The geometry of displacements at nonstereogenic atoms: the formal displacement of alkoxide from alkoxyamines by organolithium reagents.

Amination of organolithium reagents can be achieved by reaction with methyllithium-alkoxyamines. Details of the methodology and analysis of the reaction mechanism are presented. Reactions of methyl-, ethyl-, n-butyl-, sec-butyl-, tert-butyl-, phenyl-, and (o"thoxypheny1)lithium with methyllithium-methoxyamine give the corresponding amines, isolated as the benzamides, in yields of 71-97%. Lower yields are obtained with o-lithio-N,N-diisopropylbenzamide, 4-lithiodibenzothiophene, n-butylmagnesium bromide, and phenylmagnesium bromide. Reactions of n-butyl-, sec-butyl-, tert-butyl-, and phenyllithium with methyllithium-N-methylmethoxyamine provide the corresponding N-methyl amines, isolated as the benzamides, in yields of 30-77%. Retention of the N-methyl group in these reactions is considered to rule out a nitrene intermediate. Involvement of a lithium alkoxyamide is suggested by the formation and substitution of that species by two different routes. Dilithiation of N-methoxy-N-[2-(o-bromophenyl)ethyl]amine (17) gives, after an intramolecular reaction and addition of acetyl chloride, N-acetylindoline, in 78% yield. Dilithiation of N-methyl-N-[2-(o-bromophenyl)ethoxy]amine (19) gives NmethybN-[o-(2-acetoxyethyl)pheny1]acetamide (20), after reaction with acetyl chloride. The nitrogen transfer in this conversion is shown by a double labeling experiment to be intermolecular. This result is taken to suggest that the bond angles required for displacement cannot be achieved in a six-membered ring, and the mechanism of the reaction involves a complex in which displacement occurs via an SN2-like transition state. The exocyclic-endocyclic intramolecular-intermolecular test is noted to provide a general approach for deterimination of the geometry of reactions at nonstereogenic centers. W e have contributed to methodology for the amination of Scheme I" organolithium compounds by development of methyllithiummethoxyamine as a useful reagent.'-3 The original reaction, ( I ) 2CH+2CH@NH2 R L i ( 2 ) H@ (3) C.&f2OCl RNHCOC6HS discovered by Sheverdina and Kocheshkov for the conversion of "R = C2H5 (78%), n-C4H9 (71%, 77%*), sec-C4H9 (71%). t-C,H, C6HSCH2 (97%), CH2=CHCH2 (78%), C,H,Li (90%). CH, (So%), o-CH,C6H4Li (96%), O-CON(i-Pr)&H& ( 1 4%'), 4-dibenzothiophenyl (55%). bThe solution was heated at reflux for 1 h. 'The product is isolated as the amine, one-half an equivalent of an organolithium or Grignard reagent with methoxyamine to the corresponding amine, has been used in a number of l a b ~ r a t o r i e s . ~ ~ ~ The overall process is a formal