benzyne-cyclization

FULL PAPER

J. Barluenga et al.

122.3, 120.8, 112.3, 109.0, 62.9, 45.4, 29.6, 29.1, 24.0, 22.2, 16.9; MS (70 eV, EI): m/z(%): 351 (2) [M]#, 292 (100); elemental analysis calcd (%) for C22H26N2S (350.5): C 75.38, H 7.48, N 7.99; found: C 75.13, H 7.55, N 8.05.

Diethyl 2-hydroxy-2-(1,2,3,4-tetrahydro-9-methyl-9H-carbazol-4-yl)propa- nedioate (20 b): Amine 17 (0.57 g, 2 mmol) was treated with tBuLi (4.7 mL, 1.5 solution in pentane, 7 mmol). Addition of water (0.05 mL, 3 mmol), followed by diethyl ketomalonate (0.38 g, 2.2 mmol) and workup as described above yielded 20 b (0.40 g, 55 %) as a white solid. M.p. 149 ± 151 C; 1H NMR (CDCl3 , 400 MHz): $7.5 (d, J $8.0 Hz, 1H), 7.25 (d, J $ 7.4 Hz, 1H), 7.1 (dd, J $8.0, 7.4 Hz, 1 H), 7.0 (t, J $8.0 Hz, 1H), 4.4 (q, J $ 7.0 Hz, 2H), 4.30 ± 4.15 (m, 3H), 3.6 (s, 3H), 3.45 (s, 1H), 2.9 ± 2.8 (m, 1H), 2.7 ± 2.6 (m, 1H), 2.55 ± 2.4 (m, 1H), 2.05 ± 1.95 (m, 1H), 1.9 ± 1.75 (m, 2H), 1.4 (t, J $7.0 Hz, 3H), 1.2 (t, J $7.2 Hz, 3H); 13C NMR (CDCl3 , 50.5 MHz):$170.5, 170.1, 139.0, 136.7, 126.3, 120.5, 118.6, 118.5, 108.5, 105.1, 83.1, 62.6, 62.4, 37.7, 29.0, 26.4, 21.4, 19.0, 14.0, 13.7; MS (70 eV, EI): m/z(%): 359

(1) [M]#, 184 (100); elemental analysis calcd (%) for C20H25NO5 (359.4): C 66.83, H 7.01, N 3.90; found: C 66.69, H 6.87, N 3.94.

General procedure for the preparation of 5-alkyl-1-functionalized-5,6- dihydrophenanthridines (26 and 27): A solution of the starting amine 25 a or 25 b (2 mmol) in THF (15 mL) was treated with 3.5 equiv tBuLi (7 mmol) at 110 C. The reaction mixture was stirred for 15 min at this temperature. The cooling bath was then removed allowing the reaction to warm up to room temperature. The reaction mixture was then re-cooled to78 C, the electrophile (3 mmol) was added, and the mixture was stirred for 3 h at room temperature. The mixture was hydrolyzed with water and extracted with ethyl acetate (3 20 mL). The combined organic layers were dried over anhydrous Na2SO4 . After evaporation of the solvent, the residue was purified by flash column chromatography (hexane/ethyl acetate) to afford products 26 ± 27.

5,6-Dihydro-5-methylphenanthridine (26 a): Amine 25 a (0.59 g, 2 mmol) was treated with tBuLi (4.7 mL, 1.5 solution in pentane, 7 mmol). Addition of H2O (excess) and workup as described above yielded 26 a (0.32 g, 81%) as a yellow solid. M.p. 80 ± 82 C (hexane); 1H NMR (CDCl3 , 200 MHz): $7.8 (d, J $6.2 Hz, 1H), 7.45 ± 7.15 (m, 5H), 6.95 (t, J $7.6 Hz, 1H), 6.8 (d, J $7.9 Hz, 1H), 4.2 (s, 2H), 3.0 (s, 3H); 13C NMR (CDCl3 , 50.5 MHz): $147.2, 133.1, 132.1, 129.0, 127.6, 126.9, 125.6, 123.5, 123.3, 122.4, 118.5, 112.3, 55.0, 38.5; MS (70 eV, EI): m/z(%): 195 (62) [M]#, 194 (100); elemental analysis calcd (%) for C14H13N (195.3): C 86.12, H 6.71, N 7.17; found: C 86.01, H 6.90, N 7.03.

1-Bromo-5,6-dihydro-5-methylphenanthridine (26 b): Amine 25 a (0.59 g, 2 mmol) was treated with tBuLi (4.7 mL, 1.5 solution in pentane, 7 mmol). Addition of 1,2-dibromoethane (0.56 g, 3 mmol) and workup as described above yielded 26 b (0.37 g, 68%) as a yellow solid. M.p. 82 ± 84 C (hexane); 1H NMR (CDCl3 , 400 MHz): $8.6 (d, J $8.4 Hz, 1H), 7.4 (t, J $7.6 Hz, 1H), 7.3 (t, J $7.6 Hz, 1H), 7.3 ± 7.2 (m, 2H), 7.1 (t, J $8.2 Hz, 1H), 6.8 (d, J $8.0 Hz, 1H), 4.0 (s, 2H), 3.0 (s, 3H); 13C NMR (CDCl3 , 50.5 MHz): $150.4, 135.5, 130.9, 128.9, 127.2, 126.3, 125.0, 123.5, 120.3, 111.7, 55.3, 39.0; MS (70 eV, EI): m/z(%): 275 (50) [M#2]#, 274 (100), 273 (50) [M]#, 272 (100); elemental analysis calcd (%) for C14H12BrN (274.2): C 61.33, H 4.41, N 5.11; found: C 61.50, H 4.29, N 5.14.

5,6-Dihydro-5-methyl-1-phenylthiophenanthridine (26 c): Amine 25 a

(0.59 g, 2 mmol) was treated with tBuLi (4.7 mL, 1.5 solution in pentane, 7 mmol). Addition of diphenyl disulfide (0.66 g, 3 mmol) and workup as described above yielded 26 c (0.485 g, 80%) as a yellow solid. M.p. 145 ± 147 C (hexane); 1H NMR (CDCl3 , 400 MHz): $8.3 (d, J $8.0 Hz, 1H), 7.4 ± 7.2 (m, 8H), 7.1 (t, J $8.2 Hz, 1H), 6.8 (d, J $8.0 Hz, 1H), 6.7 (d, J $ 8.4 Hz, 1H), 4.0 (s, 2H), 3.0 (s, 3H); 13C NMR (CDCl3 , 50.5 MHz): $ 149.5, 136.6, 135.5, 133.0, 130.8, 128.9, 128.2, 127.5, 126.9, 126.6, 126.4, 125.2, 124.9, 123.9, 111.2, 55.3, 39.0; MS (70 eV, EI): m/z(%): 303 (66) [M]#, 302 (100); elemental analysis calcd (%) for C20H17NS (303.4): C 79.17, H 5.65, N 4.62; found: C 78.98, H 5.71, N 4.51.

Ethyl 5,6-dihydro-5-methyl-1-phenanthridinecarboxylate (26 d): Amine

25 a (0.59 g, 2 mmol) was treated with tBuLi (4.7 mL, 1.5 solution in pentane, 7 mmol). Addition of ethyl chloroformate (0.32 g, 3 mmol) and workup as described above yielded 26 d (0.42 g, 78%) as a green oil. Rf $ 0.2 (hexane/ethyl acetate 20:1); 1H NMR (CDCl3 , 400 MHz): $7.4 ± 7.2 (m, 5H), 7.1 (d, J $7.2 Hz, 1H), 6.8 (d, J $8.4 Hz, 1H), 4.3 (q, J $7.2 Hz, 2H), 4.1 (s, 2H), 2.9 (s, 3H), 1.2 (t, J $7.2 Hz, 3H); 13C NMR (CDCl3 , 50.5 MHz): $170.8, 148.4, 134.3, 130.5, 128.1, 127.0, 126.6, 126.3, 125.1, 122.4, 119.5, 114.6, 61.1, 54.8, 38.6, 13.7; MS (70 eV, EI): m/z(%): 267 (67)

[M]#, 266 (100); elemental analysis calcd (%) for C17H17NO2 (267.3): C 76.38, H 6.41, N 5.24; found: C 76.51, H 6.25, N 5.21.

5,6-Dihydro-5-methyl-1-tributylstannylphenanthridine (26 e): Amine 25 a

(0.59 g, 2 mmol) was treated with tBuLi (4.7 mL, 1.5 solution in pentane, 7 mmol). Addition of tributyltin chloride (0.96 g, 3 mmol) and workup as above yielded 26 e (0.74 g, 76%) as a yellow oil. Rf $0.35 (hexane/ethyl acetate 25:1); 1H NMR (CDCl3 , 400 MHz): $7.6 (d, J $7.7 Hz, 1H), 7.5 ± 7.2 (m, 5H), 6.9 (d, J $8.0 Hz, 1H), 4.1 (s, 2H), 3.0 (s, 3H), 1.7 ± 1.5 (m, 6H), 1.4 ± 1.3 (m, 6H), 1.1 ± 1.0 (m, 6H), 0.9 (t, J $7.3 Hz, 9H); 13C NMR (CDCl3 , 50.5 MHz): $148.5, 139.1, 135.3, 135.0, 131.7, 128.6, 128.0, 127.0, 126.6, 125.0, 124.8, 112.5, 55.4, 38.8, 28.9, 27.3, 13.6, 12.1; MS (70 eV, EI): m/z(%): 485 (4) [M]#, 312 (100); elemental analysis calcd (%) for C26H39NSn (484.3): C 64.48, H 8.12, N 2.89; found: C 64.27, H 8.17, N 2.77.

5-Allyl-5,6-dihydrophenanthridine (27 a): Amine 25 b (0.64 g, 2 mmol) was treated with tBuLi (4.7 mL, 1.5 solution in pentane, 7 mmol). Addition of H2O (excess) and workup as described above yielded 27 a (0.31 g, 71%) as

a colorless oil. Rf $0.6 (hexane/ethyl acetate 25:1); 1H NMR (CDCl3 ,
± 5.8 (m, 1H), 5.5 ± 5.2 (m, 2H), 4.3 (s,
80 MHz): $7.8 ± 6.8 (m, 8H), 6.313	C NMR (CDCl3 , 20 MHz): $145.9,
2H), 3.9 (dt, J $5.4, 1.4 Hz, 2H);

133.2, 132.9, 132.1, 128.9, 127.5, 126.9, 125.5, 123.6, 123.2, 122.3, 118.2, 117.7, 112.9, 53.3, 52.0; MS (70 eV, EI): m/z(%): 221 (77) [M]#, 220 (100); elemental analysis calcd (%) for C16H15N (221.3): C 86.84, H 6.83, N 6.33; found: C 86.62, H 6.85, N 6.19.

Ethyl 5-allyl-5,6-dihydro-1-phenanthridinecarboxylate (27 b): Amine 25 b

(0.64 g, 2 mmol) was treated with tBuLi (4.7 mL, 1.5 solution in pentane, 7 mmol). Addition of ethyl chloroformate (0.27 g, 2.5 mmol) and workup as described above yielded 27 b (0.43 g, 73%) as a yellow oil. Rf $0.35 (hexane/ethyl acetate 20:1); 1H NMR (CDCl3 , 80 MHz): $7.3 ± 6.6 (m, 7H), 6.0 ± 5.5 (m, 1H), 5.4 ± 5.0 (m, 2H), 4.2 (q, J $7.0 Hz, 2H), 4.05 (s, 2H), 3.85 (dt, J $5.3, 1.3 Hz, 2H), 1.1 (t, J $7.0 Hz, 3H); 13C NMR (CDCl3 , 20 MHz): $170.8, 147.3, 134.2, 132.9, 130.9, 128.0, 127.0, 126.6, 125.0, 122.7, 119.6, 117.7, 115.5, 61.0, 53.8, 52.2, 13.7; MS (70 eV, EI): m/z(%): 293 (63) [M]#, 292 (100); elemental analysis calcd (%) for C19H19NO2 (293.4): C 77.79, H 6.53, N 4.77; found: C 77.82, H 6.45, N 4.58.

General procedure for the preparation of 1-functionalized-5,6-dihydro- phenanthridines (28): A solution of the starting amine 25 b (0.64 g, 2 mmol) in THF (15 mL) was treated with 3.5 equiv tBuLi (7 mmol) at 110 C. The reaction was stirred for 15 min at this temperature. The cooling bath was then removed and the reaction mixture was allowed to warm up to room temperature. The reaction mixture was re-cooled to 78 C, the electrophile (3 mmol) was added, and the mixture was stirred for 3 h at room temperature. The mixture was hydrolyzed with water and extracted with ethyl acetate (3 20 mL). The combined organic layers were dried over anhydrous Na2SO4 and the solvent was removed under vacuum. The residue and [NiCl2(dppp)] (0.04 g, 0.08 mmol) were dissolved in toluene (6 mL). DIBAL-H (3 mmol, 1.5 equiv) was added to the reaction mixture at 0 C and the temperature was then raised to 20 C. After stirring at the same temperature for 2 h, the mixture was treated with 0.5 NaOH (2 mL) and Et2O (9 mL) for 1 h and then dried directly over MgSO4 . After evaporation of the solvent, the residue was purified by flash column chromatography to afford products 28.

5,6-Dihydrophenanthridine (28 a): Amine 25 b (0.64 g, 2 mmol) was treated with tBuLi (4.7 mL, 1.5 solution in pentane, 7 mmol). Water (excess) was added and the mixture was treated as described above. DIBAL-H (2.0 mL, 1.5 solution in toluene, 3 mmol) was added to a solution of the resultant residue and [NiCl2(dppp)] (0.04 g, 0.08 mmol) in toluene (6 mL). The subsequent treatment with NaOH (2 mL, 0.5 solution in water, 1 mmol), Et2O (9 mL), and workup as described above yielded 28 a (0.25 g, 70%) as a white solid. M.p. 102 ± 104 C (hexane); 1H NMR (CDCl3 , 400 MHz): $ 7.8 ± 7.7 (m, 2H), 7.35 (t, J $6.4 Hz, 1H), 7.25 (t, J $6.7 Hz, 1H), 7.2 ± 7.1 (m, 2H), 6.9 (t, J $7.4 Hz, 1H), 6.7 (d, J $8.1 Hz, 1H), 4.4 (s, 2H), 3.9 (brs, 1H); 13C NMR (CDCl3 , 50.5 MHz): $145.6, 132.6, 131.9, 128.7, 127.5, 127.0, 125.9, 123.4, 122.3, 121.8, 119.1, 115.0, 46.2; MS (70 eV, EI): m/z(%): 181 (38) [M]#, 180 (100); elemental analysis calcd (%) for C13H11N (181.3): C 86.15, H 6.12, N 7.73; found: C 85.98, H 6.10, N 7.59.

5,6-Dihydro-1-hydroxymethylphenanthridine	(28 b): Amine	25 b (0.64 g,
2 mmol) was treated with tBuLi (4.7 mL,	1.5 solution	in pentane,

7 mmol). Ethyl chloroformate (0.32 g, 3 mmol) was added and the mixture was treated as described above. DIBAL-H (2.0 mL, 1.5 solution in toluene, 3 mmol) was added to a solution of the resultant residue and

2044		¹ WILEY-VCH Verlag GmbH, 69451 Weinheim, Germany, 2002	0947-6539/02/0809-2044	$ 20.00+.50/0	Chem. Eur. J. 2002, 8, No. 9

Functionalized Heterocycles

2034 ± 2046

[NiCl2(dppp)] (0.04 g, 0.08 mmol) in toluene (6 mL) and subsequent treatment with NaOH (2 mL, 0.5 solution in water, 1 mmol), Et2O (9 mL), and workup as described above yielded 28 b (0.29 g, 69%) as a white solid. M.p. 108 ± 110 C (hexane); 1H NMR (CDCl3 , 400 MHz): $ 7.98 (d, J $7.6 Hz, 1H), 7.35 (dt, J $7.6, 1.6 Hz, 1H), 7.25 (dt, J $7.2, 1.6 Hz, 1H), 7.2 (d, J $7.6 Hz, 1H), 7.15 (t, J $7.6 Hz, 1H), 7.0 (dd, J $7.6, 1.2 Hz, 1H), 6.7 (dd, J $7.6, 1.2 Hz, 1H), 4.9 (s, 2H), 4.15 (s, 2H), 3.3 (brs, 2H); 13C NMR (CDCl3 , 50.5 MHz): $147.4, 137.6, 135.4, 131.3, 127.9, 127.2, 126.7, 125.5, 122.7, 121.5, 115.0, 63.6, 46.5; MS (70 eV, EI): m/z (%): 211 (48) [M]#, 210 (100); elemental analysis calcd (%) for C14H13NO (211.3): C 79.59, H 6.20, N 6.63; found: C 79.65, H 6.17, N 6.61.

1-Bromo-5,6-dihydrophenanthridine (28 c): Amine 25 b (0.64 g, 2 mmol) was treated with tBuLi (4.7 mL, 1.5 solution in pentane, 7 mmol). 1,2- Dibromoethane (0.56 g, 3 mmol) was added and the mixture was treated as described above. DIBAL-H (2.0 mL, 1.5 solution in toluene, 3 mmol) was added to a solution of the resultant residue and [NiCl2(dppp)] (0.04 g, 0.08 mmol) in toluene (6 mL). Subsequent treatment with NaOH (2 mL, 0.5 solution in water, 1 mmol) and Et2O (9 mL), and workup as described above yielded 28 c (0.38 g, 73%) as a yellow solid. M.p. 83 ± 85 C (hexane); 1H NMR (CDCl3 , 400 MHz): $8.55 (d, J $6.8 Hz, 1H), 7.4 (dt, J $8.0, 1.6 Hz, 1H), 7.3 (dt, J $7.6, 1.2 Hz, 1H), 7.2 (d, J $7.6 Hz, 2H), 6.9 (t, J $ 8.0 Hz, 1H), 6.65 (d, J $8.0 Hz, 1H), 4.1 (s, 3H); 13C NMR (CDCl3 , 50.5 MHz): $149.2, 135.0, 130.8, 128.6, 127.2, 126.7, 126.3, 125.5, 125.3, 122.2, 120.2, 114.5, 46.3; MS (70 eV, EI): m/z(%): 261 (50) [M#2]#, 259 (50) [M]#, 260 (100), 258 (100); elemental analysis calcd (%) for C13H10BrN (260.1): C 60.02, H 3.87, N 5.38; found: C 60.18, H 3.70, N 5.39.

5,6-Dihydro-1-tributylstannylphenanthridine	(28 d): Amine	25 b	(0.64 g,
2 mmol) was treated with tBuLi (4.7 mL,	1.5 solution	in	pentane,

7 mmol). Tributyltin chloride (0.96 g, 3 mmol) was added and the mixture was treated as described above. DIBAL-H (2.0 mL, 1.5 solution in toluene, 3 mmol) was added to a solution of the resultant residue and [NiCl2(dppp)] (0.04 g, 0.08 mmol) in toluene (6 mL), and the subsequent treatment with NaOH (2 mL, 0.5 solution in water, 1 mmol), Et2O (9 mL), and workup as described above yielded 28 d (0.67 g, 71%) as a

colorless oil. Rf $0.18 (ethyl acetate/hexane 20:1); 1H NMR			(CDCl3 ,
400 MHz): $7.55 (d, J $7.2 Hz, 1H), 7.3 (dt, J $7.6, 1.6 Hz, 1H), 7.25 (dt,
J $7.6, 1.6 Hz, 1H), 7.2 (d, J $7.6 Hz, 1H), 7.15 (t, J $7.4 Hz, 1H), 7.05 (dd,
J $7.2, 1.6 Hz, 1H), 6.7 (dd, J $7.6, 1.6 Hz, 1H), 4.2 (s, 2H), 4.0 (brs, 1H),
1.4 (m, 6H), 1.35 ± 1.25 (m, 6H), 1.1 ± 1.0 (m, 6H), 0.85 (t, J			$	7.1 Hz,
1.5 ±	13
9H);		C NMR (CDCl3 , 50.5 MHz): $147.0, 139.0, 135.0, 134.9, 130.1,

129.3, 127.8, 126.9, 126.6, 125.2, 124.6, 115.3, 46.5, 28.9, 27.2, 13.6, 11.9; MS (70 eV, EI): m/z(%): 471 (2) [M]#, 298 (100); elemental analysis calcd (%) for C25H37NSn (470.3): C 63.85, H 7.93, N 2.98; found: C 63.78, H 8.02, N 2.90.

General procedure for the preparation of 6H-dibenzo[b,d]pyrans 29, 33, and 6H-dibenzo[b,d]thiopyrans (30): A solution of the starting ether 25 c or

32, or thioether 25d (2 mmol) in THF (15 mL) was treated with tBuLi (6.6 mmol, 3.3 equiv) at 110 C. The reaction mixture was stirred for 15 min at this temperature. The cooling bath was then removed to allow the reaction to warm up to room temperature. The reaction mixture was recooled to 78 C, the electrophile (2.5 mmol) was added, and the mixture was allowed to stir for 3 h at room temperature. The mixture was hydrolyzed with water and extracted with ethyl acetate (3 20 mL). The combined organic layers were dried over anhydrous Na2SO4 . After evaporation of the solvent, the residue was purified by flash column chromatography to afford products 29, 30, and 33.

1-Bromo-6H-dibenzo[b,d]pyran (29 a): Ether 25 c (0.56 g, 2 mmol) was treated with tBuLi (4.4 mL, 1.5 solution in pentane, 6.6 mmol). Addition of 1,2-dibromoethane (0.47 g, 2.5 mmol) and workup as described above yielded 29a (0.32 g, 61%) as a white solid. M.p. 54 ± 56 C (hexane); 1H NMR (CDCl3 , 400 MHz): $8.55 (d, J $7.6 Hz, 1H), 7.4 (t, J $7.6 Hz, 1H), 7.4 ± 7.3 (m, 2H), 7.2 (d, J $6.8 Hz, 1H), 7.1 ± 7.0 (m, 2H), 4.95 (s, 2H); 13C NMR (CDCl3 , 50.5 MHz): $157.3, 133.2, 129.3, 129.1, 128.6, 127.9, 127.6, 126.3, 124.7, 123.7, 119.7, 116.8, 69.2; MS (70 eV, EI): m/z(%): 262 (71) [M#2]#, 261 (100), 260 (67) [M]#, 259 (87); elemental analysis calcd (%) for C13H9BrO (261.1): C 59.80, H 3.47; found: C 60.02, H 3.41.

Ethyl 6H-dibenzo[b,d]pyran-1-carboxylate	(29b): Ether		25c	(0.56 g,
2 mmol) was treated with tBuLi (4.4 mL,	1.5	solution	in	pentane,
6.6 mmol). Addition of ethyl chloroformate (0.27 g,		2.5 mmol) and workup

as described above yielded 29b (0.35 g, 68%) as a yellow solid. M.p. 63 ±

65 C (hexane); 1H	NMR (CDCl3 , 400 MHz): $7.4 ± 7.2			(m, 6H), 7.1 (d,
J		J	$7.2 Hz, 2H), 1.3 (t,	J	$7.2 Hz, 3H);
13$7.8 Hz, 1H), 5.1 (s, 2H), 4.3 (q,
C NMR (CDCl3 ,	50.5 MHz): $169.8, 156.1, 132.3, 130.4, 128.8, 127.8,

126.2, 124.8, 123.6, 122.5, 120.0, 69.0, 61.5, 14.0; MS (70 eV, EI): m/z(%): 254 (100) [M]#; elemental analysis calcd (%) for C16H14O3 (254.3): C 75.57, H 5.55; found: C 75.64, H 5.61.

1-(1-Hydroxy-1-phenylmethyl)-6H-dibenzo[b,d]pyran (29c): Ether 25 c

(0.56 g, 2 mmol) was treated with tBuLi (4.4 mL, 1.5 solution in pentane, 6.6 mmol). Addition of benzaldehyde (0.26 g, 2.5 mmol) and workup as described above yielded 29c (0.32 g, 56%) as a yellow solid. M.p. 47 ± 49 C (hexane); 1H NMR (CDCl3 , 400 MHz): $7.85 ± 7.75 (m, 1H), 7.4 ± 7.0 (m, 11H), 6.4 (s, 1H), 5.0 (s, 2H), 2.8 (brs, 1H); 13C NMR (CDCl3 , 50.5 MHz):$155.9, 143.6, 140.5, 134.0, 129.3, 128.9, 128.2, 127.3, 127.2, 127.1, 126.8, 124.9, 123.7, 123.3, 116.4, 72.2, 68.9; MS (70 eV, EI): m/z(%): 288 (100) [M]#; elemental analysis calcd (%) for C20H16O2 (288.3): C 83.31, H 5.59; found: C 83.18, H 5.64.

1-Tributylstannyl-6H-dibenzo[b,d]pyran (29d): Ether 25c (0.56 g, 2 mmol) was treated with tBuLi (4.4 mL, 1.5 solution in pentane, 6.6 mmol). Addition of tributyltin chloride (0.83 g, 3 mmol) and workup as described above yielded 29 d (0.565 g, 60%) as a colorless oil. Rf $0.15 (hexane/ethyl acetate 60:1); 1H NMR (CDCl3 , 200 MHz): $7.7 ± 7.0 (m, 7H), 5.0 (s, 2H), 1.7 ± 0.9 (m, 27H); 13C NMR (CDCl3 , 50.5 MHz): $155.9, 139.1, 133.2, 132.9, 131.8, 130.7, 128.7, 127.8, 127.1, 124.5, 124.1, 117.1, 68.8, 28.9, 27.2, 13.6, 11.9; MS (70 eV, EI): m/z(%): 415 [M C4H9]# (84), 301 (100); elemental analysis calcd (%) for C25H36OSn (471.3): C 63.72, H 7.70; found: C 63.58, H 7.57.

6H-Dibenzo[b,d]thiopyran (30a): Thioether 25 d (0.59 g, 2 mmol) was treated with tBuLi (4.4 mL, 1.5 solution in pentane, 6.6 mmol). Addition of water (excess) and workup as described above yielded 30 a (0.23 g, 59%) as a white solid. M.p. 70 ± 72 C (hexane); 1H NMR (CDCl3 , 200 MHz): $ 7.8 (dd, J $7.0, 2.2 Hz, 1H), 7.7 (d, J $7.2 Hz, 1H), 7.5 ± 7.2 (m, 6H), 3.85 (s, 2H); 13C NMR (CDCl3 , 50.5 MHz): $134.6, 134.4, 134.3, 133.6, 128.4, 127.8, 127.6, 126.9, 126.4, 125.9, 125.7, 31.7; MS (70 eV, EI): m/z(%): 198 (65) [M]#, 197 (100); elemental analysis calcd (%) for C13H10S (198.3): C 78.74, H 5.08; found: C 78.89, H 4.97.

Ethyl 6H-dibenzo[b,d]thiopyran-1-carboxylate (30b): Thioether 25 d

(0.59 g, 2 mmol) was treated with tBuLi (4.4 mL, 1.5 solution in pentane, 6.6 mmol). Addition of ethyl chloroformate (0.27 g, 2.5 mmol) and workup

			(0.27 g, 50%) as a yellow oil. R					$	0.18
as described above yielded 30 b 1							f
(ethyl acetate/diethylamine 50:1);				H NMR (CDCl3 , 200 MHz): $7.6 (d,
J	$7.8	7.3 ± 7.2 (m, 6H), 4.2 (q, J			$	7.2 Hz, 2H), 3.8 (s, 2H), 1.1 (t,
		Hz, 1H),	13
J $7.2		Hz, 3H);	C NMR (CDCl3 , 50.5 MHz): $170.0, 138.0, 134.7,

134.2, 133.5, 132.1, 130.4, 129.1, 128.1, 127.9, 127.0, 126.8, 126.3, 61.3, 32.3, 13.7; MS (70 eV, EI): m/z(%): 270 (100) [M]#; elemental analysis calcd (%) for C16H14O2S (270.4): C 71.08, H 5.22; found: C 70.92, H 5.16.

1-[1-Hydroxy-1-(4-methylphenyl)methyl]-6H-dibenzo[b,d]thiopyran (30c): Thioether 25d (0.59 g, 2 mmol) was treated with tBuLi (4.4 mL, 1.5 solution in pentane, 6.6 mmol). Addition of 4-methylbenzaldehyde (0.3 g, 2.5 mmol) and workup as described above yielded 30c (0.36 g, 57%) as a white solid. M.p. 84 ± 86 C (hexane); 1H NMR (CDCl3 , 200 MHz): $ 7.6 ± 7.1 (m, 11H), 6.3 (s, 1H), 3.7 (s, 2H), 2.55 (brs, 1H), 2.4 (s, 3H); 13C NMR (CDCl3 , 50.5 MHz): $141.5, 141.2, 137.1, 136.9, 136.7, 134.6, 133.1, 129.8, 129.0, 127.8, 127.6, 127.2, 127.0, 126.6, 126.2, 72.9, 32.9, 21.0; MS (70 eV, EI): m/z(%): 318 (6) [M]#, 316 (100); elemental analysis calcd (%) for C21H18OS (318.4): C 79.21, H 5.70; found: C 79.33, H 5.84.

2-Methoxy-6H-dibenzo[b,d]pyran (33a): Ether 32 (0.65 g, 2 mmol) was treated with tBuLi (4.4 mL, 1.5 solution in pentane, 6.6 mmol). Addition of water (excess) and workup as described above yielded 33 a (0.34 g, 81%) as a colorless oil. Rf $0.2 (ethyl acetate/diethylamine 40:1); 1H NMR (CDCl3 , 200 MHz): $7.7 (d, J $7.2 Hz, 1H), 7.5 ± 7.1 (m, 4H), 6.95 (d, J $ 8.8 Hz, 1H), 6.8 (dd, J $8.8, 2.8 Hz, 1H), 5.05 (s, 2H), 3.85 (s, 3H); 13C NMR (CDCl3 , 50.5 MHz): $154.8, 148.8, 131.8, 130.2, 128.3, 127.8, 124.7, 123.6, 122.0, 117.9, 115.0, 108.3, 68.6, 55.8; MS (70 eV, EI): m/z (%): 212 (100) [M]#; elemental analysis calcd (%) for C14H12O2 (212.2): C 79.22, H 5.70; found: C 78.99, H 5.73.

Ethyl 2-methoxy-6H-dibenzo[b,d]pyran-1-carboxylate (33b): Ether 32

(0.65 g, 2 mmol) was treated with tBuLi (4.4 mL, 1.5 solution in pentane, 6.6 mmol). Addition of ethyl chloroformate (0.27 g, 2.5 mmol) and workup as described above yielded 33 b (0.43 g, 75%) as a white solid. M.p. 71 ± 73 C (hexane); 1H NMR (CDCl3 , 200 MHz): $7.65 ± 7.55 (m, 1H),

Chem. Eur. J. 2002, 8, No. 9	¹ WILEY-VCH Verlag GmbH, 69451 Weinheim, Germany, 2002	0947-6539/02/0809-2045	$ 20.00+.50/0		2045

FULL PAPER

J. Barluenga et al.

7.4 ± 7.1 (m, 3H), 7.05 (d, J $8.8 Hz, 1H), 6.85 (d, J $8.8 Hz, 1H), 5.0 (s, 2H), 4.4 (q, J $7.0 Hz, 2H), 3.8 (s, 3H), 1.3 (t, J $7.0 Hz, 3H); 13C NMR (CDCl3 , 50.5 MHz): $168.3, 151.8, 149.4, 133.2, 128.7, 128.1, 127.9, 124.8, 124.3, 121.6, 120.4, 118.8, 112.5, 68.8, 61.4, 56.5, 13.8; MS (70 eV, EI): m/z (%): 284 (100) [M]#; elemental analysis calcd (%) for C17H16O4 (284.3): C 71.82, H 5.67; found: C 71.85, H 5.58.

1-[1-Hydroxy-1-(4-methylphenyl)methyl]-2-methoxy-6H-dibenzo[b,d]pyr- an (33c): Ether 32 (0.65 g, 2 mmol) was treated with tBuLi (4.4 mL, 1.5 solution in pentane, 6.6 mmol). Addition of 4-methylbenzaldehyde (0.3 g, 2.5 mmol) and workup as described above yielded 33c (0.525 g, 79%) as a white solid. M.p. 98 ± 100 C (hexane); 1H NMR (CDCl3 , 200 MHz): $ 7.40 ± 7.15 (m, 6H), 7.1 (d, J $8.8 Hz, 2H), 6.9 (d, J $8.8 Hz, 2H), 6.4 (d, J $11.6 Hz, 1H), 5.05 (d, J $12.4 Hz, 1H), 4.95 (d, J $12.4 Hz, 1H), 4.4 (d, J $11.6 Hz, 1H), 3.65 (s, 3H), 2.4 (s, 3H); 13C NMR (CDCl3 , 50.5 MHz):$153.4, 150.4, 141.1, 136.4, 134.3, 129.6, 128.8, 128.0, 127.4, 126.9, 126.4, 124.9, 124.6, 116.3, 112.7, 72.3, 69.2, 55.9, 21.0; MS (70 eV, EI): m/z(%): 332 (100) [M]#; elemental analysis calcd (%) for C22H20O3 (332.4): C 79.50, H 6.06; found: C 79.52, H 5.97.

2-Methoxy-1-phenylthio-6H-dibenzo[b,d]pyran (33d): Ether	32	(0.65 g,
2 mmol) was treated with tBuLi (4.4 mL, 1.5 solution	in	pentane,

6.6 mmol). Addition of diphenyl disulfide (0.54 g, 2.5 mmol) and workup

as above yielded			33 d (0.471 g, 73%) as a colorless oil. Rf $0.18 (ethyl
acetate/diethylamine 20:1);					H NMR (CDCl3 , 200 MHz): $8.4 ± 8.3 (m,
13					(d, J	$	8.8 Hz, 1H), 5.0 (s, 2H), 3.75 (s, 3H);
1H), 7.4 ± 7.1 (m, 9H), 6.9
C NMR (CDCl3 , 50.5 MHz): $156.2, 150.7, 138.2, 133.7, 129.7, 128.6,
127.7,	127.6,	127.4,	126.0,	124.8,		124.4,		118.9,	116.8,	112.2,	69.2,	56.6; MS
(70 eV, EI): m/z (%): 320					(100) [M]#; elemental analysis calcd (%) for
C20H16O2S (320.4): C 74.97, H 5.03; found: C 75.08, H 5.11.

Acknowledgements

Financial support from the Direccio¬n General de Investigacio¬n CientÌfica y Te¬cnica (DGICYT, PB97-1271), Junta de Castilla y Leo¬n (BU-09/99), and the Universidad de Burgos (N-038) are gratefully acknowledged. Y.F. thanks the Junta de Castilla y Leon and the Universidad de Burgos for a fellowship.

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Received: August 2, 2001 [F3464]

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