A Simple and Convenient High Yielding Synthesis of Substituted Isoindolines

Abstract

Trifluoroacetic anhydride-induced dehydration of substituted 2-(pivaloylaminomethyl)phenyl-and 2-(dimethylaminocarbonylmethyl)phenylmethanols gives the corresponding isoindolines in excellent yields when there are aryl substituents at the methanol carbon atom.

Reactions of organolithium reagents with quinazoline derivatives

“…[82][83][84][85][86] Therefore, methods for the syntheses and/or modification of this ring system are always of interest. As part of our continuing interest in quinazoline chemistry [87][88][89][90][91][92][93][94][95][96][97][98][99][100][101] and in lithiation chemistry, [102][103][104][105][106][107][108][109][110][111][112][113] we have previously reported on the modification of the quinazoline ring system via lithiation and the organolithium reagents obtained from such reactions are very useful intermediates for the synthesis of substituted quinazoline derivatives that might be difficult to prepare by other means. 114 This review will concentrate on the work published in the general area of directed and regioselective ring-lithiation of various quinazoline derivatives.…”

Lithiation and Substitution of N′-(ω-Phenylalkyl)-N,N-dimethylureas

“…Reaction of the dilithium reagent thus obtained with carbon dioxide, the only electrophile tried, gave the corresponding acid in 72% yield. 14 However, there are no reports of lithiation and substitution of N′-phenethyl-N,N-dimethylureas, and pivalamide and dimethylurea derivatives do not always behave in an identical manner towards lithiation 9 and the urea derivatives are more generally useful for synthesis.…”

“…[8][9][10] Such processes have been applied for the production of substituted isoindoline and isoquinoline derivatives.…”

“…7 As part of such studies we have successfully lithiated and substituted various N-(substituted benzyl)pivalamides and N′-(substituted benzyl)-N,Ndimethylureas selectively using n-butyllithium or tert-butyllithium in tetrahydrofuran. [8][9][10] Such processes have been applied for the production of substituted isoindoline and isoquinoline derivatives. [11][12][13] As part of such studies we became interested in directed lithiation of N′-phenethyl-N,N-dimethylureas.…”

“…[8][9][10] Such processes have been applied for the production of substituted isoindoline and isoquinoline derivatives. [11][12][13] As part of such studies we became interested in directed lithiation of N′-phenethyl-N,N-dimethylureas. Lithiation of N-phenethylpivalamide derivatives have been reported by Schlosser.…”