Directed lithiation of substituted benzylamines

CHAPTER SIX Chapter six describes a lithiation procedure that allows the production of 3-substituted isoindolin-l-ones in high yields in only one step via lithiation of various substituted N-benzyl-MN-dimethylureas with /-BuLi (3.3 mole equivalents) in THF at 0 °C followed by reactions with various electrophiles. The procedure has been proven to be simple, efficient and general.EThOS - Electronic Theses Online ServiceGBUnited Kingdo

Addition of alkyllithiums to 3H-quinazoline-4-thione and various substituted quinazoline derivatives; application in synthesis

Reaction of 3H-quinazoline-4-thione (1) with two mole equivalents of an alkyllithium (t-BuLi, n-BuLi or MeLi) at−78 °C in dry THF gave the corresponding 2-alkyl-1,2-dihydro-3H-quinazoline-4-thione (4, 5 or 6) in high yield. Similarly, reactions of 4-(methylthio)quinazoline (7), 4-(ethylthio)quinazoline (8) and 4-methoxyquinazoline (9) with alkyllithiums (one mole equivalent) gave the corresponding 4-substitued 2-alkyl-1,2-dihydroquinazolines 11–18. On the other hand, blocking position 2 with a phenyl group in 4-(methylthio)-2-phenylquinazoline (20) and 4-methoxy-2-phenylquinazoline (21) resulted in reaction with two mole equivalents of alkyllithiums to give 4,4-dialkyl-2-phenyl-3,4-dihydroquinazolines 22–24

Unexpected variations in sites of lithiation of N-(2-methoxybenzyl)- pivalamide

Directed lithiation of N-(2-methoxybenzyl)pivalamide with two mole equivalents of t-BuLi in anhydrous THF at -78 ˚C followed by reactions with various electrophiles gave ring substitution, but ortho to the methoxy group rather than ortho to the pivaloylaminomethyl group, which was unexpected in view of earlier results reported with n-BuLi

A simple and convenient procedure for lithiation and side-chain substitution of 2-alkyl-4-(methylthio)quinazolines and 2-alkyl-4-methoxyquinazolines

2-Methyl-4-(methylthio)quinazoline has been lithiated, in the 2-methyl group, with n-BuLi at -78 °C in THF. The lithium reagent thus obtained reacts with a variety of electrophiles (iodomethane, iodoethane, D2O, benzaldehyde, 4-anisaldehyde, hexan-2-one, acetophenone, benzophenone, cyclohexanone) to give modified 2-substituted 4-(methylthio)quinazolines in excellent yields. Similarly, lithiation of 4-methoxy-2-methylquinazoline followed by reactions with various electrophiles gave the corresponding modified 2-substituted 4-methoxyquinazolines in excellent yields. Lithiations of 2-ethyl-4-(methylthio)quinazoline, 4-(methylthio)-2-propylquinazoline, 2-ethyl-4-methoxyquinazoline and 4-methoxy-2-propylquinazoline, followed by reactions with a range of electrophiles, behave in a similar manner to give the corresponding modified 2-substituted derivatives in good yields

Lateral Lithiation of N'-(2-Methylbenzyl)-N,N-dimethylurea and N-(2-Methylbenzyl)pivalamide: synthesis of Tetrahydroisoquinolines

Lithiation of N′-(2-methylbenzyl)-N,N-dimethylurea and N-(2-methylbenzyl)pivalamide with two mole equivalents of tert-butyllithium at -78 ˚C takes place on the nitrogen and on the methyl group at position 2. The lithium reagents thus obtained react with a variety of electrophiles to give the corresponding side-chain-substituted derivatives in high yields. Dehydration of the products obtained from reactions with carbonyl compounds in some cases gives the corresponding tetrahydroisoquinolines in excellent yields, while in other cases dehydration takes place within the substituted side chain to produce the corresponding alkenes in excellent yields