2594
COMMUNICATIONS TO THE EDITOR
Vol. 83
A characteristic of iron pentacarbonyl is the reaction i t undergoes on irradiation to produce diiron nonacarbonyl and carbon monoxide. Accordingly, the pseudo-iron pentacarbonyl Mn (C0)cNO was irradiated in an attempt to obtain Mnz(C0)7(N0)2, a compound analogous to Fe2(C0)9. This treatment gave heptacarbonyldinitrosyldiI1 manganese (30% yield) as deep red crystals carbon (decomp. without melting a t -140°), monoxide, and lesser amounts of manganese carbonyl and carbonyltrinitrosylmanganese. Heptacarbonyldinitrosyldimanganese(O), very air sensitive, subliming a t 25' (0.1 mm.), and exceedingly difficult to purify from manganese carbonyl, probably has a structure analogous to that of Fez(CO)9,10 CH300C/ I11 viz., ON(CO)2Mn(CO)gMn(CO)sNO, with some metal-metal bonding between manganese atoms. in tert-butyl alcohol, providing the lactam I11 in The infrared spectrums shows carbonyl stretching nearly quantitative yield.6 Although the lactain bands a t 2101 (w), 2042 (vs), 2006 (vs), 1995 was found to be neither distillable nor crystallizable, (w, sh) and 1976 (s) an.-'. Bands in the bridging i t could be purified by column chromatography; carbonyl region and the nitrosyl stretching region material so obtained displayed consonant spectral occur a t 1743 (m), 1735 (m), 1731 (w), 1726 (w) properties (infrared absorption a t 2.88, 5.75, 5.80 and 1710 (m) cm.-'. and 6.09 p) (A, 221,276,284 and 292 mp) and was (10) H. M. Powell and R. V. G . Ewens, J . Chem. Soc.. 286 (1939). suitable for the succeeding steps. (11) National Science Foundation Predoctoral Fellow. First of all, ring-C was fashioned, carried out by DEPARTMENT OF CHEMISTRY P. M. TREICHEL~' means of phosphorous oxychloride closure to the HARVARD UNIVERSITY E. PITCHER CAMBRIDGE 38 R. B. KING^^ tetracyclic A3-dehydro base (P02C12- salt, m.p. MASSACHUSETTS F. G. A. STOXE RECEIVED APRIL5, 1961
CH3
THE TOTAL SYNTHESIS OF (EL-AJMALICINE
Sir : Of the numerous and widely distributed Eheterocyclic indole alkaloids, the Rauwolfia component ajmalicine (tetrahydroserpentine, &yohimbine) (I),I a peripheral vasodilator effective in the
I treatment of angina and other physical disorders, is a notable example. I n this Communication, we summarize operations leading to dl-ajmalicine, which represent the first synthesis of a member of this important natural product group.2 I n a key step which roughly parallels the presumed biogenetic p r o c e s ~ ,the ~ essentials of the desired alkaloidal system are efficiently assembled a t the outset: tryptamine, formaldehyde and the keto triester 114 undergo a Mannich condensation (1) Isolation and characterization: (a) S. Siddiqui and R . H. Siddiqui, J . Ind. Chem. SOL.,8 , 667 (1931); 9, 539 (1932); 1'2, 37 (1935); 16, 421 (1939); (b) H. Heineman, Bcr., 67, 15 (1934). Gross structure: R. Goutarel and A. LeHir, BUR. SOC.rhim., 18, 809 (1951). Partial stereochemical structure: (a) E. Wenkert and D. K. Roychaudhuri, J . A m . Chem. SOC.,79, 1519 (1957); 80, 1613 (1958); (b) N . Neuu and H. E.Boaz, J . Org. Chmm., 22, 1001 (1957). (2) First announced (March 28, 1961) at the 139th Meeting of the American Chemical Society, St. Louis, Missouri. (3) E. Wenkert and N. V. Bringi, J . Am. Chcm. SOC.,82, 1474 (1959). (4) Secured through Michael addition of methyl acetoacetate to dimethylglutaconate (cf. M. H. Dreifurs and C. K. Ingold, J. Chrm. SOC., ips, 2964 (1923).
I
ROOci
CH,
0 (X -H) Vb (X = =CHOH)
IVa (X = -COOCHI; R = -CHa) IVb (X = -H; R = -H)
\'a
148-150') (A,,, 247, 358 mfi, B = 11,900; 23,500) and then reduction over palladium-on-carbon in ethanol to the keto diester IVa (HCI salt, m.p. 152.5-154'). Removal of the ester function from the @-keto ester moiety was accomplished next, effected by prolonged heating of the keto diester IVa in refluxing dilute hydrochloric acid. The resulting keto acid IVb, isolated and purified as the hydrochloride (m.p. 236.5-23So), was accompanied by varying amounts of diacid (m.p. 268-269') formed by acid-catalyzed deacetylation of IVa. I n preparation for the construction of the E-ring, keto acid IVb was reduced with sodium borohydride to the hydroxy acid (m.p. 248-251°), which, on treatment with N,N'-dicyclohexylcarbodiimide in pyridine, was converted to the 6-lactone Va (HC1 salt, m.p. 236-238') (infrared absorption (5) Use in this case of traditional Mannich conditions, uis., formaldehyde, active hydrogen component and amine in an acidic medium, leads t o formation of tetrahydro-8-carboline (i), but no product of the type 111. When the reaction is carried out in Icrt-butyl alcohol and
cx$Li H i in the abrracs of added acid, formation of tetr8hydro-#-carboline 11 suppressed, and lactam 111 is produced instead. These observations will be treated appropriately in the future full publication.
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.
