June 5, 1963
COMMUNICATIONS TO THE EDITOR
1699
with an average line widths of 3.4 C.P.S. Examination The conversion to 3-cyclopropyl-2-propanonesapof the C-4 proton peak of the 66-deuterio derivatives of pears to be a general reaction of a$-unsaturated ketones androst-4-ene-3,17-dione,testosterone and cholest-4containing a quaternary carbon a t the y-position. Under similar conditions, 4,5,5-trimethyl-3-hexen-2-oneen-3-one revealed a marked sharpening of the peak with a line width of 2.3 C.P.S. in each case which suggested (Ib) (1.1 g. in 400 ml. of ether, irradiation for 31 hr.) is that despite the absence of a split C-4 proton peak there converted to the isomeric ketone I I b in 55% yield is a 1,3-coupling between the C-4 and C-6P protons in (based on reacted starting material ; approximately the undeuterated steroid. Three 6P-methyl-A4-3-ke10% starting ketone recovered), isolated by vapor tones similarly exhibited sharpened C-4 proton peaks phase chromatography (found: C, 76.96; H, 11.30), with an average line width of 2.3 C.P.S. (2.1, 2.4 and 2.5 7::; 3053, 1724 and 1712 (shoulder) cm.-', semicarc.P.s.), further indication of C-4, 6P proton-proton COUbazone, m.p. 143-144' (found: C, 60.99; H, 9.90; N, pling in the unsubstituted cases. 21.00). The n.m.r. spectrum revealed an unsymmetriIn contrast, the examination of four 6a-methyl-A4-3cal two-proton doublet a t 7.65 (JAB= 3 c.P.s.), threeketones demonstrated in each case a doublet for the C-4 proton singlets a t 7.98, 8.90, 8.96 and 9.00 r and a proton with J = 1.5-2.0 C . P . S . , ~ while the 6a-methyl characteristic high field cyclopropane methylene singlet group itself exhibited the normal doublet splitting pata t 9.83 r , corroborating the structural assignment as tern of a methyl group on a carbon atom bearing a single 3-(1,2,2-trimethylcyclopropyl)-2-propanone (IIb). The proton. These results can be interpreted only as C-4, mechanism and scope of this reaction are being investi6P proton-proton coupling. gated. A similar pattern was found in the isomeric 6-bromoAcknowledgment.-This research was supported, in androst-4-ene-3,17-diones.The 66-bromo isomer expart, by a grant from the Petroleum Research Fund hibited a sharpened C-4 proton peak of width 2.4 C.P.S. (Grant No. 726), administered by the American a t 355 C.P.S.(average frequency) while the 6a-proton, Chemical Society. due to coupling with the C-7 protons, appeared as a (6) Fellow of the Alfred P. Sloan Foundation. typical ABX quartet centered a t 296 C.P.S. The 6aDEPARTMENT OF CHEMISTRY MARGARET JEFRAIM JORGENSON N. C. Y A N G ~ bromo isomer, however, showed a doublet for the C-4 THEUNIVERSITY OF CHICAGO CHICAGO 37, ILLINOIS proton centered a t 391 c.P.s., J = 2.0 c.P.s., and an octet RECEIVED MARCH25, 1963 for the 66-proton (center 304 c.P.s.) due to coupling with the two C-7 protons and the C-4 proton. It is apparent that 1,3-coupling is significant only in CONCERNING THE STERIC REQUIREMENTS FOR THE the case of the axial 6P-proton while the effect of the ALLYLIC 1,J-SPIN-SPIN COUPLING OF PROTONS' 6a-equatorial proton appears to be negligible. SteriSir : cally, the 6P-axial C-H bond but not the 6a-equatorial Although the long range 1,3-s~in-spincoupling of a bond is positioned for efficient overlap with the T orbivinylic proton with an allylic proton is a well recogtals of the double bond and the transmission of spin nized2-6 phenomenon, there is a paucity of information information may be pictured as proceeding via the elecconcerning the steric requirements for such interaction. trons associated with the C-6 proton directly to the T The only definitive studies that we are aware of involve electrons.1° These findings appear to confirm the preacyclic A'-olefins with preferred conformations about diction of KarpluslO that the position of the allylic prothe c2-C~ bond due to dipole repulsions4 or to steric ton with respect to the n-orbitals of the double bond will hindrance5 and indicate strongly that coupling is minibe the predominant factor in determining the magnitude mal when the C-1 methylene group and allylic proton of 1,3-coupling. I t may be noted that although the 6a5 there appears to be no simple relaare eclipsed, 4 ~ while proton in A4-3-ketosteroids geometrically approximates tionship of coupling constants to cis-trans geometrical the eclipsed conformation of the olefins in ref. 4 and 5, configuration.3$6 We wish to present evidence that in a and confirms that coupling is minimal in this position, 19 1,3-coupling should also be minimal when the two protons are trans if the two C-H bonds are in the same plane. It was predictable that 19-nor-A4-3-keto steroids 0 should exhibit evidence of 10P-hydrogen as well as 6Phydrogen coupling with the C-4 proton since the C-H bond in both cases is approximately perpendicular to number of A4-3-keto steroids (structure I) the vinylic the plane passing through the C-4, 5 and 6 carbon C-4 proton is strongly 1,3-coupled ( J = 1.5-2.0 c.P.s.) atoms and hence in an optimal position for u-n overlap. to the axial 66-proton and, in 19-nor steroids, to the A number of 19-nor-A4-3-ketones,unsubstituted a t C-6, axial 10P-proton as well, while coupling with the equawere investigated and all exhibited marked broadening torial 6a-proton is negligible. This defines in a rigid of the C-4 proton peak (av. line width 4.3 c.P.s.) indicasystem the conditions for minimal and for significant tive of additional coupling with the 106-proton but no (probably maximal) 1,3-coupling. definite splitting was observed. However, the C-4 The C-4 vinyl proton of a number of representative approton of 66-methyl- 19-norandrost-4-ene-3,17-dione A4:3-keto steroids (e.g., testosterone) appears in the peared as a sharp doublet a t 353.5 c.P.s., J = 2.0 c.P.s., n.m.r. spectrum as a single peak a t about 344 c.P.s.' (1) Supported in part by Grants A-4044 and CY-4550, U. S. Public Health Service, and T-185, American Cancer Society. (2, S. Alexander, J. Chcm. Phys., 28, 355 (1955); 89, 1700 (1960). (3) R. R. Fraser and D. E. McGreer, Con. J. Chcm., 89, 505 (1961). and references therein. (4) E. B. Whipple, J. H. Goldstein and G. R. McClure, J . A m . Chcm. Soc., 89, 3811 (1960); E. B. Whipple, J. Chcm. Phys., 36, 1039 (1961). (5) A. A. B o t h e r - B y and C. Near-Colin, J . A m . Chcm. SOC., 83, 231 (1961); A. A. Bothner-By, C. Naar-Colin and H. Gunther, ibid., 84, 2748 (1962). (6) Cf.D. R. Davis and J. D. Roberts, ibid., 84, 2252 (1962). (7) All spectra were obtained using a Varian 4300 n.m.r. spectrometer, with field homogeneity control unit, at a frequency of 60 Mc.p.s. The
samples were dissolved in deuteriochloroform and the spectra were calibrated using the side-band technique. Peak positions are reported in C.P.S. downfield from tetramethylsilane (internal reference). (8) The full line widths were measured in each case at half-height. The homogeneity of the magnetic field was such that the average line width of the tetramethylsilane reference peak was 1.2 C.P.S. The uncertainty in measurement is estimated to be f 0 . 2 C.P.S. (9) 6a-Methyltestosterone, 2.0 C.P.S. ; 6~-methyIprogesteroae, 2.0 c.P.s.; 6a-methyl-17~,21-dihydroxypregn-4-ene-3,2~~dione, 1.5 c.P.s.; 6a-methyl17a-hydroxypregn-4-ene-3,2O-dione, 1.5 C.P.S. J-values are estimated to be accurate t o +0.2 C.P.S. (10) M. Rarplus, J. A m . Chcm. SOL, 81, 4431 (1960); J. Chcm. Phys., as, 1542 (1960).
COMMUNICATIONS TO THE EDITOR
1700 TABLE I N.M.R.SPECTRUM OF c-4 PROTON
10-Methyl
Substituent at C-6
Average 6 (C.P.S.)?
None 6P-D 6P-CHa 6P-Br 6a-Br 6a-CHa None 6P-CH3
344.2 343.5 344.3 355.0 390.6 347.4 350.0 353. 5
NCS
SCN-* O0 + 2PhaA~ + CzHoOH
OF A4+3-KETOSTEROIDS
Average line No. of width ( C . ~ . S . )
