Smart Cleavage Reactions:  the Synthesis of an Array of Ureas from Polymer-Bound Carbamates

Abstract

The solid-phase synthesis of a library of di-, tri-, and tetrasubstituted ureas is described. In this approach, an array of polymer-bound carbamates was synthesized. These polymer-bound primary and secondary amine carbamates were then treated under "smart" diversity-building cleavage conditions using a series of aluminum amide complexes to form the corresponding urea cleavage products. The crude cleavage products from this study were isolated in excellent yield and purity. To show the applicability of this strategy, a series of biaryl ureas were synthesized using sequential solid-phase Suzuki coupling and urea formation reactions.

Facile production of mono‐substituted urea side chains in solid phase peptide synthesis

“…[1][2][3] Accordingly, numerous synthetic methods have been reported, amenable to both solution and solid-phase applications, principally via isocyanate [4][5][6][7][8] or carbamate [9][10][11][12][13][14][15][16] intermediates. However, the bulk of these methods have targeted structures with considerable N-substitution.…”

AlMe3‐Mediated Regio‐ and Chemoselective Reactions of Indole with Carbamoyl Electrophiles

“…Under these conditions, secondary carbamates were reactive unlike tertiary carbamates and furnished the indole ureas. So far, only one example of the formation of an indole urea from a secondary carbamate has been reported under similar conditions 2b…”

Biochemical and microbiological evaluation of N-aryl urea derivatives against mycobacteria and mycobacterial hydrolases

“…Compound characterization matched reported characterization for 2a-g, 4a, 6a-b. [31][32][33][34][35] 1-(4-bromophenyl)-3-(cyclohexylmethyl)urea (4b). Yield: 79% (712 mg); 1 1-(3,5-Difluorophenyl)-3-(furan-2-ylmethyl)urea (6c).…”