65495-31-0Relevant academic research and scientific papers
Synthesis of oxychelerythrine using lithiated toluamide-benzonitrile cycloaddition
Le, Thanh Nguyen,Cho, Won-Jea
, p. 118 - 120 (2007/10/03)
Oxychelerythrine, benzo[c]phenanthridine alkaloid, was synthesized from easily available starting toluamide 5 and benzonitrile 6 using toluamide-benzonitrile cycloaddition reaction in 6 steps.
Total synthesis of (-)-tetrahydropalmatine via chiral formamidine carbanions: Unexpected behavior with certain ortho-substituted electrophiles
Matulenko, Mark A.,Meyers
, p. 573 - 580 (2007/10/03)
A method has been developed by alkylation of chiral lithioformamidines to construct protoberberine alkaloids with a C(9) and C(10) D-ring substitution pattern. This ring pattern was established using an ortho-substituted hydroxymethylbenzene electrophile protected as a silyl ether to ultimately provide (-)-tetrahydropalmatine in 88% ee. Additionally, we have discovered limitations with ortho-substituted electrophiles in the asymmetric formamidine alkylation. These electrophiles have the potential to disrupt the lithium formamidine chelate and cause the selectivity in the alkylation to be uncharacteristically low. The total synthesis of (±)-canadine and (-)-tetrahydropalmatine along with the limitations to the formamidine alkylation technology are delineated herein.
Influence of Alkoxyalkyl Substituents in the Regioselective Lithiation of the Benzene Ring
Napolitano, Elio,Giannone, Enrico,Fiaschi, Rita,Marsili, Antonio
, p. 3653 - 3657 (2007/10/02)
The concomitant presence of an alkoxyalkyl group (α-alkoxyalkyl, α- or β-dialkoxyalkyl) and of an alkoxy group in the relative positions 1 and 3 in a benzene ring generally permits an easy lithiation of position 2 by proton-metal exchange with n-butyllithium; the only aromatic compound tested, bearing a β-alkoxyalkyl group, gave, however, extensive decomposition in the metalation step.Reaction of the metalated species with an electrophile (such as carbon dioxide or ethyl chloroformate) leads to the corresponding substituted products in good to excellent yields.The following transformations are described: 3,4-dimethoxybenzyl α-ethoxyethyl ether (1) into 6,7-dimethoxyphthalide (15); 3,4-(methylenedioxy)benzyl α-ethoxyethyl ether (2) into 6,7-(methylenedioxy)phthalide (16); 3,4-dimethoxybenzyl methyl ether (3) into ethyl 2-(methoxymethyl)-5,6-dimethoxybenzoate (18) and into ethyl 2-(chloromethyl)-5,6-dimethoxybenzoate (20); 3,4-(methylenedioxy)benzyl methyl ether (4) into ethyl 2-(methoxymethyl)-5,6-(methylenedioxy)benzoate (19) and into ethyl 2-(chloromethyl)-5,6-(methylenedioxy)benzoate (21); 3,4-dimethoxybenzaldehyde dimethyl acetal (5) into 5,6-dimethoxyphthalaldehydic acid (22); 3,4-(methylenedioxy)benzaldehyde dimethyl acetal (6) into 5,6-(methylenedioxy)phthalaldehydic acid (23); (3,4-dimethoxyphenyl)acetaldehyde dimethyl acetal (7) into ethyl 2-(2,2-dimethoxyethyl)-5,6-dimethoxybenzoate (25); 3,4,4'-trimethoxydeoxybenzoin ethylene acetal (10) into 2-(ethoxycarbonyl)-3,4,4'-trimethoxydeoxybenzoin (26); 4,3',4'-trimethoxydeoxybenzoin ethylene acetal (11) into 2'-(ethoxycarbonyl)-4,3',4'-trimethoxydeoxybenzoin (27); 3,4,3',4'-tetramethoxydeoxybenzoin ethylene acetal (12) into a mixture of 3-(3,4-dimethoxybenzylidene)-6,7-dimethoxyphthalide (28) and 3-(3,4-dimethoxyphenyl)-7,8-dimethoxyisocoumarin (29).The dioxole ring of methylenedioxy-substituted benzenes is sometimes unstable under these metalation conditions, and partial decomposition usually causes the yields to be lower than those in the case of the corresponding methoxy-substituted benzenes.Many of the products listed above, which have been already prepared by other methods, are more conveniently obtained by the present approach.
