Efficient Synthesis of Dimeric Oxazoles, Piperidines and Tetrahydroisoquinolines from N‐Substituted 2‐Oxazolones

Abstract

A mild and practical method for the construction of heterocycles from N-substituted 2-oxazolones through cascade, BF3 ⋅Et2 O/H2 O-catalyzed reactions involving iminium ion generation and trapping by external or internal olefinic and aryl moieties is described. Mechanistic and computational studies revealed the strong protic acid HBF4 as the initiating catalyst for these cascade reactions. Providing access to novel molecular diversity, these processes may facilitate chemical biology studies, drug discovery efforts and natural products synthesis.

Cobalt-Catalyzed Carbozincation of Ynamides

“…No addition of the zinc reagent was observed. The formation of 6 , which results probably from the in situ formation of ZnBr 2 , was surprising but quite promising, as it opens a new access to a range of 3,5-disubstituted oxazolone frameworks . Some authors have already developed metal-catalyzed (e.g., Au, Pd, Cu) 5-endotrig cyclization of N -alkynyl tert -butyloxy-carbamates to synthesize this privileged structure .…”

Divergent Pd-catalyzed Functionalization of 4-Oxazolin-2-ones and 4-Methylene-2-oxazolidinones and Synthesis of Heterocyclic-Fused Indoles

“…2-Oxazolidinones and 4-oxazolin-2-ones have been synthesized through diverse and efficient methodologies and take part in many synthetic applications . A straightforward and regioselective method was developed by our group to obtain 4-methylidene-2-oxazolidinones and 4-oxazolin-2-ones .…”

PIFA-Mediated Tandem Hofmann-Type Rearrangement and Cyclization Reaction of α-Acyl-β-aminoacrylamides: Access to Polysubstituted Oxazol-2(3H)-ones

“… − In addition, they are widely used as important building blocks and versatile intermediates for complex molecule construction in organic chemistry and medicinal chemistry. , In this context, many synthetic approaches have been established for oxazol-2­(3 H )-ones and their fused analogues, including (i) Lewis-acid- or Lewis-base-catalyzed condensation of 1,2-aminoketones with carbonyl compounds, (ii) transition-metal-catalyzed cyclization of the N -alkynyl tert -butyloxycarbamates, , (iii) cycloaddition of secondary propargyl alcoholes with isocyanates or carbon dioxide and amines, (iv) cycloaddition of α-hydroxyl ketones with isocyanates or carbamates, (v) Brønsted-acid-catalyzed cyclization of β-amino-1,4-enols, (vi) transition-metal-catalyzed coupling- isomerization-elimination of propargyl carbamates with acid chlorides, (vii) transition-metal-catalyzed cyclization of β,β-dihaloenamides, and (viii) cyclization of 2-amino-phenols with different carbonylating reagents . Alternatively, some functionalized oxazol-2­(3 H )-ones have also been prepared via oxidation of 2-oxazolidones or modification of the preconstructed oxazol-2­(3 H )-one skeleton …”