87768-57-8Relevant articles and documents
Selectivities in Reactions of Organolithium Reagents with Aryl Bromides Which Bear Proton-Donating Groups
Beak, Peter,Musick, Timothy J.,Liu, Chao,Cooper, Thomas,Gallagher, Donald J.
, p. 7330 - 7335 (2007/10/02)
Studies of substrates which offer an acidic hydrogen and an aryl bromide for reaction with an organolithium reagent have been carried out with a series of benzene bromo amides and bromo anilides as well as selected benzene bromo carboxylic acids, bromoanilines, and bromobenzylamines.A representative example is the reaction of N-ethyl-N-deutero-o-bromobenzamide (6-d) with 1-lithio-3-phenylpropane to give N-ethyl-o-deuterobenzamide (46percent, 94percent-d) (7-d), N-ethyl-o-bromobenzamide (6) (49percent), 3-deutero-1-phenylpropane (51percent, 92percent-d), and 1-bromo-3-phenylpropane (48percent).Product formation in this and related cases is explained by the operation of a two step sequence in which an initial deprotonation is followed by a bromine-lithium exchange which is accelerated with respect to mixing.Such a sequence is consistent with the results of deuterium labeling and with changes in product ratios on different mixing and with differently aggregated organolithium reagents.Support is provided for the operation of two pathways for the expedited bromine-lithium exchange reactions.In one pathway a high local concentration of the organolithium reagent promotes rapid reaction and in the second the exchange reaction occurs within an initially formed complex.The selectivity for removal of a bromine ortho to a lithiated carboxamide is found to be 5-8 with n-butyllithium, and satisfactory synthetic ortho selectivity is obtained for N-ethyl-2,5-dibromobenzamide with phenyllithium.
A COMPARISON OF SECONDARY AND TERTIARY AMIDES AS DIRECTORS OF ORTHO AND ADJACENT BENZYLIC LITHIATION AND OF ASYMMETRIC INDUCTION IN ORTHO LITHIATED BENZAMIDES
Beak, Peter,Tse, Anthony,Hawkins, Joel,Chen, Chin-Wen,Mills, Sander
, p. 1983 - 1989 (2007/10/02)
Comparisons are made between the influence of secondary and tertiary amides on ortho and adjacent benzylic metallations of benzamides.In the intramolecular competition offered by N,N-diethyl-N-ethylterephthalamide (1) the tertiary amide is the more effective director of ortho lithiation, while the secondary amide is better in the intermolecular competitions offered by the pairs N-ethyl-(9):N,N-diethylbenzamide(10) and N-isopropyl-(11):N,N-diisopropylbenzamide(12).Both secondary and tertiary amides are found to direct metallation ortho to the amide in the 2-isopropylbenzamides 25 and 26; however, benzylic metallation is observed with secondary 2-ethyl- and 2-methylbenzamides 21 and 22 and with the tertiary 2-ethylbenzamide 19.Magnetic non-equivalence is noted for the anti-N-methylene group of 19.The reaction of an ortho lithio (S)-O-methyl-N-benzoylleucinol (34) with 1-naphthaldehyde-1-d gives, after lactonization, 3-(1-naphthyl-1-d)-phthalide with 10percent enantiomeric excess.The phthalide can be obtained in high enantiomeric purity by separation of the diastereoisomers prior to cyclization.Control experiments establish that the observed asymmetric induction is attributable to diastereomeric transition states.The corresponding tertiary benzamide is ineffective in inducing asymmetry.Structural and mechanistic rationales are offered for these observations.
