618 J . Org. Chem., Vol. 67, No. 3, 2002
Cazelles et al.
was chromatographed over neutral alumina with a hexane/
dichloromethane mixture (gradient from 50/50 to 0/100, v/v).
This purification afforded the chlorin-type adduct 7 (yield 20%
with respect to MnTPP) and the tetrahydrofuran derivative 9
(yield 18% with respect to trioxane 2).
7.16 (t, 3J (H, H) ) 3J (H, F) ) 8.8, 2H; pFPh), 6.28 (s, 1H;
HC12), 4.07 and 3.85 (2 × m, 2 × 1H; H2C4), 3.44 (s, 3H; H3C-
O-C12). MS (DCI/NH3+): m/z (%): 308 (39), 309 (100) [MH+],
310 (19), 326 (11) [MNH4+].
Rea ction of Tr ioxa n es 2 or 3 w ith 6 in th e P r esen ce
of Bor od eu ter id e. The synthesis and workup were the same
as for the adducts 7 and 8, except using tetra-n-butylammo-
nium borodeuteride as reducing agent. 1H NMR for 7-d 2 (δ,
Compound 7: UV/Vis (dichloromethane): λmax (rel intensity)
) 372 (16), 408 (sh), 420 (100, Soret), 518 (7), 546 (5), 596 (3),
1
650 (12). The ratio abs650/abs420 ) 0.12. H NMR (δ, CD2Cl2):
3
3
Significant chemical shifts: 8.58 (d, J (H, H) ) 4.6, 2H; pyr),
CD2Cl2): Significant chemical shifts: 4.67 (d, J (H2′R, H2C4)
3
8.40 (s, 2H; pyr), 8.20 (m; 2H pyr + Ph), 7.85 (dd, J (H, H) )
) 8.5, 1H; H2′R), 4.40 and 4.14 (2 × s, 1H; HDC12), 3.90 (s,
1H; H3′â), -1.54 (br s, 2H; NH). MS (DCI/NH3+): m/z (%):
754 (19), 755 (19), 756 (36), 757 (94) [MH+ - pFPhCOOH],
758 (60), 759 (21), 894 (13), 896 (35), 897 (100) [MH+], 898
(70), 899 (33). 1H NMR for the mixture 8-d 1 + 8-d 2 (molar ratio
1/1) (δ, CD2Cl2): Significant chemical shifts: 8.89 (br s, 2H;
pyr), 8.81 (d, 3J (H, H) ) 4.6, 1H; pyr), 8.74 [(d, 3J (H, H) ) 4.6,
4
3
3
8.8, J (H, F) ) 5.6, 2H; pFPh), 6.98 (t, J (H, H) ) J (H, F) )
8.8, 2H; pFPh), 4.67 (br t, J (H2′R, Η3′R) ) 3J (H2′R, Η2C4) )
3
2
8.5, 1H; H2′R), 4.40 and 4.18 (2 × d, J (H, Η) ) 11.6, 2 × 1H;
H2C12), 4.00-3.80 (m, 2H; Η3′R and H3′â), -1.51 (br s, 2H;
NH). MS (DCI/NH3+): m/z (%): 755 (38) [MH+ - pFPhCOOH],
756 (22), 894 (24), 895 (100) [MH+], 896 (63), 897 (23). Rf )
0.72 (SiO2, dichloromethane).
3
2H; pyr) + (br s, 0.5H; H3′), 8.62 (d, J (H, H) ) 4.6, 1H; pyr),
Compound 9: 1H NMR (δ, CD2Cl2): 8.11 (dd, 3J (H, H) )
4.39 and 4.22 (2 × s, 2 × 0.5H; HDC12), -2.85 (br s, 2H; NH).
MS (DCI/NH3+): m/z (%): 755 (26) [MH+ - pFPhCOOH for
8-d 1], 756 (12) [MH+ - pFPhCOOH for 8-d 2] 894 (99) [MH+
for 8-d 1], 895 (100) [MH+ for 8-d 2], 896 (46), 897(16).
4
3
3
8.8, J (H, F) ) 5.6, 2H; pFPh), 7.17 (t, J (H, H) ) J (H, F) )
8.8, 2H; pFPh), 6.26 (s, 1H; HC12), 4.10 and 3.85 (2 × m, 2 ×
1H; H2C4), 3.41 (s, 3H; H3C-O-C12), 2.43 (dt, 2J (H, H) ) 12.1,
3J (H, H) ) 3.5, 1H), 1.85 (m, 2Η), 1.60-0.90 (8Η). 13C NMR
(δ, CD2Cl2): 131.8 and 131.7 (pFPh), 115.1 and 114.9 (pFPh),
98.1 (C12), 66.7 (C4), 56.2 (H3C-O-C12), 47.9, 33.9, 28.1, 25.4,
23.9 and 22.0 (C5-10). F_CPh, C3_CPh, C3 and C11 were not
detected. MS (DCI/NH3+): m/z (%): 308 (17), 309 (100) [MH+],
310(24), 326 (64) [MNH4+], 327 (16), 328 (10). Rf ) 0.37 (SiO2,
dichloromethane).
Oxid a tion of th e Ch lor in Ad d u ct 7. The chlorin adduct
7 (3 mg, 3.3 µmol, 1 equiv) was heated at reflux with
2,3-dichloro-5,6-dicyano-1,4-benzoquinone (DDQ, 2.3 mg, 9.9
µmol, 3 equiv) in dichloromethane (1 mL) for 60 min. The
resulting product was passed through a column of silica gel
and eluted with a mixture dichloromethane/methanol (99.5/
0.5, v/v) to afford the porphyrin analogue 8.
Rea ction of Tr ioxa n e 4 w ith th e Hem e Mod el 6. (i) In
th e P r esen ce of Bor oh yd r id e. MnIII(TPP)Cl (10 mg, 14
µmol, 1 equiv) and trioxane 4 (16 mg, 42 µmol, 3 equiv) were
dissolved in dichloromethane (3 mL). This solution was care-
fully degassed and kept under an argon atmosphere. Tetra-
n-butylammonium borohydride (36 mg, 140 µmol, 10 equiv)
was then added as a solid. The UV/vis spectrum of an aliquot
of the reaction mixture diluted in CH2Cl2 under argon showed
an absorbance at 442 nm typical of MnIITPP in CH2Cl2. No
residual MnIII(TPP)Cl was observed at 374 and 478 nm. The
mixture was stirred for 3 h under argon at room temperature.
Demetalation was performed as previously described7 by
addition of a degassed solution of cadmium(II) nitrate [Cd-
(NO3)2‚4H2O, 85 mg, 280 µmol, 20 equiv) in dimethylforma-
mide (2 mL)] to the reaction mixture, and stirring was
continued for 10 min. An aqueous solution of acetic acid (10
vol %, 10 mL) was then added under air. The organic layer
was extracted with dichloromethane, washed with water (pH
8), dried over sodium sulfate, and evaporated to dryness.
Purification of the crude product was performed by column
chromatography on alumina using a hexane/dichloromethane
mixture (gradient from 80/20 to 0/100, v/v). The tetraphe-
nylporphyrin ligand and unreactive 4 were first eluted as a
mixture at the solvent front followed by the covalent adduct
18. (Yield of 18: 20% with respect to metalloporphyrin). Τhe
covalent adduct 19 was eluted last by a dichloromethane/
methanol mixture (99.2/0.8 v/v). (Yield of 19: 20% with respect
to metalloporphyrin). 18: UV/Vis (dichloromethane): λmax (rel
intensity) ) 408 (sh), 420 (100, Soret), 520 (9), 548 (7), 598
(7), 654 (17). The ratio abs654/abs418 ) 0.17 is characteristic of
a pure chlorin macrocycle. 1H NMR (δ, CD2Cl2): 8.58 (d, 3J (H,
H) ) 5.2, 2H; pyr), 8.39 (s, 2H; pyr), 8.28 and 8.20 (2 × d,
3J (H, H) ) 5.2, 2 × 1H; pyr), 8.18-7.96 (m, 8H; Ph), 7.70 (m,
12H; Ph), 7.21 (m, 3H; PhC15), 6.94 (m, 2H; PhC15), 4.83 (br
Compound 8: UV/Vis (dichloromethane): λmax (rel intensity)
) 418 (100, Soret), 516(3). 1H NMR (δ, CD2Cl2): Significant
3
chemical shifts: 8.89 (br s, 2H; pyr), 8.80 (d, J (H, H) ) 4.6,
1H; pyr), 8.74 [(d, 3J (H, H) ) 4.6, 2H; pyr) + (s, 1H; H3′)],
8.61 (d, 3J (H, H) ) 4.6, 1H; pyr), 8.21 and 8.11 (2 × m, 8H;
3
4
Ph), 7.87 (dd, J (H, Η) ) 8.8, J (H, F) ) 5.6, 2H; pFPh), 7.78
(m, 12H; Ph), 6.85 (t, 3J (H, Η) ) J (H, F) ) 8.8, 2H; pFPh),
3
2
4.41 and 4.23 (2 × d, J (H, Η) ) 11.9, 2 × 1H; H2C12), 3.07
and 2.76 (2 × m, 2 × 1H; H2C4), 2.31 and 1.64 (2 × m, 2 ×
1H; H2C5), -2.85 (br s, 2H; NH). 13C NMR (δ, CD2Cl2): 131.8
and 131.7 (pFPh), 115.1 and 114.9 (pFPh), 98.1(C12), 66.7 (C4),
56.2 (H3C-O-C12), 47.9, 33.9, 28.1, 25.4, 23.9 and 22.0 (C5-
10). F_CPh, C3_CPh, C3 and C11 were not detected. 19F NMR
(δ, CD2Cl2): -105.6 (m; pFPh). MS (DCI/NH3+): m/z (%): 753
(52), 754 (30) [MH+ - pFPhCOOH], 892 (16), 893 (100) [MH+],
894 (63), 895 (23). Rf ) 0.28 (SiO2, dichloromethane).
Rea ction of Tr ioxa n e 3 w ith th e Hem e Mod el 6. MnIII
-
(TPP)Cl (10 mg, 14 µmol, 1 equiv) and trioxane 3 (16 mg, 42
µmol, 3 equiv) were dissolved in dichloromethane (5 mL). This
solution was carefully degassed and kept under an argon
atmosphere. Tetra-n-butylammonium borohydride (36 mg, 140
µmol, 10 equiv) was then added as a solid. The mixture was
stirred under argon at 38 °C. After 3 h of reaction, the
manganese(II) macrocycle complex was transmetalated in situ.
For this purpose, a degassed solution of cadmium(II) nitrate
[Cd(NO3)2‚4H2O, 85 mg, 280 µmol, 20 equiv) in dimethylfor-
mamide (2 mL)] was added to the reaction mixture, and
stirring was continued for 10 min. To ensure a soft demeta-
lation, an aqueous solution of acetic acid (10 vol %, 10 mL)
was then added under air. The organic layer was extracted
with dichloromethane, washed with water (pH 8), dried over
sodium sulfate, and evaporated to dryness. The crude product
was purified by column chromatography on alumina, using a
hexane/dichloromethane gradient (from 20/80 to 0/100, v/v).
The free tetraphenylporphyrin ligand was eluted first at the
solvent front, followed by a mixture of the dark red tetraphe-
nylchlorin adduct 7 and compound 17. (Yield of 7: 20% with
respect to metalloporphyrin). Description of 7: see above.
Compound 17: 1H NMR (δ, CD2Cl2): Significant chemical
shifts: 8.13 (dd, 3J (H, H) ) 8.8, 4J (H, F) ) 5.6, 2H; pFPh),
3
2
d, J (H2′R, Η3′R) ) 9.8, 1H; H2′R), 4.35 (dd, J (H3′R, Η3′â) )
18.0, 3J (H3′R, Η2′R) ) 9.8, 1H; H3′R), 3.97 (dd, 2J (H3′â, Η3′R)
3
) 18.0, J (H3′â, Η2′R) ) 1.5, 1H; H3′â), 3.69 and 3.63 (2 × d,
2J (H, H) ) 11.9, 2 × 1H; H2C15), 3.03 and 3.00 (2 × d, J (H,
2
H) ) 11.9, 2 × 1H; H2C12), 2.06 (m, 1H; HC4), 1.91 and 1.50
(2 × m, 2 × 1H; H2C14), 1.20 (m, 1Η), 1.20 and 0.30 (2 × m,
2 × 1H; H2C5), 1.00 (m, 1H; HeC8), 0.87 (s, 3H; H3C-CO-
3
O-C12), 0.79 (d, J (H, H) ) 6.7, 3H; H3C-C4), 0.58 (m, 1H),
0.55 and 0.08 (m, 2 × 1H; H2C13), 0.43 (m, 1Η), 0.30 (m, 1Η),
-0.31 (m, 1H; HaC8), -1.17 (m, 1H; HaC6), -1.36 (m, 1H; HO-
C11), -1.44 (br s, 2H; NH), -1.60 (m, 1H; HaC10). The non
assigned signals at 1.20, 0.58, 0.43, and 0.30 ppm (4 × 1H)
are the resonances of H2C7 and H2C9. MS (DCI/NH3+): m/z
(%): 961 (5), 962 (23), 963 (100) [MH+], 964 (80), 965 (34), 966
(12). TLC: Rf ) 0.56 (SiO2; dichloromethane/methanol, 98.5/
1.5, v/v). HPLC (silica column 10 µm, 250 mm × 4.6 mm;
eluent: CH2Cl2/hexane 15:85 v/v, 1% TEA; flow rate: 0.7 mL/
min; λ ) 420 nm). Rt ) 12.7 (one single peak). 19: 1H NMR (δ,
3
CD2Cl2): 8.58 (d, J (H, H) ) 5.2, 1H; pyr), 8.39 (s, 2H; pyr),
3
8.28 and 8.20 (2 × d, J (H, H) ) 5.2, 2 × 1H; pyr), 8.19-7.94