A convenient solution and solid-phase synthesis of Δ5-2-oxopiperazines via N-acyliminium ions cyclization

N‐acyliminium intermediates in solid‐phase synthesis

“…63,64 SCHEME 33 Synthesis of 2-oxopiperazines. 65,66 SCHEME 34 Synthesis of sulfonylimidazolones. purities.…”

“…64 In this report, a urea substrate (161) was assembled on a bromoacetal resin and treated with acid to effect cleavage and cyclization to the 2-imidazolones 160 in purities exceeding 90% (yields: 11-89%). In later studies, Cheng et al 65 extended their methodology to the synthesis of 2-oxopiperazines (Scheme 33). An Ugitype multicomponent reaction was used to assemble the cyclization precursor substrate, which was then subjected to acidic reaction conditions to afford products 163 (yields: 68-97%).…”

CC Bond‐Forming Reactions

“…The final product could be cleaved from the resin with HOAc/1,2 dichloroethane 1:9 (v/v). Wang resin-bound isonitrile (419) has been employed in a Ugi MCR-N-acyliminium ion cyclization [348]. Using aminoacetaldehyde diethyl acetal (420) and then exposing the Ugi products to a 20 % dichloromethane solution of TFA, the desired D 5 -2-oxopiperazines (422) were obtained with simultaneous release from the resin (Scheme 86).…”

“…Cyclization (Scheme 84) [348]: The resin is suspended in 1 N HCl /THF 1:2 (v/v) (3 mL) and shaken for 4 h at r. t. The solvent is drained and the resin is washed as follows:…”

A Versatile Synthesis of 6-Oxo-1,4,5,6-tetrahydro-pyrazine-2-carboxylic Acid Methyl Esters via MCR Chemistry

“…Cheng et al recently published efficient one-pot two-steps syntheses in solution and solid-phase. 13 In our investigations of the Ugi reaction we used the 3-dimethylamino-2-isocyano-acrylic acid methyl ester (4) as crucial starting material. This isocyanide was first described by Schöllkopf et al and contains a dimethylamino leaving group in b-position.…”