March 5, 1964
COMMUNICATIONS TO THE EDITOR
phenyl radicals generated in this manner attack the neutral ferrocene molecule (eq. 3) seems improbable on energetic g r o ~ n d s ,and ~ Little and Clark2 accordingly formulated the phenylation reaction as proceeding by radical substitution of the ferricenium ion (eq.
953
proceed through the same intermediate, and whether this intermediate plays a part in oxidation-reduction equilibrium reactions (e.g.,eq. 5 ) , are problems currently undergoing investigation in these laboratories.
4).
FcH + Ph. +FcPh + H. (3) FcH+ + Ph. +FcPh + H + (4) Recently, these suggestions have been discounted by Rosenblum and his c o - ~ o r k e r s ,who ~ claim t h a t neither ferrocene nor the ferricenium ion reacts with I IT free phenyl radicals derived from phenylazotriphenylmethane, and who suggest that the mechanism of the Ferricenium ion also undergoes substitution by free phenylation reaction involves intermediate formation phenyl radicals generated oxidatively from phenyland intramolecular rearrangement of a ferrocenehydrazine." When the latter (0.023 mole) was diazonium salt charge-transfer complex. Nevertheslowly added with stirring to the blue solution obtained less, the most recent work has demonstrated the high by mixing ferrocene (0.007 mole) and silver oxide reactivity of ferricenium ion toward attack by free (0.022 mole) in acetic acid, phenylferrocene and 1 , l ' alkyl radicals6 and has verified the production of free diphenylferrocene were obtained in yields of 37% aryl radicals during the arylation r e a c t i ~ n , ~ both ,~ and 2% (based on unrecovered ferrocene), respectively. of which observations provide indirect evidence for The yield of disubstituted product was increased to the mechanism suggested by Little and Clark.2 In 9% when a large excess of phenylhydrazine and support of this mechanism we now describe the first silver oxide was employed. In benzene the reaction unequivocal example of free-radical phenylation of proceeded less efficiently but the concomitant formaferricenium ion. tion of biphenyl and terphenyl verified the presence When ferricenium borofluoride (0.011 mole) and of free phenyl radicals in the reaction mixture. Other phenylazotriphenylmethane (0.011 mole) in acetic oxidizing agents, e.g., mercuric oxide, benzoquinone, acid were maintained a t 75' for 1.5 hr. nitrogen was also afforded phenylferrocene in small yield. evolved and the characteristic color of the ferricenium In view of the recent report13 that oxidation of ion faded. The products isolated were phenylferrocene ferrocene with phenylmercuric acetate in the presence (0.002 mole) and triphenylcarbinol (0.006 mole) of perchloric acid affords phenyl radicals and ferricentogether with small amounts of tritylferrocene,s triium ion, we repeated this reaction in expectation of phenylmethane, and tetraphenylmethane. Some ferobtaining phenylferrocene. However, when the rerocene (0.004 mole) was recovered. Since i t has been actants were mixed in acetic acid-toluene, the only demonstrated previously that phenylazotriphenylwere benzene and ferricenium ion and no methane is without effect on neutral f e r r o ~ e n e , ~ ~products ~,~ phenylferrocene was formed. We were unable t o there can be little doubt that the formation of phenyldetect bibenzyl and other compounds characteristically ferrocene in the present instance represents an auformed by attack of phenyl radicals on toluene.14 thentic example of free-radical phenylation of ferricen Also, the reported formation of benzene in quantitative ium ion. yield in this reaction is inconsistent with a free-radical The mode of formation of tritylferrocene is less mechanism. I t thus appears that reduction of phenylobvious. The production of triphenylcarbinol sugmercuric acetate with ferrocene does not involve gests that ferriceniurn ion and triphenylmethyl radical generation of free phenyl radicals. participate in the following oxidation-reduction equilibrium (eq. 5), the occurrence of which in the reverse (12) R. L. Hardie and R H . Thomson, J . Chem. Soc., 2512 (1957). (13) C. H . Wang, J . A m . Chem. Soc., 86, 2339 (1963). direction has been observed earlier by Hawthorne.lo (14) D. H . Hey, B. W. Pengilly, and G . H. Williams, J . Chem. Soc., 6 FcH* Ph3C. [ F c H C P ~* ~ ] FcH + PhSC+ ( 5 ) (19551, 1463 (1956); C. S. Rondestvedt and H. S. Blanchard, J . A m . C h e m . Soc., 77, 1769 (1955). If, as seems possible. formation of tritylferrocene represents an alternative and irreversible mode of decomDEPARTMENT O F ORGANIC CHEMISTRY A. L.J. BECKWITH UNIVERSITY O F ADELAIDE R . J. LEYDON position of the intermediate complex in the above equiSOUTH AUSTRALIA ADELAIDE, librium, it is no longer meaningful to distinguish beRECEIVED DECEMBER 23, 1963 tween free-radical and electrophilic substitution in this system. I t may be significant t h a t our experiment when The Chemistry of Cleavamine : A Novel Transannular carried out for 24 hr. afforded 1 , l'-ditritvlferrocene8 Cyclization Relating to Biosynthesis of Aspidosperma but no triphenylcarbinol. Other products were unAlkaloids changed. Little5 has suggested that either of the structures Sir : (I or 11) may represent the intermediate complex in Recently, in connection with our interests in alkaloids free-radical substitution of ferricenium ion. Both from Vznca rosea Linn, we established the structure are of special interest in that, as drawn, they are idenof cleavamine (I)' as one of the acid rearrangement tical with hypothetical intermediates in electrophilic products of catharanthine The close structural substitution of the neutral ferrocene molecule. l 1 relationship of cleavamine t o the known alkaloid Whether, in fact, free-radical and electrophilic subq ~ e b r a c h a m i n esuggested ~ its use as an excellent model stitution of ferricenium ion and ferrocene, respectively, for evaluating some of the reactions proposed in the (7) C f . C. Walling, "Free Radicals in Solution,'' John Wiley and Sons. Inc., biosynthesis of Aspidosperma alkaloids
+
New York. N . Y . , 1957, p. 482. (8) E. W. Neuse and D. S. Trifan, J . A m . Chem. Soc., 84, 1850 (1962). (9) C D. Broadhead and P. L. Pauson, J . Chem. Soc., 367 (1955). (10) M. F. Hawthorne, J . Org. Chem., 31, 363 (1956). (11) M. Rosenblum, J. 0. Santer, and W. G . Howells, J . A m . Chem. Soc., 86, 1450 (1963).
(1) J P K u t n e y , J Trotter, T Tabata, A Kerigan, and N Camerman Chem I n d i l o n d o n ) , 648 (1963) (2) N Neuss and M Gorman, Telrahedron Leltevs, 206 (1961) (3) K Biemann and G Spiteller, J A m Chem Soc 84, 4578 (1962) and references cited therein
COMMUNICATIOXS TO THE EDITOR
954
Vol. 86
Wenkert4 proposed an elegant scheme for this class of alkaloids and his postulate involved the transannular cyclization of an ionic intermediate such as 11. This attractive proposal is of considerable interest but up to this time it has received no experimental verificat i o n s We wish now to report the first laboratory realization of such a cyclization to provide the Aspidosperma skeleton in very reasonable yield.
276 (3.59), and 287 (3.47)] so t h a t the spectrum was now in excellent agreement with that of demethoxypalosine. lo The n m r . spectrum of the acetylated product indicated the expected change in the aromatic region. The complex pattern originally observed in the spectrum of IV had collapsed to form a broad unresolved peak (area corresponding to three protons) centered. a t 7.15 p . p . m ~ ,while a single proton signal (C-17 hydrogen) was evident downfield a t 8.15 p.p.tn, (poorly resolved multiplet). These data are again in excellent agreement with those of vindolinineB and demethoxypalosine. lo Most important, the typical quartet (centered a t 4.02 p.p.m.) associated with the C-2 hydrogen atom and the "aspidospermine fingerprint" (2.9-3.3 p.p.m.) shown to he characteristic of the Aspidosperma skeleton by Djerassi and co-workersll was also evident. I II Any definite conclusions regarding the stereochemistry in I V must await an X-ray analysis which we hope to initiate in the near future, but some tentative proposals may be made from the above evidence. One significant feature evident in the mass spectrum of IV is the relative intensity of the M - 1 peak, which is considerably stronger than observed in the spectra of most Aspidosperma alkaloid^.^ It is interesting t h a t very recently Djerassi12 has observed a strong R M - 1 peak in an isomeric deacylcylindrocarpine derivaE ,R=H tive and suggests the loss of the C-19 hydrogen atom assisted by a trans electron pair on N b . Also, in the P , R=Ac n.m.r. spectrum of V, the quartet for the C-2 hydrogen atom occurs a t higher field than normally observed.ll Dihydrocleavarnine (111) on reaction with mercuric This suggests either a different stereochemistry a t this acetate in acetic acid a t room temperature (81y0 position or at other asymmetric centers so t h a t the recovery of mercurous acetate by weight) followed by over-all conformation of V provides for increased reflux provided a crude mixture (A,";:" 222, 275 shielding of the C-2 proton as compared with t h a t of (very broad), and shoulder a t 288 nip), which was not the aspidospermine or the antipodal pyrifolidine purified further but immediately subjected to reducseries.l3,l4 Finally if one assumes that the stereotion with lithium aluminum hydride. The latter chemistry previously established for cleavamine' remixture by chromatography on alumina afforded a mains unaltered during the cyclization, then the stereocrystalline material as the major product (30% yield), m.p. 128-129' (from acetone), [ c Y ] * ~ D- 10j' (CHC13). chemical center denoted by C-5 is already defined. We feel t h a t the laboratory demonstration of this The cyclic structure IV was established for this substance on the basis of the following evidence : C19H26N2, transannular cyclization has numerous interesting facets both from a biogenetic and a synthetic standmol. wt. 282 by mass spectrometryfi; ":A;: 242 mp point. It certainly provides strong support for Wen(log E 3.78) and 294 (3.42),"::A: 223 mp (log t 3.52) kert's biogenetic proposals for the Aspidosperma and 269 (2.98, unsubstituted dihydroindnle) ; n.m.r. alkaloids4 The obvious extension of this reaction to spect.runi7 showed a complex pattern of lines between the quebrachaniine series is anticipated when we ob6.4 and 7.3 p.p.m., area = 4H (aromatic protons, in tain sufficient quantities of this alkaloid. excellent agreement with known systems),8 0.9 p.p.m. Finally, it is apparent from the nature of the above (triplet, area = 3H); mass spectrum showed significant cyclization that a carbomethoxydihydrocleavainine 281 (RI - 1),254 (M - 2S), 152, peaksatmie282 (Mi), derivative possessing a carbomethoxy group a t C-3 144, 138, 130, and a very strong peak a t m!e 124. , to reduction (see 111) could lead directly ( k , prior The mass spectrum, with the exception of the intensity with lithium aluminum hydride) to the unsaturated of the M - 1 peak (discussed later), was virtually idenester systeni present in such alkaloids as vincadiffortical with t h a t of aspidospermidine (alkaloid %%A). g mine's and the related Akuamma alkaloids. We Further evidence for the Aspidosperma skeleton (1V) hope to present some evidence in this direction in the was obtained from the N-acetyl derivative V, C21near future. H2sN20,m.p. 99-100' (petroleum ether, b.p. 61)-SO'). Acknowledgment.--We are greatly indebted to ProThe expected alteration in the ultraviolet spectrum fessor Carl Djerassi, Stanford University, for the 253 rnp (log t 3.13), 280 was indeed observed [A":': mass spectroinetric nieasurements. Financial aid from (3.61), and 2S9 (3.53); A,",:" 220 mp (log E 3 . 5 2 ) , the National Cancer Institute of Canada and the Na-
m
( 4 ) E . Wenkert, J . A m Chrm Soc , 8 4 , 98 (1962). (;i) Biemann a n d Spitellera provide mass spectrometric evidence for a cyclization of quehrachamine during a high temperature zinc dust distillaThey visualize a participation of a free-radical process. tion ( 6 ) Satisfactory elemental analyses were ohtained for all substances reported ( 7 ) All n m.r spectra were measured in deuteriochloroform with tetramethylsilane a. the internal standard using a Varian A60 spectrometer. All signals drc reported as 6-units ( c p s /60) in p p rn (8) See, for example. C . Djerassi, S. E . Florei, H. Budzikiewicz, J. M Wilson, 1. J Durham J 1.e h l e n , h l . >I Janot. h.i Plat, M Gorman. and N . S e u s s . P i o c Yo11 Acnd Scz C S . , 48, 113 (1062) (9) K. Biemann. hi. SFiteller-Friedmann, and G. Spiteller, J A m . Chem S o c , 86, 631 (1963).
(10) B. Gilbert, J . A Brissolese, J . M Wilson, H. Budzikiewicz, I, J . Durham, and C. Djerassi, Chem f n d . (London). 1940 (1962). (11) C. Djeraqsi, A . A P G Archer, T George, B Gilbert, J N. Shoolery. and I,, I). Johnson, E x p r i e n l i a , 16, 532 (1960) 112) K S Brown, H Budzikiewicz, and C Djeracci. T e l r o h e d v o n I d I I r r s , 1731 (1963) (17) C. Djeraesi. B Gilbert, J . N Shoolery. I. F Johnson, and K. Biem a n n , E x p r r i e n l i n , ll, 162 (1961) (14) M Plnt, J. Le .Men. M M Janot, J . M . Wilson, H. Budzikiewicz, I,, J Durham. Y S a k e g a w a , and C Djerassi. 7'eluahedron L e l l r v s , 271 (1962) (1.5) C Djerassi, H. Budzikiewicz, J. M . Wilson. J Gosset, J I,e Men, and M M . Janot. ibid.. 23.5 (1962).
COMMUNICATIONS TO THE EDITOR
March 5 , 1964
tional Research Council of Canada is gratefully acknowledged. CHEMISTRY DEPARTMENT JAMES P. KUTNEY UNIVERSITY OF BRITISHCOLUMBIA VAXCOUVER 8, CANADA
hv 0 CHICHOHCHD
YH31 P H-C-C-C-0-C-H I
I
CH3 CH3 I
Photolysis of Tetramethyl- 1 ,J-cyclobutanedione Potentially, the photolytic decarbonylation of tetrasubstituted 1,3-cyclobutanediones in solution or in the gas phase is an attractive and simple route to substituted cyclopropanones, either as stable species or as intermediates. Photodecarbonylation reactions are well known in the gas phase,' b u t they usually occur with very low efficiencies in solution. * However, irradiation of a benzene solution of tetramethyl-1 ,3cyclobutanedione (I) through Pyrex leads to the rapid evolution of carbon monoxide and the formation of tetramethylethylene in 80yo net yield. The quantum yield for disappearance of I under these conditions is 0.4 a t 3660 f i . Apparently, a small amount of dimethyl ketene is also produced since the photolyzed solution quickly develops a yellow color and a strong band in the infrared3a t 4.7 p. Addition of a few drops of isopropyl alcohol to the irradiated solution results in disappearance of both the yellow color and the 4.7 p band.
CH3 I I
+
I1
T3f:
CH3 / H-C-C-0-C-H / \ CH3 CH3 product, the methyl ester 111 (methyl 2,P,B-trimethylbutyrate), the quantum yield for disappearance of I being 0.5. 111 possesses an n.m.r. spectrum consisting of a sharp singlet a t 3.40 p.p.m. (3 protons), a septet centered a t 1.G p.p.m, (one proton), a sharp singlet a t 0.82 p.p.m. (6 protons), and a doublet centered a t 0.60 p.p.m. (0 protons). Anal. Calcd. for CeHleOz: C, 6G.6; H, 11.2. Found: C, 6&7; H, 11.2. Methyl isobutyrate is also fornied as a major product upon irradiation of I in methanol. These results show that a t least two paths for reaction are possible during the photolysis of I : (a) a bis-fragmentation without decarbonylation to yield dimethyl ketene5; and, more importantly (b) decarbonylation to yield products which are consistent with the intermediacy of either tetrainethylcyclopropanone (IV), or the diradical resonance hybrid (V), or a combination of both. The intermediate decarbonylates in CO
Sir :
"*
CH3
CH3 CH3
EDWARD PIERS
RECEIVED DECEMBER 27, 1963
CH3, ,CH3
C F
955
+
0
0
,CH3
F=GCHI
t 2co
(1)
CH3
IV
I
Irradiation of I in isopropyl alcohol leads to rather different results, as no tetramethylethylene is produced (although carbon monoxide is still formed), and several products appear in the vapor chromatogram of the irradiated solution. The quantum yield for the disappearance of I in this case is 0.5. The two major products of the photolysis, both formed in about 30yo net yield, are isopropyl isobutyrate (presumably formed by addition of isopropyl alcohol to dimethyl ketene) and compound 11. The latter was obtained pure by preparative V.P.C. and possesses an n.m.r. spectrum4 consisting of two septets centered a t 4.8 (one proton) and 1.65 p.p.m. (one proton), two doublets centered at 1.10 (six protons) and 0 . 7 0 p.p.m. (six protons), and a. singlet at 0.90 p.p.m. (six protons). This spectrum, as well as the infrared spectrum of the compound, is completely consistent with I1 being the ester isopropyl 2,2,3-trimethylbutyrate.A nul. Calcd. for CloHzoOz: C, 69.6; H , 11.7. Found: C, 69.2; H, 11.8. In methanol, competing reactions similar to both eq. 1 and 2 take place, with formation of both tetramethylethylene in about 5% net yield and, as the major (1) W. A. Xoyes, Jr.. G . Porter. and E. J . Jolley, Chem. Rea., 66, 49 (1956); J . h' Pitts, J . Chem E d u c . . 34, 112 (1957). (2) Numerous reports concerning photodecarbonylations in solution have appeared recently. I< H . Eastman. J . E . Starr. I t . S t . Martin, and M K . Sakata. J . Org. Chem , 88, 2162 (1963); 0. I,. Chapman, D. J . Pasto, G. W . Borden. and A. A . Griswold, J . A m . Chem. S O L . , 84, 1220 (1962): D . C England, i b i d . , 84, 2205 (1962); G . Quinkert, K . Opitz, and J. Weinlich, Angezu Chem., 74, 507 (1962); C . D . Gutsche and C. W Armhruster, Tetrohedion Letters, No. 96, 1297 (1962): K . Mislow and A . J. Gordon, J . Ant Chem Soc.. 86, 3521 (1963); G . Quinkert, K Opitz, and V Weinlich, Tefrnhrdros Letfevs. 1863 (1963); P A . Leermakers, P. C . Warren, and G . F. Vesley, J . A m . Chem. S O L in , press. (3) Dimethyl ketene possesses a strong intrared absorption at 4.7 p , [ R . A Holroyd and F. E. Blacet, ibid., 79, 4830 (1957)l. (4) N.m.r. spectra were taken at 60 M c . in carbon etrachloride, employing tetramethylsilane as an external standard.
V
inert solvents6 to give good yields of tetramethylethylene, while in nucleophilic solvents, such as alcohols, addition to form the respective 2,2,3-trimethylbutyrate esters competes with decarbonylation. I t is not clear at this time why isopropyl alcohol should be more efficient in this capacity than methanol. Piperylene ( 0 . 3 M), a quencher of triplet states of energy greater than 55 kcal.,' has virtually no effect on the photolysis of the diketone in both benzene and alcohol solvents, and benzophenone was ineffective a t sensitizing the photoreaction. Although we have not yet obtained a low temperature emission spectrum of the compound, these results (while not rigorously excluding the triplet) are consistent with the assumption t h a t the above reactions occur only from the singlet state. Preliminary experiments on the photolysis of I in the vapor phase reveal t h a t tetramethylethylene, a lower boiling material, and carbon monoxide are the only isolable products. Further investigation of this and related systems as well as complete characterization of all products in the various solvents is in progress. ( 5 ) It must he pointed out that while the yields o f ketene adducts in alcohol solvents (the isobutyrate esters) account for :30-4070 of the products, only 15 -20'/, n f the reaction proceeds by this path since lwo molecules of dimethyl ketene will he formed from one molecule of I Several reports concerning photochemical elimination of ketene have appeared rrcently : J . C . Anderson and C . R . Reese, T r l l n h e d r o n I . r f l w c , 1 (1962); W H . Urry, D . J . Trecker, and D. A. Winey, ibid , 609 (196"; D. I . Schuster, M . Axelrod. and J . Auerhach, $ b i d , , 1911 (1869), G . 0 . Schenck and I
