P-lactam via

Scheme 31 Preparation of A -aryl-suhstituted spiro-P-lactams via Studinger cycloaddition...

Scheme 41 Synthesis of spiro-P-lactams via cyclization of lithiated pyridine and quinoline carboxamides...

Scheme 45 Novel synthetic approach to spiro-P-lactams via halogen-mediated intrasulfenyl cyclization...

Scheme 49 Solid-phase synthesis of P-lactams via ester enolate-imine condensation...

The synthesis of monocyclic p-lactams via the ester-enolate imine condensation route has been reported to be carried out utilizing triazene esters (Scheme 54), [141], Esters were attached to benzylamine resin by a triazene linker employing the respective diazonium salts. Immobilized ester-enolates were reacted with various imines to give polymer-bound p-lactams in different substitution patterns. Traceless cleavage from the triazene linker yielded the desired p-lactams. 

Scheme 91 Liquid-phase synthesis of alicyclic P-lactams via Ugi three-component reaction...

Scheme 9 Enzymatic and chemical ring opening of P-lactams via N1-C2 bond cleavage...

Other strategies for the ring opening of p-lactams via Nx-C4 bond cleavage have seldom appeared in literature. Ahn [150] has reported the LDA-promoted ring enlargement of /V-benzyl p-lactams 194 to the corresponding /V-H y-lactams, Scheme 59. The reaction proceeds diastereoselectively to provide exclusively the ira ,v-4,5-disubstituted y-lactams 195. 

Gallop et al. [80] reported the preparation of p-lactams via a [2+2] cycloaddition reaction of ketenes with resin-bound imines derived from amino acids (Scheme 9). This is another solid-phase adaptation of the Staudinger reaction, which could lead to the synthesis of structurally diverse 3,4-bis-substituted 2-azetidinones [81]. In addition, a novel approach to the synthesis of A-unsubstituted-p-lactams, important building blocks for the preparation of p-lactam antibiotics, and useful precursors of chiral p-amino acids was described [82]. 

Computational Studies on the Synthesis of p-Lactams via [2+2] Thermal Cycloadditions... 

SCHEME 10.7 Mechanism of the formation of p-lactams via the [2+2] cycloaddition of imines with ketenes. 

The synthesis of the azetidin-2-one nucleus, via the classical annulation of acetyl-chlorides with imines, requires more than stoichiometric amounts of Uiethylamine (about 3 equivalent), which cannot be recovered and reused. In addition, the procedure needs a large amount of organic solvents (VOCs) and, as a consequence, causes a large amount of waste. To overcome these difficulties, the possible ytterbium (III) triflate-catalysed stereoselective synthesis of P-lactams via [2+2] cyclocondensation in ionic liquids has been investigated by Su et al. (Scheme 16.4) [93]. 

Scheme 16.4 Ytterbium (III) triflate-catalysed synthesis of P-lactams via [2+2] cyclocondensation in ionic liquids (Reprinted from Ref. [93] with kind permission of Taylor Francis)...

Scheme 16.13 Synthesis of P-lactams, via deprotonation of bromoamides by electrogenerated bases, in RTILs and in VOCs (Reprinted from Ref. [113] with kind permission of Elsevier)...

Chen R, Yang B, Su W (2006) Ytterbium(III) triflate-catalyzEd stereoselective synthesis of P-lactams via [2 + 2] cyclocondensation in ionic liquid. Synth Commun 36 3167-3174... 

Feiod M, Orsini M, Palombi L, Rossi L, Inesi A (2005) An electrochemical alternative strategy to the synthesis of P-lactams via NC4 bond formation. Electrochim Acta 50 2029-2036... 

Amino acids are practical chiral educts (chirons), and they also steer stereoselective reactions as catalysts. Phenylalanine-controlled aldol condensations with 2-dialkyl-cyclopenta-l,3-dione give just one enantiomer (Danishefsky and Cain, 1976) Intramolecular cyclization reactions of serine yield chiral P-lactams via an active hydroxyl amide and after protection of the amino group of serine. The addition of aldehydes to cysteine produces chiral thiazolidinecarboxylic acids in quantitative yield. Aspartic and glutamic acids have been converted to... 

The synthesis of tricyclic p-lactams via palladium-catalyzed cyclization of iodoaryl p-lactams using a catalyst system comprising 10 mol% Pd(AcO)2, 20 mol% PPh3, and TI2CO3 (2 mol) has been afforded [94]. The methallyl p-lactam 161 underwent 1-endo-trig cychzation to give an 8 1 mixture of double bonds isomers 162 and 163 (Scheme 56). 

Scheme 23 Incorporation of 3 (prop 2 enylidene)azetidin 2 one for the synthesis of spiro P lactams via Diels Alder reactions...

In 2004, bis-(cyclophanyldiol)A10Tf complex has been reported to catalyze the enantio- and diastereoselective synthesis of p-lactams via Staudinger reaction (Scheme 25), [87]. 

A combined theoretical and experimental study has been reported for the formation of silylated p-lactams, via Staudinger [2+2] cycloaddition reaction from silylketenes and imines, in the presence or in the absence of a Lewis acid... 

Scheme 64 Synthesis of a amino P lactams via ynamide Kinugasa reaction...

In 2002, a-oxoamides have been reported to be transformed into p-lactams via photochemical rearrangement [172]. Good results were obtained via irradiation of ionic and covalent chiral auxiliary-containing reactants in the crystalline state and in the interior supercages of zeolites (Scheme 73). 

In 2008, Sakamoto and coworkers have reported the synthesis of optically active p-lactams via photochemical intramolecular y-hydrogen abstraction reaction of thioimides [177]. This reaction provides the first example of a chiral-memory effect for the photochemical y-hydrogen abstraction reaction of thiocarbonyl or carbonyl compounds, and a useful synthetic methodology for preparing optically active p-lactams (Scheme 78). 

In 2008 Yang and coworkers have reported an efficient synthesis of substituted a-alkilidene-p-lactams via aNaOH- promoted intramolecular aza-Michael addition of a-carbamoyl, a-(l-chlorovinyl) ketene-S,S-acetals and subsequent nucleophilic vinylic substitution reaction in alcoholic media (Scheme 90), [198]. 

Scheme 94 Synthesis of a trifluoromethyl P lactams via reductive cleavage of isoxazolidines...

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