1161
Organometallics 1995, 14, 1161-1167
Platinum-Catalyzed Oxidations with Hydrogen Peroxide: The (Enantioselective)Epoxidation of a#-Unsaturated Ketones Carla Baccin, Andrea GUSSO, Francesco Pinna, and Giorgio Strukul" Department of Chemistry, University of Venice, Dorsoduro 2137, 30123 Venezia, Italy Received July 8, 1994@ The catalytic epoxidation of a,B-unsaturated ketones with hydrogen peroxide catalyzed by a variety of (P-P)Pt(CF&olv)+ and (P-P)Pt(2-van) complexes (P-P = a variety of diphosphines, including chiral diphosphines; 2-van = the bis anion of 2-vanillin) is reported. The reaction can be carried out at room temperature under mild conditions and is moderately selective. Loss of chemical selectivity is related to the acidity of the medium with both classes of catalysts. The enantioselective transformation can be easily accomplished with chiral diphosphine modified catalysts, but a significant loss of enantioselectivity is observed during the course of the reaction. If the reaction is carried out stoichiometrically with the use of (P-P)Pt(CFd(OOH) oxidants, the ee can be as high as 63% and stable with time.
Introduction The epoxidation of a,P-unsaturated ketones with hydrogen peroxide under basic conditions was first discovered by Weitz and Scheffer in 1921 and is one of the oldest applications of hydrogen peroxide as oxidant in synthetic organic chemistry.l As was later demonstrated,2 the reaction involves (Scheme 11, as the ratedetermining step, the nucleophilic attack of the hydroperoxide anion generated in the alkaline medium at the carbon-carbon double bond made electrophilic by the electron-withdrawing carbonyl substituent. The requirement of a nucleophilic peroxy oxygen appears to be the main reason why metal catalysis with the traditional do transition metal complexes was never applied to this interesting synthetic reaction. On the other hand, the efficiency and versatility of the purely organic system3provided no incentive to search for other possible transition-metal catalysts. The enantioselective version of the Weitz-Scheffer oxidation was first reported by W ~ n b e r gutilizing ,~ a chiral organic base (a quininium salt) and hydrogen peroxide under phase-transfer conditions. In the oxidation of chalcones, ee values in the range 25-55% were observed. Alternatively, but still limited to the oxidation of chalcones, Julia and co-workers5employed the traditional alkaline system, but carried out the reaction within the a-helix of a poly(a-amino acid).6 With this methodology ee values up to 93% were reported. The need for a more versatile synthetic approach (not limited
* To whom correspondence should be addressed. FAX: (39) 41 529 8517. e-mail:
[email protected]. Abstract published in Advance ACS Abstracts, January 15, 1995. (1)Weitz, E.; Scheffer, A. Ber. Dtsch. Chem. Ges. 1921, 54, 2327. (2) Bunton, C. A,; Minkoff, G. J . J . Chem. Soc. 1949, 665. (3)(a) Plesnicar, B. In Oxidation in Organic Chemistry; Trahanovsky, W. S., Ed.; Academic Press: New York, 1978; Part C, p 243. (b) Plesnicar, B. In The Chemistry of Peroxides; Patai, S., Ed.; Wiley-Interscience: New York, 1983; Chapter 17, p 566. (c) Hudlicky, M. Oxidations in Organic Chemistry; American Chemical Society: Washington, DC, 1990; p 60. (4) (a) Helder, R.; Hummelen, J . C.; Laane, R. W. P. M.; Wynberg, H. Tetrahedron Lett. 1976, 1831. (b) Hummelen, J . C.; Wynberg. H. Tetrahedron Lett. 1978,1089. ( c ) Wynberg, H.; Greijdanus, B. J . Chem. Soc., Chem. Commun. 1978,427. (d) Wynberg, H.; Marsman, B. J . Org. Chem. 1980, 45, 158. (e) Meijer, E. W.; Wynberg, H. Angew. Chem., Int. Ed. Engl. 1988,27, 975.
Scheme 1
H W
HOO
+
HO-
0
to chalcones) to the asymmetric transformation suggests that transition-metal catalysis should be investigated. Indeed, the diastereoselective epoxidation of (already) chiral P-hydroxy enones has been reported recently by Markb et al.' using the Sharpless system and is an elegant application of the well-known epoxidation of allylic alcohols. In the general case of a,&unsaturated ketones, given the nature of the substrates, only catalysts able to increase the nucleophilicity of hydrogen peroxide seem to be suited t o this purpose. Over the years we have investigated the catalytic properties of a class of platinum(I1) complexes of the type (P-P)Pt(CFdX (P-P = various diphosphines; X = solvent, -OH)that are still the only transition-metal catalysts capable of increasing the nucleophilicity of hydrogen peroxide,6 similarly to alkali metals. In this work we report our attempts to accomplish with these catalysts the Weitz-Scheffer oxidation along with the enantioselective version of the same reaction. Results and Discussion Catalysts. The catalysts employed in the present study are shown in Chart 1. The first type (1) of
@
0276-7333/95/2314-1161$09.00/0
(5) (a)Julia, S.; Guixer, J.; Masana, J.; Vega, J . Angew. Chem., Int. Ed. Engl. 1980, 19, 929. (b) Julia, S.; Guixer, J.; Masana, J.; Rochas, J.; Colonna, S.; Annunziata, R.; Molinari, H. J . Chem. Soc., Perkin Trans. 1 1982, 1317. (c) Colonna, S.; Molinari, H.; Banfi, S.; Julia, S.; Masana, J.; Alvarez, A. Tetrahedron 1983,39, 1635. (6) Aglietto, M.; Chiellini, E.; DAntone, S.; Ruggeri, G.; Solaro, R. Pure Appl. Chem. 1988, 60, 415 and references therein. (7) (a) Bailey, M.; Markb, I. E.; Ollis, W. D. Tetrahedron Lett. 1990, 31, 4509. (b) Bailey, M.; Markb, I. E.; Ollis, W. D. Tetrahedron Lett. 1991, 32, 2687. (8) Strukul, G. In Catalytic Oxidations with Hydrogen Peroxide as Oxidant; Strukul, G., Ed.; Kluwer: Dordrecht, The Netherlands, 1992; p 177, and references therein.
0 1995 American Chemical Society
1162 Organometallics, Vol. 14,No. 3, 1995
Baccin et al.
Chart 1
Chart 2
n P
la
P = d m R,R-pyrphos S,S-chiraphos
lb 1c
0
R-prophos
S,S-chiraphos
2 02
I
OCH3 n P P = dppe R,R-pyrphos S,Schiraphos R-prophos S-binap
PkP
2a 2b 2c 2d 29
Ph2P R,R-pyrphos
Scheme 2
K2PtCl4
+
DMSO
H% HO
140°C
~
PPh2
2 PPh3 1oooc
OCHB 2-vanHz
OCH3 (PPh3)2Pt(2-van)
compounds belongs to the general class of Pt(I1) complexes reported above, that were found active in a variety of other catalytic oxidation^.^,^ The synthetic procedure for these and other complexes of the same type is reported elsewhere.1° The second class of complexes (2)was recently reported to catalyze the Baeyer-Villiger oxidation of cyclic ketonedl (including the enantioselective transformation) and were synthesized according to the procedure (Scheme 2) reported by Pregosin et al. some years ago12for (PPh3)&(2-van) (2-van = the bis anion of 2-vanillin). Details on the synthesis and characterization of these complexes is reported in ref 11. For the meaning of the diphosphine acronyms, see Chart 2. General Reactivity. For the screening procedure toward a class of different a,P-unsaturated ketones (Chart 31, the two prototype complexes [(dppe)Pt(CF3)(CH2C12)1BF4(la) and (dppe)Pt(B-van) (2a)were chosen, while in the search for the best operating (9) Strukul, G. In Advances in Catalyst Design; Graziani, M., Rao, C. N. R., Eds.; World Scientific: Singapore, 1993; Vol. 2, p 53, and references therein. (10)(a) Sinigalia, R.; Michelin, R. A,; Pinna, F.; Strukul, G. Organometallics 1987,6,728. (b) Zanardo, A,; Michelin, R. A,; Pinna, F.; Strukul, G. Inorg. Chem. 1989,28,1648. (11) Gusso, A,; Baccin, C.; Pinna, F.; Strukul, G. Organometallics 1994,13,3442. (12) Pregosin, P. S.; Anklin, C.; Bachechi, F.; Mura, P.; Zambonelli, L. J. Organomet. Chem. 1981,222,175.
PPhp
S-binap
conditions catalyst la and 2-cyclohexen-1-one(3)were tested. The epoxidation of 3 was carried out at room temperature under N2 atmosphere using 35% H202 as the oxidant. Since the catalyst is moderately soluble in the substrate, reactions were tested in the absence of solvent. Under these conditions a two-phase (ketone/ H2O) reaction medium forms. A summary of the data observed when the operating conditions are changed is shown in Table 1. All reactions start immediately upon addition of the oxidant and display a relatively constant initial rate that is maintained for about 1h. A progressive slowdown follows, reaching asymptotically the maximum conversion. Although even at low catalyst concentration (Table 1, entry 6) the maximum epoxide productivity is still acceptable, an increase of the catalyst amount is obviously beneficial. As can be seen from Table 1,the maximum amount of epoxide is in all cases much lower than the amount of oxidant used. Similarly to previous oxidations with HzO2 when the carbonyl functional group is present in the substrate,11J3 even in this case no more than 30-35% of the H202 introduced is converted into products. As was already suggested, this is probably due to catalytic decomposition of the oxidant via formation of dioxirane species.13 The use of a solvent (DCE) is detrimental, resulting in a lowering of both the initial rate and the maximum productivity (entry 2), and similar effects are observed when the catalyst is changed from the solvato cationic complex la t o the complex (dppe)Pt(CF3)(0H)(entry 3). Comparison with previous results obtained with cyclohexene (no epoxidation was observed)14indicates that the presence of an electron-withdrawing substituent in the substrate molecule strongly increases the reactivity of the system, in agreement with the mechanistic suggestion14 that the effect of Pt is to increase the electrophilicity of the olefin through coordination while, at the same time, increasing the nucleophilicity of H202. The operating conditions of Table 1, entry 1 were applied to the epoxidation of the a$-unsaturated ke(13) (a) Del Todesco Frisone, M.; Giovanetti, R.; Pinna, F.; Strukul, G. Stud. Surf: Sci. Catal. 1991,66,405. (b) Del Todesco Frisone, M.; Pinna. F.: Strukul. G. Oreanometallics 1993.12.148. (14) Strukul, G.’; Michelin, R. A. J . Chem. SOC, Chem. Commun. 1984,1538.
Organometallics, Vol. 14, No. 3, 1995 1163
Pt-Catalyzed Oxidations with H202
Chart 3
2-pentyl-2-cyclopenten-1-one 4
2-cyclohexen-I -one 3
mesityloxide 6
methykinylketone 7
a-iomne 9
p-iomne 10
Table 1. Epoxidation of 2-Cyclohexen-1-one (3): Effect of Catalyst Amount on the Productivity of the Reaction" entry no.
amt of catalyst (mmol)
max amt of epoxide (mmol)
time (min)
104(initrate) (M s-l)
1 26 3' 4
0.05 0.05 0.05 0.02 0.01 0.005
1.67 0.11 0.89 1.14 1.26 1.07
384 1669 7065 160 357 255
2.1 0.03 0.22 1.1 0.65 0.41
5
6
a Experimental conditions: catalyst [(dppe)F't(CF3)(CH2Cl2)1BF4; 2-cyclohexen-1-one, 10 mmol; 3 5 8 H202, 5 mmol; T, 25 "C; N2, 1 atm. DCE (2 mL) added as solvent. Catalyst used (dppe)Pt(CF3)(OH).
Table 2. Epoxidation of @-Unsaturated Ketones with Hydrogen Peroxide Catalyzed by Complexes l a and 2aa entry no. 1
2 3 4 5 6
I 8 9 1Od 11 12 13d
catalyst
substrate
la 2a la 2a
3
C
5
la 2a la 2a la 2a
4
6 7
max amt of epoxideb(mmol) 1.61 1.71 1.37 1.56 0.66 (39) 0.56 (40) 0.61 (40) 0.48 (12) 0.49 (1 1) 0.35 (9) 0.26 (10) 0.98 (12) 0.60 (10)
time (h)
I 4 164 30 4 26 27 82 92 84 124 146 180
T("C)
25 25 25 25 50 50 25 25 25 25 25 25 25
a Experimental conditions: catalyst, 0.05 m o l ; substrate, 10 m o l ; 35% H202. 5 mmol; N2, 1 atm. With catalyst 2a, HC104 (0.05 mmol) added prior to reaction (see Experimental Section). When other products are formed, numbers in parentheses refer to the percent selectivity with respect to the epoxide. [(o-dppb)Pt(CF3)(CH~Cl~)]C104 as catalyst. DCE (2 mL) added as solvent.
tones shown in Chart 3. No reaction was observed with substrates 8-11 even for long reaction times (up to 120 h) or an increase in the reaction temperature up to 80 "C. Similarly, no reaction was observed when two a,punsaturated esters were tested, namely ethyl acrylate and ethyl crotonate. The results obtained in the epoxidation of substrates 3-7 are reported in Table 2. The following general comments can be made. (1)The reactivity of catalyst 2a is generally higher than that of catalyst l a (entries 2, 4, 7, and 12). The
isophorone 5
1 ,CnapMhoquinone 8
trans-chalcone 11
use of 2a as catalyst requires activation with a stoichiometric amount of perchloric acid. The evolution of 2a t o produce the catalytically active species has already been reported.ll (2) As was already observed in the epoxidation of l-octene,lobthe substitution of dppe in l a with a flat, less sterically demanding diphosphine such as o-dppb results in a higher catalytic activity (entry 5). (3) With the exception of substrates 3 and 4, where epoxides are the only oxidation products, in the other cases (entries 5-13) the yield of epoxide is rather poor and relatively independent of the catalyst used. This point will be further discussed below. Byproduct Formation. The problem of the formation of byproducts has been fully addressed in the case of mesityl oxide (6). Typically, after an initial time (about 1 h) where only epoxide is observed, a series of byproducts start forming that eventually become the main products. These have been identified as acetone (38%),the terminal epoxide (lo%), and the two glycols (internal 36%,terminal 5 % ) arising from the epoxides, with the use of GC-MS analysis in comparison with authentic samples. The selectivities given refer t o the final reaction mixture for la as catalyst and are typical. As t o the pathways with which these compounds form, these have been identified with the following experiments. A mixture of 6 and the corresponding epoxide in CH2Cl2 was independently synthesized with the traditional (NaOWH202) Weitz-Scheffer procedure.2 When this mixture was placed in contact with an aqueous solution containing an amount of HzS04or HC104 identical with the amount of catalyst used in the catalytic experiments, formation in solution of acetone and the glycol arising from the epoxide were observed. When the same mixture of 6 and the corresponding epoxide were contacted with l a in the absence of water, no reaction was observed. A possible reaction pathway summarizing these observations is shown in Scheme 3. It is known14 that the catalytic activity of [(P-P)Pt(CFa)(solv)]+complexes is related t o the Pt+/PtOOH hydrolysis equilibrium
-
Baccin et al.
1164 Organometallics, Vol. 14, No. 3, 1995
Scheme 3
Rt + H202
+
Ht
U-*-(p p-isomer (7%)
H202 +
ROOH
R*/ROOH catalysis
H+/H20
HC/H20
OH
+o
Table 3. Enantioselective Epoxidation of 2-Cyclohexen-1-one (3) with Hydrogen Peroxide Catalyzed by [ ( P Y ~ P ~ ~ ~ ) P ~ ( C F ~ ) ( C H Z(1bY CI~)IBF~ entry no.
amt of catalyst (mmol)
0.05 0.05 0.05 0.05 0.025 0.02 0.01 0.005 a
T ("(3 -10 0 25 50 25 25 25 25
time (h) 1.4 1.1 0.7
0.5 0.8 0.8 0.8 2.6
Experimental conditions: 2-cyclohexen-l-one, 10 mmol; 3 5 8
H202,
final time (h)
final amt of epoxide (mmol) (8ee)
0.02 (72) 0.08 (60) 0.10 (34) 0.10 (22) 0.09 (44) 0.10 (49) 0.20 (56) 0.08 (72)
25 45 32 28 45 28 166 127
0.30 (39) 0.45 (49) 0.58 (7) 1.52 (4) 0.53 ( 5 ) 0.53 (10) 1.32 (1) 1.25 (1)
5 mmol; N2, 1 atm.
shown in Scheme 3, where protons are produced, making the system acidic. Due to their moderate solubility in the (acidic) water phase of the catalysis medium, the epoxides, once formed, can be hydrolyzed t o produce the corresponding glycols. Furthermore, it has t o be pointed out that the commercial (Janssen) mesityl oxide used as substrate is a mixture of a- and p-isomers. Since the latter is a terminal olefin and the present system is very reactive toward terminal olefins, significant amounts of terminal epoxide (and the corresponding glycol) are produced. As to the formation of acetone, it should be pointed out that mesityl oxide is the dimer of acetone made by aldol condensation, the most likely explanation for its presence being the inverse reaction,15 again due to the acidic aqueous medium. In summary, our experiments seem to demonstrate that transition-metal catalysis is involved only in the epoxide formation, thereby confirming the good intrinsic selectivity of the catalysts, which are only indirectly responsible for the (probably unavoidable) formation of the byproducts. In the epoxidation of 5, acetone (18%)(isophorone is the trimer of acetone), the unsaturated lactone (29%), arising from Pt-catalyzed Baeyer-Villiger oxidation, and two unidentified products (14% in total) are formed as byproducts. Finally, in the epoxidation of 7, in addition t o the epoxide, also the formation of acetone (58%),glycol (lo%), and an unidentified product (20%) (formaldehyde could not be detected) were observed in the reaction mixture. (15)See for example: Reeves, R. L. In The Chemistry ofthe Carbonyl Group; Patai, S., Ed.; Wiley-Interscience: New York, 1971; Chapter 12, p 580.
init amt of epoxide (mmol) (% ee)
Enantioselective Epoxidation. Catalysts lb,c and 2b-e were employed in the enantioselective epoxidations. These were carried out in pure substrate using 35%H202 as oxidant. Evaluation of the ee in the course of the reaction was performed by GC using a commercial (Chrompack) P-cyclodextrin capillary column. Prior to the complete screening of the substrates reported in Chart 3, a search for the best operating conditions was carried out with catalyst l b on substrate 3. Results are reported in Table 3. The reaction was checked at different temperatures and changing catalyst amounts. As can be seen, independent of the conditions used, there is always a strong decrease of the ee during the course of the reaction. In fact, at the beginning of the reaction, when low amounts of epoxide are produced, a relatively high asymmetric induction is observed, while at the end of the reaction, almost complete loss of ee may occur. This fact, coupled with the small size of the catalytic runs, prevented the possible determination of the absolute configuration of the preferred enantiomer. A dramatic case (Table 3, entry 8) showing the decrease of the ee during the course of the reaction is shown in Figure 1. In general, if the final ee is compared with the values observed during the reaction, a simple mass balance seems t o show that the dropping down of the ee is indeed due to a (partial) racemization of the epoxide rather than a loss of the enantioselective properties of the catalyst. Major factors affecting the initial ee are the reaction temperature (Table 3, entries 1-4) and the catalyst amount (entries 3 and 5-8). The lower the catalyst amount, the higher the initial ee. Therefore, it seems that the catalyst is actively involved in the loss of ee. On the other hand, the final ee seems to be related mainly t o the duration of the experiment.
Organometallics, Vol. 14, No. 3, 1995 1165
Pt-Catalyzed Oxidations with H202
Table 4. Catalytic Enantioselective Epoxidation of a$-Unsaturated Ketones 4-6 with Hydrogen Peroxide" entry no.
catalyst
substrate
T ("C)
time (h)
init amt of epoxide (mmol) (% ee)
final time (h)
final amt of epoxide (mmol) (% ee)
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21
lb
4
25 50 25 0 50 0 25 0 50 0 25 50 0 25 50 25 0 0 25 0 25
0.4 0.5 0.4 0.6 0.1 1 0.5 0.2 0.1 1.5 0.6 0.1 1.7 1.4 0.8 2.9 1.8 0.1 0.02 0.1 0.05
0.04 (13) 0.06 (28) 0.06 (38) 0.04 (42) 0.04 ( 5 ) 0.06 (39) 0.05 (1) 0.06 (57) 0.04 (2) 0.09 (41) 0.08 (22) 0.09 ( 5 ) 0.04 (1 1) 0.05 (47) 0.04 ( 5 ) 0.07 (14) 0.06 (4) 0.08 (12) 0.09 (9) 0.06 (10) 0.08 ( 5 )
96 28 53 98 3 98 53 98 3 98 31 3 45 13 23 49 48 26 4 27 5
0.5 (1) 0.6 (1) 0.3 (2) 0.08 (0) 1.3 (0) 1.5 (4) 1.4 (0) 0.1 (0) 1.o (0) 1.0 (18) 0.9 (1 1) 0.9 (4) 0.3 (2) 0.5 (4) 0.3 (1) 0.6 (3) 0.2 (1) 0.5 (4) 0.6 (0) 0.6 (7) 0.6 (0)
IC 2b 2c 2d 2e 2b
5
2c 2d 2d
6
2e
a Experimental conditions: catalyst, 0.05 mmol; substrate, 10 mmol; 35% H202, 5 mmol; Nz, 1 atm. With catalysts 2b-e, HC104 (0.05 mmol) added prior to reaction (see Experimental Section).
Scheme 4
- 08 H202 t Pt'
201
0
e
Pt-OOH
+
H'
\\ 0.2 0.4 0.6 0.8
1
1.2
1.4
mmol
Figure 1. Decrease of the ee of 2,3-epoxycyclohexanone with the amount produced in the epoxidation of 2-cyclohexen-1-onewith HzOz catalyzed by [(pyrphos)R(CF3)(CHzCldIBF4 (lb).See Table 3, entry 8. Since, from a practical point of view, what is important is the final asymmetric induction, in order to shorten the reaction time, the other catalysts and substrates were checked at high catalyst concentration, i.e. under the conditions of entries 1-4 (Table 3). The results obtained in the epoxidation of substrates 4-6 with catalysts lb,c and 2b-e are reported in Table 4. As can be seen, although in several cases the initial ee may be interesting, with the exception of entries 9 and 10 the extent of the asymmetric induction a t the end of the catalytic reaction is almost negligible. Again, this made the determination of the absolute configuration impossible. Loss of Enantiomeric Excess. The role of the catalyst in the apparent racemization process was investigated in the case of substrate 4 with catalyst lb. It is known from previous kinetic studies on the epoxidation of l-octene16that the catalytic reaction proceeds through the mechanism shown in Scheme 4. On this basis the enantiotopic discrimination will occur at the time of metal-olefin complex formation.loa Since ep(16)Zanardo, A,; Pinna,F.; Michelin, R. A,; Strukul, G.Inorg. Chem. 1988,27,1966.
oxide forms from the interaction between the metalolefin complex and the actual oxidant PtOOH, a stoichiometric reaction leading to the formation of 1equiv of chiral epoxide can be set up. This will mimic the early stage of the catalytic reaction and, in the absence of aqueous H202, give the intrinsic enantiodifferentiating properties of the catalyst. Complex lb (0.05 mmol) was dissolved in pure 4 (1 mL) at 25 "C, and to this solution was added (RPpyrphos)F't(CF3)(OOH)(0.05 mmol). GC analysis revealed the immediate formation of the epoxy ketone with an optical purity of 63%, significantly higher than the initial ee of the catalytic reaction (13%,Table 4, entry 1); this value remained constant for many hours. The same experiment was repeated with complex IC and (S,S-chiraphos)Pt(CF3)(OOH),yielding 1 equiv of epoxy ketone with ee 47%)again constant with time (see Scheme 5 for a summary). These experiments demonstrate that the intrinsic enentiodifferentiating properties of the catalysts (at least for lb,c) are good and seem to support the idea that the reaction intermediates involved in Scheme 5 have no direct role in the apparent racemization process. However, the catalytic reaction differs from the stoichiometric one in the presence of excess water and hydrogen peroxide. Other pathways, involving the acidity of the medium (formed from the hydrolysis equilibrium in Scheme 3) and leading to reversible enol
1166 Organometallics, Vol. 14, No. 3, 1995
Bacczn et al. seems promising and deserves further investigation. This is particularly important with respect to the enantioselective epoxidation, since it represents the first example of asymmetric catalysis applied to this class of substrates and the intrinsic enantioselective properties of the catalysts, a s demonstrated by the stoichiometric reactions, appear to be interesting.
Scheme 6
Experimental Section *Pt (R,R-pyrphos)Pt(CF3) (S,S-chiraphos)Pt(CF3)
8.8.
63% 47%
1
Scheme 6
r>ll 0
unknown organic products
0
e.e. > 0
formation via protonation of the carbonyl functional group, might be plausible but would apply only to substrate 6, where only one chiral center is produced. Indeed, the loss of ee in the catalytic reaction would be accounted for in the presence of a consecutive reaction, probably a further oxidation, leading to products undetectable by GLC analysis. This possibility is illustrated in Scheme 6: if the further reaction of the epoxide is mediated by the catalyst, the transformation will be stereoselective and, if mismatched with respect to the first step, will lead to a decrease of the observed ee in the remaining epoxide. This possibility was tested by checking the feasibility of the second step of Scheme 6, using racemic 2-pentyl2,3-epoxycyclopentanone and complex l b in the presence of 35% H202. GLC analysis in the presence of an internal reference (cyclooctane) revealed no reaction. Therefore, a tentative explanation can be offered only for catalysts 2b-e, which constitute the majority of the catalysts tested and where the nature of the active species involved in the oxygen-transfer step is still undefined. The complexity of the catalyst activation process evidenced in a previous paperll leads t o the formation of a variety of potential catalytically active intermediates. These may produce opposing effects on the asymmetric induction, and this fact may be a possible explanation for the observed loss of optical purity. Conclusions
The results reported in this work represent the first successful example of transition-metal catalysis applied to the Weitz-Scheffer oxidation reaction. Given the nature of the carbon-carbon double bond in a,@unsaturated ketones, this is undoubtedly due to the unique ability of the Pt(I1) catalysts here reported to increase the nucleophilicity of hydrogen peroxide. Although the potential applications seem limited by the low selectivity displayed in some cases and attributed to the acidity generated by the catalysts, the system
Apparatus. IR spectra were taken on a Perkin-Elmer 683 spectrophotometer and on a Digilab FTS 40 interferometer either in Nujol mulls using CsI plates or in CHzCl2 solution using CaF2 windows. GLC measurements were taken on a Hewlett-Packard 5790A gas chromatograph equipped with a 3390 automatic integrator. GLC-MS measurements were performed on a Hewlett-Packard 5971 mass selective detector connected t o a Hewlett-Packard 5890 I1 gas chromatograph. Identification of products was made with GLC or GLC-MS by comparison with authentic samples. Optical rotation measurements were performed on a Perkin-Elmer 241 polarimeter operating at 589 nm. Materials. Solvents were dried and purified according to standard methods. a$-Unsaturated ketone substrates were purified by passing through neutral alumina, prior t o use. 1,4Naphthoquinone was purified by recrystallization from EtOH; methyl vinyl ketone was distilled in vacuo and stored at 0 "C. Hydrogen peroxide (35%from Fluka), 90% n-chloroperbenzoic acid (MCPBA,Janssen), 85% t-BuOOH (Aldrich),dppe, o-dppb, R-prophos, and S,S-chiraphos (Strem),RP-pyrphos (Degussa), and S-binap (Janssen) were commercial products and were used without purification. The following compounds were prepared according to lit[(o-dppb)erature procedures: [(dppe)Pt(CF3)(CH2C12)lBF4,17 Pt(CF3)(CH2C12)1BF4,10b [(S,S-C~~~~~~OS)P~(CF~)(CH~C [ ( R P - ~ ~ ~ ~ ~ O S ) P ~ ( C F ~ ) ((dppe)Pt(2-van),12 C H ~ C ~ ~ ) I B(RPF~,~~~ pyrphos)Pt(2-~an),~l (S,S-~hiraphos)Pt(2-van),~~ (R-prophos)Pt(2-van),11and (S-binap)Pt(2-van).11 Synthesis of Epoxy Ketones. Epoxy ketones used as standards for gas chromatographic determinations in the individual catalytic reactions were synthesizedl8 from the starting a,P-unsaturated ketone (10 mmol) in 10 mL of MeOH (or THF), to which 30 mmol of 35% H202 was added under N2 with stirring at 0 "C. After a few minutes 30 pL of a 10% aqueous solution of NaOH was added, and after -30 min the solution was extracted from CH2Clfl20. The dry organic phase containing 45-60% epoxy ketone was used for qualitative identification and for the determination of the separation conditions of the lactone enantiomers on the chiral p-cyclodextrin GC column. In the cases of the epoxidation of a-ionone, p-ionone, trunschalcone, and isophorone, t-BuOOH was used instead of H2Oz. Catalytic Reactions. These were carried out in a 25 mL round-bottomed flask equipped with a stopcock for vacuum/ N2 operations and a side arm fitted with a screw-capped silicone septum to allow sampling. Constant temperature ( f O . l "C) was maintained by water circulation through an external jacket connected with a thermostat. For reactions carried out at temperatures >25 "C the reaction vessel was equipped with a reflux condenser. Stirring was performed by a Teflon-coated bar driven externally by a magnetic stirrer. Absence of diffusional problems below the 3 x M initial rate was determined by the conversion vs time plot independence of the stirring rate in randomly selected catalytic experiments. The concentration of the commercial H2Oz solution was checked iodometrically prior to use. The following general procedure was followed. The required amount of catalyst was placed as the solid in the reactor, which (17) Michelin, R. A.; Napoli, M.; Ros, R. J . Organomet. Chem. 1979, 175, 239. (18)MacAlpine, G. A.; Warkentin, J. Can. J . Chem. 1978,56, 308.
Organometallics, Vol. 14, No. 3, 1995 1167
Pt-Catalyzed Oxidations with HzOz was evacuated and filled with N2. Purified, N2-saturated substrate was added under N2 flow, followed, if necessary, by the required amounts of solvent. After it was thermostated at the required temperature with stirring for a few minutes, the H202 solution in the appropriate amount was injected through the septum and the time was started. When (P-PIPt(2-van) catalysts were used, an amount of 70% HC104 equivalent to the amount of catalyst was added prior to HzOz addition. The solution was stirred for 1h, and then HzO2 was injected. All reactions were monitored with GLC by direct injection of samples taken periodically from the reaction mixtures with a microsyringe. Where appropriate, initial rate data were determined from conversion vs time plots. Prior quenching of the catalyst with LiCl did not show any differences in randomly selected analyses. Separation of the products was performed on 25 m HP-5 capillary columns using a flame ionization detector. The amount of residual H202 at different times was determined by sampling 10 pL aliquots from the aqueous phase. These were diluted in water and titrated iodometrically. Determination of ee. The ee values during the catalytic reaction were determined by GLC using a 25 m Chrompack
CP-P-cyclodextrin-2,3,6-M-19 capillary column. Since even for racemic mixtures there is a n apparent ee which depends on the peak area, a calibration curve (apparent ee/peak area) was first determined using the racemic lactones synthesized according t o the above procedure. This calibration curve was used to correct the experimental values obtained in the enantioselective reactions. ee data reported in Tables 3 and 4 for short times refer to the first detectable amount of product formed after addition of HzO2.
Acknowledgment. This work was supported jointly by MURST (40% programs) and the CNR (Progetto Finalizzato Chimica Fine 11). Thanks are expressed to Professor 0. De Lucchi of this department and Professor F. Di Furia (University of Padova) for many helpful discussions and to Dr. M. Selva for help in the interpretation of the mass spectra. We thank also Miss T. Fantinel for skillful technical assistance. OM9405375
