Generation of the dianion of N-(trimethylsilyl)acetamide and reaction of the dianion with electrophilic reagents

Synthesis of functionalised β-keto amides by aminoacylation/domino fragmentation of β-enamino amides

“…With regard to acylation reactions, maybe most important among these are some nitriles, which can be successfully acylated at the alpha position [ 13 – 15 ] and then hydrated [ 13 , 16 – 20 ] to reveal a primary amide functionality. The dianion of silylated acetamide is another such example, although with very limited scope [ 21 ]. A contribution of ours in this area is the application of ethylenediamine-derived β-enamino amides as synthetic equivalents of primary and secondary amide enolate synthons in reactions with acid chlorides [ 22 ].…”

Synthesis of 5-(Hydroxymethyl)pyrrolidin-2-ones by Cyclization of Amide Dianions with Epibromohydrin

“…The cyclization of epibromohydrin (2) with N-arylacetamides 1a-e afforded the 1-aryl-5-(hydroxymethyl)pyrrolidin-2-ones 3a-e 12b,c in good yields (Scheme 2, Table 1). The cyclization of 2 with the dianion of N-(trimethylsilyl)acetamide 13 afforded the labile TMS-substituted pyrrolidin-2-one 3f. The chromatographic purification (silica gel) of crude 3f afforded parent pyroglutaminol (3g).…”

“…THF was freshly distilled from Na. For the 1 H and 13 C NMR spectra ( 1 H NMR: 250 MHz, 13 C NMR: 62.9 MHz), the deuterated solvents indicated were used. The multiplicities of the 13 C NMR signals were determined with the DEPT 135 technique.…”

“…For the 1 H and 13 C NMR spectra ( 1 H NMR: 250 MHz, 13 C NMR: 62.9 MHz), the deuterated solvents indicated were used. The multiplicities of the 13 C NMR signals were determined with the DEPT 135 technique. Mass spectral data were obtained using the electron ionization (70 eV) or the chemical ionization technique (CI, H 2 O).…”

Route exploration and synthesis of the reported pyridone-based PDI inhibitor STK076545

“…Alternatively, addition of a ketone or enamine to an isocyanate have also been reported (approach 'e'). Cross Claisen-like condensations of esters with amide enolates have been reported (approach 'f'), [19][20] or alternatively an aldol reaction between a pyridone-containing amide and a benzaldehyde (Ar = Ph for STK076545) could be envisaged (step 'g'), followed by alcohol oxidation (step 'h').…”