J. Am. Chem. SOC.1991, 113, 2141-2153
crystal structure of the homologous al-antitrypsin, and (iv) molecular dynamics simulations provides for the first time detailed insight in the binding Of a polysawharide (glycosaminoglycan) fragment with a protein a t the molecular level. We feel that specific binding of other proteins with sulfated wlysaccharides may also involve well-defined. relatively small complementary domains on both the carbohydrate polymer and
2141
the protein.
Acknowledgment. We thank Dr. Kees Haasnoot (Organon S W ) and Dr. Maurice petitou (Sanofi Recherche, pais, France) for useful discussions and Mr. Theo van Dinther (Organon SDG) for determining the aXa activities. Registry No. AT-111, 9000-94-6; heparin, 9005-49-6.
Nature of the Epoxidizing Species Generated by Reaction of Alkyl Hydroperoxides with Iron( 111) Porphyrins. Oxidations of cis-Stilbene and (2)-1,2-Bis(trans-2,trans-3-diphenylcyclopropyl)ethene by t-BuOOH in the Presence of [ meso-Tetrakis(2,4,6-trimethylphenyl)porphinato]-, [meso-Tetrakis(2,6-dichlorophenyl)porphinato]-, and [ meso-Tetrakis(2,6-dibromophenyl)porphinato]iron( 111) Chloride GongXin He and Thomas C. B r i c e * Contribution from the Department of Chemistry, University of California a t Santa Barbara, Santa Barbara, California 931 06. Received August 30, 1990
Abstract: The mechanism of the oxidation of alkenes by t-BuOOH in the presence of iron(II1) tetraphenylporphyrins has been explored (CH2C12sovent). The alkenes, cis-stilbene and (Z)- 1,2-bis(tranr-2,rranr-3-diphenylcyclopropyl)ethene(1-Z), have been chosen because they serve as traps for radical intermediates. The substituted iron(II1) tetraphenylporphyrin catalysts employed are [meso-tetrakis(2,4,6-trimethylphenyl)porphinato]iron(III) chloride ((TMP)FelI1(CI)), [meso-tetrakis(2,6-dichlorophenyl)porphinato]iron(III) chloride ((Cl8TPP)Fe1I1(C1)), and [meso-tetrakis(2,6-dibromophenyl)porphinato]iron(III) chloride ((Br8TPP)Fe1I1(Cl)).In separate experiments, azobisisobutyronitrile (AIBN) was used as a radical chain initiator for the oxidation of the alkenes by t-BuOOH. Oxidation of cis-stilbene with iron(II1) porphyrins as catalysts provides tram-stilbene oxide as a major product along with diphenylacetaldehyde, deoxybenzoin (trace), and a compound assigned ['HNMR, MS(CI)] We conclude that the reaction products are derived from initial combination the structure PhCH[OO(t-Bu)]CH[O(t-Bu)]Ph. of r-BuOO', rather than (+'Porph)FeIV(0),with cis-stilbene. Oxidation of 1-Z with iron(II1) porphyrins as catalysts provides A ('H NMR, MS(CI), FT-IR) as the major product. Other products are B (whose structure has not been determined), which groups, tranr-2,tranr-3diphenylcyclopropanecarboxaldehyde, contains intact one of the two rram-2,tranr-3-diphenylcyclopropane and deoxybenzoin. In A, one cyclopropyl group has undergone a cyclopropylcarbinyl to homoallylcarbinyl radical rearrangement (CPCRR) while the other has remained intact. The major product A arises from initial combination of t-BuOO' with 1-Z followed by CPCRR. Reaction sequences are suggested. The cis-epoxide of 1-Z (2-c) is formed in 3.2% yield when (C18TPP)FelI1(CI)is the catalyst. A trace of 2-c is obtained with (TMP)Fe"I(CI), but 2-c could not be detected with (Br8TpP)Fdr1(Cl). The cis-epoxide 2-c most likely arises from the concerted reaction of 1-Z with the iron(IV)-oxo porphyrin ?r cation radical (+*C18TPP)Fe1v(0)(C1). The species (+*C18TPP)Fe1v(0)(Cl) may be the direct product of reaction of (C18TPP)Fe111(CI)with t-BuOOH in a mechanism that involves heterolytic 0-0 bond breaking. Alternatively, (+'C18TPP)Fe1V(0)(C1)may arise via (C18TPP)Fe111(CI)+ t-Bu00H (C18TPP)Fe1V(0)+ t-BuO' followed by oxidation of (C18TPP)FeIV(0)by t-BuOOH (or other). It is pointed out that (C18TPP)Fe1V(0),unlike (TMP)FeIV(0),accumulates in relatively high concentration and that r-BuOOH is present at 0.3 M.
-
Introduction Iron(II1) porphyrins have been established as effective catalysts for the epoxidation of norbornene (Nb) with t-BuOOH at high concentrations of alkene.'J Epoxidation has been proposed to involve the reactions of eqs 1 and 2.' The mechanism of the t-BuOOH + (Porph)Fe1I1(X) t-BuOH + (+*Porph)FetV(O)(X)(1)
-
+
-
(+*Porph)Fe(O)(X) Nb (Porph)Fe"'(X)+ endo-NbO/exo-NbO (2) 0002-786319 1115 13-2147$02.50/0
reaction of eq 1 is suggested to involve an intermediate complex of iron(ll1) porphyrin and hydroperoxide that decomposes to products with 0-0 bond heterolysis and oxygen transfer to iron(ll1) porphyrin accompanied by its 2 2 oxidation. The ratio of endo- to exo-norbornene epoxides (NbO) has been interpreted as showing that the epoxidations are carried out by a ( I ) (a) Traylor, T. G.; Xu, F. J . Am. Chem. Soc. 1987, 109,6201. (b) Traylor, T. G.; Fann, W-P.; Bandyopadyay, D. J. Am. Chem. Soc. 1989,111, 8009.
(2) We have repeated Traylor's study with norbornene and found that we obtained similar yields of epoxide under the same conditions.
1991 American Chemical Society
He and Bruice
2748 J. Am. Chem. SOC., Vol. 113, No. 7, 1991 (+'Porph)Felv(0)(X) species1 The formation of both endo-NbO and exo-NbO was attributed to an initial le- oxidation of Nb to a cation radical (Nb'+) as shown in eqs 3 and 4.3 Homolytic
+ +
(+*Porph)FerV(O)(X)+ N b (Porph)FeIV(0)
+ Nb'+
(Porph)FeIV(0) + Nb'+
X(Porph)FelI1(X)
+ X(3)
endo-NbO/exo-NbO (4)
0-0bond cleavage with le- oxidation of the iron(II1) porphyrin (eq 5) was ruled out on the basis that the (Porph)FeIV(0) species is, at best, a very poor epoxidant for Nb. tert-Butyl hydroperoxide r-BuOOH
-
+ (Porph)FelI1(X) t-BuO' + (Porph)FeIV(0) + H+ + X- ( 5 )
radical, which is known to be formed from t-BuOOH in the presence of iron(II1) porphyrins (eqs 6 and 7), was also dismissed
-
+
(+*Porph)FeIv(O)(X) r-BuOOH (Porph)FeIV(O)+ t-BuOO'
-
(Porph)FeIV(0) + t-BuOOH (Porph)FelI1(OH)
+ H+ + X+ t-BuOO'
(6)6 (7)6*7
as the epoxidizing agent.' Other inve~tigations,8*~ however, provide significant evidence in favor of the homolytic mechanisms of eqs 5 and 7 and the involvement of ROO' radicals as epoxidizing agents. We now describe our detailed studies of the products formed on oxidation of cis-stilbene and (2)1,2-bis(trans-2,fruns-3-diphenylcyclopropy1)ethene (1-Z) by t-BuOOH in the presence of [meso-tetrakis(2,4,6-trimethylphenyl)po~~nato]iron(III)chloride ((TMP)FeI'I(Cl)], [meso-tetrakis(2,6-dichlorophenyl)porphinatoIiron(II1) chloride ((Cl,TPP)Felll(CI)), and [meso-tetrakis(2,6-dibromophenyl)porphinato]iron(III) chloride ((Br8TPP)Fe"'(C1)). Experimental Section
General Procedures. Melting points were determined on a Bristoline hot-stage microscope and are uncorrected. Infrared (IR) spectra were obtained in KBr on a Perkin-Elmer monochromator grating spectrometer (Model 1330) or in CHCll on a Bio-Rad Fourier transform spectrometer (Model FTS-60). Low-resolution mass spectra (LRMS) were recorded on a VG Analytical spectrometer (Model VGII-250) by electron impact (EI) and chemical ionization (CI) with CHI. 'H NMR spectra were obtained in CDC13 with Nicolet NT-300 and General Electric GN-500 spectrometers. Chemical shifts are reported in b relative to Me4Si with s, d, t, q, and m signifying singlet, doublet, triplet, quartet, and multiplet; coupling constants J are reported in hertz. For GC, a Varian Model 3700 with flame ionization detector using a 0.2 mm X 25 m WCOT vitreous S i 0 2 capillary column operating at -80-200 OC (3 OC/min) was employed. Preparative thin-layer chromatography (TLC) was performed on glass-backed plates (20 X 20 cm) with 1.5-mm A1203 60-F254 (Merck). High-pressure liquid chromatography (HPLC) used two Perkin-Elmer Series IO pumps. For analytic HPLC, a Hewlett-Packard variable-wavelengthdetector (Model HP1050) at 254 nm and integrator (Model 3392A) and, for semipreparative HPLC, an ISCO variablewavelength absorbance detector (Model V4) at 254 nm and fraction collector (Model Retriever 11) were used. Chromatographic conditions (3) It has been pointed out that le- oxidation of alkenes to provide carbocation radical intermediates cannot be the first step in epoxidations by (+'Porph)Fe(O)(X) or (Porph)Crv(0)(X) species' and that steric and electronic factors serve to explain the endc-NbO to exc-NbO ratio.5 (4) Garrison, J. M.; Ostovic, D.; Bruice, T. C. J. Am. Chem. Soc. 1989, I I I, 4960. (5) Ostovic, D., Bruice, T. C. J . Am. Chem. Soc. 1989, I I I, 65 1 I . (6) Balasubramanian, P. N.; Lindsay Smith, J. R.; Davies, M. J.; b a r e t , T. W.;Bruice, T. C. J. Am. Chem. Soc. 1989,111, 1477. (7) Murata. K.; Panicucci, R.;Gopinath, E.;Bruice, T. C. J. Am. Chem. Soc. 1990,112, 6072. (8) (a) Labeque, R.;Marnett, L. J. J . Am. Chem. Soc. 1987, 109, 2828. (b) Labeque, R.; Marnett, L. J. Biochemisrry 1988,27,7060. (c) Labeque, R.;Marnett, L. J. J. Am. Chem. Soc. 1989, 111, 6621. (9) Arasasingham, R.D.; Comman, C. R.;Balch, A. L. J. Am. Chem. Soc. 1989, 111, 7800.
are given in the following order: column (col), solvent system (sys), solvent composition, and flow rate (mL/min) (as subscript). Altex columns: 4.6 X 250 mm, 5-pm RSiI-CN (col A); 4.6 X 250 mm, 5-pm Lichrosorb SI-60 (col B); 4.6 X 250 mm, 5-pm Spherisorb alumina (col C); IO X 150 mm, 10-pm R S i l C N (Col D); and Whatman column 10 X 500 mm, IO-pm Partisil Si02(col E). The columns eluted with the solvent systems hexane (sys A), hexaneCH2CI2(sys B), hexantEtOAc (sys C) were employed. Materials. Methylene chloride was distilled over calcium hydride, degassed by three freeze-pumpthaw cycles, and stored in a N2 glovebox. rerr-Butylhydroperoxide (r-BuOOH) was purchased from Aldrich, and the concentration was determined by iodometric titrationlo cis-Stilbene, from Aldrich, was distilled and stored in the N2 glovebox. Azobisisobutyronitrile (AIBN) was purchased from Eastman Kodak Co. and used as received. HPLC-CC standards (Aldrich) were purified to homogeneity as established by HPLC or 'H NMR. The possible epoxide products cis- and trans- 1,2-bis(rrans-2,frans-3-diphenylcyclopropyl)oxirane (2-c and 2 4 , respectively) were synthesized with published methods." The porphyrin catalysts, [meso-tetrakis(2,4,6-trimethylphenyl)porphinato]iron(IIl) chloride ((TMP)Fe"'(CI)), [meso-tetrakis(2,6-dichlorophenyl)porphinato]iron(III) chloride ((CI8TPP)Fe1l1(CI)),and [mesotetrakis(2,6-dibromophenyl)porphinato]iron (111) chloride ((Br8TPP)and (E)FelI1(CI)), were available from previous studies.'J1J2 (Z)1,2-bis(rruns-2,rruns-3-diphenylcyclopropyl)ethene(1-Z and 1 4 , respectively) were prepared by an improved procedure of Wittig condensation of [(rrons-2,frans-3-diphenylcyclopropyl)methyl]triphenylphosphonium bromide and rruns-2,rrans-3-diphenylcyclopropanecarbxaldehyde, which were synthesized as previously reported." (Z)- and ( E ) - l , ~ B l s ( ~ - S 6 - ~ ~ y I c (1-Z yc~~yI)~ and I-E). An 18% sodium acetylide slurry (400 mg, 1.5 mmol of NaCCH) was washed with dry hexane (2 X 5 mL), and the remaining solid was dried over N2 stream. To the solid were added 740 mg of [ (rrans-2,rrans-3-diphenylcyclopropyl)methyl] triphenylphosphonium bromide (1.35 mmol) and 5 mL of dry DMF at 0 OC. After the solution was stirred at 0 OC for 0.5 h, 300 mg of rrans-2,rrunr-3-diphenylcyclopropanecarboxaldehyde (1.35 mmol) was added. The temperature was allowed to rise gradually to room temperature, and the color of the solution changed from orange to pale yellow. After being stirred for 1 h at room temperature, the reaction mixture was poured into cold water (100 mL) and extracted with E t 2 0 (4 X 50 mL). The combined organic solutions were dried (MgS04) and concentrated in vacuo. The residue was purified by column chromatography (A1203,neutral activity 11, 100% = 9). To the CCI,) to give 470 mg of a I-Z/I-E mixture (85%, I-Zl-E mixture, 100 mL of MeOH was added and the solution refluxed for 1 h. The solution was filtered while hot to remove insoluble white solid. The filtrate was concentrated, 50 mL of MeOH was added to the residue, and the solution was refluxed and filtered again while hot. The solid obtained on concentration of the filtrate was recrystallized twice from MeOH to provide 250 mg of 1-Z as colorless prisms, and HPLC (col B, sys B, 9:12) showed that I-Zcontained less than 0.1% 1-E. Recrystallization of the white MeOH-insoluble solid from MeOH-CHCI3 (3:l) gave 25 mg of I-E as white needles, which contained
