Synthesis of 1,2,4-Trimethoxybenzene and Its Selective Functionalization at C-3 by Directed Metalation

Convergent synthesis of 2H-chromenes—a formal [3+3] cycloaddition by a one-pot, three-step cascade

“…Quinone 3b was most conveniently prepared by the AgO oxidation of the 1,3,4-trimethoxyphenyl butenoate 12 derived from the known 2-bromo-1,3,4-trimethoxybenzene ( 11 ; Scheme 5). 32 Heating vinyl quinone substrate 3-3e in toluene in the presence of small amounts of HMPA gave, as expected, the corresponding chromene in each case. Yields for each step and the overall yields for the stepwise preparative sequence are shown in Table 1.…”

“…From 2-bromo-1,3,4-trimethoxybenzene ( 11 ) 32 (151 mg, 0.61 mmol) and vinyl stannane 2 (mixture of cis/trans isomers) according to general procedure 2; reaction time: 18 h. Pale yellow oil (84 mg, 52 %, mixture of trans/cis isomers 3:1): IR (neat) ν 2951, 2837, 1738, 1483, 1257, 1164, 1100, 796 cm -1 ; 1 H-NMR (CD 2 Cl 2 ) δ 6.82 and 6.78 (each d, total 1H, 3 J = 9.0 Hz, cis/trans 1:3 in the order given), 6.79-6.64 (m, 1.75H), 6.59 (d, 0.75H, 3 J = 9.0 Hz, trans -isomer), 6.40 (dt, 0.25H, 3 J = 11.3 Hz, 4 J = 1.6 Hz, cis -isomer), 5.97 (dt, 0.25H, 3 J = 11.3 Hz, 7.2 Hz, cis -isomer), 3.80, 3.79, 3.78, 3.76, 3.72, 3.69, 3.66 and 3.65 (each s, total 12H), 3.26 (d, 1.5H, 3 J = 6.2 Hz, trans -isomer), 3.01 (dd, 0.5H, 3 J = 7.2 Hz, 4 J = 1.6 Hz, cis -isomer) ppm; 13 C-NMR (CD 2 Cl 2 ) δ 172.8, 172.7, 152.8, 151.9, 148.6, 148.1, 147.8, 147.7, 120.6, 127.5, 126.6, 124.6, 123.5, 120.4, 112.3, 111.9, 106.4, 106.1. 40.3, 35.5, 60.6, 56.72, 56.70, 56.4, 56.2, 52.2, 52.0 ppm; LRFAB-MS: [M+Na] + = 289 (calc.…”

Structure-Based Molecular Networking for the Target Discovery of Oxahomoaporphine and 8-Oxohomoaporphine Alkaloids from Duguetia surinamensis

“…The 1 H NMR spectrum of 10 showed aromatic and methoxy group hydrogen resonances in addition to methylene and methine (both oxygenated signals), indicative of a tetrasubstituted benzenoid derivative . The planar structure of this substance was found to be 1-(2,4,5-trimethoxyphenyl)­ethane-1,2-diol based on 13 C NMR resonances , and key HMBC correlations of the methoxy group hydrogens with the arene carbons (Figure A). The proposed structure was supported by the deduced chemical formula of C 11 H 16 O 5 Na (4 degrees of unstauration) from the HRESIMS data ( m / z 251.0893 [M + Na] + , calcd 251.0889) of 10 ( m / z 251 [M + Na] + ).…”

“…The 1 H NMR spectrum of 10 showed aromatic and methoxy group hydrogen resonances in addition to methylene and methine (both oxygenated signals), indicative of a tetrasubstituted benzenoid derivative. 32 The planar structure of this substance was found to be 1-(2,4,5trimethoxyphenyl)ethane-1,2-diol based on 13 C NMR resonances 33,34 and key HMBC correlations of the methoxy group hydrogens with the arene carbons (Figure 5A). 5B).…”

“…By NMR data analysis and comparison with the reported spectroscopic data, the seven known compounds were identified as 1,2,4-trimethoxybenzene ( 1 ), dicentrine ( 2 ), 7-hydroxynordicentrine ( 6 ), (−)-duguetine ( 7 ), pallidine ( 8 ), dicentrinone ( 9 ), , and duguetine N- oxide ( 11 ) . Unequivocal assignment and full NMR data for compounds 2 , 6 , 7 , 9 , and 11 at 500 MHz are made available in Tables S1 and S2 (Supporting Information) since previously published data are outdated and some signals are missing.…”