3, 1.2 Hz, 1 H), 4.99 (dd, ramethyltricyclo-[6. 1.1.02s]deca-3,5-dien-2-yl] )dichlorotiJ = 10.7, 1.1 Hz, 1 H), 2.19 (d, J = 16.0 Hz, 1 H), 2.08 (m, 1 tanium (ent-29).In the drybox, the lithium cyclopentadienide H), 1.80 (m, J = 6.2 Hz, 1 H), 1.74 (d, J = 16.0 Hz, 2 H), 1.34 37a described earlier (300 mg, 1.55 mmol) was weighed into (s, 1 H), 1.31 (s, 3 H), 1.26 (s, 3 H), 1.22 (d, J = 10.2 Hz, 1H), a round-bottomed flask equipped with a side arm. Another 0.98 (d, J = 5.6 Hz, 1 H), 0.86 (d, J = 6.8 Hz, 3 H), 0.84 (s, 3 flask was charged with cyclopentadienyltitanium trichloride H), 0.63 (d, J = 6.8 Hz, 3 H); 13CNMR (75 MHz, CDCl3) 146.6, (339 mg, 1.55 mmol). After addition of 30 mL of tetrahydro111.0, 77.1, 51.6, 50.9, 43.7, 39.4, 37.8, 35.2, 29.6, 26.1, 24.9, furan to the lithium salt, the flask was cooled to -78 "C. To 19.6, 17.8, 16.2 ppm; HRMS m l z (M+) calcd for C15H260 this near colorless solution was added the titanium reagent 222.1984, obsd 222.1956. in 15 mL of dry tetrahydrofuran via cannula dropwise over 20 min. Upon addition, the reaction mixture turned brick red. (+)-( 1S,4S,5R)-4-Isopropy1-4,6,6-trimethyl-2-vinylAfter addition was complete, the reaction mixture was stirred tricyclo[3.l.l]hept-2-ene (34b). The mixture from above at -78 "C for 1 h, allowed to warm to rt, and stirred for an was adsorbed onto basic alumina (200 g, activity I, activated additional 10 h. The solvent was removed in vacuo leaving a at 450 "C for 12 h) until the solid adsorbent was evenly coated, brown-red residue, which was taken up in dichloromethane placed into a Kugelrohr apparatus after standing at rt for 4 (30 mL) and filtered through a Celite pad. The red solution h, and heated to 160 "C under 1.5 mmHg for 1h. The oil was was again quickly concentrated to give a brown-red solid. This collected in a receiver cooled to -78 "C. The alumina mixture solid was dissolved in a small amount of dry toluene and cooled was eluted with several portions of ether until TLC analysis t o -20 "C. After 6 h, crystals of ent-29 formed and were indicated no product in the washings. The eluents were collected as a brown fluffy microcrystalline solid, 243 mg (42%). combined, dried, and evaporated to leave a light yellow oil, Spectral data are identical to those reported for the purification of which by chromatography on silica gel (elution enantiomer;8e [a];' -225 (c 0.14, toluene). with 1% ether in petroleum ether) afforded 5.24 g (65%)of 34b: IR (neat, cm-l) 1498,1450,900,769,706; 'H NMR (300 (+)-~~,4S,~~4Isopropyl-4,6,6-~ethyltricyclo~3.1.llMHz, C6D6) 6 6.37 (dd, J = 17.4, 10.7 Hz, 1 H), 5.55 (br s, 1 heptan-2-one(32b). In a flame-dried 1000 mL three-necked H), 5.11 (d, J = 17.4 Hz, 1 H), 4.92 (d, J = 10.7 Hz, 1 H), 1.61 round-bottomed flask fitted with a gas inlet, addition funnel, (t,J = 5.4 Hz, 1 H), 2.19 (m, 1HI, 1.97 (m, 1 HI, 1.77 (m, J = and large stir bar was placed CuBr-DMS complex (1.03 g, 5.0 6.8 Hz, 1 H), 1.46 (d, J = 9.3 Hz, 1 H), 1.31 (s, 3 H), 0.99 (s, 3 mmol). Tetrahydrofuran (200 mL) and 4-(dimethylamino)H), 0.86 (s, 3 H), 0.85 (d, J = 6.9 Hz, 3 H), 0.67 (d, J = 6.9 Hz, pyridine (24.40 g, 0.20 mol) were added, and the resulting 3 H); 13CNMR (75 MHz, CsDs) 144.2, 138.9, 133.4, 110.6, 51.5, slurry was cooled t o -78 "C. Isopropylmagnesium chloride 43.1, 41.8, 41.2, 35.3, 29.1, 28.0, 24.5, 17.6, 16.02, 15.99 ppm; (60.0 mL, 2.0 M in ether, 0.20 mol) was added, causing the


Puquette et ul.

4-(dimethylamino)pyridine(21.14g, 0.173mol) were added, and the resulting slurry was cooled to -78 "C. Phenylmagnesium bromide (63.0mL, 3.0M in ether, 0.190mol) was then introduced causing the gray-tan slurry to turn bright yelloworange. After 15 min, a solution of 31 (13.0g, 0.087mol) and chlorotrimethylsilane (18.8g, 0.173mol) in 150 mL of tetrahydrofuran was added slowly over 60 min. After 4 h of stirring a t -78 "C, the reaction mixture was allowed to warm to rt and quenched by the slow addition of a saturated NH4C1 solution (200mL) and, after 2 h, 75 mL of concentrated NH4OH. The slurry was allowed to stir until the aqueous layer was blue. After separation and extraction with ether (4x 200 mL), the combined organic layers were washed with 1 N HCl (3 x 100 mL), water (100mL), and brine (100mL), prior to drying, and concentrated to give a light yellow oil. Purification of this residue on silica gel (elution with 10% ethyl acetate in petroleum ether) afforded 16.0 g (81%) of 32c as a white crystalline solid, mp 72 "C; IR (CC14, cm-'1 1715,1495,1445, 990,710;'H NMR (300MHz, CDCld 6 7.35-7.15(m, 5 H), 3.20(d, J = 19.9Hz, 1 H), 2.81(d, J = 19.9Hz, 1 H), 2.66(m, J = 9.9Hz, 1 H), 2.60(m, J = 3 .1 Hz, 1 H), 2.57(m, 1 H), 1.48(s,3H),1.47(s,3H),1.40(dd,J=9.9,3.1Hz,1H),1.16 (s,3 H); 13CNMR (75MHz, CDC13) 212.4,151.5,128.2,125.5, 125.4, 56.5,50.6,48.4,40.2,39.7,31.6,27.4,26.5,25.4ppm; HRMS m l z (M+)calcd for C&20O 228.1514,obsd 228.1513; [a]:' +66.3 (c 3.0,ethanol). Anal. Calcd for C16H200: C, 84.16;H, 8.77.Found: C, 84.10; H, 8.81. (+)-(lS,4R,5S)-4-Phenyl-4,6,6-trimethyl-2-vinyltricyclo[3.l.llhept-2-ene(34c). Placed in a 1000 mL three-necked round-bottomed flask fitted with condenser, addition funnel, and gas inlet was 300 mL of dry THF'. The flask was cooled t o 0 "C, and vinylmagnesium bromide (113.9mL, 1.0M in THF, 0.114mol) was added followed by the slow addition of 32c (13.0g, 0.057mol) in 50 mL of THF over 30 min. The mixture was stirred at 0 "C for 1 h and at rt for 10 h, before being quenched at 0 "C with saturated NHlCl solution (200 mL). The layers were separated, and the aqueous layer was extracted with ether (4 x 150 mL). The combined organic layers were dried and concentrated. The remaining oil was purified by chromatography on silica gel (elution with 20% ethyl acetate in petroleum ether) to give a n inseparable mixture of 33c (major) and unreacted 32c. This material was taken directly into the next step. The mixture from above was evenly adsorbed onto basic alumina (25g, activated at 450 "C for 24 h), placed into a Kugelrohr apparatus afier standing a t rt for 4 h, and heated to 160 "C under 1.5mmHg for 1 h. The oil was collected in a receiver at -78 "C. The alumina mixture was eluted with 51.3,43.7,42.4,40.3,34.0,28.0,27.9,27.8,24.4,18.6,18.1, several portions of ether until the eluate became clear. The 16.8ppm; HRMS m l z (M+) calcd for C16H24 216.1878,obsd eluates were combined, dried, and evaporated to leave an 216.1876;[a]? -6.9(c 1.0, hexane). orange oil, purification of which by chromatography on kie(-)-Sis[$-( lS,7S,W)-6-isopropyl-7,9,9-trimethyltricyclo- selghur (elution with 1% ether in pentane) afforded 34c as a colorless oil (2.67g, 19% based on recovered 32c): IR (neat, [6.1.1.02~s]deca-2,5-dien-3-yl]dichlorotitanium (21). A socm-'1 1960,1630,1368,1260;'H NMR (300MHz, C6D6) 6 lution of 37b (1.33g, 5.98mmol) in dry l,2-dimethoxyethane 7.16-7.23(m, 4 H), 7.02-7.07(m, 1 H), 6.50(dd, J = 17.4, (30mL) was cooled to -78 "C and transferred via cannula to 10.7Hz, 1 H), 5.70(s, 1 H), 5.13(d, J = 17.4Hz, 1 H), 4.98(d, an equally cold slurry of titanium(II1) chloride (459mg, 2.98 J = 10.8Hz, 1 H), 2.53(t, J = 5.4Hz, 1 H), 2.25(dt, J = 5.9, mmol) in the same solvent. After 1 h at this temperature, the 2.1Hz, 1 H), 2.03(dt, J = 11.5,5.7Hz, 1 H), 1.36(s, 3 H), mixture was heated at reflux for 48 h and processed as 1.29(9, 3 H), 1.23(d, J = 9.4Hz, 1 H), 1.05( 8 , 3 H); 13CNMR described below for 22. There was obtained a 20% yield of 21 (75MHz, CsDt3) 151.2,145.4, 138.3, 130.9,126.7,125.8,111.5, as purple crystals, mp 195-196 "C (from toluene): 'H NMR 53.5,46.8,42.1,40.9,30.6,27.9,26.7,24.3ppm (one C not (300MHz, CDC13) 6 6.39(br s, 2 H), 6.29(t,J = 2.5Hz, 2 H), observed); HRMS m l z (M+)calcd for C18H22 238.1724,obsd 5.91(br s, 2 H), 2.76(br m, 4 H), 2.43(br m, 4 H), 1.97(t, J = 238.1742; [a]:' f16.2(c 1.5,CHC13). Anal. Calcd for CrsH22: 4.8Hz, 2 H), 1.40(5, 6 H), 1.11(d, J = 6.5Hz, 6 H), 1.02(s, 6 C, 90.70; H), 0.74(d, J = 6.2Hz, 6H), 0.42(s, 6HI; 13C NMR (75MHz, H, 9.30.Found: C, 90.33; H, 9.49. 147.3, 122.1,114.9,111.4,51.2,46.6,45.3,44.8, Dibromocarbene Addition to Diene 34c. A 250 mL CDC13) 150.2, 31.2,28.0,27.9, 24.5,20.1,19.6,16.8ppm; HRMS m l z calcd three-necked round-bottomed flask was fitted with a mechanfor C32H46ClTi (M+ - C1) 513.2767,obsd 513.2782;[a]: -250 ical stirrer, addition funnel, and gas inlet. To the flask was (C 0.07, CHCl3). added 34c (2.20g, 9.2mmol), dichloromethane (100 mL), benzyltriethylammonium chloride (56mg, 0.20mmol), bro~+~-~1R,4R,5S~-4-Phenyl-4,6,6-tri"thylt~cyclo[3.l.llmoform (3.50g, 13.8mmol), and ethanol (0.5 mL). The heptan-2-one(32~).In a flame-dried 1000mL three-necked mixture was vigorously stirred at 0 "C while a 50% sodium round-bottomed flask fitted with gas inlet, addition funnel, and hydroxide solution (4.6mL) was added dropwise over 20 min large stir bar was placed copper(1) bromide dimethyl sulfide and for an additional 24 h a t rt before it was poured into a complex (0.5g, 2.5mmol). Tetrahydrofuran (200mL) and

HRMS m l z (M+) calcd for C&24 204.1878,obsd 204.1866; [a]: -24 (c 3.0,CHC13). Anal. Calcd for C15H24: C, 88.16;H, 11.84.Found: C, 88.11;H, 11.90. Dibromocarbene Addition to 34b. In a 250 mL threenecked round-bottomed flask fitted with a mechanical stirrer and addition funnel was placed diene 34b (2.20g, 10.7mmol), dichloromethane (75 mL), bromoform (4.04g, 16.0 mmol), benzyltriethylammonium chloride (64mg, 2.3x mmol), and ethanol (5 drops). The mixture was vigorously stirred at 0 "C while a 50% NaOH solution (5.3mL) was slowly added to the flask and for an additional 24 h at rt before water (100 mL) was added. The aqueous layer was extracted with dichloromethane (3x 40mL), and the combined organic layers were dried, filtered, and concentrated to leave a brown oil which was taken up in 50 mL of hexane and passed through a 0.5-in. pad of silica gel (elution with several small portions of hexane). Solvent removal gave 35b as a light yellow oil (2.93 g, 70%): IR (neat, cm-') 1472,1370,1109,660; 'H NMR (300 MHz, CDC13) 6 5.49(br s, 1 H), 2.12 (m, 2 H), 1.91(dd, J = 5.7,1.6Hz, 2 H), 1.77(m, J = 6.8Hz, 1 H), 1.52(d, J = 9.2 Hz, 1 H), 1.43(dd, J = 7.6, 4.4Hz, 1 H), 1.38(dd, J = 16.1, 8.6Hz, 1 H), 1.24(s, 3 H), 1.00(s, 3 H), 0.84(9, 3 H), 0.82(d, J = 7.1Hz, 3 H), 0.66(d, J = 7.1Hz, 3 H); 13CNMR (75MHz, CDC13) 139.9, 132.5,50.9,45.5,43.1,42.2,37.2,35.5,29.8,28.9, 28.0,26.5,25.5,17.6,15.9,15.8ppm; HRMS m l z (M+)calcd for C16H2479Br81Br 376.0224,obsd 376.0226. (+)-( 1S,7S,8S)-7-Isopropyl-7,9,9-trimethyltricyclo[6.1.1.O2p6]deca-2,5-diene (36b). Dibromide 35b (2.90g, 7.71 mmol) was dissolved in 300 mL of anhydrous ether. The solution was cooled to 0 "C, and methyllithium (22.0mL, 1.4 M in ether, 30.8mmol) was introduced via syringe. The solution was allowed to warm to rt and t o stir for 24 h before it was added t o 300 mL of ice water via cannula. The layers were separated and brine (100mL) was added t o the aqueous phase. Three extractions of the aqueous layer were completed using ether (75mL). After the combined organic layers were dried, the solvent was removed to leave a light yellow oil, which was placed atop a short column of kieselghur and eluted with pentane t o afford 1.31g (78%)of a mixture of cyclopentadienes from which the lithium salt was prepared in the predescribed fashion. Reprotonation of 37b provided 36b in pure condition: IR (neat, cm-l) 1388,1379;'H NMR (300MHz, CDC13) 6 6.09(t, J = 1.2Hz, 1 H), 5.75(9, J=1 .6Hz, 1 H), 2.95(dd, J = 5.1,3.5Hz, 2 H), 2.63(t,J = .1Hz, 1 H), 2.40(ddd, J = 10.0, 6.1,4.3Hz, 1 H), 1.94(t,J = 5.6Hz, 1 H), 1.84(m, J = 4.9Hz, 1 H), 1.53(d, J = 10.1Hz, 1 H), 1.36(s, 3 H), 1.06(s, 3 H), 1.03(d, J = 6.8Hz, 3 H), 0.76(d, J = 6.8Hz, 3 H), 0.75 (s,3 H); 13C NMR (75MHz, CDC13) 152.3,151.9, 125.4, 119.4,



separatory funnel and diluted with water (100 mL). The 546.31, obsd 616.37, 581.39, 582.39, 546.41; [a]:' -2600 (c separated aqueous layer was extracted with dichloromethane 0.02, CHC13). (3 x 100 mL). The combined organic layers were dried and (-)-(q6-Cyclopentadienyl)(q5-[exo-( lS,SS)-7,7,9,9-tetconcentrated to leave a brown-red oil. The oil was diluted to ramethyltricyclo-[6.1.1.0296deca-3,5-dien-2-yl] 1 )dimethtwice its volume with ether and passed through a 1-in. pad of yltitanium (30). Dichloride ent-29(36 mg, 0.097 mmol) was silica gel (elution with ether). Concentration of the eluent gave dissolved in dry ether (3 mL) under argon. To the cooled (0 3.50 g (92%) of 36c as a yellow-orange oil: IR (CHCl3, cm-l) "C) violet solution was added methyllithium (135 pL, 0.2 1491, 1441, 1109, 1030, 761, 700, 657; lH NMR (300 MHz, mmol). A color change to orange ensued. After 20 min, the CDC13) 6 7.18-7.26 (m, 4 H), 7.05 (dt, J = 6.6, 1.4 Hz, 1H), heterogeneous yellow mixture was quenched by the addition 5.64(t,J=0.8Hz,lH),2.20(brm,3H),1.97(dt,J=9.0,5.5of water and extracted with ether (3 x 20 mL). The combined Hz, 1H), 1.91 (dt, J = 4.5, 1.0 Hz, 1 HI, 1.45 (d, J = 9 .8 Hz, organic layers were washed with brine, dried, and evaporated 1H), 1.35 (s, 3 H), 1.22 (s,3 H), 1.08(d, J =7.2 Hz, 1H), 1.07 to give 30 as a yellow-orange solid (29 mg, 87%) that was (5, 3 H); 13CNMR(75 MHz, CDC13) 151.1, 141.5, 130.1, 126.7, immediately dissolved in dry toluene (20 mL, 4.2 x M) 126.6,125.9,53.0,46.8,45.2,42.6,37.0,31.3,28.0,26.62,26.57, and stored at -10 ' C until needed: 'H NMR (300 MHz, C6Ds) 25.2 ppm (one C not observed); HRMS m / z (M+) calcd for 6 5.87 (9, 5 HI, 5.86-5.84 (m, 2 H), 5.48 (dd, J = 2.7, 2.3 Hz, C14H22Br2 410.0068, obsd 410.0032. lH),2.32(t,J=5.3Hz,lH),2.15(ddd,J=12.0,6.4,5.6Hz, (+)-(lS,7R,~-7-Phenyl-7,9,9-trimethyltricyclo[6.1.1.02,81-1 H), 1.43 (dd, J = 6.3, 5.2 Hz, 1H), 1.25 (s, 3 H), 1.23 (s, 3 HI, 0.87 (s, 3 H), 0.79 (d, J = 9.9 Hz, 1 H), 0.67 (9, 3 Hj, 0.21 deca-2,S-diene(36c). The above oil (3.50 g, 8.53 mmol) was (s, 3 H), 0.19 (9, 3 H); 13CNMR (75 MHz, c13Ds) 135.5, 133.5, dissolved in anhydrous ether (500 mL) under an inert atmo115.3,113.8,111.9,110.3,55.2,48.5,47.0,45.3,44.2,39.5,32.1, sphere. The flask was cooled to 0 "C, and methyllithium (22.7, 30.7, 30.3, 27.9, 24.9 ppm; HRMS m l z calcd for CzoH2,Ti (M+ 1.5 M in ether, 34.1 mmol) was added via syringe. After 2 h, - CHd 315.1592, obsd 315.1580; [a];' -146.5 (c 1.63, CHC13). the reaction mixture was warmed to rt and stirred for 24 h prior to its addition to ice water via cannula. The ethereal (+)-Bis[q5-(llE,7S)-1,10,l0-trimethyltricyclo[5.2.1.02~6ldeca-3,S-dien-2-ylldichlorozirconium (39). In a drybox, layer was separated, and the aqueous layer was extracted with zirconium tetrachloride (324 mg, 1.39 mmol) and camphorcyether (3 x 200 mL). After the combined organic layers were clopentadienide lithium salt" (500 mg, 2.77 mmol) were placed dried, the solvent was removed to give a yellow-brown oil, in an oven-dried, side-arm flask equipped with a magnetic which was placed atop a short column of silica gel (elution with stirring bar and septum. The solids were cooled to -78 "C, 1%ether in pentane) to give 1.56 g (73%)of 36c as a colorless and dry CHzClz (10 mL) was slowly introduced. The slurry oil: IR (neat, cm-l) 1494, 1446, 1387, 1375,765,704; 'H NMR was allowed to stir overnight with slow warming to rt, filtered (300 MHz, C & 5 )6 7.38 (dd, J =7.3, 1.4 Hz, 2 H), 7.18 (t,J = through Celite under argon, and concentrated in vacuo. The 7.3 Hz, 2 H), 7.06 (t, J = 7.3 Hz, 1 Hj, 6.13 (t, J = 1.2 Hz, 1 Torr to solid residue was sublimed at 140 "C and 3 x H), 5.86 (9, J = 1.7 Hz, 1H), 3.03 (d, J =0.8 Hz, 1H), 2.98 (t, give 210 mg (30%) of 39 as yellow crystals.8c J = 1.6 Hz, 1H), 2.27 (d, J = 5.7 Hz, 1H), 2.20 (d, J = 5.0 Hz, 1H), 2.16 (dt, J = 9.7, 5.7 Hz, 1H), 1.63 (s, 3 HI, 1.26 ( s , 3 H), (+)-Bis[qs-( llE,8R)-7,7,9,9-tetramethyltricyc10[6.1.1.~~]1.13 (d, J = 6.4 Hz, 1 H), 0.93 (s, 3 H); 13C NMR (75 MHz, deca-2,5-dien-4-yl]dichlorozirconium (40).Zirconium tetCsHs) 150.2, 149.6, 132.6, 129.5, 127.2, 125.9, 125.8, 120.4, rachloride (1.17 g, 5.02 mmol) was slurried in dry 1,253.9, 46.7, 43.8, 42.4, 41.0, 30.9, 29.9, 27.8, 24.6 ppm; HRMS dimethoxyethane (20 mL), cooled to -78 "C, and treated via cannula with a solution of ent-37a(2.00 g, 10.3 mol). After 1 m l z (M+) calcd for C19H22 250.1722, obsd 250.1712; [a];' h of stirring at -78 "C, the mixture was allowed t o warm t o +74.9 (c 1.8,hexane). ( -)-Bis(q5-[ (lS,7S,S,&S)-7-pheny1-7,9,9-trimethyltricyclo-rt, stirred overnight, refluxed for 2 days, cooled t o rt, and freed of solvent in vacuo. The yellow residue was dissolved in dry [6.1.1.02~6]deca-2,5-dien-3-yl]dichlorotitanium (22). Into CHzClz (25 mL), cooled to 0 "C, treated wtih 4 N HCl(5 mL), a dry 250 mL three-necked round-bottomed flask was placed and stirred at 0 "C for 15 min. The separated organic layer a solution of 36c (1.56 g, 0.23 mmol) in 45 mL of hexane. Ether was washed with water (25 mL), and the combined aqueous (20 mL) was added, the solution was cooled to 0 "C, and phases were extracted with CHzCl2 (3 x 30 mL). The organic n-butyllithium (4.8 mL, 1.3 M in hexane, 6.3 mmol) was solutions were combined, dried, and evaporated t o leave a light introduced over a few minutes as a white solid precipitated. brown residue, which was sublimed at 165 "C and 3 x The mixture was stirred at 0 "C for 1 h and at rt for 24 h. Torr. There was obtained 290 mg (11%)of 40 as yellow Concentration in vacuo left a white solid which was redissolved crystals;8e [a]:' +229 (c 0.76, CHC13). in 10 mL of ether and 50 mL of DME. In a drybox, titanium(+)-Bis[qs-(1R,7R,~R)-7-isopropyl-7,9,9-trimethyl(111) chloride (481 mg, 3.12 mmol) was weighed into a flask tricyclo[6.l.l.0a~61deca-2,5-dien-4-ylldichlorozirconium equipped with a side arm. DME (50 mL) was added, the (41). In a drybox, zirconium tetrachloride (262 mg, 1.12 mmol) purple-blue slurry was cooled to -78 "C, and the anion solution and 37b (500mg, 2.25 mmol) were placed in an oven-dried, was introduced via cannula over 20 min. After 1h at -78 "C, side-arm flask equipped with a stir bar and septum. The solids the mixture was heated t o reflux for 48 h, cooled to 0 "C, and were cooled t o -78 "C under argon, and dry CHzCl2 (10 mL) treated with 50 mL of concentrated HC1 in air for 5 min. The was added very slowly via syringe with stirring. The slurry now red mixture was poured into a separatory funnel, the was allowed to stir for 1h at -78 "C before being warmed to organic phase was washed with saturated CaClz solution (50 rt and stirred overnight. The reaction mixture was filtered mL), and the combined aqueous layers were extracted with through Celite under argon and concentrated in uucuo. The 50 mL of dichloromethane. The combined organic fractions Torr to solid residue was sublimed at 150 "C and 2.5 x were dried, filtered, and concentrated t o give a red-brown give 0.18 g (27%) of 41 as yellow crystals, mp '190 "C, dec: residue, which was dissolved in 5 mL of dry toluene and cooled 'H NMR (300 MHz, CDC13) 6 6.25 (t,J = 2.5 Hz, 2 H), 6.21 (t, to -20 "C. The resulting crystals were collected and washed J =3.0 Hz, 2 H), 5.87 (t,J =2.5 Hz, 2 H), 2.75 (t,J =5.1 Hz, with pentane to give 234 mg (12%) of 22 as a green microc2 H), 2.62 (m, J = 6.7 Hz, 2 H), 2.51-2.43 (m, 2 H), 2.33 (d, J rystalline solid, mp 195 "C (dec, toluene): lH NMR (300 MHz, = 10.3 Hz, 2 H), 1.99 (t, J = 5.7 Hz, 2 HI, 1.40 (5, 6 HI, 1.07 CDCl3) 6 7.47 (d, J = 7.4 Hz, 4 H), 7.33 (t, J = 5.3 Hz, 4 H), (d, J = 6.6 Hz, 6 H), 1.00 (s, 6 H), 0.76 (d, J = 6.8 Hz, 6 H), 7.19(t, J = 7.4Hz,2H),6.83(t, J = 2 . 2 H z , 2 H ) , 5 . 8 4 ( t , J = 0.38 (s, 6 H); 13C NMR (75 MHz, CDC13) 142.9, 141.1, 116.5, 2.1Hz,2H),5.56(t, J = 2 . 9 H z , 2 H ) , 2 . 6 5 ( d t ,J = 1 0 . 7 , 5 . 6 111.5, 109.4, 51.4,45.7,45.3,43.9, 32.1,28.4, 27.7, 24.4, 19.8, Hz, 2 H), 2.59 (t, J = 5.2 Hz, 2 H), 2.43 (t, J = 5.3 Hz, 2 H), 19.3, 16.6 ppm; HRMS m / z (M+)calcd for C~2&ClZr 590.2020, 2.15 (d, J = 10.2 Hz, 2 H), 1.55 (s, 6 H), 1.45 ( 8 , 6 H), 0.45 (s, obsd 590.2035; [a]:' +115 (c 0.15, CHC13). Anal. Calcd for 6 H); I3C NMR (62.5 MHz, CDC131 149.0, 147.4, 142.8, 127.9, C32H&12Zr: C, 64.83; H, 7.82. Found: C, 64.75; H, 7.79. 126.9, 126.1, 122.4, 115.1, 114.5, 50.8, 48.0, 45.2, 44.1, 32.5, Asymmetric Hydrogenation Procedure. A. Reduc31.3, 27.8, 24.4 ppm; HRMS m l z calcd for C38H42C12Ti (M+), tion of 2-Phenyl-1-butenewith Optically Active TiC38H4zClTi (M+ - Cl), C38H42Ti(M+ - 2C1) 616.25, 581.28,

Paquette et al.

4878 Organometallics, Vol. 14, No. 10, 1995 tanocenes. An optically active titanocene dichloride (0.020.04 mmol) and 2-phenyl-l-butene were placed in a dry Fischer-Porter bottle. The mixture was degassed briefly and dissolved in 5 mL of toluene. The red solution was subjected to three freeze-pump-thaw cycles before a hydrogen atmosphere was established. When the solution reached rt, nbutyllithium (0.20-0.40 mmol in hexane) was introduced via syringe. The typically gray-green solution was blanketed with 20 psi of hydrogen and placed in a thermostated bath. After 48 h, the reaction mixture was quenched with 6 N HCl, extracted with ether (2 x 2 mL), and dried. Yields were determined by capillary GC-MS. A portion of the product was purified by preparative gas chromatography using a column (5.5 ft x 0.25 in. diameter) packed with 5% SE 30 on Chromosorb W. Separation was achieved with an oven temperature of 80 "C, injector temperature at 180 "C, detector temperature at 180 "C, and a helium gas flow of 40 mumin. The optical rotations measured in 95% ethanol at 20 "C were compared to [a];' f22.7 (c 1, 95% ethanol) reported for optically pure (S)-(+)-2-phenylb~tane.~~ B. Reduction of 2-(a-Naphthyl)-l-buteneunder Medium Pressure. A Fischer-Porter thick-walled bottle was charged with 7 (1equiv) and the catalyst (0.01-0.05 equiv). The container was attached to a medium pressure hydrogenation apparatus and evacuated for several hours. Freshly distilled toluene (from CaH2) or hexanes was introduced via syringe, and the solution was subjected to three freeze-thaw cycles before a hydrogen atmosphere was reestablished. Butyllithium or methyllithium (0.1-0.2 equiv) was added at rt, and the pressure was raised to the appropriate level. Cooling was carried out if required. After reaction was deemed complete, 5% HCl was added and the mixture was extracted with ether as above. Purification through silica gel (hexane elution) gave a colorless oil with varying amounts of 7 and 8. The unreacted 7 was removed as follows. The crude mixture containing 7 and 8 was dissolved in dry THF under an atmosphere of argon and cooled in an ice bath. BH3.SMez in THF (5 equiv based on unreacted 7) was added, and the mixture was stirred for several hours. After the mixture was recooled to 0 "C, excess aqueous NaOH solution was slowly added followed by excess 30% HzOz solution. After an additional 2 h, the mixture was diluted with ether, the layers were separated, and the organic layer was washed once with water, once with saturated brine, and dried. Purification of the concentrate by chromatography (silica gel, hexanes) yielded pure 8 as a colorless oil. C. Reduction Studies Involving 30. The solution of 7 (253 mg, 1.388 mmol) was prepared as in method B. A solution of 30 in toluene (6.6 mL, 0.2776 mmol) was added under an atmosphere of argon. The yellow solution was degassed by three freeze-thaw cycles before a hydrogen atmosphere was

established. The pressure was set to 29 psi, and the mixture was stirred overnight at rt. No reduction in pressure occurred; therefore, the solution was degassed once more as above and the pressure reset to 29 psi. Several hours later with no drop in pressure or color change methyllithium (0.035 mmol) was added at rt and the pressure was readjusted to 29 psi. A color change from yellow to gray-violet occurred immediately. After 15 min, the pressure gauge indicated 24.1 psi. After an additional 23.5 h, the pressure decreased only slightly and the reaction mixture was quenched as in method B. 'H NMR analysis indicated that > 97% hydrogenation had occurred. The level of enantioselectivity was determined to be 13% ee. D. Prototypical Zirconocene Reduction. An optically active zirconocene dichloride (0.02 mmol) and 6 or 7 (2.00 mmol) were placed in a dry Fischer-Porter bottle containing a magnetic stir bar. The mixture was briefly degassed under vacuum and dissolved in dry toluene (5 mL) under a hydrogen atmosphere. This mixture was subjected to three freezepump-thaw cycles before reestablishing the hydrogen atmosphere. A solution of alkyllithium in hexane (0.20 mmol) was added via syringe at rt. The resulting mixture was then placed in a thermostated bath, and the hydrogen pressure was increased to 40 psi. After being stirred for the specified time period, the reaction mixture was quenched with 6 N HC1. The aqueous layer was extracted with ether (2 x 5 mL), and the combined organic layers weree dried. In the case of 6,the 2-phenylbutane was separated from residual olefin via preparative gas chromatography at an oven temperature of 80 "C, injector and detector temperatures of 180 "C, and a helium gas flow of 40 mumin. For 7, the concentrated mixture was dissolved in dry THF (2 mL) in an oven-dried, side-arm flask equipped with a stir bar and septum. The solution was cooled to 0 "C, and BH3.THF (0.56 mL, 1.0 M in THF, 0.56 mmol) was added dropwise via syringe. The mixture was allowed to stir at rt overnight, followed by the addition of a 15% NaOH solution (0.5 mL, 2.00 mmol). A solution of 30% hydrogen peroxide (0.7 mL, 7.00 mmol) was added dropwise and the mixture allowed to stir 1 h before being poured into water (3 mL). The aqueous layer was extracted with ether (3 x 5 mL), and the combined organic layers were washed with brine (3 x 5 mL), dried, and concentrated to give a yellow oil, which was directly subjected to silica gel chromatography (elution with hexanes) to afford 8.

Acknowledgment. This work has been supported by a grant from the National Science Foundation. M.R.S.,E.I.B.,and K.J.S.acknowledge with gratitude their receipt of the fellowship awards cited in ref 1. OM950282P

Catalytic Enantioselective Hydrogenation of 1,1-Disubstituted Alkenes

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