Cesium Effect:  High Chemoselectivity in Direct N-Alkylation of Amines

Abstract

A novel method for the mono-N-alkylation of primary amines, diamines, and polyamines was developed using cesium bases in order to prepare secondary amines efficiently. A cesium base not only promoted alkylation of primary amines but also suppressed overalkylations of the produced secondary amines. Various amines, alkyl bromides, and alkyl sulfonates were examined, and the results demonstrated this methodology was highly chemoselective to favor mono-N-alkylation over dialkylation. In particular, use of either sterically demanding substrates or amino acid derivatives afforded the secondary amines exclusively, offering wide applications in peptidomimetic syntheses.

Computational study of carbon–hydrogen bond deprotonation by alkali metal superbases

“…Changes in the distances between Cs + and the ring centroid of the toluene substrate along the reaction coordinate suggest that metal cation-p interactions facilitate scission of benzylic C-H bonds. Several C-H functionalizations have been reported [63][64][65] in which Cs salts are required. The present calculations suggest a possible role for this alkali metal in facilitating such a transformation.…”

Inhibition of Golgi Mannosidase II with Mannostatin A Analogues: Synthesis, Biological Evaluation, and Structure–Activity Relationship Studies

“…Conventional procedures involving Na(CN)BH 3 in combination with solvents such as trimethyl ortho-formate (TMOF), [24] TMOF/methanol, or dichloromethane/methanol in the presence or absence of benzotriazole [25] resulted in mixtures of products. Alkylation of the amines with benzyl bromide in the presence of CsOH [26] gave, apart from the required product, a substantial amount of disubstituted amine. Fortunately, addition of a methanolic solution of the hydrochloride salts of 1 a and 2 a, pretreated with methanolic sodium hydroxide (0.2 equiv), to a slurry of an aromatic aldehyde (2.5 equiv), Na(CN)BH 3 (1.0 equiv), and molecular sieves (3 ), followed by stirring for 18 hours, gave the secondary amines 1 b-g and 2 b-g in reasonable to good yields.…”

Cesium carbonate mediated exclusive dialkylation of active methylene compounds

“…In recent years, cesium carbonate has found extensive applications as an excellent base for a variety of synthetic transformations [1][2][3][4][5][6][7][8][9][10][11][12][13] and has received even industrial acceptance. In most of the cases, it is superior to other bases in terms of yield, reaction time, reaction temperature and sensitivity towards moisture, thus compensating the rather high cost of this reagent compared to that of potassium carbonate or other cheaper bases.…”