876
J. Org. Chem. 1992,57,876-882
totaling 100 min. Concentrated methanolic ammonia (2 h at 25 “C) was used to cleave the dimer from the support and to deprotect the phosphorus. HPLC Methods. A Beckman high-performance liquid chromatography system equipped with System Gold software, a 126 solvent module, and a 168diode array detector was used with an Ultrasphere reversed-phaw 5 pm spherical 80-Apore C-18 guard (4.6 X 45 mm) and dytical(4.6 X 250 mm) column. A gradient elution was carried out with an aqueous triethyl ammonium acetate (TEAA, 0.1 M, pH 7) vs CH3CN with a flow rate of 1 mL/min. The gradient used was as follow: 100% TEAA to 22% CHSCN CH3CNover 5 miu, Z-30%CH&N over 15min, W % over 25 min, and 5&100% CH3CN over 15 min. Synthetic Procedures. Preparation of 3’-[6’-0-(4,4’-Dimethoxytrityl)deoxythymidinyl] Methyl [2-[(Dicarbonyl)(~-cyclopentadienyl)iron]ethyl]phosphonate (7). Compound Sa (99 mg,0.14 mmol), tetrmle (43 mg, 0.61 mmol), methanol (24 &,0.56 mmol), and CH&N (10 mL) were combined in a 50-mL schlenck tube under an atmosphere of argon. After 30 minutes 1 (90 mg,0.3 mmol) was added; an IR assay showed complete conversionafter an additionalhour. IR (v CO, CHSCN): 2011 and 1953 cm-’. The solvent was removed in vacuo and coevaporated with acetone (3 x 5 mL). The resulting oil was dissolved in acetone (5 mL) and combined with NaI (300 mg, 2 mmol). This reaction mixture was allowed to stir at ambient temperature for 1h under an atmosphere of argon, at which time the reaction mixture was diluted with CHzClz (10 mL) and extracted with water (4 X 15 mL). The organic layer waa dried (MgS04), fiitered, and dried in vacuo. The resulting oil was dissolved in a minimal amount of CHzClzand loaded onto an activated (Brock” III)aluminum oxide (neutral) column (10 g), which was eluted with CHzClz/NEh (9911). The yellow fractions were combined and concentrated to yield a thick gold oil which was triturated with hexane to yield 7, a beige powder (77 mg,67%). IR (V CO, CH2Cl.J: 2011 and 1953~m-’. “P NMR (6,acetoneds): 32 ppm (d, RP=O). ‘H NMR (6,acetoneds) 7.59 (m, H-6), 7.486.92 (m, aromatic), 6.38 (m, H-l’h4.99 (8, Cp), 4.27 (m, H-39, 3.91 (m,H-4‘), 3.79 (8, OCH3),3.65 (d, POCHS), 3.44 (m, H-59, 2.55 (m, H-2’), 1.83 (m, PCHz), and 1.46 (m, CH3and FeCH2) ppm. Ms: low-resolutionm / e calcd (M + Na+)849, obed 849; high-resolution m / e calcd for daughter ion C8H7O2Fe 190.9795, obsd 190.9790; m l e calcd for CmHMO&PNa658.2056, obsd 658.2061. In an alternate procedure, compound 6b (R = CHzCH&N) was used in place of 8a in order to determine if a &cyano ethyl group could be selectivelyremoved by concentrated methauolic ammonia (5 mL). The remainder of the work up was identical, yielding
a similar product. IR (v CO, acetone): 2009 and 1953cm-’. NMR (6,acetone-d,): 32 ppm (d, RP=O). Preparation of 6’4 (3’-0 -Levulinyl)deosythymidinyl] 3’-[w-Benzoyl-6’- 0 -(4,4’-dimethoxytrityl)deoxyadenosyl] [2-[ (Dicarbonyl)(~s-cyclopentadienyl)iron]ethyl]phosphonate (11). Compound 8a (100 mg,0.12 mmol), tetramle (43mg,0.61 mmol), compound Sa (41mg,0.12 mmol), and CH&N (10 mL) were combined in a SO-mL schlenk tube under an atmosphere of argon. After 30 min 1 (36 mg,0.12 “01) was added to the reaction mixture and stirred under an atmosphere of argon for 1h. The solvent was removed in vacuo and coevaporated with acetone (3 X 5 mL) and then dissolved in acetone (5 mL). NaI (300 mg,2 “01) was added and the solution allowed to stir for 1h at ambient temperature. The reaction mixture was diesolved in CHzClz(10 mL) and washed with water (4 X 15 mL). The organic layer was dried (MgSO1), filtered, and dried in vacuo to yield an amber oil. The oil was triturated with hexane to yield 11as a beige solid (101mg,53%). IR (v CO, acetone): 2009 and 1953 an-’. 31PNMR (6,acetone-d,): 32 ppm (d, RP-0). ‘H NMR (6,acetone-de): 8.60 (e, H-8 A), 8.30 (8, H-2 A), 7.59 (m, H-6 T), 8.04 (m, aromatic), 7.65-6.85 (m, aromatic),6.55 (m, H-1‘ A), 6.28 (m, H-1’ T), 5.31 (m, H-3’ T), 5.03 (e, Cp), 4.68 (m, H-3’ A), 4.46 (m, H-4’ A), 4.15 (m, H-4’ T), 3.78 (8, OCHS),3.59 (m, H-5’ T), 3.48 (m, H-5’ A), 2.81-2.57 (m, H-2” and H-3’’ T), 2.36 (m, H-2’ T), 2.13 (8, H-5” T), 1.84 (8, CH3T), and 1.83-1.66 (m, FeCH, and PCHJ ppm (A = deoxyadenosine and T = thymidine). MS: low-resolution m / e calcd (M + Na+) 1270, obsd 1270; high-resolution m / e calcd for daughter ion C8H702Fe190.9795, obsd 190.9792; m / e calcd for CUHmOl4N7PNa1079.3442, obsd 1079.3445.
Acknowledgment. The National Institutes of Health is gratefully acknowledged for support of this research through NIH Grant AI26029 and NIH Grant AI72771. We also gratefully acknowledge NSF Instrument Grant C H E W 8 7 2 for contributing to the purchaae of the VXR 300 NMR spectrometer. We also gratefully acknowledge the support by the Walther Cancer Institute. Supplementary Material Available: ‘H NMR spectra of 7 and 11 and NMR spectrum of 11 (3 pages). This material is contained in many libraries on microfiche, immediately follow this article in the microfii version of the journal, and can be ordered from the ACS; we any current d e a d page for ordering information.
Inversion of the Ground-State Spin Multiplicity by Electron-Withdrawing Groups in Trimethylenemethane Derivatives Generated Photochemically from Methylenequadricyclane Derivatives Takashi Hirano, Tsutomu Kumagai, and Tsutomu Miyashi* Department of Chemistry, Faculty of Science, Tohoku University, Sendai 980, Japan
Kimio Akiyama* and Yusaku Ikegami Institute for Chemical Reaction Science, Tohoku University, Sendai 980,Japan Received August 1,1991
An inversion of the ground-state spin multiplicity of trimethylenemethane (TMM) by electron-withdrawing groups was investigated by EPR spectroscopy, for a series of TMMs 2b-g generated photochemically from methylenequadricyclanes lb-g. Curie law analyses between 4 and 50 K proved the triplet ground states of the monophenyl derivative 2b and the monocyano derivatives 2c-d as well as that of the diphenyl derivative 2a. The dicarbomethoxy derivative 28 also exhibited the EPR signal, but the Curie plot was nonlinear and the signal disappeared irrevemiblyabove 10K. The triplet ground state was inverted to the singlet by the carbomethoxy-cyano and dicyano substitutions, and 2f and 2g were EPR silent species similar to the singlet oxyallyl (OA)derivative 2h. The singlet ground state of 2g was demonstrated by its chemical behaviors which resemble those of 2h.
We previously reported that photoreactions of benzhydrylidenequadricyclane (la)and quadricyclanone (la) 0022-326319211957-0876$03.00/0
formed the triplet trimethylenemethane 0derivative 2a and the singlet OA derivative 2h,respectively.’ Theee Q 1992 American Chemical Society
Ground-State Spin Multiplicity Inversion
J. Org. Chem., Vol. 57, No.3, 1992 877
Scheme I
2a
la-h
\
0 2b
2a
2h-g
a: X s ( C 6 H d 2 d: X=CHCN b: XsH(C6H5) e: X=C(CO,CH,), c: X=C(CN)C6Hs
2h
3n-h
f: X=C(C02CH3)CN g: X=C(CN), h: X=O
a: X=C(SOCH,), b: X=C(S0,C6Hs),
2c
results experimentallyverified theoretical predictions that replacement of one terminus of TMM by a heteroatom would result in the splitting of two degenerate nonbonding orbitals (NBMO) of TMM, and the OA’s singlet state would be preferred to be the lowest ground state or would become energetically close to the triplet state.24 The splitting of NBMOs of TMM had been also theoretically predicted to be induced by substitution of electron-de nating or electron-withdrawing groups at one methylene group of TMM.6 Experimental verification of this prediction was examined for TMMs of P-methylenecyclopentane-1,3-diyl series by Berson and co-workem.~~~6 For instance,Curie law anal* established the triplet ground state of the methylsulfinyl derivative 3a,whereas no EPR signal was observed for the phenylsulfonyl derivative 3 b . w However, it was noted that an inversion of the spin multiplicity due to the phenylsulfonyl substitution was not fully confirmed because of some practical problems.2”@gf In connection with this, our procedure, i.e., the photochemical generation of TMM from the methylenequadricyclane system, is convenient for systematic test of substituent effects on an inversion of the TMM spin multiplicity by electron-withdrawing groups, because electron-withdrawing groups such as the carbomethoxy and cyano groups can be readily introduced to the exocyclic position of the methylenequadricyclane system. In order to investigate substituent effects on an inversion of the TMM ground-state spin multiplicity, a series of symmetrical disubstituted and unsymmetrical mono- and disbuetituted methylenequadricyclanes lb-g was synthesized from l h and subjected to EPR spectroscopy. Spectro(1) Hirauo, T.; Kumagai, T.; Miyashi, T.; Akiyama, K.; Ikegami,Y. J. Org.Chem. 1991,56, 1907. (2) Reviewa for TMM: (a) Bereon, J. A In Diradicals; Borden, W. T., Ed.;Wdey-Interscience: New York, 1982; pp 151-194. (b)Berson, J. A.
Acc. Chem. Res. 1978,11,446. (c) Dowd, P. bid. 1972,5,242. (d) Web, F. 8.Rev., Chem. SOC.1970,24,278. (e) Shen, L. Ph.D. Diesertion, Yale University, New Haven, CT, 1984. (f) Hilinslri,E. F. PhD. Dissertation, Yale University, New Haven, CT, 1982. (3) Review for theoretical inveetigationefor TMM: Borden, W. T. In Diradicals; Borden, W. T., Ed.;WWy-Interscience: New York, 1982; p 1-72. (4) Recent theoreticaletudiea on OA, (a) Osamura, Y.; Borden, W. T.; Morokuma, K.J. Am. Chem. Soc. 1984,106,5112. (b) Coolidge, M. B.; Yamashita, K.;Morokuma, K.;Borden, W. T. Ibid. 1990, 112,1751. (c) Ichimura, A. S.; Lahti, P. M.; Matlin, A. R. Ibid. 1990,112, 2868. (5) Carpenter, B. K.;Little, R. D.; Berson, J. A. J. Am. Chem. SOC. 1976,98,5723. (6) Platz, M. 5.; McBride, J. M.; Little, R. D.; Harrison,J. J.; Shaw, A.; Potter, S. E.; Berson, J. A. J. Am. Chem. SOC.1976,98,5726.
2d
2e
I
165
I
I
350
300
B,/mT
Figure 1. Steadystate EPR spectra of 2a-e obtained during irradiation of la-e in toluene at 20 K in the presence of benzophenone.
scopic results for the photogenerated TMMs 2b-g and chemical behaviors of 2g were compared with those’ for 2a and 2h. Herein we report that the carbomethoxy-cyano and dicyano substitutions are strong enough to invert a ground state from the triplet to the singlet in a series of TMMs 2a-g. Results and Discussion
EPR Spectroscopy of TMM Derivatives 2b-g. Me-
le
thylenequadricyclane derivatives lb,’ lf,8 and were prepared according to the literature, and lc-e were prepared by the Knoevenagel condensation or the Wittig reaction from quadricyclanone (la)? Upon separate irra(7) Hoffmann, R.W.; Riemann, A.; Mayer, B. Chem. Ber. 1986,118, 2493. (8)Babsch, H.; Fritz, H.; Prinzbach. H. Tetrahedron Lett. 1976,4677.
Hirano et al.
878 J. Org. Chem., Vol. 57, No.3, 1992 Table 1. ZFS Parametera and Hfs Constants of 2a-e Obtained during Irradiation of la-e in Toluene at 20 K IEl/cm-l aH/mT compd Pl/cm-' 1.05 (4H) 0.0179
