Organometallics 1995, 14, 4343-4348
4343
Homogeneous Catalysis. Mechanism of Diastereoselective Hydroacylation of 3-Substituted-4-pentenals Using Chiral Rhodium Cata1ysts Richard W. Barnhart and B. Bosnich" Department of Chemistry, The University of Chicago, 5735 South Ellis Avenue, Chicago, Illinois 60637 Received May 31, 1995@ Catalytic hydroacylation of 4-pentenals using [Rh(diphosphine)l+ catalysts leads to the formation of cyclopentanones. Catalytic kinetic resolution of racemic 3-phenyl-4-pentenal using the chiral catalyst, [Rh((S)-binap)l+,leads not only to the diastereoselective formation of ,f3-phenylcyclopentanone but also to the diastereoselective production of 4-phenyl-4pentenal. The kinetics of the formation of these two products, together with deuterium distribution studies, indicates that hydroacylation proceeds by a variety of reversible steps. The 4-phenyl-4-pentenal is formed by carbonyl deinsertion-insertion steps. Although the steps appear t o be reversible, equilibrium is not established. It is concluded that asymmetric hydroacylation is not governed by a single enantioselective step, but rather that the enantioselection is controlled by a number of reversible steps involving reaction intermediates. Catalytic intramolecular hydroacylation of 4-pentenals (eq 1) is promoted by complexes of the type [Rh-
+ 4 R
tertiary or ester or ketone groups into essentially optically pure products 2.3 This high enantioselectivity has prompted us to consider the possibility that efficient kinetic resolutions of 3-substituted pentenals (eq 2) might be achieved
H
0
2 R
1
(diphosphine)(S)21+where S is a weakly coordinating solvent molecule.1,2 The turnover number depends on the nature of the diphosphine and to some extent on the solvent and is controlled by a secondary reaction, namely, the formation of the catalytically inactive species [Rh(diphosphine)(C0)21f formed by decarbonylation of 1. Despite the presence of the secondary decarbonylation path, turnover numbers of the order of 500 can be achieved with high turnover frequency, making the process practical for the production of P-substituted cyclopentanones 2. Incorporation of the chiral diphosphine (5')-binap 3 generates a catalyst
W
P
P
h
Z
R
H R
using the (SI-binap catalyst. The efficiency of the kinetic resolution relies on achieving a favorable differentiation for the rates of conversion of the two ~ 3-substituted enantiomers of the ~ u b s t r a t e . ~ 2Two pentenals were investigated, namely when R = Ph and t-Bu. Although only modest kinetic resolution was observed, the origins of this resolution is surprising. We
WPPh2 (S)-binap
3 which converts 4-substituted-4-pentenals1 bearing @Abstractpublished in Advance ACS Abstracts, August 15,1995. (1)Fairlie, D.P.;Bosnich, B. Organometallics 1988,7, 936. (2)Fairlie, D.P.;Bosnich, B. Organometallics 1988,7, 946.
(3)(a) Barnhart, R. W.; Wang, X.; Noheda, P.; Bergens, S. H.; Whelan, J.; Bosnich, B. J . Am. Chem. SOC.1994,116,1821.(b)Wu, X. M.; Funakoshi, K.; Sakai, K. Tetrahedron Lett. 1992,33,6331. (4)(a) Kuhn, W.; Knopf. E. 2. Phys. Chem. B 1930, 7 , 292. (b) Newman, P.;Rutkin, P.; Mislow, K. J.Am. Chem. SOC.1958,80,465. (c) Horeau, A.Tetrahedron 1975,31,1307.(d) Horeau, A. Tetrahedron Lett. 1962,965.(e) Balavoine, G.; Moradpour, A,; Kagan, H. B. J . Am. Chem. SOC.1974,96,5152.(fl Martin, V.S.; Woodard, S. S.; Katsuki, T.; Yamada, Y.; Ikeda, M.; Sharpless, K. B. J . Am. Chem. SOC.1981, 103,6237. (5)James and Young have reported kinetic resolutions of 2,2'disubstituted-4-pentenals and a 3,3'-disubstituted-4--pentenalusing [Rh(chiraphos)&l at -150 "C. See: (a) James, B. R.; Young, C. G. J . Chem. SOC.,Chem. Commun. 1983,1215.(b) James, B. R.; Young, C. G. J . Organomet. Chem. 1985,285,321.
0276-733319512314-4343$09.00/0 0 1995 American Chemical Society
4344 Organometallics, Vol. 14,No. 9, 1995
Barnhart and Bosnich
Table 1. Product Ratios for the Hydroacylation of the Mubstituted Pentenals Using the [Rh(chiral diphosphine)l+Catalysts at 25 "C (%)
Substrate
Diphosphine
Solvent
(S) - binap
CHzClz acetone CH2Clz acetone
vo F ' h H
i?i)b-yLaphos
(SS)- chiraphos
report the results here together with the possible mechanism and its implications for enantioselection. 1. Results
Table 1 lists the results using -4 mol % of the catalysts incorporating the (5')-binap and (S,S)-chiraphos (Ph2PCH(CHs)CH(CH3)PPhz)ligands and the two 3-substituted-4-pentenal substrates. The ratios of products are those observed when all of the 3-substituted pentenal has been consumed. Since the rates of catalysis of the 4-substituted pentenals are at least 15 times slower than that of the 3-substituted pentenal substrates, it is possible to determine the ratio of the cyclopentanone product t o that of the 4-substituted pentenal derived directly from the 3-substituted pentenal with good accuracy. The double-bond migration products, when observed, do not react further with the catalysts; thus, in all cases examined 3-substituted pentenals give both the cyclopentanone product and the 4-substituted pentenal. These ratios vary with the nature of the catalyst, the solvent, and the substrate. Eventually the 4-substituted pentenal is converted t o the final cyclopentanone product. Because the absolute configuration of the ,!?-phenylcyclopentanone has been established6 and because the cyclopentanone and the 4-phenylpentenal are formed in nearly equal proportions in CH2C12 solution using the (5')-binapcatalyst, we chose this system for closer study. The small amount of double-bond migration that is observed with this system is not expected to affect the overall conclusion even if the process is diastereoselective in the sense that the (R)-and ($)-3-phenyIpentenals have different rates of double-bond migration. The time dependent evolution of the various isomers of the substrate and products is given in Table 2. The percent distribution of isomers was determined after quenching the catalysis by rapid addition of oxygen and removal of the inactivated catalyst by passing the solution through Florisil. The ratios of the various species were established by lH NMR spectroscopy. The enantiomer ratios of the substrate and the j3-phenylcyclopentanone enantiomers were determined by 13CN M R spectroscopy of the SAIVIP,~ 4, hydrazones of the aldehydes and ketones. The absolute configuration of the (6)Taber, D. F.; Raman, K. J. Am. Chem. SOC.1983, 105, 5935. Posner, G. H.; Hulce, M.Tetrahedron Lett. 1984,25,379. ( 7 ) Enders, D.; Eichenauer, H. Tetrahedron Lett. 1977,191.
R
51 91 21 38
H
7 5
42 5 79 62
0 0
prevailing enantiomer of P-phenylcyclopentanone was established by optical rotation.6 The absolute configu-
(NWOMe n I
kHz
4
ration of the prevailing enantiomer of the remaining 3-phenyl-4-pentenal was determined indirectly by converting these pentenals to the ,!?-phenylcyclopentanone by means of the achiral catalyst derived from the dcpe ((CsH11)2PCH2CH2P(CsHll)z) 1igand.l It should be noted that (R)-3-phenyl-4-pentenal correlates with the (S)-,Bphenylcyclopentanone absolute configuration because of the priority conventions. Inspection of the substrate and product enantiomer ratios (Table 2) reveals that the faster-disappearing substrate enantiomer does not produce the faster-appearing product enantiomer. This surprising result suggests that the substrate enantiomers have different rates for the production of the 4-phenyl-4-pentenal. An analysis of the data (Table 2) indicates that the relative rate constants for the pseudofirst-order catalytic production of the products is as illustrated in Scheme 1. The (5')-3-phenylpentenal is converted to the 4-phenylpentenal nearly 7 times faster than the corresponding conversion of the ( R )enantiomer, but the (R)-3-phenylpentenal is transformed to the P-phenylcyclopentanone about twice as fast as the ($1 enantiomer. Consequently, an unusual kinetic resolution operates where the (5')-,!?-phenylcyclopentanone is kinetically amplified not only by the faster catalytic rate of the (Rb3-phenylpentenal to the cyclopentanone product but also by the more rapid conversion of the (Sl-3-phenylpentenal to the 4-phenylpentenal. 2. Mechanism
Mechanistic pathways that provide an explanation for the formation of the products are shown in Scheme 2.2 The steps in Scheme 2 are the following, starting from the (Rl-3-phenylpentenal 5. Oxidative addition of the formyl C-H bond leads to 6, which, upon hydride-olefin insertion, gives the metallocyclohexane 7, which can reductively eliminate t o give the (S) product. Alternatively, 7 may decarbonylate to give the metallocyclo-
Homogeneous Catalysis
Organometallics, Vol. 14,No. 9, 1995 4345
Scheme 1 Ph I
a
H
R
H
1'.
0
0
(i s\
Ph
pentane 8, which, upon carbonyl reinsertion at the other metal-carbon bond, gives 9, which also can give the (S) product; but the metallocyclohexane 9 can /?-hydride eliminate to 10, and 10 can reductively eliminate to the 4-phenylpentenal 12. In principle, the intermediate 10 can invert its enantiomeric olefin coordination t o give the diastereomer 11, which now can enter the (S)-3phenylpentenal 17 domain via the intermediates 13 14 15 16. It will be noted that the conformations of the metallocycles are shown and are those in which the phenyl group is in the preferred equatorial disposition. Scheme 2 illustrates how the 3-phenylpentenal substrates 5 and 17 can be converted to the 4-phenylpentenall2, an unusual form of metal-catalyzed isomerization. Further, the mechanism embodied in Scheme 2 implies that, if the system is under complete equilibrium via all of the equilibrating species, the ee would be the same from either the 4-phenylpentenal or from either of the two enantiomers of the 3-phenylpentenal, implying that the irreversible reductive elimination of the metallocyclohexanes (7,9, 13, 15) t o give the products is the enantioselective step. This is not the case for any of the present systems. Thus, although the 4-tert-butylpentenal is converted to the P-tert-butylcyclopentanone in '99% ee by the (SI-binap catalyst in CH2C12 the (R,S)-3-tert-butylpentenal gives only 20%ee after 70%reaction using the same catalyst under the same conditions. Were the equilibrium established and the product-forming reductive elimination the enantioselective step, we would expect the same ee starting from either substrate. Similarly, the 3-phenylpentenal analogues undergo kinetic resolution (Table 2) rather than producing a constant ee of 35%, which is observed for the 4-phenylpentenal. The lack of complete equilibration among the intermediates indicates that the enantioselection of 4-substituted pentenals using these chiral catalysts is not governed by a single enantioselective step. Rather, the ee is controlled by the relative rates of a number of reversible steps involving a variety of intermediates and probably including the rate of a final irreversible reductive elimination step. If this is generally the case for hydroacylationwith these catalysts, identifying the origins of the enantioselection is made exceedingly difficult.8
- -
-
That each step in Scheme 2, aside from the productforming step, is likely to be reversible was demonstrated by the use of formyl-deuterated 3-phenylpentenal with the W b i n a p catalyst. When the deuterated substrate was mixed with the catalyst in CHzCl2 solution, 2H NMR showed that there was rapid deuterium scrambling between the formyl position and the terminus of the double bond where both the cis and trans positions were occupied by deuterium. The probable mechanism for this deuterium scrambling is illustrated in Scheme 3, which invokes the formation of the catalytically unproductive five-membered metallocycle 19 followed by /?-eliminationt o give 20, which in turn eliminates to the substrate. As a consequence, deuterium is found in both the a- and ,&positions of the cyclopentanone product as well as in the a- and /?-positions of the 4-phenylpentenal (see Scheme 2). No deuterium is found at the 4-position of the 3-phenylpentenal23. This suggests that the rate of elimination of the sixmembered metallocycle 21 to give 23 via 22, if elimination occurs at all, is a much slower process than that of the 4-phenyl analogue, 10 12 or 11 12 (Scheme 2). Consistently, when the 4-phenylpentenal is the substrate, no 3-phenylpentenal is observed during catalysis. This is the case for both the binap and chiraphos catalysts in either acetone or CH2C12 solution and for the 4-tert-butylpentenal using either catalyst in CH2Cl2 solution. Since the structural relationship between the transformed substrate and the phosphine of the intermediates is not known, it seems imprudent to speculate on the origins of these rate differences. Speculation is further restrained by the solvent effects observed (Table 1) which may imply that solvent coordination is present in the intermediates.
-
-
3. Conclusions These results demonstrate that the mechanism of hydroacylation with these catalysts must involve numerous intermediate steps, most of which appear t o be reversible. The steps preceding the product-forming step do not appear to be at equilibrium, for, if they were, the corresponding 3-substituted and 4-substituted pentenals would give the same ee. The enantioselection appears to be controlled at least to some extent by these intermediates, an assertion which is supported by the diastereoselective production of the 4-phenylpentenal. Finally, the existence of the carbonyl deinsertioninsertion steps suggests that 4-substituted pentenals may form products from any of the intermediates 7 , 9 , 13, and 15 rather than from only 9 and 13. Experimental Section The following compounds were prepared according to literature methods: [Rh((S)-binap)(NBD)1C104,9[Rh((S,S)-chiraphos)12(C104)2,' and [Rh(d~pe)(NBD)lC10~.~ Reagents were purified by standard methods. 3-Phenyl-4-pentenal. This substrate was prepared by the Hg2+-catalyzed vinylation of cinnamyl alcohol followed by Claisen rearrangement.1° A mixture of cinnamyl alcohol (9.00 mL, 70 mmol), butyl vinyl ether (200 mL), and Hg(0Ac)z (0.80 (8) Wang, X Bosnich, B. Organometallics 1994,13, 4131.
(9) Miyashita, A,;Yasuda, A.; Takya, H.; Toriumi, K.; Ito, T.; Sauchi, T.; Noyori, R. J . Am. Chem. SOC.1980,102, 7932. (10) Watanabe, W. H.; Conlon, L. E. J. Am. Chem. SOC.1957,79, 2828.
Scheme 2
v
/yyo
P h H
P h H
.. RH :> I.uPh
16
6
2
? H
0
H
2
C
I
Ph
14
hP+
13
10
11
0
7
-1. 0
GPh
b R
h P‘
ch
8
9
-1.
-1.
co
I
6 15
k
co
*,’ Ph
Table 2. Product and Substrate Distributions and Enantiomer Ratios during the Conversion of 3-Phenyl-4-pentenal(4.6x lop3M)Catalyzed by CRh((S)-binap)lC104(1 mol %) in CHzClz Solutions at 25 “C n
vo P h H
Time (min) 6 11 20 45
% remaining
68 42 10 0
.. .
R :S
%product
S :R
% product
% product
56 : 44 64 : 36 72:28
16 25 44 51
65 : 35 68 : 32 12 :28 74 : 26
14
2 5 5 7
__
28 41 42
R
3
R
Organometallics, Vol. 14, No. 9, 1995 4347
Homogeneous Catalysis
Scheme 3
Dvo
To P
h
P
D
-
b
H
3 p 0
L
D2
I
'
h
H H
H
[Rhl
22 D g, 2.5 mmol) was refluxed under NOfor 24 h. The mixture was cooled to room temperature, and K2CO3 (2.0 g, 14 mmol) was added. After the mixture had been stirred for 30 min, it was filtered using pentane as a rinse. The solvents were distilled off under vacuum. The product was distilled under vacuum t o yield a colorless liquid, which was purified twice by flash chromatography (silica gel, 12% EtOAc in hexane): 4.34 g, 39% yield; bp 53-56 "C (0.4 mmHg); lH NMR (500 MHz, CDC13) 6 9.66 (t, J = 1.6 Hz, 1 H), 7.30-7.15 (m, 5H), 5.95 (m, lH), 5.08 (d, J = 9.9 Hz, 1 H), 5.04 (d, J = 17.3 Hz, 1 H), 3.93 (9, J = 7.1 Hz, 1 HI, 2.82 (m, 2 HI. 3-tert-Butyl-4-pentenal. This compound was also prepared by Hg2+-catalyzedvinylation of the 3-substituted allyl alcohol followed by Claisen rearrangement. The allyl alcohol (4,4-dimethyl-2-pentenol) was prepared by the method of Kulkarni" in 50% yield. The volatility of the product aldehyde and high boiling point of butyl vinyl ether (bp 96 "C) makes it necessary t o do the vinylation a t a lower temperature in ethyl vinyl ether (bp 33 "C), isolate the allyl vinyl ether, and carry out the Claisen rearrangement in a separate step. A mixture of 4,4-dimethyl-2-pentenol (2.47 g, 22 mmol), ethyl vinyl ether (60 mL), and Hg(OAc)z (0.50 g, 1.6 mmol) was refluxed for 9 h under N2. After the reaction was cooled to room temperature and KzC03 (0.65 g, 4.7 mmol) was added with stirring for 15 min, the mixture was filtered and the solids were washed with EtzO. After the solvents were removed by rotary evaporator, the product was dissolved in Et20 and run through a plug of silica gel (15g), giving the impure allyl vinyl ether as a colorless oil. The thermal Claisen rearrangement results in substantial polymerization and very low yields of product. The rearrangement proceeds rapidly and cleanly at room temperature with the addition of Et2AlCl and PPh3.12 E t A C l ( 4 0 mL of a 1.0 M solution in hexane, 40 mmol) was rapidly added dropwise to a solution of PPh3 (14.14 g, 54.0 mmol) in dry degassed CHzClz (50 mL) under Ar. The solution was stirred at room temperature for 25 min before the addition of the impure allyl vinyl ether (2.78 g, 20.0 mmol). The reaction was stirred for 15 min, dry Et20 (100 mL) was added, and the reaction was immediately poured into a 1.0 M solution (11) Kelkar, S. V.; Reddy, G. B.; Kulkarni, G. H. Indian J . Chem. 1991,30B,504. (12)Takai, K.; Mori, I.; Oshima, K.; Nozaki, H. Tetrahedron Lett. 1981,22,3985.
Ph
23
H
of tartaric acid (50 mL), causing the rapid evolution of gas. The mixture was separated, and the organic phase was washed with brine (3 x 50 mL) and dried over NaZS04. The resulting white solid (product in 2.7 equiv of PPh3) was dissolved in CH2Clz (100 mL) under N2, and Me1 (7.7 mL, 54 mmol) was added dropwise over 20 min, causing the solvent to reflux. The reaction was stirred overnight at room temperature and then concentrated to about 50 mL on a rotary evaporator. Addition of Et20 caused immediate precipitation of off-white crystalline [Ph3PMelI. Additional Et20 was added before filtration, and the solids were washed with CH~Clfit20. The filtrate was evaporated to give a deep yellow oil. The product was purified twice by flash chromatography (silica gel, 7% EtOAc in hexane) t o give pure product as a colorless oil: 0.62 g, 22% yield (assuming pure starting allyl vinyl ether); lH NMR (400 MHz, CDzC12) b 9.61 (m, 1H), 5.74-5.65 (m, 1H), 5.09-4.99 (m, 2 H), 2.53-2.48 (m, 1 HI, 2.42-2.36 (m, 1 H), 2.32-2.25 (m, 1 HI, 0.89 (s, 9 HI. l-Deuterio-3-phenyl-4-pentenal. A solution of NaBD4 (0.26 g, 6.2 mmol, in 25 mL EtOH) was added dropwise over 5 min to a stirring solution of 3-phenyl-4-pentenal(1.00 g, 6.2 mmol, in 35 mL EtOH). After the reaction mixture had been stirred for 15 min, it was concentrated to about 5 mL on a rotary evaporator. After the addition of 0.5 M HC1 (55 mL, 27.5 mmol), the reaction was extracted with Et20 (4 x 25 mL). The organic layer was washed with H2O (3 x 30 mL) until neutral and was then washed with brine (1 x 30 mL) and dried over Na2S04, yielding 1.02 g (100%)as a colorless oil. The crude alcohol was oxidized by the method of Swern13 using oxalyl chloride as the activator and triethylamine as the base. The deuterated aldehyde was purified by flash chromatography (silica gel, 10% EtOAc in hexane) to give a colorless oil in 84% yield from the starting aldehyde. The substitution at the formyl position was 67% atom D. The reduction and oxidation was repeated once more t o give aldehyde with '90% atom D a t the formyl position. Catalytic Reactions. The NMR scale and small preparative scale catalytic reactions have been previously de~cribed.~" To measure the reaction composition (i.e., the percentages of 3-phenyl-4-pentena1, 4-phenyl-4-pentenal,3-phenyl-3-pentenal, and 3-phenylcyclopentanone) and to simultaneously measure the ee's of 3-phenyl-4-pentenal and 3-phenylcyclo(13)Omura, K.; Swern, D. Tetrahedron 1978,34,1651.
4348 Organometallics, Vol. 14, No. 9, 1995
Barnhart and Bosnich
pentanone during catalysis, it was necessary to run large ((S)-binap)]C104catalyst. Any 4-phenyl-4-pentenal that cycatalytic reactions and remove aliquots that could be quenched clizes will simply decrease the ee by diluting the product with and later analyzed. racemic product. This product is 3-phenylcyclopentanone.The relationship between absolute configuration, optical rotation, Under Ar in flame-dried glassware was dissolved [Rh((S)and 13C NMR imine peak position of the SAMP derivative has binap)(NBD)]C104 (34.0 mg, 0.0371 mmol) in dry, degassed CHzClz (800 mL). Oxygen-free Hz was bubbled through the already been made above. Calculation of the Rate Constants. The percent comsolution for 10 min, and then the catalyst solution was stirred under Hz (1 atm) for 40 min. Argon was bubbled through the position of the aliquots was found by IH NMR of the crude solution for 35 min to purge all excess Hz.The solution was mixtures after quenching by air and removal of catalyst by Florisil. The ee's of enantiomeric compounds (3-phenyl-4placed in a water bath to restore it to room temperature before pentenal and 3-phenylcyclopentanone)were found by 13CNMR injecting the 3-phenyl-4-pentenal (593 mg, 3.70 mmol). The reaction was stirred at room temperature. Aliquots (-110 mL) of the SAMP derivatives. The assumption was made that were transferred under Ar to flame-dried 250 mL flasks where there was no exchange between the ( R )and ( S )regimes except they were quenched by pulling air through the mixture for 30 through 4-phenyl-4-pentena1, which was slow to react under s. Pentane (50 mL) was added to each aliquot before passing these conditions. A second assumption was made that the double-bond migration from chiral 3-phenyl-4-pentenal to it through Florisil (2 g) followed by CHZC12 (50 mL). The achiral unreactive 3-phenyl-3-pentenal was approximately colorless solutions were placed under Ar and kept at -20 "C equal for the ( R )and (S) enantiomers. If this assumption is until they could be further analyzed. IH NMR was used t o not true, its effect on the outcome will be small and its effect measure percent composition of the reaction mixture. Since on the conclusions will be inconsequential because the total all species have the same formula weight and since all species amount of double-bond migration product formed is small have one carbonyl group, it is possible to calculate the required amount of (S)-(-)-l-amino-2-(methoxymethyl)pyrrolidine compared to the amounts of cyclized product and 4-phenyl-4(SAMP)from the total mass of the aliquot. The diastereomeric pentenal formed. SAMP derivatives were made by the method of Enders' using The amounts of (R)-3-phenyl-4-pentenalat time t can easily 1.1equiv of SAMP to ensure complete reaction of all carbonyl be calculated using eq 3 groups. 13CNMR of the diastereomeric mixture was used to measure nR-SM= (ntotal)x (% composition,,) x (% R) (3) the ee's of the 3-phenylcyclopentanone product and 3-phenyl4-pentenal starting material. The hydrazone may be syn or where nR.SM is the number of moles of ( R )starting material at anti with respect to the 3-substituent of the cyclopentanone time t , ntotalis the total number of moles of racemic starting and syn or anti with respect t o the carbon chain of the material, % compositionsM is the percent of starting material aldehyde. For the 3-substituted cyclopentanones, the syn and in the mixture at time t , and % R = [RsM/(RsM+ SSM)] x 100%. anti isomers form in approximately equal amounts to give four The amount of (S)-3-phenylcyclopentanoneat time t ( n ~ - ~ ~ ~ l ) possible diastereomers, one pair for each enantiomer of the can be found similarly (eq 4) cyclopentanone product. For the aldehyde only the less hindered anti hydrazone is formed, giving one diastereomer ns-cycl- (ntotal)x (% compositioncycl)x (% S ) (4) for each enantiomer of 3-phenyl-4-pentenal. The imine carbon of the hydrazone of the cyclopentanone where n ~ . is~ the ~ ~number l of moles of (S)-3-phenylcyclopenhas a 13C NMR resonance a t 168 to 171 ppm in CDC13. The tanone at time t , ntotalis the number of total moles of racemic two downfield resonances are assigned as the syn and anti starting material, % compositioncyclis the percent of 3-phenisomers of the (R)-(+)-3-phenylcyclopentanone.The upfield ylcyclopentanone in the mixture at time t , and % S = [Scycl/ peaks correspond to (SI-(-) product. Absolute configuration (Scycl + Rcycdl x 100%. assignments were made using pure 3-phenylcyclopentanone The above assumptions lead to eqs 5 and 6 prepared from 4-phenyl-4-pentenal and the literature assignment of a negative optical rotation as the (SI e n a n t i ~ m e r . ~ ~ , ~ The benzylic carbon of the hydrazone of the 3-phenyl-4pentenal shows a 13C NMR resonance at 48.1-48.2 ppm in CDC13. In 4-phenyl-4-pentenal and 3-phenyl-3-pentenal the nR-total - IZR-SM + nS-cycl + ItR-4-Ph + 1/2ndbm (6) phenyl group is conjugated t o the olefin, shifting the benzylic carbon resonance and leaving the region at 48 ppm clear. where nR.total is the number of moles of compounds in or from The following procedure was used t o assign the absolute the ( R )domain, nR.4.Ph is the number of moles of 4-phenyl-4configuration of the 3-phenyl-4-pentenal. A small preparative pentenal formed from ( R )starting material at time t , and ndbm scale catalytic reaction was carried out. The reaction was is the total number of moles of double-bond migration product quenched as above after 15 min. The composition of the formed at time t. reaction mixture was as follows: 33% 3-phenyl-4-pentena1, By eq 6 the amount of achiral 4-phenyl-4-pentenal formed 35% 4-phenyl-4-pentena1, 25% 3-phenylcyclopentanone, and can be mathematically separated as coming from the ( R )or 6% 3-phenyl-3-pentenal. The mixed aldehydes were separated ( S ) starting material and can be found for each time t by from the cyclopentanone by flash chromatography (silica gel, solving for nR.4.ph. So the concentrations of all species are now 7%, EtOAc in hexane). The achiral catalyst [Rh(dcpe)(NBD)]known at each time t and can be used to calculate observed c104 (where dcpe = 1,2-bis(dicyclohexylphosphino)ethane) first-order rate constants. cyclizes 3-phenyl-4-pentenal to 3-phenylcyclopentanone and 4-phenyl-4-pentenal more than l o x faster than it cyclizes Acknowledgment. This work was supported by 4-phenyl-4-pentenal. Since this catalyst is achiral, any ee in grants from the National Institutes of Health. the cyclopentanone must have its origins in the nonracemic 3-phenyl-4-pentenal which was kinetically resolved by the [RhOM9504056
