Catalytic one-pot synthesis of 4-(hetero)aryl substituted 5-(2-oxoethyl) oxazol-2(3H)-ones by coupling–isomerization–elimination (CIE) sequence

Abstract

N-Boc protected 1-aryl propargyl carbamates and acid chlorides can be readily transformed in a one-pot fashion by a coupling-isomerization-elimination (CIE) sequence into 4-substituted 5-(2-oxoethyl) oxazol-2(3H)-ones in moderate to good yield. † Dedicated to Professor Dr Barry M. Trost on the occasion of his 75 th birthday. ‡ Electronic supplementary information (ESI) available: 1 H and 13 C NMR spectra and analytical data of compounds 2, and 1 H and 13 C NMR spectra of compounds 3, cif file of the X-ray structure analysis of compound 3r. CCDC 1465496. For ESI and crystallographic data in CIF or other electronic format see Scheme 1 One-pot amidation-coupling-cyclization-isomerization (ACCI) synthesis of 4-substituted 5-(2-oxoethyl) oxazol-2(3H)-ones.Scheme 2 Competing formation of oxazol-2-ones in the three-component coupling-addition-cyclocondensation synthesis of N-Boc 2-substituted 4-iodopyrroles.Scheme 3 Optimization of the coupling-isomerization-elimination synthesis (CIE) of the 2-oxoethyl oxazol-2(3H)-one 3a. Research Article Organic Chemistry Frontiers 888 | Org. Chem. Front., 2016, 3, 887-896 This journal is

X-ray Structures of 3-Acetyloxazolidin-2-one, 3-Acetyloxazolin-2-one and Oxazolin-2(3H)-one

“…The resulting high R factor means that unfortunately little meaningful data can be obtained on the precise molecular dimensions of this fundamental heterocyclic molecule in the crystalline state. We have located one published X-ray structure of a 4,5-disubstituted-3-unsubstituted oxazolin-2(3H)-one, compound 7 (CCDC Ref Code ENALEM) [21] which forms heterodimers between two slightly different independent molecules (Figure 2), and its hydrogen bonding parameters are comparable with those for 4 (Table 3).…”

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

“…Oxazol-2­(3 H )-ones constitute the key units of many natural products and designed molecules along with diverse bioactivities, such as antibacterial, antitumor, cyclooxygenase-2 inhibitory, neuroleptic, and herbicidal activities (Figure ). − 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 …”