June 5, 1961
COMMUNICATIONS TO THE
a t 2.90 and 5.78 p ) . Conversion to the a-hydroxymethylene-&lactone Vb (not purified) was managed by treatment of Va with methyl formate in the presence of excess sodium triphenylmethyl in dioxane. Upon being heated in refluxing methanolic hydrogen chloride,6 the hydroxymethylene lactone was transformed readily t o the dihydroInfrared pyran carboxylic ester (m.p. 222-225'). spectral comparison (chloroform solution) of authentic ajmalicine with the base thus produced demonstrated the latter to be dl-ajmdli~ine.~ Proper utilization of certain intermediates described above should permit establishment of the complete stereochemistry of ajmalicine and other hetero-ring E indole alkaloids, and such studies are now under way in this Laboratory.
E. E.
VAN
x, ,,CHS
a
,CH3
v -
(7) Complete spectral, physical, and analytical data will he recorded in the full paper to be published. (8) Allied Chemical Corporation (Plastics Division) Fellow, 19591080.
MADISON,WISCONSIN
2595
was added over a period of ten minutes. The exothermic reaction brought the solution to reflux temperature (65') and this temperature was maintained for an additional ten minutes. The reaction mixture was poured into Dry Ice and worked up in the usual manner to yield the optically active acid I1 (0.766 g., 3870), [ t r I z 3 ~5.3 f 1.2' (c, 2.173). The infrared spectrum of the acid was identical in all respects with that of an authentic sample4 and its rotation represents an optical purity of 14 f 2%. A neutral fraction (0.624 g., 38%) was obtained and shown to be l-methyl-2,2-diphenyIcyclopropane by its b.p., infrared spectrum and retention time on vapor phase chromatog~ j= raphy. The hydrocarbon 111, [ a I z 3-13.6 1.2', was 11 f 2% optically pure.
Acknowledgment.-The authors are grateful to the National Institutes of Health (RG3892) and to the Wisconsin Alumni Research Foundation for financial support; to Mr. Ian G. Wright for the preparation of starting materials; and to Dr. Thomas A. Spencer, Jr., who first isolated intermediate IVb. (8) F. Korte and R. H. Bochel, Angcv. Chcm., 71,709 (1959).
DEPARTMENT OF CHEMISTRY UNIVERSITY OF WISCONSIN
EDITOR
f
l
-
0O , H
+ ,,CH3
TAMELEN
C.PLACEWAW
RECEIVED APRIL19, 1961 (-) - I11
CYCLOPROPANES. X. AN OPTICALLY ACTIVE GRIGNARD REAGENT'
In another experiment an excess of magnesium powder was treated with a solution of ethylene Sir: dibromide in tetrahydrofuran until gas evolution To date, all previous attempts to prepare opti- ceased and then a solution of I in tetrahydrofuran cally active Grignard reagents from optically active was added slowly, over a period of 40 minutes, in halides have been unsuccessful2. We wish a t this order to maintain the temperature between 25time to report that optically active (+)-1-bromo-1- 27'. Carbonation of the reaction mixture gave methyl-2,2-diphenylcy~lopropane~ reacts with mag- these results: Acid 11 was isolated in 45y0 yield nesium to form a Grignard reagent which on carbon- and was 12 A 2% optically pure: Hydrocarbon I11 ation followed by hydrolysis produces optically was obtained in 36y0 yield with an optical purity ( - ) -l-methyl-2,2-diphenylcyclopropane- of 10 =I=2%. active Since (+)-I has been related to (-)-I1 and (-)carboxylic acid (11)5 and (-)-l-methyl-2,2-diphenylcyclopropane. This result represents the I11 the stereochemistry of the over-all reaction is first example of an optically active Grignard that of retention oE configuration.a*s A similar stereochemical result is obtained when l-methylreagent.6 Magnesium powder (0.5 8.) and 2.30 g. of I, 2,2-diphenylcycloprop yllithi~m~ (by reaction of butyllithium with (+)-I) is carbonated to yield [a:]% f106 f 1' (c, 2.229)R, were placed in 12 There is, however, an ml. of tetrahydrofuran and a solution of 0.5 mi. of (-)-I1 and (-)-111) important difference in these two reactions. ethylene dibromide' in 2.5 ml. of tetrahydrofuran Whereas carbonation of the lithium reagent gives (1) This work was supported in part b y a grant from the National 1 0 0 ~ oretention of configuration and activity, the Science Foundatlon and i n part by R grant from the U. S. Army Grigriard reagent yields only cu. 12% retention of Research O5ce (Durham). (2) R. € Pickard I . and J. Kenyon, J . Chcm. Soc.. 99, 45 (1911); activity and 56% retention of configuration. Since a carbon-magnesium bond has less ionic character A. M. Schaartz and J. R. Johnson, J . A m . Chcm. Soc., 63, 1083 (1931); C. W. Porter, ibid., 67, 1436 (1935); H. L. Goering and B. H. associated with i t than does the carbon-lithium McCarron, ibid., 80,2287 (1958). bond,'O one might have expected a high retention (3) H. M. Walborsky and F. J. Impastato, ibid., 81, 5835 (1969). (4) F. J. Impastato, L. Barash and H. M. Walhorsky, ibid., 81, 1514 (1959). (6) For the constitution of Grignard Reagents see, R . E. D e s y and G. S. Handler, ibid.# 80,6824 (1958). (6) All rotations were taken in chloroform solution. (7) D . E. Pearson, D. Cowan and J. D. Beckier, J . Org. Chcm., P4, 504, (1958).
(8) H. M. Walborsky, L. Barash. A. E. Young and F. J. Impastoto, J . A m . Chem. SOC.,88,2517 (1981). (9) I t has been demonstrated that (-)-I11 is formed hy reaction of 2,2-diphenylcyclopropyllithium with the solvent (unpublished results). (IO) L. Pauling, "The Nature of the Chemical Bond," Cornel1 University Press, Ithacs, N. Y., 1980.
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BOOKREVIEWS
of activity for the Grignard reagent. The fact that a large amount of racemization was obtained suggests that racemization is occurring in the Grignard formation step. Further work pertaining to the mechanism of
Vol. 83
Grignard formation as well as to the optical stability of organometallics is now in progress. DEPARTMENT O F CHEMISTRY FLORIDA STATE UNIVERSITY H. 31,WALBORSKY TALLAHASSEE, FLORIDA A. E. YOUNG RECEIVED APRIL 7, 1961
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BOOK REVIEWS Modern Probability Theory and its Applications. By studies of the physiological effects of insulin in the face of EMAKUEL PARZES, Associate Professor of Statistics, pressing problems in the commercial production of the lifeStanford University John SYiley and Sons, Inc., 4-10 saving hormone. Supplementing a never-tiring description Fourth Avenue, New York 16, S.T. 1960. xv 464 pp, of his classical work on insulin structure, the article by F . 15.5 X 23.5 em. Price, $10.75. Sanger is followed by a n excellent treatment by Ieuan Harris on the structures of oxytocin, vasopressin, corticotropin The title of this book should perhaps be: Introduction to Probability Theory, since by mathematical standards i t is a and MSH with emphasis on the relation of structure and amino acid replacements t o biological activity. Of theofirst undergraduate textbook. Content : Chapter I, Probaretical interest but also of great practical import are the bility Theory as the Study of Mathematical Models of articles dealing with the measurement of insulin concentraRandom Phenomena; Chapter 11, Basic Probability Theory; tions, the metabolic fate of insulin and the presence of Chapter 111, Independence and Dependence; Chapter IV, insulin antagonists and antibodies in blood. These subSuxnerical-Valued Random Phenomena; Chapter V, Mean jects comprise five articles by G. A. Stewart, A. J. Kennep, and Variance of a Probability Law; Chapter VI, Normal, P. J. Randle and K . W.Taylor, J. Vallance-Owen, and Poisson, and Related Probability Laws; Chapter VII, P. H.Wright. Random Variables, Chapter VIII,Expectation of a Kandom There follows a group of four articles concerned with the 1-ariable; Chapter I X , Sums of Independent Random action of insulin on metabolism, particularly at the tissue 1-ariables; and Chapter X, Sequences of Random Variables. and enzyme levels. I n weighing many reports, R . B . Fisher The knowledge of Lebesgue integration is not assumed. is led toward the conclusion t h a t the stimulation of carboSome theorems are stated without proof, the author usually hydrate metabolism is through the increased transport of pointing out this fact carefully. The book is written vividly, glucose into the cell, while S. J. Folley and A. L . Greencontains interesting bibliographical and historical remarks. haum present the case for a possible primary role of insulin Some points worth mentioning: Detailed treatment of elements of combinatorics in Chapters 1-11; definition of con- in the synthesis of fatty acids, and A. Korner and I;. L. 5Ianchester gather information which indicates a direct ditional probability of a n event given a randon; variable, cffect of insulin on the biosynthesis of protein. Finally P. without use of the Radon-Sikodym theorem, Chapter VII; J . Randle and F. G . Young provide a critical and provocaan article on the measurement of the signal-to-noise ratio of a random variable, Chapter VIII; treatment of convergence tive paper with a unifying concept of insulin action based on its effect on cell permeability, which may account in in distribution by the method of characteristic functions, ways not entirely clear a t the present time, for the apparent including in Chapter IX the proof of the inversion formulas diversity of actions of insulin on metabolism. for characteristic functions, in Chapter X the proof of the The issue is concluded with articles by R . Fraser 011 the “continuity theorem of Probability Theory.” A trivial interplay of insulin with other hormones, by 1%’. Oakley on flaw: the definition of a function, p. 269, is not correct. types of insulin available for clinical practice, and finally In conclusion, it may be appropriate to compare this work the xrticles on the chemistry of the newer hypoglycemic agents with the classic treatise in the field, Feller’s “Introduction (I
