4112 study and a more detailed analysis of the nortriquinacenesystem will appear elsewhere. (50) This procedure was initially developed by Dr. James D. Kramer in these
laboratories. (51) R. C. Kelly, Ph.D. Thesis, Harvard University, 1965; R. Russo, Y. Lambert, and P. Deslongchamps, Can. J. Chem., 49, 531 (1971).
Catalysis of Transimination Through Trapping by Acids and Bases' John L. Hogg, David A. Jencks, and William P. Jencks" Contribution No. 1150f r o m the Graduate Department of Biochemistry, Brandeis University, Waltham, Massachusetts 021 54. Receiljed December 27, I976
Abstract: Catalysis of the transimination reaction of N-p-methoxybenzylidenepyrrolidiniumcation and hydroxylamine by buffer acids and bases and by the proton exhibits a sharp rate incre.ase followed by a leveling off to a pH-independent rate at high catalyst concentrations. This is evidence for a change in rate-determining step and an intermediate in a stepwise reaction mechanism. Catalytic constants, k H A , for cacodylic and carboxylic acids show a small or no increase with increasing acidity, but k H A for the proton is 57 times larger and k H A for hydroxylammonium ion is more than ten times Smaller than k H A for cacodylic and acetic acids. Catalytic constants for buffer bases drop sharply for catalysts of pK, < 4.6. The reaction with N methylhydroxylamine shows similar behavior in acetate buffers, but exhibits approximately tenfold slower rates, presumably because of steric hindrance. The observed catalysis by acids and bases is attributed to trapping of the initially formed cationic addition intermediate by proton transfer. Catalysis by cacodylic and carboxylic acids and by water is attributed to a bifunctional, proton switch mechanism.
also in enzymic reactions, if the enzyme can bring together the reacting groups as effectively as in the model r e a ~ t i o n . ~ It was shown by Cordes and co-workers4 that the transimination reaction of benzhydrylidenedimethylammonium ion H(1) ~ (1) and hydroxylamine is subject to general base catalysis
Transimination (eq l ) , such as occurs in the reaction of an amino acid with the imine formed from pyridoxal phosphate and the lysine C=N+ 10' M-! s-!, with no evidence for a change in rate-determining step up to 0.16 M phosphate buffer, 8Phdianion) and Kl isconsiderably smaller ( K i = 3.7 X M-I) than for the transimination of 2. On the other hand, no general-base catalysis by methoxyamine has been observed for the methoxyaminolysis of N-protonated benzylideneanilines.26 The value of k-1 is expected to be smaller for this reaction because of the relatively small electron-donating ability of the aniline nitrogen atom. The absence of catalysis may therefore reflect a solvent-mediated proton transfer that is faster than k-1, so that buffer-mediated trapping is not significant. References and Notes (1) Supported by grants from the National Science Foundation (BMS71-01501 A03) and the National Institute of General Medical Sciences of the National Institutes of Health (GM 20666). (2)E. H. Abbott and A. E. Martell, J. Am. Chem. SOC., 93,5852 (1971). (3)P. S. Tobias and R. G. Kallen, J. Am. Chem. Soc., 97, 6530 (1975). (4)K. Koehler. W. Sandstrom, and E. H. Cordes, J. Am. Chem. Soc., 88,2413 (1964).
(5) S . Moore and W. Reenstra, unpublished experiments. (6)J. P. Fox and J. M. Chalovich, personal cummunication. (7)N. J. Leonard and J. V. Paukstelis, J. Org. Chem., 28, 3021 (1963). (6) N. J. Leonard and V. W. Gash, J. Am. Chem. Soc., 76, 2761 (1954). (9)J. E. Reimann and W. P.Jencks, J. Am. Chem. Soc., 88,3973(1966). (IO) J. L. Hogg and W. P. Jencks, J. Am. Chem. Soc., 98,5643(1976). (11) M. Eigen. Angew. Chem., Int. Ed. Engl., 3, l(1964). (12)J. M. Sayer and W. P. Jencks, J. Am. Chem. SOC.,95,5637(1973);J. P. Fox and W. P. Jencks, ibid., 96, 1436 (1974). (13)W. P. Jencks and J. Regenstein, "Handbook of Biochemistry", 2nd ed, H. A. Sober, Ed., Chemical Rubber Publishing Co., Cleveland, Ohio, 1970, p J-150. (14) L. F. Blackwell. A. Fischer, I. J. Miller, R. D. Topsom, and J. Vaughan, J. Chem. SOC.,3586 (1964). 15) W. P. Jencks, J. Am. Chem. SOC.,94,4731 (1972). 16) B. A. Cunningham and G. L. Schmir, J. Am. Chem. SOC.,88,551 (1966); R. K. Chaturvedi and G. L. Schmir, ibid., 90,4413(1966);T. Okuyama, T. C. Pletcher, D. J. Sahn. and G. L. Schmir, ibid., 95, 1253 (1973);T. Okuyama. D. J. Sahn, and G. L. Schmir, ibid., 95,2345 (1973);R. E. Barnett and W. P. Jencks, ibid., 91,2356 (1969). 17) M. Eigen, Discuss. Faraday Soc., 39, 7 (1965).
16) P. Deslongchamps, Tetrahedron, 31,2463 (1975). 19) E. Grunwald, P. J. Karabatsos, R. A. Kromhont, and E. L. Purlee, J. Chem. Phys., 33,556 (1960);E. Grunwald and S. Meiboom, J. Am. Chem. SOC., 85,2047(1963);D. D. Eley, A. S. Fawcett, and M. J. Hey, J. Chem. Soc., Faraday Trans. 7, 399 (1973);J. Hine, J. Am. Chem. Soc., 94,5766(1972); E. Grunwald, Prog. Phys. Org. Chem., 3,317(1965); S. Rosenberg, S.M. Silver, J. M. Sayer, and W. P. Jencks, J. Am. Chem. Soc., 98, 7966 (1974). (20)When proton transfer is half rate determining the rates of the forward and back reactions are e ual, i.e.. k-,[H+] = k2 in eq 7.Since k-, = k c K ~ / K c = 2 X 1O'O X 10-3Q/100.4 = 2.5 X 106M-'s-' (KAand KC are defined in eq 6),k2 = X 2.5 X IO6 = 5 X IO3 s-'. (21) J. P. Fox and W. P. Jencks, in preparation. (22)W. P. Jencks, "Catalysis in Chemisby and Enzymology", McGraw-Hill, New York, N.Y., 1969,pp 542-548;S.J. Benkovic. T. H. Barrows, and P. R. Farina, J. Am. Chem. Soc., 95, 6414 (1973). (23)W. P. Bullard, L. J. Farina, P. R. Farina, and S. J. Benkovic, J. Am. Chem. SOC., 96,7295 (1974). (24)T. H. Barrows, P. R. Farina, R. L. Chrzanowski, P. A. Benkovic. and S. J. Benkovic, J. Am. Chem. SOC., 98,3676 (1976). (25)E. S. Hand, unpublished experiments. (26)L. do Amaral, W. A. Sandstrom, and E. H. Cordes, J. Am. Chem. Soc., 88,
2225 (1966).
A Method of Synthesis of @-Methylfuransand a-Methylene and @-Methyleney-Lactones. Two Menthofuran Syntheses' Ernest Wenkert,** Miguel E. A l ~ n s o Brian ,~ L. Buckwalter, and Kechia Joseph Chou Contribution from the Department of Chemistry, Indiana University, Bloomington. Indiana 47401. Received December 10, 1976
Abstract: The copper-catalyzed thermolysis of a-diazo-0-dicarbonyl compounds, diazoacetylacetone, methyl diazoacetoacetate, and dimethyl diazomalonate, in the presence of enol ethers of an aldehyde and a ketone is described. The first two diazo compounds produce 5-alkoxy-3-acyl-4,5-dihydrofurans, while diazomalonic ester is transformed into a cyclopropane derivative with the first enol ether and into an olefinic equivalent with the second enol derivative. The diazomalonate-derived products are convertible into 0-methylfurans or their methylene lactone equivalents by simple reduction, oxidation, and isomerization operations. A method for the regioselective synthesis of one enol ether of 0-methylcyclohexanone is introduced and the product converted into menthofuran by the above diazomalonate-initiated scheme as well as by a photolysis of methyl a-diazopropionate in its presence, followed by reduction, oxidation, and acid-induced dealcoholation.
As part of an ongoing program of study of the use of 8oxycyclopropylcarbonyl compounds, prepared by the interaction of diazomethyl ketones and carboxylates with enol ethers or esters, in organic ~ y n t h e s i s , ~especially -~ directed toward terpenic natural product^,^ a n investigation of the chemistry of functionally more complex a-diazoketo systems was initiated.8 The present paper deals with a-diazo-6-dicarbony1 compounds and their use in the construction of the 0methylfuran (I), a-methylene y-lactone (2), and &methylene y-lactone (3) units, common to many furanoid terpene^.^
Journal of the American Chemical Society
/
99:14
M 0
1
33
@o 2
3
The aldehyde and ketone enol ethers ethoxymethylenecyclohexane (4) and 1-methoxycyclohexene (5), respectively, served as substrates for 3-diazo-2,4-pentanedione(6),1°methyl 2-diazo-3-oxobutanoate (7),l I and dimethyl diazomalonate
/ July 6, I977
