N-Heterocycle construction via cyclic sulfamidates. Applications in synthesis

Abstract

When combined with an appropriate nucleophilic component, 1,2- and 1,3-cyclic sulfamidates function as versatile precursors to a range of substituted and enantiopure heterocyclic classes. Functionalised enolates provide a direct entry to C-3 functionalised lactams, as exemplified by total syntheses of (-)-aphanorphine, (+)-laccarin and (-)-paroxetine. Heteroatom nucleophiles, such as thiol esters, amino esters and bromo phenols, provide concise access to a range of enantiomerically pure thiomorpholine, piperazine and benzofused heterocyclic scaffolds. The latter methodology enables a facile synthesis of the antibacteriocidal agent levofloxacin.

Total Synthesis of Tambromycin by Combining Chemocatalytic and Biocatalytic C−H Functionalization

“…Initial attempts using Appel or Mitsunobu reactions on 5 resulted in undesired β‐elimination to the 2‐amidoacrylate product. This issue was overcome by converting the amino alcohol motif into the corresponding sulfamidate ( 6 ), followed by simple heating in DMA to generate the protected tambroline fragment ( 7 ) in excellent yield and complete diastereoselectivity. Notably, all transformations in this sequence have been performed on at least one‐gram scale, which serves as a testament to the robustness and practicality of the route.…”

Total Synthesis of Tambromycin by Combining Chemocatalytic and Biocatalytic C−H Functionalization

“…Initial attempts using Appel or Mitsunobu reactions on 5 resulted in undesired b-elimination to the 2-amidoacrylate product. This issue was overcome by converting the amino alcohol motif into the corresponding sulfamidate (6), [16] followed by simple heating in DMA to generate the protected tambroline fragment (7)i ne xcellent yield and complete diastereoselectivity.N otably,a ll transformations in this sequence have been performed on at least one-gram scale, which serves as atestament to the robustness and practicality of the route.I na ddition, an X-ray crystal structure of the carboxylate salt of 7 was obtained to confirm the stereochemical assignment of the cyclized product (see the Supporting Information).…”

Asymmetric Mannich Reaction of Aryl Methyl Ketones with Cyclic Imines Benzo[e][1,2,3]oxathiazine 2,2‐Dioxides Catalyzed by Cinchona Alkaloid‐based Primary Amines

“…[9, 10c, d, e, 13, 14] The catalytic asymmetric addition to cyclic imines benzo[e] [1,2,3]oxathiazine 2,2-dioxides has been shown to be an efficient methodf or the synthesis of chiralb enzo-fusedc yclic sulfamidateheterocycles, [15] which can undergo anucleophilic displacementt oc onvert optically active amines. [16] Moreover,o ur group reportedt he highly enantioselective direct Mannich reaction of alkyl ketones with benzo[e][1,2,3]oxathiazine 2,2-dioxides using ac inchonaa lkaloid-derived primary amine as organocatalyst. [14b] Primary amines as catalysts generally feature as mall steric hindrance compared to secondary amines.…”