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Catalytic asymmetric hydrogenation by some homogeneous and silica-bound μ-thiolato-μ-chlorodicarbonylbis- (neomenthyldiphenylphosphine) dirhodium complexes
329
CATALYTIC AS~METRIC HYDROGENATION BY SOME HOMOGENEOUS AND SILICA-BOUND i(-THIOLATO-~-CHLORODICARBONYLBIS(NEOMENTHYLDIPHENYLPHOSPHINE)DIRHODIUM
COMPLEXES
Summary
(+)-Dicarbonyl-y-ahloro[p-(2 - methyl - 2 - propanethialato * S:S)]bis([limethyl-2-(l-methyletbyl)cyclohexyl]diphenylphosphine~dirhodi~ @a) and ( t”) * dicarbonyl - p - chloroftr - (2 - tr~ethoxysilyl~et~ethiolato - S:Slbis(f5methyl-~-~~-~ethylethyl~~y~lohexy~]diphe~ylph~phine~~rh~i~ (Gbj were prepared by inte~~tion of ( + ~*~~~enthyld~phenylph~phi~e (3) with ~hlo~di~~rbonylrhodi~ dimer (2>* followed by treatment of the product with the appropriate ~alkylthio~tr~ethylsilane, ei. Complex Sb was immobilized by attachment to silica gel. Both the homogeneous and hybrid catalyts proved capable of promoting the asymmetric hy~genatio~ of prochiral unsaturated acids and esters. While the soluble complexes fsa and 6b led to the formation of dextro-rotatory products, the recyclable supported catalyst gave laevorotatory compounds,
We have reported previously tl- 3] that homogeneous and ~obil~~~ di~hod~nM complexes of formula 1 which have one bridging tbiofato and one bridging chloro ligand, are efficient hydrogenation catalysts that retain their dinuclear structures during the catalytic processes. We now find that the replacement of the two tri-t-butylphosphines in 1 by chiral ( +)-neornenthyldiphenylphosphine (( 1aR) - [ t$ e methyl - 2a - (I-methylethyl)cyclohexyl] diphenylphasphine) ligands yields dinuclear complexes that support asymmetric hydrogenation of several prochiral olefinic compounds.
330
[C(CW,I,P
\
7’\
/
P[C(CW,I,
oC/RZS/Rh\co k (1)
Experimental All experiments were carried out under freshly purified and degassed solvents.
an argon
atmosphere
with
(+)-Dicarbonyl-~-chloro[~-(2-methyl-2-propanethiolato-S:S)]bis{[5-methyl-Z-(l- me thy 1e thy l)cyc 1o h exyl]diphenylphosphine}dirhodium @a) To a stirred solution of 300 mg (0.77 mmol) freshly sublimed chlorodicarbonylrhodium dimer (2) in 10 ml benzene was added dropwise a solution of 498.5 mg (1.54 mmol) ( +)-neomenthyldiphenylphosphine (3) in 10 ml of the same solvent. The mixture was stirred for 2 h at room temperature and 125 mg (0.77 mmol) (t-butylthio)trimethylsilane (5a) [4] in 10 ml benzene was added during 1 h. After further stirring for 4 h, the solvent was removed under reduced pressure. The orange residue of dirhodium complexes was dissolved in 10ml toluene and heated at I10 “C for 10min. Evaporation of the solvent followed by recrystallization from a mixture of pentane and methanol afforded 218 mg (27%) of a mixture of cis-6a and trans-6a in a 2:l ratio; m.p. (dec.), 94 “C; [a]&, = + 135”(c, 1, C&H,); [a]$ = + 115”(c, 1,&H,). IR (KBr): 1980, 1952 cm-l (CrO). 200 MHz ‘H NMR (&He): 6 0.60 and 0.68 (two d, 6H, J1 = J, = 6 Hz, CHCH, of trans-6a and cis-6a in a 1:2 ratio, respectively), 0.75 - 1.18 (m and four d, 12H, J1 = J, = J3 = J4 = 6 Hz), 1.20 1.92 (m, 16H), 1.98 and 2.09 (two s, 9H, C(CH,), of cis-6a and trans-6a in a 2:l ratio, respectively), 2.17 (m, lH), 2.79 (m, lH), 3.16 (m, 2H), 6.90 -7.10 (m, 14H, Arm, 7.62 (m, 2H, Arm, 7.95 (m, 4H) ppm. 81 MHz 31P(H} NMR (C&H,, 85% H,PO, external standard): 6 33.7 ppm (J(PRh) = 129.6 Hz). Analysis: Found: C, 58.34; H, 6.57; Cl, 3.90; P, 5.76%. C,H,,ClO,P,Rh,S requires: C, 58.06; H, 6.47; Cl, 3.42; P, 5.99%.
cis-(+)-Dicarbonyl-~-chloro[~-(2-triethoxysilyl~thanethiolato-S:S]bis~[5-methyl-2-(l-methylethyl)cyclohexyl]diphenylphosphine)dirhodium (6b) As above, a benzene solution consisting of 0.77 mm01 2 was reacted with 1.54 mm01 3. The mixture was heated to 60 “C and stirred at that temperature for 2 h. A solution of 228 mg (0.77 mmol) trimethyl[ 2-( triethoxysilyl) ethylthiolsilane (5b) [l] in 10 ml benzene was added dropwise and the reaction mixture stirred at 50 “C for 4 h. The solvent was removed under
331
reduced pressure and the residue dried at 5 x 1O-3 mmHg. Rec~stallization from pentanelmethanol gave 420 mg (46%) of cis-6b as orange crystals; m.p. (dec.), 89 “C; [LY]$!~ = +83.3” (c, 0.6, t&H,). IR (KBr): 1995, 1955 cm-l (CEO). 200 MHz “H NMR (C,H,): 6 0.72 (d, 6H, J = 6 Hz, CHC&), 0.80 - 0.94 (m, 6H), 0.98 (d, 6H, J=6Hz, CHCH,), 1.04 (d, 6H, J=6 Hz, CHCH,), 1.12 (t, 9H, J = 5.5 Hz, CH,C&), 1.25 - 3.10 (m, lOH), 2.69 - 2.81 (m, 2H), 2.84 - 2.98 (m, 2H), 3.39 (m, BH), 3.72 (q, 6H, J = 5.5 Hz, CLCH,), 4.02 (m, 2H), 7.05 (m, 12H, Arm, 7.92 (m, 8H, ArIl) ppm. 81 MHz 31P(H) NMR (C,H,, 85% H,PO, external standard): S 34.03 ppm (J(PRh) = 121.2 Hz). Analysis: Found: C, 55.18; H, 6.29; Cl, 3.15; P, 5.14%. C,H,,ClO,P,Rh,S requires: C, 55.39; H, 6.58; Cl, 3.03; P, 5.30%. Anchoring of 4% to silica A mixture of 0.77 mequiv 6b, 10 ml benzene and 1.00 g Merck’s Silica 60 (60 - 200 pm; 500m2 g-l) (predried by heating for 48 h at 150 “C at 5 x 10m3mmHg) was stirred in a sealed vessel for 8 d. The solvent was decanted, and the solid washed repeatedly with hot benzene and dried at 5 x 10---3mmHg. The dissolved rhodium in the combined benzene solutions was analyzed by atomic absorption and the silica-bound metal calculated 131to be 0.089 mequiv g-l. General!procedure for catalytic hydrage~atio~ of ~~h~~al substrates 7- 10 Typically, a mixture of 184.5 mg (0.84 mmol) Z-methyl ~-acet~ido~innamate (8), 49.1 mg (0.042 mmol) 6b, 10 ml benzene and 5 ml MeOH was introduced under argon into a mini-autoclave. The sealed apparatus was cooled to 0 “C, purged with argon and charged with 100 psi H,. The mixture was heated to 120 + 0.5 “C and stirred at that temperature for 4 h. The reaction vessel was cooled, opened under argon and the solvent evaporated. The residue was chromatographed on neutral alumina 90, using a mixture of MeOH/CH,Cl, as eluent, and subjected to GC and NMR analyses. The optical activity was determined with the aid of a Perkin Elmer Model 141 polarimeter. When the silica-bound catalyst 11 was used, the reaction mixture was decanted and the solid particles washed under argon with MeOH (5 x ). After drying in a stream of argon, the catalyst was either applied immediately in a second run or stored under argon to await recycling.
Results and discussion The soluble complexes 6a and 6b were obtained by modification of the general syntheses of p-alkyl- and ,u-arylthiolato-~--chlorodicarbonylbis(tri-tbutylphosphine)dirhodium complexes outlined in eqn. (1) [ 1,5], While syntheses of compounds of type 1, in which bulky tri-t-butylphosphine ligands were employed, proceeded smoothly at room temperature, the
332
[(p-Cl)~,(CO),],
2R*PhzP’9’.[R*Ph,P{gO)Rh(/&l)]a
(a), R = CMe, (b), R = CH,CH,Si(OEt)s R* = (lug)-[5~-methyl-2~-( l-methylethyl)cyclahe~l~
formation of the chiral complexes 6a and 6b required the application of elevated temperatures either in the first or second step. At room temperature, the reaction of 2 with alkyldiphenylphosphines and (alkylthio) trimethylsilane afforded a mixture of products with carbonyl bridging ligands. The structure of such compounds will be reported in a separate paper. The ‘H and 31P NMR spectra of 6a and 6b reveal that while 6b is a single steroisomer having the cis configuration, 6a is a 23 mixture of cis and truns complexes. Incidentally, the doublets in the a1P NMR spectra of ck-6a and trans-6a co-appear at 33.1 ppm. The observation that a mixture of stereoisomers of 6a induces the asymmetric hydrogenation of Z-~-acet~idocinnamic acid, C,H,CH=: C(NHCOCH~~COOH (7), Z-methyl ~-acet~idocinnamate, C,H,CH= C(NHCOCH,)COOCH, (8) and to some extent also of a-acetamidoacrylic acid, H&=C( NHCOCH,)COOH (9) and methyl a-acetamidoacrylate, H,C=C(NHCOCH,)COOCH, (lo), in fair to very good optical purity (just as with the isomerically pure catalyst 6b), suggests that the geometric constraints which control the sterochemi~al course of the hydrogenations are of similar nature whether the two chiral phosphines are cis or trans to each other. Some typical hydrogenation experiments with 6a and 6b are summarized in Table 1. TABLE 1 Hy~genation of compounds 7 - 10 in the presence of the soluble dirh~i~ under comparable conditions”
complexes 6a and 6b
Substrate
Catalyst
Yield (%)b
Optical purity (% ee)
7 7 8 8 9 9 10 10
6a 6b 6a 6b 6a 6b 6a 6b
17 11 13 15 70 53 100 82
10 45 96 97 c c c c
“Reaction conditions: 0.64 mm01substrate, 0.042 mm01catalyst in 10 ml benzene and 5 ml MeOH for 16 h at 120 + 5 “C under 1000psi of Hz. bProduct isolated by column chromatography on alumina 90. “Varying, < 5% ee.
333
The table indicates that the yields of the hydrogenated products, as well as their optical purity, depend both on the nature of the substrate and the catalyst employed. Since the phenyl groups in 7 and 8 extend steric hindrance around the C-C double bonds, these compounds are hydrogenated at slower rates than 9 and 10.The optical purity of the phenylalanine derivatives, however, was found to be considerably higher than that of the non-phenylated compounds. These results are attributed to the fact that the homogeneous catalysts are converted, in part, during the hydrogenation process into metallic rhodium that competes with the residual chiral catalyst regarding reduction of the substrate. It seems that steric hindrance has a larger effect on the symmetric, rather than the asymmetric, course of hydrogenation. Thus, for example, 8 is reduced in practice only by the chiral catalysts and gives the (S)-( +)-N-acetylphenylalanine methyl ester in very high optical purity, while the sterically less-hindered ester 10 yields mainly the racemic product. Control experiments, in which the hydrogenation of 8 and 10 by rhodium powder was compared (at 500 psi and 120 “C), revealed that the less-hindered unsaturated ester was reduced more than lo-times faster than the phenylated compound. Decomposition of 6a and 6b into metallic rhodium was found to be more pronounced at high pressure of hydrogen than at low pressures. For this reason, when hydrogenation of 7 and 8 by 6a was conducted under a hydrogen pressure that did not exceed 100 psi, the yields [and optical purity (ee) values] were 40 (30%) and 8 (95%), respectively. The silicon-containing complex 6b was immobilized by attachment to silica gel via the ethanethiolato side chain to give catalyst 10 [eqn. (2)]: PPh,R*
6b +
OH / /O\ (silica)-OH -+ (silica)-0-Si(CH,),S \o H
10
OC\ /Rh\
’
Cl + 3EtOH
(2)
‘Rh’ OC’
R* = laR-[fib-methyL2a-(
/
\PPh,R*
1-methylethyl)cyclohexyl]
The amount of 6b employed for immobilization was precisely that required for the formation of a monolayer on the support [3,6]. As reported previously for some achiral dirhodium complexes [2,3], the anchoring of the soluble catalysts to the inorganic support increased the efficiency. In addition, the immobilization of 6b also affected the chirality of the products: while both soluble catalysts led to the formation of dextro-rotatory compounds, the application of 11 gave laevo-rotatory acids and esters. We assume that this difference in chirality is associated with the different orientations of the phosphine ligands in the homogeneous and immobilized catalysts. Fixation of
334
molecules of 6b as a monohyer on the silica surface is likely to block one side of the dirhodium complex and may force the substrate to approach the metal from a different direction than under homogenous conditions. The hybrid catalyst was found to be considerably more stable than the soluble complexes under our reaction conditions (uide infra). Yet, even the immobilized catalyst formed substantial quantities of achiral hydrogenation products after some time. As mass spectral studies revealed the occurrence of considerable H-D exchange in the presence of the heterogenized catalyst during deuteration of 6 [7], we presume that 1%catalyzed hydrogen scrambling at the chiral carbon atom of the hydrogenation product is responsible for the gradual accumulation of racemic products. A typical series of hydrogenation experiments of 8 in the presence of 11 under different hydrogen pressure conditions is summarized in Table 2. The supported catalyst was found to be fully activated only after one to three runs. During the first run (but not thereafter), some decomposition of the catalyst took place and minute amounts of the chiral phosphine were ejected into the solution. Usually, only slightly over the stoichiometric amount of substrate was reduced in this run to give a practically optically pure product. In subsequent runs, substantially higher yields were obtained but the rate of formation of racemic products increased as well. Consequently, a retardation in the optical activity was observed after a few initial runs. Table 2 reveals a strong dependence of both the conversions and ee values on the hydrogen pressure employed. By gradually reducing the pressure from 1000 to 25 psi, it was found that optimal results were obtained at cu. 166 psi. It seems that at higher pressures the active sites of the catalyst become saturated with hydrogen, and consequently coordination of the olefinic substrate is restricted. On the other hand, at too low a pressure, insufficient hydrogen molecules are activated by the chiral catalyst. TABLE 2 Hydrogenation of methyl ~-acet~docinn~ate (8) to the (R)-( -)-~-acetylphenylalanine methyl ester in the presence of the silica-bound catalyst lla Run No.
Hydrogen pressure (psi)
Yieldb (%)
Optical purity (%ee)
Run No.
Hydrogen pressure (psi)
Yieldb (%)
Optical purity (% ee)
1 2 3 4 5 6
1000 1000 1000 1000 500 500
5.8 25 24 24 27 25
95 40 40 41 23 22
7 8 9 10 11 12
100 100 50 50 25 25
66 69 30 26 10 8
16 17 12 12 6 7
“Reaction conditions: 0.84 mm01 8, 0.011mequiv 11 in a mixture of 10 ml benzene and 5 ml MeOH; 16 h at 120 + 0.5 “C. bProduct isolated by column chromatography on alumina 90.
335
Under the conditions listed in Table 2, activation of 11 takes place entirely during the first run. Thereafter the catalyst does not change and gives absolutely reproducible results. For example, when the experiments of Table 2 were extended by applying H, pressures of 1000, 500, 100 and 50 psi once again, the corresponding yields and optical purity were identical with those of runs 2,5,7 and 9. When, however, the solvent was changed to benzene-free MeOH, substantial catalyst deterioration was found to take place at 1000 psi even in advanced runs. Consequently, the ee values dropped rapidly. Typical ee values for 11-catalyzed hydrogenation in MeOH under 1000 psi Hz (the other conditions as in Table 2) were 49,19 and 16% in the first three runs. On reducing the pressure to lOOpsi, the optical purity dropped to 3 - 4%. In experiments in MeOH conducted under a H, pressure of < 100 psi, no catalyst deterioration was observed right from the beginning. The dependence of the optical purity on the reaction period is demonstrated by the results listed in Table 3. As in the homogeneous catalyses, short reaction periods led to higher optical purities than longer ones. Further factors that affected the optical purity of the product were the catalyst:substrate ratio (Table 4), the nature of the solvent (Table 5) and the reaction temperature. TABLE
3
Effect of reaction period on the optical purity of the (R)-( -)-N-acetylphenylalanine formed by the l&catalyzed hydrogenation of 8”
methyl ester
Run No.
Reaction time (h)
Yield
Optical purity (% ee)
Run No.
Reaction time (h)
Yield
(%)
(%)
Optical purity ( % ee)
1 2 3 4 5
16 16 16 16 46
5.4 16 17 16 53
98 43 43 44 17
6 7 8 9
8 4 3 2
13 10 7 5
48 60 74 85
*Reaction conditions as in Table 2 except reaction period varied as specified. TABLE
that the hydrogen
pressure
was 109 psi and the
4
Effect of catalystzsubstrate
ratio on the l&catalyzed Catalyst:substrate
yield (%) optical purity (% ee)
hydrogenation
of 8”
ratiob
1:39
1:78
1:156
1:312
1:624
28 95
22 78
10 60
8 36
6.5 24
“Reaction conditions: 2.16 x 10W3 mequiv catalyst, the required amount of 8, 2 ml benzene, 1 ml MeOH; 4 h at 120 + 0.5 “C; hydrogen pressure 100 psi. bQuantities expressed in equiv mol-‘.
TABLE 5 Solvent effect on the hydrogenation of 8 by Ila
_ solvent
CH,OH CD,OD GXH, 33% CH,OH $67% Ce&
Yield (%I 8 8 30 10
Optical purity (% ee)
Solvent
40 40 2 60
25% CH,OH -I-75% C,H, 17% CH,OH -I-83% C&H, THF
(% ee) 22 $5 I1
44 26 10
“Reaction conditions: 0.34 mm01 substrate, i?.Olt mequiv fully activated catalyst, 15 ml solvent, 4 h at 120 “C and 100 psi of H,.
After the first run, the immobilized catalyst was found to be perfectly leach-proof in the various media with the exception of THF. The hydrogenation of methyl a-acetamidocinnamate under 100 psi Hz proceeded very slowly in MeOH. In benzene, however, the reaction was quite fast but the product was of extremely low optical purity. For these reasons, we used mixtures of both solvents in which reasonable yields and fair optical activity were recorded. When methanol-d, was used, mass-spectral analysis indicated the formation of a substantial amount of deuterated products as a result of catalytic H-D exchange between the solvent and the substrate. By virtue of the NMR spectrum, it was found that the main product was the I-ID adduct C~H~CHDCH(NHC~~H~)GOO~H~ in which the deuterium atom is in the benzylic position. Di- and tri-deuter~ted compounds were also formed during the initial stages of the process, but deuterium-free ~~H~CH~~~~NH~O~H~)COOCH, could be detected only after prolonged treatment of t;he substrate with Dz. In some recovered starting material, the NH group was exchanged by ND. The absence of a measurable kinetic isotope effect in these experiments suggests that the various hydrogen-transfer processes involved in the hydrogenation are not r&~-controlling. It is remarkable that, in contrast to Z-methyl ~-a~et~idoci~~~ate (6), the E isomer hardly undergoes hy~ogenation although its NH group is replaced by ND when CD30D is used as solvent. While 6a and 6b were shown to deteriorate at elevated temperatures, and could not be applied above 125 “C, the hybrid catalyst proved thermally stable at least up to 160 “C. Thus, hydrogenation of 8 by 11 could be performed over quite a wide range of temperatures. For example, under the conditions listed in Table 2, using a 1:2 mixture of MeOH and benzene and 100 psi Hz, the yields (and optical purity values) at 90,120,140 and 160 “C were 5.4 (68), 10 (60), 36 (18) and 45% (9% ee), respectively. The thermal stability of the catalyst was also demonstrated by a series of experiments in which the first run was performed at 160 “C and following runs at 140, 120 and 90 “C. The results were exactly the same as those listed above where the first experiment was carried out at 90 “C.
337 TABLE
6
Hydrogenation Substrate
7 9 10
of some unsaturated
acids and esters by 11 under comparable
Product
Yield (%) (optical
(R)-( -)-C,H,CH,CH(NHCOCH,)COOH (S)-( -)-CH,CH,CH(NHCOCH,)COOH (S)-( -)-CH,CH,CH(NHCOCH,)COOCH,
BReaction conditions: at 120 _+0.5 “C.
conditions” purity, % ee)
Run 1
Run 2
Run 3
Run 4
20 (49) 99 (2) 66 (35)
26 (37) 92 (2) 85 (25)
35 (28) 83 (2) 87 (25)
46 (24) 73 (6) 86 (25)
0.84 mm01 substrate, 0.011 mequiv catalyst,
10 ml benzene, 5 ml MeOH; 4 h
Substrates other than 8 were also hydrogenated by the silica-bound catalyst 11.Some typical results are summarized in Table 6. Tables 4 and 6 indicate that, by analogy to the homogeneous catalyses described in Table 1, the cinnamic acid derivatives yield hydrogenation products of higher optical purity than the less bulky compounds 9 and 10. The free acids were found to be inferior to their methyl esters and thus 9, which reacted very rapidly, gave virtually no optically active products whatsoever.
Acknowledgements The authors thank the Deutsche Forschungsgemeinschaft (DFG), the Fonds der Chemischen Industrie and the Technical University of Berlin for financial support of this study, as well as Degussa, Hannau for a valuable gift of rhodium.
References 1 H. Schumann, G. Cielusek, S. Jurgis, E. Hahn, J. Pickardt, J. Blum, Y. Sasson and A. Zoran, Chem. Ber., 117 (1984) 2825. 2 M. Eisen, J. Blum and H. Schumann, J. Mol. Catal., 31 (1985) 317. 3 M. Eisen, T. Bernstein, J. Blum and H. Schumann, J. Mol. Catal., 43 (1987) 199. 4 E. W. Abel, J. Chem. Sot., (1969) 4466. 5 H. Schumann, G. Cielusek and J. Pickardt, Angew. Chem., 92 (1980) 60; idem, Angew. Chem., Znt. Ed. En&., 19 (1986) 70. 6 E. Wellner, M. Ottolenghi, D. Avnir and D. Huppert, Lungmuir, 2 (1986) 616. 7 M. Eisen, J. Blum, G. HGhne, H. Schumann and H. Schwan, Chem. Ber., 122 (1989) 1599.
CATALYTIC AS~METRIC HYDROGENATION BY SOME HOMOGENEOUS AND SILICA-BOUND i(-THIOLATO-~-CHLORODICARBONYLBIS(NEOMENTHYLDIPHENYLPHOSPHINE)DIRHODIUM
COMPLEXES
Summary
(+)-Dicarbonyl-y-ahloro[p-(2 - methyl - 2 - propanethialato * S:S)]bis([limethyl-2-(l-methyletbyl)cyclohexyl]diphenylphosphine~dirhodi~ @a) and ( t”) * dicarbonyl - p - chloroftr - (2 - tr~ethoxysilyl~et~ethiolato - S:Slbis(f5methyl-~-~~-~ethylethyl~~y~lohexy~]diphe~ylph~phine~~rh~i~ (Gbj were prepared by inte~~tion of ( + ~*~~~enthyld~phenylph~phi~e (3) with ~hlo~di~~rbonylrhodi~ dimer (2>* followed by treatment of the product with the appropriate ~alkylthio~tr~ethylsilane, ei. Complex Sb was immobilized by attachment to silica gel. Both the homogeneous and hybrid catalyts proved capable of promoting the asymmetric hy~genatio~ of prochiral unsaturated acids and esters. While the soluble complexes fsa and 6b led to the formation of dextro-rotatory products, the recyclable supported catalyst gave laevorotatory compounds,
We have reported previously tl- 3] that homogeneous and ~obil~~~ di~hod~nM complexes of formula 1 which have one bridging tbiofato and one bridging chloro ligand, are efficient hydrogenation catalysts that retain their dinuclear structures during the catalytic processes. We now find that the replacement of the two tri-t-butylphosphines in 1 by chiral ( +)-neornenthyldiphenylphosphine (( 1aR) - [ t$ e methyl - 2a - (I-methylethyl)cyclohexyl] diphenylphasphine) ligands yields dinuclear complexes that support asymmetric hydrogenation of several prochiral olefinic compounds.
330
[C(CW,I,P
\
7’\
/
P[C(CW,I,
oC/RZS/Rh\co k (1)
Experimental All experiments were carried out under freshly purified and degassed solvents.
an argon
atmosphere
with
(+)-Dicarbonyl-~-chloro[~-(2-methyl-2-propanethiolato-S:S)]bis{[5-methyl-Z-(l- me thy 1e thy l)cyc 1o h exyl]diphenylphosphine}dirhodium @a) To a stirred solution of 300 mg (0.77 mmol) freshly sublimed chlorodicarbonylrhodium dimer (2) in 10 ml benzene was added dropwise a solution of 498.5 mg (1.54 mmol) ( +)-neomenthyldiphenylphosphine (3) in 10 ml of the same solvent. The mixture was stirred for 2 h at room temperature and 125 mg (0.77 mmol) (t-butylthio)trimethylsilane (5a) [4] in 10 ml benzene was added during 1 h. After further stirring for 4 h, the solvent was removed under reduced pressure. The orange residue of dirhodium complexes was dissolved in 10ml toluene and heated at I10 “C for 10min. Evaporation of the solvent followed by recrystallization from a mixture of pentane and methanol afforded 218 mg (27%) of a mixture of cis-6a and trans-6a in a 2:l ratio; m.p. (dec.), 94 “C; [a]&, = + 135”(c, 1, C&H,); [a]$ = + 115”(c, 1,&H,). IR (KBr): 1980, 1952 cm-l (CrO). 200 MHz ‘H NMR (&He): 6 0.60 and 0.68 (two d, 6H, J1 = J, = 6 Hz, CHCH, of trans-6a and cis-6a in a 1:2 ratio, respectively), 0.75 - 1.18 (m and four d, 12H, J1 = J, = J3 = J4 = 6 Hz), 1.20 1.92 (m, 16H), 1.98 and 2.09 (two s, 9H, C(CH,), of cis-6a and trans-6a in a 2:l ratio, respectively), 2.17 (m, lH), 2.79 (m, lH), 3.16 (m, 2H), 6.90 -7.10 (m, 14H, Arm, 7.62 (m, 2H, Arm, 7.95 (m, 4H) ppm. 81 MHz 31P(H} NMR (C&H,, 85% H,PO, external standard): 6 33.7 ppm (J(PRh) = 129.6 Hz). Analysis: Found: C, 58.34; H, 6.57; Cl, 3.90; P, 5.76%. C,H,,ClO,P,Rh,S requires: C, 58.06; H, 6.47; Cl, 3.42; P, 5.99%.
cis-(+)-Dicarbonyl-~-chloro[~-(2-triethoxysilyl~thanethiolato-S:S]bis~[5-methyl-2-(l-methylethyl)cyclohexyl]diphenylphosphine)dirhodium (6b) As above, a benzene solution consisting of 0.77 mm01 2 was reacted with 1.54 mm01 3. The mixture was heated to 60 “C and stirred at that temperature for 2 h. A solution of 228 mg (0.77 mmol) trimethyl[ 2-( triethoxysilyl) ethylthiolsilane (5b) [l] in 10 ml benzene was added dropwise and the reaction mixture stirred at 50 “C for 4 h. The solvent was removed under
331
reduced pressure and the residue dried at 5 x 1O-3 mmHg. Rec~stallization from pentanelmethanol gave 420 mg (46%) of cis-6b as orange crystals; m.p. (dec.), 89 “C; [LY]$!~ = +83.3” (c, 0.6, t&H,). IR (KBr): 1995, 1955 cm-l (CEO). 200 MHz “H NMR (C,H,): 6 0.72 (d, 6H, J = 6 Hz, CHC&), 0.80 - 0.94 (m, 6H), 0.98 (d, 6H, J=6Hz, CHCH,), 1.04 (d, 6H, J=6 Hz, CHCH,), 1.12 (t, 9H, J = 5.5 Hz, CH,C&), 1.25 - 3.10 (m, lOH), 2.69 - 2.81 (m, 2H), 2.84 - 2.98 (m, 2H), 3.39 (m, BH), 3.72 (q, 6H, J = 5.5 Hz, CLCH,), 4.02 (m, 2H), 7.05 (m, 12H, Arm, 7.92 (m, 8H, ArIl) ppm. 81 MHz 31P(H) NMR (C,H,, 85% H,PO, external standard): S 34.03 ppm (J(PRh) = 121.2 Hz). Analysis: Found: C, 55.18; H, 6.29; Cl, 3.15; P, 5.14%. C,H,,ClO,P,Rh,S requires: C, 55.39; H, 6.58; Cl, 3.03; P, 5.30%. Anchoring of 4% to silica A mixture of 0.77 mequiv 6b, 10 ml benzene and 1.00 g Merck’s Silica 60 (60 - 200 pm; 500m2 g-l) (predried by heating for 48 h at 150 “C at 5 x 10m3mmHg) was stirred in a sealed vessel for 8 d. The solvent was decanted, and the solid washed repeatedly with hot benzene and dried at 5 x 10---3mmHg. The dissolved rhodium in the combined benzene solutions was analyzed by atomic absorption and the silica-bound metal calculated 131to be 0.089 mequiv g-l. General!procedure for catalytic hydrage~atio~ of ~~h~~al substrates 7- 10 Typically, a mixture of 184.5 mg (0.84 mmol) Z-methyl ~-acet~ido~innamate (8), 49.1 mg (0.042 mmol) 6b, 10 ml benzene and 5 ml MeOH was introduced under argon into a mini-autoclave. The sealed apparatus was cooled to 0 “C, purged with argon and charged with 100 psi H,. The mixture was heated to 120 + 0.5 “C and stirred at that temperature for 4 h. The reaction vessel was cooled, opened under argon and the solvent evaporated. The residue was chromatographed on neutral alumina 90, using a mixture of MeOH/CH,Cl, as eluent, and subjected to GC and NMR analyses. The optical activity was determined with the aid of a Perkin Elmer Model 141 polarimeter. When the silica-bound catalyst 11 was used, the reaction mixture was decanted and the solid particles washed under argon with MeOH (5 x ). After drying in a stream of argon, the catalyst was either applied immediately in a second run or stored under argon to await recycling.
Results and discussion The soluble complexes 6a and 6b were obtained by modification of the general syntheses of p-alkyl- and ,u-arylthiolato-~--chlorodicarbonylbis(tri-tbutylphosphine)dirhodium complexes outlined in eqn. (1) [ 1,5], While syntheses of compounds of type 1, in which bulky tri-t-butylphosphine ligands were employed, proceeded smoothly at room temperature, the
332
[(p-Cl)~,(CO),],
2R*PhzP’9’.[R*Ph,P{gO)Rh(/&l)]a
(a), R = CMe, (b), R = CH,CH,Si(OEt)s R* = (lug)-[5~-methyl-2~-( l-methylethyl)cyclahe~l~
formation of the chiral complexes 6a and 6b required the application of elevated temperatures either in the first or second step. At room temperature, the reaction of 2 with alkyldiphenylphosphines and (alkylthio) trimethylsilane afforded a mixture of products with carbonyl bridging ligands. The structure of such compounds will be reported in a separate paper. The ‘H and 31P NMR spectra of 6a and 6b reveal that while 6b is a single steroisomer having the cis configuration, 6a is a 23 mixture of cis and truns complexes. Incidentally, the doublets in the a1P NMR spectra of ck-6a and trans-6a co-appear at 33.1 ppm. The observation that a mixture of stereoisomers of 6a induces the asymmetric hydrogenation of Z-~-acet~idocinnamic acid, C,H,CH=: C(NHCOCH~~COOH (7), Z-methyl ~-acet~idocinnamate, C,H,CH= C(NHCOCH,)COOCH, (8) and to some extent also of a-acetamidoacrylic acid, H&=C( NHCOCH,)COOH (9) and methyl a-acetamidoacrylate, H,C=C(NHCOCH,)COOCH, (lo), in fair to very good optical purity (just as with the isomerically pure catalyst 6b), suggests that the geometric constraints which control the sterochemi~al course of the hydrogenations are of similar nature whether the two chiral phosphines are cis or trans to each other. Some typical hydrogenation experiments with 6a and 6b are summarized in Table 1. TABLE 1 Hy~genation of compounds 7 - 10 in the presence of the soluble dirh~i~ under comparable conditions”
complexes 6a and 6b
Substrate
Catalyst
Yield (%)b
Optical purity (% ee)
7 7 8 8 9 9 10 10
6a 6b 6a 6b 6a 6b 6a 6b
17 11 13 15 70 53 100 82
10 45 96 97 c c c c
“Reaction conditions: 0.64 mm01substrate, 0.042 mm01catalyst in 10 ml benzene and 5 ml MeOH for 16 h at 120 + 5 “C under 1000psi of Hz. bProduct isolated by column chromatography on alumina 90. “Varying, < 5% ee.
333
The table indicates that the yields of the hydrogenated products, as well as their optical purity, depend both on the nature of the substrate and the catalyst employed. Since the phenyl groups in 7 and 8 extend steric hindrance around the C-C double bonds, these compounds are hydrogenated at slower rates than 9 and 10.The optical purity of the phenylalanine derivatives, however, was found to be considerably higher than that of the non-phenylated compounds. These results are attributed to the fact that the homogeneous catalysts are converted, in part, during the hydrogenation process into metallic rhodium that competes with the residual chiral catalyst regarding reduction of the substrate. It seems that steric hindrance has a larger effect on the symmetric, rather than the asymmetric, course of hydrogenation. Thus, for example, 8 is reduced in practice only by the chiral catalysts and gives the (S)-( +)-N-acetylphenylalanine methyl ester in very high optical purity, while the sterically less-hindered ester 10 yields mainly the racemic product. Control experiments, in which the hydrogenation of 8 and 10 by rhodium powder was compared (at 500 psi and 120 “C), revealed that the less-hindered unsaturated ester was reduced more than lo-times faster than the phenylated compound. Decomposition of 6a and 6b into metallic rhodium was found to be more pronounced at high pressure of hydrogen than at low pressures. For this reason, when hydrogenation of 7 and 8 by 6a was conducted under a hydrogen pressure that did not exceed 100 psi, the yields [and optical purity (ee) values] were 40 (30%) and 8 (95%), respectively. The silicon-containing complex 6b was immobilized by attachment to silica gel via the ethanethiolato side chain to give catalyst 10 [eqn. (2)]: PPh,R*
6b +
OH / /O\ (silica)-OH -+ (silica)-0-Si(CH,),S \o H
10
OC\ /Rh\
’
Cl + 3EtOH
(2)
‘Rh’ OC’
R* = laR-[fib-methyL2a-(
/
\PPh,R*
1-methylethyl)cyclohexyl]
The amount of 6b employed for immobilization was precisely that required for the formation of a monolayer on the support [3,6]. As reported previously for some achiral dirhodium complexes [2,3], the anchoring of the soluble catalysts to the inorganic support increased the efficiency. In addition, the immobilization of 6b also affected the chirality of the products: while both soluble catalysts led to the formation of dextro-rotatory compounds, the application of 11 gave laevo-rotatory acids and esters. We assume that this difference in chirality is associated with the different orientations of the phosphine ligands in the homogeneous and immobilized catalysts. Fixation of
334
molecules of 6b as a monohyer on the silica surface is likely to block one side of the dirhodium complex and may force the substrate to approach the metal from a different direction than under homogenous conditions. The hybrid catalyst was found to be considerably more stable than the soluble complexes under our reaction conditions (uide infra). Yet, even the immobilized catalyst formed substantial quantities of achiral hydrogenation products after some time. As mass spectral studies revealed the occurrence of considerable H-D exchange in the presence of the heterogenized catalyst during deuteration of 6 [7], we presume that 1%catalyzed hydrogen scrambling at the chiral carbon atom of the hydrogenation product is responsible for the gradual accumulation of racemic products. A typical series of hydrogenation experiments of 8 in the presence of 11 under different hydrogen pressure conditions is summarized in Table 2. The supported catalyst was found to be fully activated only after one to three runs. During the first run (but not thereafter), some decomposition of the catalyst took place and minute amounts of the chiral phosphine were ejected into the solution. Usually, only slightly over the stoichiometric amount of substrate was reduced in this run to give a practically optically pure product. In subsequent runs, substantially higher yields were obtained but the rate of formation of racemic products increased as well. Consequently, a retardation in the optical activity was observed after a few initial runs. Table 2 reveals a strong dependence of both the conversions and ee values on the hydrogen pressure employed. By gradually reducing the pressure from 1000 to 25 psi, it was found that optimal results were obtained at cu. 166 psi. It seems that at higher pressures the active sites of the catalyst become saturated with hydrogen, and consequently coordination of the olefinic substrate is restricted. On the other hand, at too low a pressure, insufficient hydrogen molecules are activated by the chiral catalyst. TABLE 2 Hydrogenation of methyl ~-acet~docinn~ate (8) to the (R)-( -)-~-acetylphenylalanine methyl ester in the presence of the silica-bound catalyst lla Run No.
Hydrogen pressure (psi)
Yieldb (%)
Optical purity (%ee)
Run No.
Hydrogen pressure (psi)
Yieldb (%)
Optical purity (% ee)
1 2 3 4 5 6
1000 1000 1000 1000 500 500
5.8 25 24 24 27 25
95 40 40 41 23 22
7 8 9 10 11 12
100 100 50 50 25 25
66 69 30 26 10 8
16 17 12 12 6 7
“Reaction conditions: 0.84 mm01 8, 0.011mequiv 11 in a mixture of 10 ml benzene and 5 ml MeOH; 16 h at 120 + 0.5 “C. bProduct isolated by column chromatography on alumina 90.
335
Under the conditions listed in Table 2, activation of 11 takes place entirely during the first run. Thereafter the catalyst does not change and gives absolutely reproducible results. For example, when the experiments of Table 2 were extended by applying H, pressures of 1000, 500, 100 and 50 psi once again, the corresponding yields and optical purity were identical with those of runs 2,5,7 and 9. When, however, the solvent was changed to benzene-free MeOH, substantial catalyst deterioration was found to take place at 1000 psi even in advanced runs. Consequently, the ee values dropped rapidly. Typical ee values for 11-catalyzed hydrogenation in MeOH under 1000 psi Hz (the other conditions as in Table 2) were 49,19 and 16% in the first three runs. On reducing the pressure to lOOpsi, the optical purity dropped to 3 - 4%. In experiments in MeOH conducted under a H, pressure of < 100 psi, no catalyst deterioration was observed right from the beginning. The dependence of the optical purity on the reaction period is demonstrated by the results listed in Table 3. As in the homogeneous catalyses, short reaction periods led to higher optical purities than longer ones. Further factors that affected the optical purity of the product were the catalyst:substrate ratio (Table 4), the nature of the solvent (Table 5) and the reaction temperature. TABLE
3
Effect of reaction period on the optical purity of the (R)-( -)-N-acetylphenylalanine formed by the l&catalyzed hydrogenation of 8”
methyl ester
Run No.
Reaction time (h)
Yield
Optical purity (% ee)
Run No.
Reaction time (h)
Yield
(%)
(%)
Optical purity ( % ee)
1 2 3 4 5
16 16 16 16 46
5.4 16 17 16 53
98 43 43 44 17
6 7 8 9
8 4 3 2
13 10 7 5
48 60 74 85
*Reaction conditions as in Table 2 except reaction period varied as specified. TABLE
that the hydrogen
pressure
was 109 psi and the
4
Effect of catalystzsubstrate
ratio on the l&catalyzed Catalyst:substrate
yield (%) optical purity (% ee)
hydrogenation
of 8”
ratiob
1:39
1:78
1:156
1:312
1:624
28 95
22 78
10 60
8 36
6.5 24
“Reaction conditions: 2.16 x 10W3 mequiv catalyst, the required amount of 8, 2 ml benzene, 1 ml MeOH; 4 h at 120 + 0.5 “C; hydrogen pressure 100 psi. bQuantities expressed in equiv mol-‘.
TABLE 5 Solvent effect on the hydrogenation of 8 by Ila
_ solvent
CH,OH CD,OD GXH, 33% CH,OH $67% Ce&
Yield (%I 8 8 30 10
Optical purity (% ee)
Solvent
40 40 2 60
25% CH,OH -I-75% C,H, 17% CH,OH -I-83% C&H, THF
(% ee) 22 $5 I1
44 26 10
“Reaction conditions: 0.34 mm01 substrate, i?.Olt mequiv fully activated catalyst, 15 ml solvent, 4 h at 120 “C and 100 psi of H,.
After the first run, the immobilized catalyst was found to be perfectly leach-proof in the various media with the exception of THF. The hydrogenation of methyl a-acetamidocinnamate under 100 psi Hz proceeded very slowly in MeOH. In benzene, however, the reaction was quite fast but the product was of extremely low optical purity. For these reasons, we used mixtures of both solvents in which reasonable yields and fair optical activity were recorded. When methanol-d, was used, mass-spectral analysis indicated the formation of a substantial amount of deuterated products as a result of catalytic H-D exchange between the solvent and the substrate. By virtue of the NMR spectrum, it was found that the main product was the I-ID adduct C~H~CHDCH(NHC~~H~)GOO~H~ in which the deuterium atom is in the benzylic position. Di- and tri-deuter~ted compounds were also formed during the initial stages of the process, but deuterium-free ~~H~CH~~~~NH~O~H~)COOCH, could be detected only after prolonged treatment of t;he substrate with Dz. In some recovered starting material, the NH group was exchanged by ND. The absence of a measurable kinetic isotope effect in these experiments suggests that the various hydrogen-transfer processes involved in the hydrogenation are not r&~-controlling. It is remarkable that, in contrast to Z-methyl ~-a~et~idoci~~~ate (6), the E isomer hardly undergoes hy~ogenation although its NH group is replaced by ND when CD30D is used as solvent. While 6a and 6b were shown to deteriorate at elevated temperatures, and could not be applied above 125 “C, the hybrid catalyst proved thermally stable at least up to 160 “C. Thus, hydrogenation of 8 by 11 could be performed over quite a wide range of temperatures. For example, under the conditions listed in Table 2, using a 1:2 mixture of MeOH and benzene and 100 psi Hz, the yields (and optical purity values) at 90,120,140 and 160 “C were 5.4 (68), 10 (60), 36 (18) and 45% (9% ee), respectively. The thermal stability of the catalyst was also demonstrated by a series of experiments in which the first run was performed at 160 “C and following runs at 140, 120 and 90 “C. The results were exactly the same as those listed above where the first experiment was carried out at 90 “C.
337 TABLE
6
Hydrogenation Substrate
7 9 10
of some unsaturated
acids and esters by 11 under comparable
Product
Yield (%) (optical
(R)-( -)-C,H,CH,CH(NHCOCH,)COOH (S)-( -)-CH,CH,CH(NHCOCH,)COOH (S)-( -)-CH,CH,CH(NHCOCH,)COOCH,
BReaction conditions: at 120 _+0.5 “C.
conditions” purity, % ee)
Run 1
Run 2
Run 3
Run 4
20 (49) 99 (2) 66 (35)
26 (37) 92 (2) 85 (25)
35 (28) 83 (2) 87 (25)
46 (24) 73 (6) 86 (25)
0.84 mm01 substrate, 0.011 mequiv catalyst,
10 ml benzene, 5 ml MeOH; 4 h
Substrates other than 8 were also hydrogenated by the silica-bound catalyst 11.Some typical results are summarized in Table 6. Tables 4 and 6 indicate that, by analogy to the homogeneous catalyses described in Table 1, the cinnamic acid derivatives yield hydrogenation products of higher optical purity than the less bulky compounds 9 and 10. The free acids were found to be inferior to their methyl esters and thus 9, which reacted very rapidly, gave virtually no optically active products whatsoever.
Acknowledgements The authors thank the Deutsche Forschungsgemeinschaft (DFG), the Fonds der Chemischen Industrie and the Technical University of Berlin for financial support of this study, as well as Degussa, Hannau for a valuable gift of rhodium.
References 1 H. Schumann, G. Cielusek, S. Jurgis, E. Hahn, J. Pickardt, J. Blum, Y. Sasson and A. Zoran, Chem. Ber., 117 (1984) 2825. 2 M. Eisen, J. Blum and H. Schumann, J. Mol. Catal., 31 (1985) 317. 3 M. Eisen, T. Bernstein, J. Blum and H. Schumann, J. Mol. Catal., 43 (1987) 199. 4 E. W. Abel, J. Chem. Sot., (1969) 4466. 5 H. Schumann, G. Cielusek and J. Pickardt, Angew. Chem., 92 (1980) 60; idem, Angew. Chem., Znt. Ed. En&., 19 (1986) 70. 6 E. Wellner, M. Ottolenghi, D. Avnir and D. Huppert, Lungmuir, 2 (1986) 616. 7 M. Eisen, J. Blum, G. HGhne, H. Schumann and H. Schwan, Chem. Ber., 122 (1989) 1599.