An unprecedented two-step sequence was designed by combining batch and continuous flow (CF) protocols for the upgrading of two aminodiol regioisomers derived from glycerol, i.e., 3-amino-1,2-propanediol and 2-amino-1,3-propanediol (serinol). Under batch conditions, at 80–90 °C, both substrates were quantitatively converted into the corresponding amides through a catalyst-free N-acetylation reaction mediated by an innocuous enol ester as isopropenyl acetate (iPAc). Thereafter, at 30–100 °C and 1–10 atm, the amide derivatives underwent a selective CF-acetalisation in the presence of acetone and a solid acid catalyst, to afford the double-functionalized (amide-acetal) products.
1,3-Dimethyl-5-imino-imidazolidine-2,4-dione (7a) undergoes thiolysis (H2S) to give the corresponding imidazolidine-2,4-dione-5-thione derivative 6. The 5-N-methylimino analogue 7b can be obtained from 7a by methylation. Further methylation of 7b affords the crude iminium salt 8c from which the heterocyclic orthoamide derivatives 10, 11 can be prepared. The heterocyclic amide acetal 9a can be obtained from 7a and dimethyl sulfate in methanol and subsequent addition of sodium methanolate in a one-pot reaction. The aminal ester 10 is converted to the amide acetal 9a on treatment with hydrogen chloride in methanol
Spirocyclic Amide Acetal Synthesis by [CpRu]‐Catalyzed Condensations of α‑Diazo‐β‐Ketoesters with γ‐Lactams