Notes
J. Org. Chem., Vol. 40, No. 5, 1975
though as yet no biphenyl alkaloid corresponding to 1 has been isolated.
657
R. B. Horhammer, A. E. Schwarting,and J. M. Edwards, Lloydia, 33, 483 (1970).
R. B. Horhammer, A. E. Schwarting,and J. M. Edwards, 2. Naturforsch. B, 26, 970 (1971). J. P. Ferris, J. Org. Chern., 27, 2985 (1962): 28, 817 (1963). D. E. Zacharias, G. B. Jeffrey, 8. Douglas, J. A. Weisbach, J. L. Kirkpatrick, J. P. Ferris, C. B. Boyce, add R. C. Briner, Experientia, 21, 247
Experimental Section
Nmr spectra were recorded on a Perkin-Elmer-Hitachi R24 or a (1965). Varian Associates 220 MHz in CDC13 solution. The tlc systems B. Loev, I. Lantos, and H. Van Hoeven, Tetrahedron Lett., 1101 (1974). used throughout were silica gel with (a) benzene saturated with M. Hanaoka, H. Sassa, C. Shimezawa, and Y. Arata, Chem. Pharm. NH40H-MeOH (17:3); (b) benzene saturated with NHIOHBull., 22, 1216 (1974). MeOH (3:l); (c) chloroform-Et0H (1O:l); (d) benzene-EtOAcM. Hanaoka, N. Ogawa, and Y. Arata, Tetrahedron Lett., 2355 (1973); Chem. Pharm. Bull., 22, 973 (1974). MeOH (5:5:1); (e) benzene-MeOH (15:4); (e) benzene-MeOH (15: M. Hanaoka, H. Sassa, N. Ogawa, Y. Arata, and J. P. Ferris, Tetrahe4); (f) chloroform-Et0H (3:l); (g) benzene-EtOAc (3:l); (h) chlodron Lett., 2533 (1974). roform-EtOH (20:l); (i) toluene-CHC13-acetone (8:5:7); (j) benM. Hanaoka, N. Hori, N. Ogawa, and Y. Arata, Chern. Pharrn. Bull., 22, zene-MeOH-HOAc (23:3:2); (k) hexane-acetone-HCOzH (10:7.5: 1684 (1974). 0.5); and (1) CHCl3-EtOH (19:1.5). Compounds were visualized eiJ. T. Wrobel and M. W. Golebiewski, Rocz. Chem., 45, 705 (1971): Tetrahedron Lett., 4293 (1973). ther with modified Dragendorff's reagent or diazotized p-nitroaniJ. P. Ferris, C. 8. Boyce. and R . C. Briner, J. Arner. Chern. Soc., 93, line. 2942 (1971). Isolation of Abresoline (1). Heimia salicifolia was extracted as P. Comte. G. Zwingelstein, A. Ville, and C. Mentzer, C. R. Acad. Sci., previously described.7 The most polar alkaloid fraction, e h t e d 245, 1144(1957) A. Rother and A. E. Schwarting, Experientia, 30, 222 (1974). from the basic AZO3column7 with MeOH-HOAo (20:l) and which F. Bohlmann, Chem. Ber., 91, 2157 (1958). contained some ten uncharacterized alkaloids, was further chroF. Bohlmann, D. Schumann, and C. Arndt, Tetranedron Lett., 2705 matographed (tlc system a). Six compounds were isolated of which (1965). one, abresoline, was isolated as an amorphous solidz4by attempted H. S. Aron. G. E. Wicks. and C. P. Rade. J. Ora. Chern.. 29, 2248 crystallization from CHCl3-hexane. The compound was homoge(1964). neous as indicated by tlc (systems a and b): mass spectrum m/e (22) L. M. Jackman and S.Sternhell, "Appiicatlons of Nuclear Magnetic Resonance Spectroscopy in Organic Chemistry," 2nd ed, Pergamon Press, 453.2166 (Cz6H31NOo requires 453.2151), 435 (M+ HzO), 276, Elmsford, N.Y., 1968, p 288. 284 and 323 nm (log c 3.73 and 3.76); ir 259, 177, and 150; uv, , ,A (23) J. P. Ferris. C. B. Boyce, and R. C. Briner, Tetrahedron Lett., 5129 vmax 3356, 2933, 2793, and 1706 cm-l; nmr 6 1-3 (m, 13 H), 3.22 (9, (1966). J = 10 and 1 Hz, 1 H), 3.85 (s, 3 H ) , 3.95 (s, 3 H), 5.18 (br s, 1 H ) , (24) A number of the alkaloids of H. sallclfdia and their derivatives have con6.36 (d, J = 8 Hz, 1H), 7.63 (d, J = 18 Hz, 1H), 7.02 (m, 6 H). stantly been obtained as noncrystalline solids. (25) J. P. Wlbaut, C. C. Kloppenburg, and M. G. J. Beets, Red. Trav. Chirn. Reduction of 1. A methanolic solution of 1, reduced (10%Pd/C) Pays-Bas, 83, 134 (1944). to yield dihydroabresoline (7), was purified by tlc (system h), and (26) J. P. Rosazza, J. M. Bobbitt, and A. E. Schwarting, J. Org. Chem., 35, obtained as a noncrystalline solid. 2564 (1970). Hydrolysis of 1. The alkaloid was hydrolyzed by warming with 2 N NaOH for 15 min. The acidified solution was extracted with EtOAc. The organic phase was shown to contain trans-ferulic acid by co-chromatography with authentic material (tlc systems b and h-k). The aqueous phase was similarly proved to contain 4 (tlc system b). Vinyl Triflates in Synthesis. 11. 2-Keto-4(e)-(3-ben~yloxy-4-methoxyphenyl)-tra~s-quinol1,l-Di-, Tri-, Tetrasubstituted and Deuterio Allenes izidine ( 5 ) . Compound 5 was obtained in 56% yield from the confrom Ketones via Vinyl Triflates' densation of pelletierineZ6 with isovanillin in 1 N NaOH,16 followed by benzylation: mp 169-171O (lit.26169-170O). Peter J. Stang* and Robert J . Hargrovez 2(a)-(3-Metlioxy-4-benzyloxycinnamoyloxy)-4(e)-(3-benzyloxy-4-methoxyphenyl)-trans-quinolizidine (6). A suspenDepartment of Chemistry, The University of Utah, sion of 5 as its tetraphenyl borate in MeOH was reduced to a mixSalt Lake City, Utah 84112 ture of epimeric alcohols with NaBH4. The alcohols were converted to a mixture of ferulate esters by transesterification with methReceived October 15,1974 yl benzyloxyferulate in refluxing xylene containing an equimolar amount of NaOMe. The esters were resolved by chromatography Recently we reported the preparation of tert- butylacetyover silica gel with C&j-EtOAc (3:l) as eluting solvent; the axial lene and certain other acetylenes from ketones uia vinyl ester,had the lower Rp; yield from 5, 21%. The ester could not be crystallized but was shown to be homogeneous by tlc (system g): triflates.3 Interest in allene chemistry4 and the limited mass spectrum m/e 633.3078 (C40H4&"~ requires 633.3067); ir ways of their preparation prompts us to report in this note vmax 2890,2809 (Bohlman bands), and 1712 cm-I; nmr 6 1-3 (m, 13 the ready synthesis of di-, tri-, and tetrasubstituted allenes H), 3.25 (q, 1 H), 3.80 (8, 3 H), 3.87 (6, 3 H), 5.10 (8, 5 H),6.40 (d, J from the appropriate ketones. Although the overall yields = 16 Wz, 1 H), 7.68 (d, J = 16 Hz, 1 H), 7.10 (m, 6 H), 7.34 (br s, 10 achieved in this preparation are only low to moderate the HI. mild reaction conditions, and in particular the low basicity Dihydroabresoline (7). Compound 6 was reduced in MeOH (10%Pd/C) to yield 7 in quantitative yield. The alkaloid could not required for elimination, compare favorably with previousbe crystallized, but was homogeneous (systems a-g), and was idenly known procedures4 such as the geminate dichlorination tical with the reduced natural product: mass spectrum m/e of ketones or the carbene-olefin procedures. , , ,A 282, inf 287 (log c 455.2298 (C26HaaNO6 requires 455.2308); uv The reaction consists of conversion of the appropriate 3.76); ir vmax 3401, 2933, and 1733 cm-*; nmr 6 1-3.5 (m, 18 H), ketone into its vinyl triflate, 1, by previously reported pro3.80 (s, 6 H), 5.01 (br s, 1 H), 5.50 (br s, exchangeable with DzO,2 c e d u r e ~and , ~ the elimination of triflate, 1, by quinoline to H), 6.65 (m, 6 H).
-
Registry No.-I, 53778-14-6; 4, 52656-92-5; 5, 53778-15-7; 6, 53778-16-8; 7, 53778-17-9; pelletierine, 6302-02-9; isovanillin, 62159-0.
References and Notes (1) R . N. Blomster, A. E. Schwartlng, and J. M. Bobbitt. Lloydla, 27, 15 (1964). (2) B. Douglas, J. L. Kirkpatrick, R. F. Raffauff, 0. Rlbeiro, and J. A Weisbach, Lloydla, 27, 25 (1964). (3) H. G. Appel, A. Rother, and A. E. Schwarting, Lloydla, 28, 84 (1965). (4) A. Rother, H. G. Appel, J. M. Klely, A. E. Schwarting, and J. M. Bobbitt, Lloydla, 28, 90 (1965). (5) M. M. El Olemy, S. J. Stohs, and A. E Schwarting, Lloydia, 34, 439 (1970).
the desired allene, 2. Although unsymmetrical ketones give both positional as well as geometric isomers of the triflate, 1, the mixture can 0
1I
RIRZCHCCHRaRd
TfOTf
1
R1\
/RJ
R2/c=c=c
R ',
2
658 J . Org. Chem., Vol. 40, No. 5, 1975
Notes
Table I Preparation a n d Yields of Allenes via Triflates from Ketones R
R; R1
R2
R3
R4
Compd
,c=c
-
,OTf
R'\
\CHR,R,
K,/c=c=c 'Re
M jle1dQ
I R,
Yield, mg' (%)
Compd
I I
CH3 CH3 CD3 CH,CH, CH3 CH3
CH3 CH, CD3 CH3 CH3 CH3
H D H H
c H3 CH3
H D H H H CH3
3b 5"
44 40
76
35
6 8
9"
44 41 48
10 12 14
11' 13g
4
135 32 85 580
(70) (45) (44) (85)
320 (76) 130 (79)
a Isolated yields. Prepared as previously reported.5b Prepared from (CH3)&DC(O)CD3 obtained I J ~ Qexchange with D2O. d Prepared from (CD3)2CHC(0)CH3made as previously reported.? E Prepared from 3-methyl-2-pentanone. f Prepared from 2-methyl-3-pentanone. 6 Prepared from 2,4-dimethyl-3-pentanone via the silyl enol ether.5c
be used directly in the elimination step as all isomers yield the same allene.6 The procedure may, however, only be used for the preparation of 1,l-di or higher substituted allenes, as elimination from a triflate containing an olefinic hydrogen yields the isomeric acetylene as the major product with only small amounts of allene. Typical examples together with yields are summarized in Table I. As the data in the table indicate although overall yields are low they represent isolated yields of small scale preparations. Moreover, control experiments demonstrated that no rearrangement of the allene to the isomeric acetylene occurs under the reaction conditions employed. The chief quinoline
(CH,),2C=C=CH,
(CH,),CHC=CH
-4 1000
usefulness of this preparation lies in the ready availability of the precursor ketones and the simplicity of the procedure. We believe this procedure to be general, limited only by the availability of starting ketones, and hence provides another manifold into allene chemistry. Experimental Section Boiling points are uncorrected. Ninr spectra were recorded on a Varian A-60 spectrometer using TMS as an internal standard; infrared spectra were obtained on a Beckman IR-.? spectrophotometer and mass spectra were obtained on an AEI MS-30 spectrometer. Gas-liquid chromatography was performed on a Varian Aerograph Model 90-P unit using a 15 ft X 0.375 in. column with 15% SF-96 on Chromosorb 6'. General Procedure for the Preparation of Vinyl Triflates. Vinyl triflates were prepared from the appropriate ketones and triflic anhydride on a 10-50 mmol scale using pyridine as base and anhydrous CC14 as solvent by standard procedure^.^ Triflates 3, 5, and 7 have been previously prepared' as have 11 and 1X8Triflate 9 was prepared from commercial 3-methyl-2-pentanone:hp 5445' (13 mm); ir (thin film) 2967 (CHI, 1692 (C=C), 1412 (S=O), and I211 cm-I (CF); nmr (CC14) 6 2.06 (9,2 H, J = 7.0 Hz, -CHz-), 1.98 (br s, 3 H, cu-CHs), 1.70 (br s, 3 M,P-CHa), 1.02 (t, 3 H, J = 7.0 Hz, CH3CH2). General Procedure for the Preparation of Allenes. To a 10ml round-bot,tom flask, equipped with a magnetic stirrer and containing 3-6 ml of dry freshly distilled quinoline, was added 1 L l O mmol of the appropriate vinyl triflate. The flask was connected to a bulb-to-bulb distillation apparatus and a receiver flask. The reaction flask and cross arm were heated to 100" for 2-6 days and the product collected with the receiver cooled to -78O. Yields of isdated products are reported in the table. The products so obtained usually contained small amounts of unreacted triflate and ketone as impurities. Final purification was achieved by means of preparative glc. For 4: nmr (CC14) 6 4.43 (sept, 2 H, J = 3.2 Hz, C=CHz), 1.64 [t. J = 3.2 Hz, (CHs)&=] [lit9 6 4.43, J = 3.0 Hz, and 6 1.65, J = 3.0 Hz]; ir (thin film) 1960 (C-C=C) and 847 cni-.J; mass spectrum 68 (M+, loo), 67 (541, 6 5 (IS), 53 (52), 51 (211,50 (20), 41 (401, 40 ( 2 2 ) , 39 (40). For 6: ir (CC14) 2941 (CH), 2288 (CD), and 1949 cm-* (C=C=C); mass spectrum 70 (M+, 61). For 8: mass spectrum 74 (M+, 13). For 10: nmr (CC14) 6 4.50 (sext., 2 H, J = 3.0 Hz, C=CH?), 1.90 (m, 2 13, -CHz-), 1.65 (t, 3 H, J =
3.0 Hz, CH&=C), 0.99 (t, 3 H, J = 7.0 Hz, CHBCH~) [lit.9 nmr (CC14) 6 4.55 (m, 2 H, C=CHz)]; ir (thin film) 1961 cm-l (C=C=C) [lit.'O 1960 cm-'1. For 12: nmr (CC14) 6 4.88 (m 1 H, C=CH), 1.63 (m 6 H, (CH&C), 1.58 (m 3 H,CH3CH===); ir 1965 cm-l (C=C=C) [ l k 9 nmr 6 4.80 (m 1 €I), 1.63 (m, 6 H), 1.57 (m 3 H); ir 1959 cm-l]. For 14: nmr (CC14) 6 1.75 (s, 12 H, CH3); ir (CC14) 2940, 1629, 1447, 1379, 1186, and 1074 cm--'; mass spectrum 96 (M+, 871, 81 (1001, 79 (381, 57 (191, 56 (25), 55 (151, 54 (501, 48 (IO), 42 ( 7 5 ) .
Acknowledgment. Financial support by the Research Corporation and the University of Utah Research Committee is gratefully acknowledged. Registry No.-3, 28143-80-8; 4, 698-25-4; 5, 53730-65-7; 6, 53730-66-8; 7, 52847-16-2; 8, 53730-67-9; 9, 53730-68-0; 10, 741748-3; 11, 52149-34-5; 12, 3043-33-2; 13, 52149-35-6; 14, 1000-87-9; 3-rnethyl-Z-pentanone, 565-61-7.
References a n d Notes (1) Abstracted in part from the PhD. Thesis of R. J. Hargrove, The University of Utah, 1974. (2) University of Utah Graduate Research Fellow. (3) R. J. Hargrove and P. J. Stang, J. Org. Chem., 39, 581 (1974). (4) T. F. Rutledge, "Acetylenes and Allenes," Reinhoid, New York, N.Y., 1969; D. R. Taylor, Chem. Rev., 67, 317 (1967); S. Patai, Ed.. "The Chemistry of Alkenes." Interscience, London, 1964. (5)(a) T. E. Deuber, eta/., Angew, Chem., Int. Ed. Engb. 9, 521 (1970); (b) P. J. Sang and T. E. Dueber, Org. Syn., in press: (c) P. J. Stang, M. G. Mangum. D. P. Fox, and P. Haak, J. Amsr. Chem. Soc., 96, 4562 (1974). (6) Racemic ketones of course yield racemic allenes. (7) P. J. Stang, R. J. Hargrove, and T. E. Deuber, J. Chem. Soc., Perkin Trans. 2, 843 (1974). (8) R. H. Summerville, C. A. Senkler, P. v. R . Schleyer, T. E. Deuber, and P. J. Stang, J. Amer. Chem. Soc., 96, 1100 (1974). (9) R. M. Fantazier and M. L. Poutsma, J. Amer. Chem. Soc., 90, 5490 (1968). (10) W. J. Bailey and C. R. Peiffer, J. Org. Chem., 20, 95 (1955).
Synthesis a n d Reactions o f 6-Methylsulfonyl-9-~-D-ribofuranosylgurine Ron Wetzel and Fritz Eckstein* , ! a x - P / a n c h - P n s t z t ufur t Experrmente/k Medzzzn, Abteilung Chemze, Gottzngen, Germany Received September 3,1974
Although sulfones are generally quite stable, methyl sulfonyl substituents at low electron density positions of a pyrimidine or purine can be excellent leaving groups, and this fact has been employed in the past in nucleoside synthes i ~ l - Early ~, attempts t o prepare 6-methylsulfonyl-9-P-Dribofuranosylpurine (1) gave only its hydrolysis product inosine;3 a similar sulfone was recently proposed as an intermediate but no attempt to characterize it was described.l We wish to report the isolation of pure 1 in good yield and
