Acyloxylation at the 4-position of azetidin-2-ones

Abstract

The copper-catalysed reaction of azetidin-2-ones with t-butyl perbenzoate or peracetate affords the corresponding 4-benzoyloxy-and acetoxy-substituted p-lactams, respectively. N -Unsubstituted 4acyloxyazetidinones can be synthesized by dearylation of the N-(4-methoxyphenyl) -substituted products with ceric ammonium nitrate. Acyloxylation of p-lactams that are monosubstituted at C-3 affords predominantly trans-products.4-Acetoxy-and benzoyloxy-substituted azetidin-2-ones have been used extensively in organic synthesis, particularly as precursors of p-lactam antibiotics.Consequently, there is considerable interest in the development of methods for the synthesis of compounds of this type. Here7 we describe a method for the synthesis of 4-acyloxy-substituted azetidinones through the copper-catalysed reaction of p-lactams with t-butyl peresters.The only alternative procedure that has been reported for the direct acyloxylation of p-lactams at the 4-position involves the electrochemical oxidation of azetidin-2-ones in acetic acidacetonitrile.* This latter method is an extension of previous work on the introduction of alkoxy substituents through electrolysis of P-lactam~.~*'~ It has also been reported that oxidation of N-hydroxyazetidines with lead tetra-acetate gives the corresponding 1,4-diacetoxyazetidinones, but this process is thought to occur by 1,4-addition of the oxidizing agent to intermediate nitrones, not by direct substitution of p-lactams.'

Chirospecific Synthesis of Spirocyclic β-Lactams and Their Characterization as Potent Type II β-Turn Inducing Peptide Mimetics

“…Ozonolysis of the vinyl group and subsequent reduction with an excess of Na[BH(OAc) 3 ] yielded the hydroxymethyl-substituted derivative 10a in 86% yield. Formation of the β-lactam was accomplished by intramolecular Mitsunobu reaction with DEAD and PPh 3 , , furnishing the molecular scaffold 11a . Finally, the molecular probe 2 was prepared by aminolysis of 11a .…”

Anodic Oxidation of Aliphatic and Aromatic Amides, Bisamides and Related Derivatives

“…For comparison, the chemical oxidation of β-lactam by copper-catalyzed reaction of azetidin-2-ones with t-butyl perbenzoate (or peracetate) forms the corresponding 4-benzoyloxy-and acetoxy-substituted β-lactams, respectively [34] (Eq. 6): (6) Noticeably, acyloxylation of β-lactams that are monosubstituted at C-3 position affords predominantly trans-products.…”