V. V. Filichev et al.
198.00 (CO), 136.19 (2C), 135.59, 135.48 (2C), 135.30, 129.79, 128.36,
126.15 (2C), 126.13 (2C), 126.11, 28.23 (2C), 28.13 (2C), 26.60 ppm
(CH3). One portion of 2,3-dichloro-5,6-dicyano-1,4-benzoquinone (DDQ;
5.06 g, 22.3 mmol) was added to a solution of 2-acetyl-4,5,9,10-tetrahydro-
pyrene (2.38 g, 9.6 mmol) in toluene (150 mL) and the solution was re-
fluxed for 1 h, cooled, and then passed through an Al2O3 layer (4 cm) in
toluene to yield pure 2-acetylpyrene (2.0 g, 85%), m.p. 121–1248C
(AcOH/H2O) (lit. m.p. 145–1478C[50] and 145–1468C[40]), Rf =0.37 (5%
EtOAc/toluene, v/v). 1H NMR (CDCl3): d=8.72 (s, 2H, 1-H, 3-H), 8.20
(d, 2H, J6,7 =7.7 Hz, 6-H, 8-H), 8.12 (m, 4H, J4,5 =8.9 Hz, 4-H, 5-H, 9-H,
10-H), 8.06 (t, 1H, J6,7 =7.7 Hz, 7-H), 2.89 ppm (s, 3H, CH3); 13C NMR
(CDCl3): d=198.69 (CO), 134.21, 131.81 (2C), 131.04 (2C), 128.29 (2C),
127.88 (2C), 127.11 (C7), 127.01, 125.49 (2C), 124.47 (2C), 124.27,
27.11 ppm (=CH3). The 2-acetylpyrene was transformed further into 3-(2-
pyrenyl)-3-chlor-2-propenal by using the following procedure: POCl3
(5.0 mL, 54 mmol) was added dropwise to ice-cooled DMF (4.3 mL,
55 mmol) over 1 h. The mixture obtained was added dropwise at RT to a
solution of 2-acetylpyrene (1.86 g, 7.6 mmol) in DMF (70 mL) and the re-
action mixture was left to stir overnight. Then the reaction mixture was
poured into cold water (500 mL), and solid AcONa·3H2O was added
until the pH value reached 6. The mixture was extracted with CHCl3
(200 mL), the organic layer was washed with water (3300 mL), dried
over Na2SO4 and concentrated in vacuo. The residue was chromatograph-
ed on silica gel in toluene to yield 3-(2-pyrenyl)-3-chlor-2-propenal
(1.86 g, 84%) as a yellow solid. Rf 0.46 (5% EtOAc-toluene v/v). NMR
spectroscopy showed the compound to be the mixture of E- (97%) and
Z- (3%) stereoisomers. 1H NMR (CDCl3): d=10.34 (d, 0.97H, J=
6.8 Hz, (E)-CHO), 9.56 (d, 0.03H, J=7.6 Hz, (Z)-CHO), 8.48 (s, 2H, 1-
agent (POCl3 (3.6 mL, 39 mmol) with DMF (3.0 mL, 39 mmol)). Yield
1.49 g (94%), yellow solid. Rf =0.4 (5% EtOAc/toluene, v/v). 1H NMR
(CDCl3): d=10.46 (d, 0.46H, J=7.0 Hz, (E)-CHO), 9.43 (d, 0.54H, J=
7.4 Hz, (Z)-CHO), 8.45–8.05 (m, 9H, ArH), 6.90 (d, 0.54H, J=7.4 Hz,
(Z)-CHCHO), 6.71 ppm (d, 0.46H, J=7.0 Hz, (E)-CHCHO). 3-(4-Pyren-
yl)-3-chlor-2-propenal (291 mg, 1.0 mmol) in dioxane (10 mL) with KOH
(177 mg, 3.16 mmol) was converted to 4-ethynylpyrene (12), colorless
crystals, m.p. 103–1048C (lit. m.p. 103–1058C[47]). Yield 190 mg (84%).
Rf =0.6 (toluene). 1H NMR (CDCl3): d=8.69 (d, 1H, J=7.8 Hz, 3-H),
8.38 (s, 1H, 5-H), 8.22 (d, 1H, J=7.8 Hz, 1-H), 8.20 (d, 1H, J=7.8 Hz, 8-
H), 8.15 (d, 1H, J=7.3 Hz, 6-H), 8.11–8.04 (m, 3H, 2-H, 9-H, 10-H), 8.00
(m, 1H, 7-H), 3.55 ppm (s, 1H, CH); 13C NMR (CDCl3): d=133.26
ꢂ
(C5), 131.22 (C10a), 131.03 (C8a), 130.30 (C3a), 130.07 (C5a), 127.61
(C10), 127.20 (C9), 126.25 (C8), 126.20 (C2), 126.12 (C7), 125.75 (C1),
125.23 (C6), 124.40 (2C, C10b, C10c), 123.72 (C3), 119.28 (C4), 82.01
ꢂ
ꢂ
(ArC ), 81.69 ppm ( CH).
Synthesis of DMT-protected oTINA precursor: (S)-1-(4,4’-dimethoxytri-
phenylmethyloxy)-3-(2-iodobenzyloxy)-propan-2-ol (DMT-14): (S)-(+)-
2,2-Dimethyl-1,3-dioxolane-4-methanol (13, 1.17 g, 8.9 mmol) and 2-iodo-
benzylbromide (2.5 g, 8.4 mmol) were refluxed under Dean–Stark condi-
tions in toluene (125 mL) in the presence of KOH (4.4 g, 77.0 mmol) for
7 h. The reaction mixture was allowed to cool and H2O (50 mL) was
added. After separation of the phases, the water layer was washed with
toluene (225 mL). The combined organic layers were washed with H2O
(30 mL) and concentrated in vacuo. The residue was treated with 80%
aq. CF3CO2H (25 mL) for 4 h at RT. The solvent was removed in vacuo
and the residue was coevaporated twice with toluene/EtOH (30 mL, 5:1,
v/v) and then with dry pyridine (20 mL). The residue was dried under di-
minished pressure to afford (R)-3-(2-iodobenzyloxy)propane-1,2-diol (14,
100%, 2.3 g) as yellowish oil that was used in the next step without fur-
ther purification. This oil (2.3 g, 8.4 mmol) was dissolved in anhydrous
pyridine (25 mL) and 4,4’-dimethoxytrityl chloride (3.5 g, 10.4 mmol) was
then added under nitrogen. After 24 h, ethanol (2 mL) followed by
EtOAc (150 mL) were added and the mixture was extracted with saturat-
ed aqueous NaHCO3 (340 mL). The water phase was extracted with
EtOAc (50 mL). The combined organic layers were dried (Na2SO4), fil-
tered, and evaporated under diminished pressure. The residue was coeva-
porated twice with toluene/EtOH (25 mL, 1:1, v/v). The residue was ad-
sorbed on silica gel (3.0 g) from EtOAc (30 mL) and purified by using
dry column vacuum chromatography with EtOAc (0–25%, v/v) in cyclo-
hexane to afford (S)-1-(4,4’-dimethoxytriphenylmethyloxy)-3-(2-iodo-
H, 3-H), 8.20 (d, 2H, J6,7 =7.8 Hz, 6-H, 8-H), 8.13–8.02 (m, 5H, J4,5
=
9.0 Hz, 4-H, 5-H, 7-H, 9-H, 10-H), 6.98 (d, 0.97H, J=6.8 Hz, (E)-
CHCHO), 6.74 ppm (d, 0.03H, J=7.6 Hz, (Z)-CHCHO). To a solution
of 3-(2-pyrenyl)-3-chlor-2-propenal (648 mg, 2.23 mmol) in dioxane
(90 mL), pulverized KOH (394 mg, 7.0 mmol) was added with stirring
under argon and the reaction mixture was refluxed for 2 h, cooled, and
then the pH value was adjusted to 3 through the addition of 5% aq.
citric acid. Solvents were removed in vacuo and the residue was dissolved
in toluene (150 mL), washed with water (3200 mL), dried over Na2SO4,
and concentrated in vacuo. The residue was chromatographed on silica
gel by using a step gradient of 50!70!90!100% (v/v) of toluene in
ACHTREUNGpetroleum ether to give 2-ethynylpyrene (11) as colorless crystals. Yield
480 mg (95%). Rf 0.6 (CHCl3). m.p. 112–1148C (ethanol; lit. m.p. 125–
1278C,[50] 110–1128C,[49] and 103–1048C[47]). 1H NMR (500 MHz, CDCl3):
d=8.27 (s, 2H, 1-H, 3-H), 8.16 (d, 2H, J6,7 =7.6 Hz, 6-H, 8-H), 8.06 (m,
2H, J4,5 =9.1 Hz, 5-H, 9-H), 8.00 (m, 3H, 4-H, 7-H, 10-H), 3.24 ppm (s,
1H,=CH); 13C NMR (CDCl3): d=131.26 (2C, C5a, C8a), 131.00 (2C,
C3a, C10a), 128.16 (2C, C1, C3), 128.12 (2C, C5, C9), 126.82 (2C, C4,
C10), 126.41 (C7), 125.40 (2C, C6, C8), 124.46 (C10b), 124.29 (C10c),
AHCTREbUNG enzyloxy)propane-2-ol (62%, 3.0 g) as a
yellow foam. 1H NMR
(CDCl3): d=2.46 (d, 1H, J=5.0 Hz; OH), 3.25 (dd, 2H, J=1.9, 5.0 Hz;
CHOHCH2OCH2), 3.67 (m, 2H; CH2ODMT), 3.75 (s, 6H, 2CH3), 4.00
(m, 1H; CHOH), 4.50 (s, 2H; CH2Ar), 6.81 (d, 4H, J=8.5 Hz; DMT),
6.97 (m, 1H; phenyl), 7.20–7.30 (m, 9H; phenyl+DMT), 7.41 (m, 2H;
phenyl), 7.80 ppm (d, 1H, J=7.9 Hz; phenyl). 13C NMR (CDCl3): d=
55.17, 55.19 (OCH3), 64.39 (CH2ODMT), 69.93 [CH(OH)CH2OCH2],
72.04 (CHOH), 76.9 (CH2-phenyl), 86.09 (CAr3), 97.79 (C-1) , 113.10
(DMT), 126.76 (DMT), 127.81 (iodophenyl), 128.11 (DMT), 128.17
(DMT), 128.87 (iodophenyl), 129.25 (iodophenyl), 130.04 (DMT), 135.96
(DMT), 139.17 (iodophenyl), 140.21 (iodophenyl), 144.8 (DMT),
158.45 ppm (DMT). HR-MALDI-MS: calcd for C31H31IO5Na [M+Na]+:
m/z 633.1108; found: m/z 633.1082.
ꢂ
ꢂ
119.39 (C2), 84.28 (ArC ), 77.43 ppm ( CH).
Synthesis of 4-ethynylpyrene (12): For a preliminary report, see refer-
ence [67]. In a manner similar to that described in the above procedure,
4-acetyl-1,2,3,6,7,8-hexahydropyrene was prepared from 10 (8.06 g,
39 mmol), AlCl3 (11.37 g, 85 mmol), and Ac2O (4.03 mL, 43 mmol). The
ketone was purified by chromatography on silica gel in toluene. Yield
8.93 g (92%), yellow crystals. Rf =0.31 (toluene). m.p. 78–798C (benzene;
lit. m.p. 85–868C[49]). 1H NMR (CDCl3): d=7.38 (s, 1H, 5-H), 7.19 (m,
2H, J=7.1 Hz, 9-H, 10-H), 3.28 (t, 2H, J=6.0 Hz, 3-H), 3.12–3.03 (m,
6H, 1-H, 6-H, 8-H), 2.64 (s, 3H, CH3), 2.10–1.97 (m, 4H, 2-H, 7-H) ppm;
13C NMR (CDCl3): d 203.31 (CO), 136.15, 134.73, 134.03, 134.00, 133.48,
131.27, 130.22, 125.38, 124.47, 122.40, 31.51, 31.30, 31.27, 30.56, 29.32,
Synthesis of (S)-2-O-[2-cyanoethoxy(diisopropylamino)phosphino]-1-O-
(4,4’-dimethoxytriphenylmethyl)-3-O-(2-iodobenzyl)glycerol (15): (S)-1-
(4,4’-Dimethoxytriphenylmethyloxy)-3-(2-iodobenzyloxy)propane-2-ol
(1.5 g, 2.46 mmol) was dissolved under nitrogen in anhydrous CH2Cl2
(50 mL). N,N-Diisopropylammonium tetrazolide (0.660 g, 3.85 mmol) was
added followed by dropwise addition of 2-cyanoethyl tetraisopropyl-
23.19,
23.01 ppm.
4-Acetyl-1,2,3,6,7,8-hexahydropyrene
(770 mg,
3.08 mmol) was aromatized with DDQ (2.27 g, 10 mmol) in toluene
(20 mL) to give 4-acetylpyrene as yellow crystals. Yield 560 mg (75%).
Rf =0.45 (toluene), m.p. 136–1388C (toluene; lit. m.p. 132.5–133.58C[45]).
1H NMR (CDCl3): d=9.09 (d, 1H, J=8.0 Hz, 3-H), 8.52 (s, 1H, 5-H),
8.25–8.17 (m, 3H, 1-H, 6-H, 8-H), 8.08–7.97 ppm (m, 4H, 2-H, 7-H, 9-H,
10-H); 13C NMR (CDCl3): d=201.64 (CO), 134.90, 131.64, 131.11, 131.02,
129.17, 128.17, 127.34, 127.24, 126.71, 126.64, 126.48, 126.17, 125.92,
125.54, 125.27, 124.47, 29.83 ppm (CH3). 3-(4-Pyrenyl)-3-chlor-2-propenal
was prepared from 4-acetylpyrene (1.338 g, 5.5 mmol) and Vilsmeier re-
ACHRTEpGNU hosphorAHCTREdUGN iamidite (0.854 g, 2.82 mmol) with external cooling with an ice-
water bath. After stirring overnight, analytical TLC showed no more
starting material, and the reaction was quenched with H2O (45 mL). The
layers were separated and the organic phase was washed with H2O
(30 mL). Combined water layers were washed with CH2Cl2 (25 mL). The
organic phase was dried (Na2SO4) and filtered, silica gel (1.5 g) and pyri-
dine (0.5 mL) were added, and solvents were removed under reduced
pressure. The residue was purified by using silica gel dry column vacuum
chromatography with Et3N (0.5%)/EtOAc (0–25%, v/v)/petroleum
9978
ꢁ 2008 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Chem. Eur. J. 2008, 14, 9968 – 9980