, Ethyl 4-methylenechromane-2-carboxylate (1a)
, Colorless oil, 172 mg, 79%; 1 H NMR (300 MHz, Chloroform-d, ? ppm) 7.53 (dd, J = 7.9, 1.6 Hz, 1H), vol.7
,
,
, Ethyl 7-fluoro-4-methylenechromane-2-carboxylate (1b)
, Colorless oil, 156 mg, 66%; 1 H NMR (300 MHz, Chloroform-d, ? ppm) 7.47 (dd, J = 8.7, 6.4 Hz, 1H), 6.71-6.60 (m, 2H), 5.47-5.44 (m, 1H), vol.154
, Ethyl 7-methoxy-4-methylenechromane-2-carboxylate (1c)
, Colorless oil, 198 mg, 80 % (mixture 1c and 10c)
,
,
, Ethyl 7-methoxy-6-methyl-4-methylenechromane-2
, 47 (s, 1H), 5.38 (s, 1H), Colorless oil, 152 mg, 58%; 1 H NMR (400 MHz, Chloroform-d, ? ppm) 7.27 (s, 1H), vol.6
1H)), 2.14 (s, 3H), 1.28 (t, J = 7.1 Hz, 3H), vol.13, p.101 ,
,
, Ethyl 6-chloro-4-methylenechromane-2-carboxylate. (1f)
, Colorless oil, 192 mg, 76%; 1 H NMR (400 MHz, Chloroform-d) ? 7.48 (d, J = 2.5 Hz, 1H), 7.15 (dd, J = 8.8, 2.5 Hz, 1H), vol.6
, Ethyl 8-fluoro-4-methylenechromane-2-carboxylate. (1g)
, Colorless oil, 208 mg, 88%; 1 H NMR (300 MHz
,
, Ethyl 6-methyl-4-methylenechromane-2-carboxylate (1h)
, Colorless oil, 179 mg, 77%; 1 H NMR (400 MHz, Chloroform-d, ? ppm) 7.33 (dd, J = 2.0, 0.9 Hz, 1H), 7.01 (dd, J = 8.4, 2.1 Hz, 1H), 6.88 (d, J = 8.3 Hz, 1H), 5.55-5.53 (m, 1H)
, Colorless oil, 21 mg, 95 %; 1 H NMR (400 MHz, Chloroform-d, ? ppm) 7.22-7.12 (m, 2H), 6.96-6.88 (m, 2H), 5.65-5.60 (m, 1H), 5.35-5.29 (m, 1H), 4.29-4.14 (m, 2H), 2.05 (t, J = 1.6 Hz, 3H), 1.27 (t, J = 7.1 Hz, 3H). 13 C NMR (101 MHz
, Ethyl 7-fluoro-4-methyl-2H-chromene-2-carboxylate (10b)
, Chloroform-d) ? 7.13 (dd, J = 8.2, 6.3 Hz, 1H), 6.74-6.58 (m, 2H), 5.58 (dt, Colorless oil, 22 mg, 94 %; 1 H NMR (300 MHz, p.75
CDCl3) ? 169.8, 163.3 (d, J = 247.2 Hz), 154.2 (d, J =, vol.12, issue.3 ,
, , vol.124
, 103.8 (d, J = 25.3 Hz)
Chloroform-d, ? ppm) -111.1. HRMS (ESI + ) calculated for ,
, Ethyl 7-methoxy-4-methyl-2H-chromene-2-carboxylate (10c)
, Colorless oil, 24 mg, 96 %; 1 H NMR (300 MHz, Chloroform-d)
,
81 (s, 3H), 2.04 (t, J = 1.5 Hz, 3H), 1.30 (t, J = 7.1 Hz, 3H). 13 C NMR (101 MHz, CDCl3), vol.3 ,
, Chloroform-d, ? ppm) 6.92 (s, 1H), 6.52 (s, 1H), 5.48 (dt, Colorless oil, 23 mg, 88 %; RMN 1 H (400 MHz
, Hydrogenation of ethyl 4-methylenechromane-2-carboxylate (1a): access to ethyl 4-methylchromane-2-carboxylate (11a)
, A solution of compound 1a (22 mg, 0.1 mmol) in methanol (5 mL) was stirred under hydrogen (1 atm.) in the presence of 5%
, , vol.1
, Colorless oil, 20 mg, 92 %; major isomer: 1 H NMR (400 MHz, Chloroform-d, ? ppm) 7.23 (d, J = 7.7 Hz, 1H), vol.7
,
, Hz, 1H), 1.85 (dt, J = 13.5, 11.0 Hz, 1H), 1.38 (d, 6.8 Hz, 3H), 1.35 (t, J = 7.1 Hz, 3H). 13 C NMR (75 MHz
, Cu(OAc)2 (145 mg, 0.8 mmol) were added to the pinacol boronate 7a (173 mg, 0.8 mmol) in MeOH (5 mL). The solution was stirred vigorously at reflux for 5 hours. The mixture was concentrated and then extracted with dichloromethane. After evaporation of the solvent, the residue was purified by chromatography on silica gel, NaN3 (107 mg, 1.6 mmol) and
, Colorless oil, 73 mg, 55%; 1 H NMR (300 MHz
, Hz, 1H), 7.18-7.02 (m, 2H), 5.34 (q, J = 1.3 Hz, 1H), 5.14 (d, J = 1.7 Hz, 1H)
, A mixture of 12a (94 mg, 0.36 mmol) and triphenylphosphine (94 mg, 0.36 mmol) in THF (2 mL) was heated at 60°C for 6h
, White solid, 160 mg, 90%; 1 H NMR (300 MHz, Chloroform-d, ? ppm) ? 7.80-7.70 (m, 6H), 7.56-7.41 (m, 9H), vol.7
,
, Hz, 1H), 2.92 (ddd, J = 13.4, 9.4, 0.7 Hz, 1H), 1.16 (t, J = 7.1 Hz, 3H). 13 C NMR (75 MHz Chloroform-d
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, A 85% yield was obtained from isolated 7a that confirms that the modest overall yield came from the ene reaction step 32 For similar isomerisation reactions, see ref 14d
Synthesis 2010, 1441. 34 CCDC 1878844 contains the supplementary crystallographic data for 13a. These data can be obtained free of charge from The Cambridge Crystallographic Data Centre via www ,
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