1304
Journal of the American Chemical Society
The reaction of bis(ethylene)palladium(II) chloride’* in water-acetonitrile at -20 to -25 OC in the presence of carbon monoxide (3 atm) gave 0-propiolactone 2 in a 72% yieldI3 (eq 1). The direct catalytic conversion of ethylene to 0-propiolactone could also be effected from a 2:l ethylene-carbon monoxide charge (total 3 atm) using catalytic amounts of palladium, provided equivalent amounts of copper(1I) chloride and sodium acetate (buffer) were present (eq 2). Although (C,H,),PdClJ t H,O + CO
-
+ 2HC1 + Pd + CZH,
CHZ-CH,
I 1 0-c
(1)
\O 2
2CuC1,
+ CH,=CH, + H,O + CO
-+ PdCl.
2
Cu2C1,
+ 2HC1
(2)
carbon monoxide is rapidly oxidized to carbon dioxide under these conditions, the low reaction temperature apparently slows down this oxidation relative to the hydroxypalladation, and a 37% conversion of ethylene to 0-propiolactone is realized. Since copper(1) can be reoxidized to copper(I1) by air, this represents a unique catalytic synthesis of 0-lactones from olefin, carbon monoxide, and water. The stereochemistry of the hydroxypalladation step was determined by using the bis(ethylene)palladium( 11) chloride complex 3 obtained from cis- 1,2-dideuterioethyIene.l4Thus, the reaction in water-acetonitrile in the presence of carbon monoxide afforded trans- 2,3-dideuterio-P-propiolactone( 6 ) : IH NMR(CDC13 6 4.3 ( d , J = 4 Hz),3.8 ( d , J = 4 Hz).ISThe insertion of carbon monoxide into a carbon-palladium u bond (4 5) is knownI6 to proceed with retention of configuration at carbon; therefore, the hydroxypalladation step (3 4) must proceed with trans stereochemistry.
-
-
I
1
0-c 6
No
These results for the stereochemistry of hydroxypalladation are consistent with those reported” for the reaction of trans1,2-dideuterioethylene under the conditions of the Wacker process. The formation of threo- 1,2-dideuterio-2-chIoroethanol also requires trans hydroxypalladation. Thus, the attack of water on the ethylene-palladium complex is from outside the coordination sphere, and the addition of OH and palladium is trans.
1 100:4 /
February 15, 1978
(10) T. Majima and H. Kurosawa, J. Chem. SOC., Chem. Commun., 610 (1977). 97, 674 (1975); J. Orga(1 1) J. K. Stille and D. E. James, J. Am. Chem. SOC., nomet. Chem., 108 401 (1976). (12) M. S.Kharasch, R. C. Seyler, and W. Frank, J. Am. Chem. SOC., 60, 382 (1938). (13) The IR and NMR spectra were superimposable with those of an authentic sample: IR (CHCls) 1820 cm-’; ’H NMR (CDC13) 6 4.4-4.2 (m. OCH2), 3.6-3.3 (m, CH2CO). (14) P. 0. Nicholas and R. T. Carroll, J. Org. Chem., 33, 2345 (1968). (15) (a) Calculated coupling JAB(cis) = 7.2 Hz; &(trans) = 3.7 Hz; M. Karplus, J. Am. Chem. Soc., 85, 2870 (1963). (b)Coupling constants for 2,3diphenylpropiolactone are JAB(cis) = 7.0 Hz. and JAB(trans)= 4.5 Hz: 0. L. Chapman and W. R. Adams, J. Am. Chem. SOC.,90, 2333 (1968). (16) L. F. Hines and J. K. Stille, J. Am. Chem. SOC., 94, 485 (1972). (17) J. E. &ckvall, B. Akermark, and S.0. Ljungren, J. Chem. SOC., Chem. Commun., 264 (1977).
J. K. Stille,* R. Divakaruni Department of Chemistry, Colorado State University Fort Collins, Colorado 80523 Received, October 25, I977
Specific Catalysis of Ester Hydrolysis by A New WaterSoluble Heterocyclophane Sir: Substrate specificity in enzymic reactions is understood to indicate that a specific substrate has a “best fit” to a unique array of binding site residues and that the spatial arrangement of atoms relevant to the catalysis is particularly favorable for the stabilization of the transition state.’ Among the variety of ways in which such stabilization can arise, electrostatic stabilization is very important since most enzymic reactions involve various charged transition states. In an active site, cationic residues of protonated basic amino acids such as Lys or Arg can stabilize an anion generating in the transition state of an enzyme-catalyzed reaction.2 For example, in ribonuclease action it is hypothesized that electrostatic stabilization of a dianionic pentacoordinate intermediate is provided by a cationic residue (probably protonated lysine). In a previous communication we reported that certain water-soluble macrocyclic heterocyclophanes are excellent inclusion hosts toward organic substrate^.^^-^ In this communication we wish to report evidence supporting the formation of markedly stabilized transition state complexes of aromatic ester substrates with a new member of the group of watersoluble heterocyclophanes, 11, leading to remarkably effective catalysis. The observed substrate specificity is shown herein
R CH,CI
% &h...o-c-x - I
Acknowledgments. This research was supported by the National Science Foundation, Grant CHE77-08349.
(1)
I
0
I
References and Notes (1) P. M.Henry, J. Am. Chem. SOC., 86, 3246 (1964); 88, 1595 (1966). (2) J. K. Stille and R. A. Morgan, J. Am. Chem. SOC.,88, 5135 (1966). (3) (a) W. A. Whitla, H. M. Powell, and L. M. Venanti, Chem. Commun., 310 (1966); (b) C. Panattoni, G. Bombieri, E. Forsellini. E. Crociani, and U. Belluco. ibid., 187 (1969). (4) P. M. Henry, Adv. Chem. Ser., No. 70, 151 (1968): Div. Pet. Chem. Prepr., Am. Chem. SOC.,14, F17 (1969). (5) R. F. Heck, Fortschr. Chem. Forsch., 18, 221 (1971). (6) M.Green and R . F. Hancock, J. Chem. SOC.A, 2054 (1967). (7) E. L. Shaw, Chem. Commun., 464 (1968); Div. Pet. Chem., Prepr., Am. Chem. Soc., 14, F17 (1969). (8) F. R . Hartley, Nature(London), 223, 615 (1969). (9)J. K. Stille, D.E. James, and L. F. Hines, J. Am. Chem. SOC., 95, 5062 (1973).
R
0
I
R quasi-tetrahedral transition state
0002-7863/78/lS00-1304$01.00/0 0 1978 American Chemical Society
Communications to the Editor
1305
Table 1. Catalytic Action of Heterocyclophane I I on Hydrolyses of Aromatic EstersUZb Substrate
pH
BufferC
P-NpCIA (IVC)
8.10
P
6.96
p-NpCIA (IVa)
8.10 6.96
a-NpCIA (1Vb)
8.10 6.96
b P b P b P b P P
ko ( 1O3 S-I) 0.77 f 0.0 I 0.51 f 0.05 0.10 f 0.01 0.12 5.54 6.01 2.55 f 0.06 0.89 0.82 f 0.01 0.16 f 0.01
k,,, ( I O3 s - I ) ~
K,, mMf
k cat 1k 0
19.2 f 2.4 9.7 f 0.8 1.85 f 0.08 2.12 14.6 10.5 6.0 1.6 3.53 f 0.26 1.7 f 0.1
0.54 f 0.05 0.90 f 0.04 2.23 f 0.22 1.89 0.5 1 0.91 0.90 2.4 0.14 f 0.04 0.60 f 0.02
25 19 18 17 2.6 1.7 2.4 1.8 4.3 10.6
Average of at least three independent kinetic runs, 20.2 f 0.2 O C . CTAB micellar catalysis, IVc: kcat, 5.9 X s-l; K , = 0.03 mM; k c a t / k o , = 6.8. IVb: k,,, = 4.5 X s-I; K, = 0.024 mM; k c a t / k o = 5.6. Abbreviations p and b refer to phosphate (1/15 M) and borate ( 1 / 15 M) buffers, respectively. Uncatalyzed rate constant. e See ref 6b. f Michaelis constant defined by K , = ( k - l kcat)/kl. (I
+
to be the result of differences in the ease of stabilization of the transition state (eq 1). A new water-soluble heterophane (11) was prepared by the action of EtsOBF44 on N,N',N",N"'-tetramethyl2,11,20,29-tetraaza[3.3.3.3]paracyclophane (I).5 11: mp 273-277 O C dec (CH3CN-CH3OH = 1:l); IR (KBr) 3020, 2960, 1480, 1300,1130, and 1040 cm-I; N M R (DMSO-d6) 6 3.18 (24 H, CH3-N), 3.96 (16 H, -CH2-), 7.30 (16 H, aromatic). Anal. Calcd for C ~ O H ~ ~ N ~ B ~c, F 49.08; ~ V ~H, H~ 6.15. Found: C, 49.22; H, 5.78.
I
inclusion-electrostatic catalysis. The hypothesis that a productive inclusion complex was formed was also supported by the drastic fluorescence change of a substrate a n a l o g ~ e , ~ 1,8-ANS, in a separate experiment, where the observed K , was 2.6 mM. Although the binding ofp-nitrophenyl ( K , = 0.51 mM) and @-naphthyl ( K , = 0.54 mM) substrates by I1 was almost equally effective, the subsequent catalysis showed marked Ospecificity : and the rate constant enhancements observed, k c a t / k o , were 25 for @-naphthyland 3 for p-nitrophenyl in phosphate buffer at pH 8.10 and 20.2 O C . On the other hand, the CTAB micellar catalyst was found to be less effective and exhibited no substrate specificity, the ratio of kcat/ko being 5.6 and 6.8 for a-and @-naphthylsubstrates, respectively. It is concluded, therefore, that the spatial arrangement of the carbonyl group which is directed to the quaternary ammonium residue of the host (11) in the inclusion complex favors stabilization of the negatively charged quasi-tetrahedral transition state as proposed in eq 1. The a-naphthyl derivative (IVb) was the second best substrate. When the buffer was changed from borate to phosphate, an appreciable increase in the k,,, value was generally observed (Table I), suggesting a possibility of general base catalysis by phosphate schematically shown in V. Also a drop in the pH from 8.10 to 6.96 resulted in an increase in the K , values regardless of the substrate species, strongly suggesting competitive inhibition by the anion H2PO4- ( K I = ca. M).'
__
CH-C1
I1
+ V . 2 BF4I11
The kinetics of the catalytic action of the heterocyclophane I1 in hydrolyses of chloroacetates6a CICHzCOzR (IV) (R = p-nitrophenyl (IVa), a-naphthyl (IVb), @-naphthyl (IVc)) were analyzed by use of the Lineweaver-Burk (Table I). It is evident from Table I that the heterocyclophane catalyst (11) accelerates the hydrolysis rate of each substrate, while much smaller catalytic effects were observed for 111, an open-chain analogue of the catalyst (kcal/K, = 0.5 s-' M-I, for IVc at pH 8.10). Therefore, the rate accelerations seen with I1 are due not just to simple electrostatic catalysis, but also to
The enzyme-like behavior of the ammonium residue of 11, stabilization of the transition state, and provision of a base (or a nucleophile) offer the promise of further successes in the future in modelling hydrolase functions. The covalent introduction of effective functional groups on the heterocyclophane I1 may provide improved models of a variety of enzymes.
References and Notes (1) (a) M. L. Bender. "Mechanism of Homogeneous Catalysis from Protons to Proteins", Wiley-lnterscience, New York. N.Y., 1971, Chapter 19; (b) E. Zeffren and P. L. Hall, "The Study of Enzyme Mechanism", Wiley-lnterscience, New York, N.Y., 1973, pp 128-129. (2) D. Robertus, 8iochemistry, 11, 4293 (1972). (3) (a) I. Tabushi. H. Sasaki, and Y. Kuroda, J. Am. Chem. Soc., 98,5727 (1976); (b)I. Tabushi, Y. Kuroda. and Y . Kimura, Tetrahedron Lett., 3327 (1976); (c)
Journal of the American Chemical Society
1306
previous work on ammonium substituted cyclophane catalyst: I. Tabushi and Y. Kuroda, Catalyst, 16, 78 (1974).
/
100:4
/ February
15, 1978
Scheme I
X
(4) H. Meerwein, Org. Syn., 46, 120 (1966).
(5) See ref 3b and the references cited therein for our modified preparation of I. (6) (a) Chloroacetates IV were chosen as the substrates in the present studies because the rates of spontaneous and catalyzed hydrolyses can be adequately compared under the condition. (b) The kinetics of the catalytic action of the heterocyclophane II in the hydrolyses of the ester substrates (W) were analyzed, based on the following assumptions of hydrolysis mechanisms,
C+S&CSk”’C+P k-
1
s 2 - P where the eq 2 refers to the Michaelis-Menten type hydrolysis of the subskate (S)to the product (P) catalyzed by C, and eq 3 refers to the uncatalyzed (spontaneous)hydrolysis. (c) R. L.VanEtten, J. F. Sebastlan, G. A. Clowes, and M. L. Bender, J. Am. Chem. SOC.,89,3242 (1967). (7) KI constant was determined from pH dependence and phosphate concentration dependence of the apparent K,,, value.
-CH3
(1) (a) X
=
N-CH3
(b) X = N - C D 3 (c) X = K-tBu
(d) X = 0 (e)
X =S
Iwao Tabushi,* Yoshio Kimura, Kazuo Yamamura Department of Synthetic Chemistry, Kyoto University Sakyo-ku, Kyoto 606, Japan Received September 30, I977
II
H3ClNAN--R \ I N=N
( 4 a ) R = CD3 (4b)
R
= tBu
since they readily lose nitrogen on photolysis, l a and Id thereby affording the diaziridine derivatives 2a and 2d, respectively, Scheme I.6 When la, at -195 OC in a butyronitrile matrix’ Tris(imin0)methanes. An Electron Spin Resonance degassed at Torr, was irradiated inside the cavity of an Identification of Nitrogen Analogues ESR spectrometer,8 a centrosymmetrical four-line spectrum, of Trimethylenemethane’ centered a t 3286 f I O G (Figure I ) , was observed after only 30 s. The spectrum persisted after the irradiation had been Sir: terminated and lost about half of its intensity on warming to Increasing numbers of both experimental2 and theoretical3 - 150 “C. Under the same conditions, very similar, but less investigations center around trimethylenemethane. The triplet intense, ESR spectra appeared in methylcyclohexane, 2,2character of its ground state survives even rather severe perdimethylbutaneln-pentane (73:27), hexafluorobenzene, and turbations by substituents.2bIn contrast, virtually nothing is perfluoromethylcyclohexane. known experimentally about the influence of heteroatoms in The four-line spectrum of Figure 1 can be assigned to the the trimethylenemethane skeleton. Thus, attempts to detect “parallel” (z) and “perpendicular” ( x y ) signals of randomly oxyallyl, for which a triplet ground state has been p r e d i ~ t e d , ~ oriented triplet molecules having an axis of threefold or higher by ESR spectroscopy during low temperature photolysis of symmetry, i.e., E/hc = -0 ~ m - ’ From . ~ ID’I = 356 f I O G 1,3-cyclobutanediones have met with f a i l ~ r eWe . ~ report here the zero-field splitting parameter is calculated as I D/hcI = the ESR spectra observed when the iminotetrazoline l a is ir0.033 f 0.001 cm-I. The half-field (Am = 2) transition which radiated a t low temperatures. We assign the spectra to a niis a criterion of triplets was observed a t 1644 f I O G. It extrogen analogue oftrimethylenemethane, Le., the tris(imin0)hibited a hyperfine structure of at least nine equidistant lines methane 3. separated by 11.7 f 0.5 G. The absorption near the center of In the search for heteronuclear analogues of trimeththe four-line high-field spectrum was produced by monoradiylenemethane the tetrazolines 1 were designed as precursors, cals generated during the irradiation. I
Figure 1. First derivative of the ESR absorption obtained during irradiation of the iminotetrazoline la (lower trace) and the perdeuterated iminotetrazoline [Dgl-la, respectively (upper trace), both in a butyronitrile matrix at -195 “ C . Klystron frequency 9285 M H z , calculated from the resonance field
of Fremy’s salt. 0002-7863/78/ 1500-1306%01.OO/O
0 1978 American Chemical Society
