One-Pot Synthesis of Five-, Six-, and Seven-Membered Lactams via Bu₃SnH-Mediated Reductive Cyclization of Azido Amides

Review on Synthetic Approaches toward Rivaroxaban (Xarelto), an Anticoagulant Drug

“…A dehydrogenative ring closure of an α,ω-aminoalcohol, catalyzed by a pincer-ligated divalent iron complex, was reported to yield 49% of the product (Scheme , eq 2) . Much higher yields were obtained , when an acyclic azide was converted into morpholin-3-one in Bu 3 SnH- or Ph 3 P-mediated processes (Scheme , eq 3), but in both cases, formation of stoichiometric byproducts makes the synthesis relatively unattractive, especially on a large scale. In the only scaled example of the target compound preparation a high-temperature reaction between dioxanone and a large excess of ammonia was used (Scheme , eq 4).…”

Base-Promoted Tandem Synthesis of 3,4-Dihydroisoquinolones

“…13 Consequently, the development of efficient methods for the synthesis of this important N-heterocycle core has attracted much attention.Traditional approaches to access 3,4-dihydroisoquinolones mainly rely on intramolecular cyclization of activated amide or amide precursors, including carbamates, 14−16 isocynates, 17,18 ureas, 19 and azidoamides. 20,21 However, most of these methods suffer from limited substrate scope resulting from the use of strongly acidic conditions. Recently, significant effort has been devoted to the preparation of 3,4-dihydroisoquinolones, with representative methods including (1) palladium catalyzed carbonyl insertion (Scheme 2a); 22−24 (2) oxidation of cyclic amines (Scheme 2b); 25−27 and (3) [4 + 2] cycloaddition of activated arylamides with alkenes via transition-metal-catalyzed C−H activation (Scheme 2c).…”

“…Traditional approaches to access 3,4-dihydroisoquinolones mainly rely on intramolecular cyclization of activated amide or amide precursors, including carbamates, − isocynates, , ureas, and azidoamides. , However, most of these methods suffer from limited substrate scope resulting from the use of strongly acidic conditions. Recently, significant effort has been devoted to the preparation of 3,4-dihydroisoquinolones, with representative methods including (1) palladium catalyzed carbonyl insertion (Scheme a); − (2) oxidation of cyclic amines (Scheme b); − and (3) [4 + 2] cycloaddition of activated arylamides with alkenes via transition-metal-catalyzed C–H activation (Scheme c). − Despite substantial progress, most of these methods still leave room for improvement to address the use of prefunctionalized substrates, expensive metal catalysts and ligands, the need for excess oxidants, or tedious procedures.…”