Download PDF
Synlett 2010(19): 2867-2870  
DOI: 10.1055/s-0030-1259046
LETTER
© Georg Thieme Verlag Stuttgart ˙ New York

A Convenient Entry to 3-Methylidenechroman-2-ones and 2-Methylidenedihydrobenzochromen-3-ones

Jakub Modranka, Anna Albrecht, Tomasz Janecki*
Institute of Organic Chemistry, Technical University of ŁódŸ, Żeromskiego 116,90-924 ŁódŸ,Poland
Fax: +48(42)6365530; e-Mail: tjanecki@p.lodz.pl;
Further Information

Publication History

Received 27 September 2010
Publication Date:
11 November 2010 (online)

    Permissions and Reprints All articles of this category

Abstract

A simple and versatile synthesis of 3-methylidenechroman-2-ones and 2-methylidenedihydrobenzochromen-3-ones has been developed. The reaction of phenols or naphthols with 3-methoxy-2-diethoxyphosphorylacrylate gave intermediate 3-diethoxyphosphorylchromen-2-ones or 2-diethoxyphosphorylbenzo-chromen-3-ones, respectively. These compounds were employed as Michael acceptors in the reaction with Grignard reagents to yield 4-substituted 3-diethoxyphosphorylchroman-2-ones or 1-substituted 2-diethoxyphosphoryldihydrobenzochromen-3-ones. The obtained adducts were next used as Horner-Wadsworth-Emmons reagents for the olefination of formaldehyde to give the final products.

Key words

Friedel-Crafts electrophilic aromatic substitution - Michael addition - Horner-Wadsworth-Emmons olefination - 3-methylidenechroman-2-ones - 2-methylidenedihydrobenzochromen-3-ones

16

General Procedure for the Synthesis of 3-Diethoxy-phosphorylchromen-2-ones 6a-c and 2-Diethoxy-phosphoryldihydrobenzochromen-3-ones 8a,b: To a solution of the corresponding phenol 5a-c (11 mmol) or naphthol 7a,b (11 mmol) in CH2Cl2 (50 mL), trifluoro-methanesulfonic acid (3.00 g, 20 mmol) or methanesulfonic acid (1.92 g, 20 mmol) and acrylate 4 (2.66 g, 10 mmol) were added and the resulting mixture was stirred at r.t. for the period of time given in Table  [¹] . Next, sat. aq NaHCO3 solution was added (100 mL). Extraction with CH2Cl2 (3 × 30 mL), drying (MgSO4) and evaporation of the solvent gave the crude product, which was purified by crystallization from Et2O.
Diethyl (7-Methoxy-2-oxo-2 H -chromen-3-yl)-phosphonate (6a): orange solid; mp 64-65 ˚C. IR (film): 1726, 1601, 1228, 1134, 1016 cm-¹. ¹H NMR (250 MHz, CDCl3): δ = 1.35 [t, ³ J HP = 7.1 Hz, 6 H, (CH 3CH2O)2P(O)], 3.88 (s, 3 H, MeO), 4.14-4.31 [m, 4 H, (CH3CH 2O)2P(O)], 6.69 (d, 4 J HH = 2.4 Hz, 1 H, CH-Ar), 6.87 (dd, ³ J HH = 8.7 Hz, 4 J HH = 2.4 Hz, 1 H, CH-Ar), 7.46 (d, ³ J HH = 8.7 Hz, 1 H, CH-Ar), 8.43 (d, ³ J HP = 17.4 Hz, 1 H, H-4). ¹³C NMR (62.9 MHz, CDCl3): δ = 16.18 [d, ³ J PC = 6.4 Hz, (CH3CH2O)2P(O)], 55.81 (s, MeO), 62.97 [d, ² J PC = 5.8 Hz, (CH3 CH2O)2P(O)], 100.38 (s, C-Ar), 111.49 (d, ³ J PC = 14.3 Hz, C-Ar), 112.84 (d, ¹ J PC = 198.9 Hz, C-3), 113.16 (s, C-Ar), 130.33 (s, C-Ar), 153.19 (d, ² J PC = 7.0 Hz, C-4), 157.31 (s, C-Ar), 158.37 (d, ² J PC = 15.0 Hz, C-2), 164.72 (s, C-Ar). ³¹P NMR (101 MHz, CDCl3): δ = 12.47. Anal. Calcd for C14H17O6P: C, 53.85; H, 5.49. Found: C, 53.64; H, 5.52.
Diethyl (3-Oxo-3 H -benzo[ f ]chromen-2-yl) phosphonate (8a): orange solid; mp 136-137 ˚C. IR (film): 1732, 1604, 1256, 1136, 1024 cm-¹. ¹H NMR (250 MHz, CDCl3): δ = 1.38-1.44 [m, 6 H, (CH 3CH2O)2P(O)], 4.15-4.39 [m, 4 H, (CH3CH 2O)2P(O)], 7.48 (d, ³ J HH = 9.0 Hz, 1 H, CH-Ar), 7.61 (t, ³ J HH = 9.0 Hz, 1 H, CH-Ar), 7.75 (t, ³ J HH = 9.0 Hz, 1 H, CH-Ar), 7.93 (d, ³ J HH = 7.2 Hz, 1 H, CH-Ar), 8.10 (d, ³ J HH = 7.2 Hz, 1 H, CH-Ar), 8.37 (d, ³ J HH = 9.0 Hz, 1 H, CH-Ar), 9.30 (d, ³ J HP = 17.6 Hz, 1 H, H-1). ¹³C NMR (62.9 MHz, CDCl3): δ = 16.27 [d, ³ J PC = 6.3 Hz, (CH3CH2O)2P(O)], 63.30 [d, ² J PC = 5.9 Hz, (CH3 CH2O)2P(O)], 112.20 (s, C-Ar), 115.70 (d, ¹ J PC = 197.0 Hz, C-2), 116.52 (s, C-Ar), 121.45 (s, C-Ar), 126.43 (s, C-Ar), 128.97 (s, C-Ar), 129.12 (s, 2 × C-Ar), 130.08 (s, C-Ar), 135.82 (s, C-Ar), 148.99 (d, ² J PC = 7.4 Hz, C-1), 155.79 (s, C-Ar), 158.23 (d, ² J PC = 14.5 Hz, C-3). ³¹P NMR (101 MHz, CDCl3): δ = 12.38. Anal. Calcd for C17H17O5P: C, 61.45; H, 5.16. Found: C, 61.67; H, 4.89.

17

General Procedure for the Synthesis of 3-Diethoxy-phosphorylchroman-2-ones 12a-l and 3-Diethoxy-phosphoryldihydrobenzochromen-2-ones 14a-h: To a solution of the corresponding chromenones 6a-c (1 mmol) or benzochromenones 8a,b (1 mmol) and a catalytic amount of CuI (19 mg, 0.1 mmol) in THF (10 mL) a solution of Grignard reagent 11a-d (5 mmol) was added dropwise, under an argon atmosphere at r.t. (Me, n-Bu and i-Pr magnesium iodides were prepared from the corresponding alkyl halides and magnesium in Et2O; vinylmagnesium bromide was purchased from ALDRICH®). The solution was stirred for 48 h. After this time the reaction mixture was quenched with H2O (2 mL), acidified to pH ca. 1.5 with 10% aq HCl solution and extracted with CHCl3 (4 × 10 mL). The organic extracts were washed with brine (10 mL) and dried over MgSO4. Evaporation of the solvent gave the crude product which was purified by column chromatography (eluent: EtOAc-hexane, 3:1).
Diethyl trans -(7-Methoxy-4-methyl-2-oxochroman-3-yl)phosphonate (12a): colorless oil. IR (film): 1762, 1625, 1257, 1229, 1147, 1015 cm-¹. ¹H NMR (250 MHz, CDCl3): δ = 0.94 [t, ³ J HH = 7.1 Hz, 3 H, CH 3CH2OP(O)], 1.29 (dd, ³ J HH = 7.2 Hz, ³ J HH = 1.8 Hz, 3 H, Me), 1.31 [t, ³ J HH = 7.1 Hz, 3 H, CH 3CH2OP(O)], 3.28 (dd, ² J HP = 25.0 Hz, ³ J HH = 1.1 Hz, 1 H, CH-3), 3.42-3.58 [m, 2 H, CH3CH 2OP(O)], 3.71-3.85 (m, 4 H, MeO, CH-4), 4.05-4.17 [m, 2 H, CH3CH 2OP(O)], 6.59 (d, 4 J HH = 2.5 Hz, 1 H, CH-Ar), 6.70 (dd, ³ J HH = 8.4 Hz, 4 J HH = 2.5 Hz, 1 H, CH-Ar), 7.12 (d, ³ J HH = 8.4 Hz, 1 H, CH-Ar). ¹³C NMR (62.9 MHz, CDCl3): δ = 15.74 [d, ³ J PC = 6.1 Hz, CH3CH2OP(O)], 15.96 [d, ³ J PC = 6.3 Hz, CH3CH2OP(O)], 23.64 (d, ³ J PC = 18.6 Hz, Me), 31.56 (d, ² J PC = 4.3 Hz, C-4), 47.19 (d, ¹ J PC = 127.7 Hz, C-3), 55.32 (s, MeO), 61.75 [d, ² J PC = 7.0 Hz, CH3 CH2OP(O)], 62.92 [d, ² J PC = 6.8 Hz, CH3 CH2OP(O)], 91.80 (s, C-Ar), 102.05 (s,
C-Ar), 110.64 (s, C-Ar), 117.26 (s, C-Ar), 128.10 (s, C-Ar), 151.37 (s, C-Ar), 159.65 (s, C-Ar), 163.50 (d, ² J PC = 6.0 Hz, C-2). ³¹P NMR (101 MHz, CDCl3): δ = 19.20. Anal. Calcd for C15H21O6P: C, 54.88; H, 6.45. Found: C, 54.97; H, 6.61.

Diethyl trans -(1-Methyl-3-oxo-2,3-dihydro-1 H -benzo[ f ]chromen-2-yl)phosphonate (14a): yellow oil. IR (film): 1764, 1440, 1392, 1260, 1232, 1224, 1160, 1024 cm-¹. ¹H NMR (250 MHz, CDCl3): δ = 0.73 [t, ³ J HH = 7.1 Hz, 3 H, CH 3CH2OP(O)], 1.27 [t, ³ J HH = 7.1 Hz, 3 H, CH 3CH2OP(O)], 1.44 (dd, ³ J HH = 7.2 Hz, ³ J HH = 1.8 Hz, 3 H, Me), 3.28-3.38 (m, 1 H, CH-1), 3.47 (dd, ² J HP = 25.3 Hz, ³ J HH = 1.2 Hz, 1 H, CH-2), 3.59-3.69 [m, 1 H, CH3CH 2OP(O)], 4.04-4.16 [m, 2 H, CH3CH 2OP(O)], 4.24-4.39 [m, 1 H, CH3CH 2OP(O)], 7.21-7.26 (m, 1 H, CH-Ar), 7.44-7.50 (m, 1 H, CH-Ar), 7.56-7.63 (m, 1 H, CH-Ar), 7.76-7.87 (m, 2 H, 2 × CH-Ar), 7.96-8.00 (m, 1 H, CH-Ar). ¹³C NMR (62.9 MHz, CDCl3): δ = 15.64 [d, ³ J PC = 6.1 Hz, CH3CH2OP(O)], 16.07 [d, ³ J PC = 6.2 Hz, CH3CH2OP(O)], 21.72 (d, ³ J PC = 18.4 Hz, Me), 28.48 (d, ² J PC = 4.2 Hz, C-1), 47.01 (d, ¹ J PC = 127.6 Hz,
C-2), 62.84 [d, ² J PC = 6.9 Hz, CH3 CH2OP(O)], 63.15 [d, ² J PC = 6.7 Hz, CH3 CH2OP(O)], 116.95 (s, C-Ar), 118.49 (s,
C-Ar), 122.35 (s, C-Ar), 125.16 (s, C-Ar), 127.48 (s, C-Ar), 128.71 (s, C-Ar), 129.13 (s, C-Ar), 130.25 (s, C-Ar), 131.04 (s, C-Ar), 148.29 (s, C-Ar), 163.74 (d, ² J PC = 5.8 Hz, C-3). ³¹P NMR (101 MHz, CDCl3): δ = 18.72. Anal. Calcd for C18H21O5P: C, 62.07; H, 6.08. Found: C, 62.37; H, 6.23.

18

General Procedure for the Synthesis of 3-Methylidene-chroman-2-ones 13a-l and 2-Methylidenedihydro-benzochromen-3-ones 15a-h: To a solution of the corresponding chromanones 12a-l (0.5 mmol) or benzochromenones 14a-h (0.5 mmol) in THF (5 mL), t-BuOK (67 mg, 0.6 mmol) or NaH (14 mg, 0.6 mmol) was added and the resulting mixture was stirred at r.t. for 30 min. Then paraformaldehyde (75 mg, 2.5 mmol) was added in one portion. After 1.5 h, the reaction mixture was quenched with brine (5 mL), THF was removed under reduced pressure and the aqueous layer was extracted with CH2Cl2 (3 × 10 mL). The organic layer was dried over MgSO4 and the solvent was evaporated. The crude product was purified by column chromatography (eluent: CH2Cl2).
7-Methoxy-4-methyl-3-methylidenechroman-2-one (13a): colorless oil. IR (film): 1755, 1441, 1258, 1192, 1014 cm-¹. ¹H NMR (250 MHz, CDCl3): δ = 1.39 (d, ³ J HH = 7.1 Hz, 3 H, CH 3CH), 3.78 (s, 3 H, MeO), 3.74 (q, ³ J HH = 7.1 Hz, 1 H, CH-4), 5.73 (dd, 4 J HH = 0.9 Hz, ² J HH = 1.3 Hz, 1 H, CH2=C), 6.33 (dd, 4 J HH = 0.9 Hz, ² J HH = 0.9 Hz, 1 H, CH 2=C), 6.61 (d, 4 J HH = 2.5 Hz, 1 H, CH-Ar), 6.69 (dd, ³ J HH = 8.4 Hz, 4 J HH = 2.5 Hz, 1 H, CH-Ar), 7.08 (d, ³ J HH = 8.4 Hz, 1 H, CH-Ar). ¹³C NMR (62.9 MHz, CDCl3): δ = 22.81 (s, Me), 36.59 (s, C-4), 55.50 (s, MeO), 102.54 (s,
C-Ar), 110.94 (s, C-Ar), 118.85 (s, C-5), 126.99 (s, CH2=C), 127.33 (s, C-Ar), 138.20 (s, CH2=C), 150.76 (s, C-6), 159.64 (s, C-Ar), 163.49 (s, C-2). Anal. Calcd for C12H12O3: C, 70.57; H, 5.92. Found: 70.30; H, 5.81.
1-Methyl-2-methylidene-1,2-dihydrobenzo[ f ]chromen-3-one (15a): pale-yellow oil. IR (film): 1756, 1440, 1224, 1160, 1024 cm-¹. ¹H NMR (250 MHz, CDCl3): δ = 1.51 (d, ³ J HH = 7.2 Hz, 3 H, CH 3CH), 4.47 (q, ³ J HH = 7.2 Hz, 1 H, CH-1), 5.88 (s, 1 H, CH2=C), 6.44 (s, 1 H, CH2=C), 7.25-7.28 (m, 1 H, CH-Ar), 7.46-7.52 (m, 1 H, CH-Ar), 7.58-7.65 (m, 1 H, CH-Ar), 7.76-7.97 (m, 3 H, 3 × CH-Ar). ¹³C NMR (69.2 MHz, CDCl3): δ = 21.76 (s, Me), 33.11 (s, C-1), 115.83 (s, C-Ar), 118.23 (s, C-Ar), 120.44 (s, C-Ar), 123.38 (s,
C-Ar), 125.53 (s, CH2=C), 126.37 (s, C-Ar), 127.22 (s,
C-Ar), 127.29 (s, C-Ar), 128.37 (s, C-Ar), 129.38 (s, C-Ar), 136.18 (s, CH2=C), 145.60 (s, C-Ar), 161.48 (s, C-3). Anal. Calcd for C15H12O2: C, 80.34; H, 5.39. Found: 80.01; H, 5.23.