4- carbonyl-2-azetidinones

R = Hydroxy protecting group N-(Sulfonamido carbonyl) azetidinones RHN... 

Merck s thienamycin synthesis commences with mono (V-silylation of dibenzyl aspartate (13, Scheme 2), the bis(benzyl) ester of aspartic acid (12). Thus, treatment of a cooled (0°C) solution of 13 in ether with trimethylsilyl chloride and triethylamine, followed by filtration to remove the triethylamine hydrochloride by-product, provides 11. When 11 is exposed to the action of one equivalent of tm-butylmagnesium chloride, the active hydrogen attached to nitrogen is removed, and the resultant anion spontaneously condenses with the electrophilic ester carbonyl four atoms away. After hydrolysis of the reaction mixture with 2 n HC1 saturated with ammonium chloride, enantiomerically pure azetidinone ester 10 is formed in 65-70% yield from 13. Although it is conceivable that... 

In 1991, Ohfune and coworkers reported palladium(O)-catalyzed carbonylation of vinylaziridines 262 with carbon monoxide (1 atm.) in benzene (Scheme 2.65) [31]. Interestingly, 3,4-trans-azetidinone 264 was exclusively obtained from a dia-stereomeric mixture of trans- and cis-vinylaziridines 262 (3 1). Tanner and Somfai synthesized (+)-PS-5 (267) by use of palladium(O)-catalyzed trons-selective (3-lactam formation in the presence of Pd(dba)3 CHC13 (15mol%) and excess PPh3 in toluene. 

Cationic Fp (olefin) complexes [Fp = f/5-C5H5Fe(CO)2] undergo regio-specific addition of heteroatomic nucleophiles.32 Subsequent ligand transfer (carbonyl insertion) occurs with retention of configuration at the migrating center (R—Fe—CO -> RCOFe).33 A combination of these processes has provided a novel stereospecific azetidinone synthesis which can also be applied to condensed systems.34... 

The nonacarbonyldiiron-induced transformation of oxazabicyclo[2.2.2] octenes (12) into condensed azetidinones is intriguing mechanistically but will obviously have limited synthetic application (Scheme 15).37 The /(-lactam (14a), among other products, is isolated directly from the iron carbonyl reaction but the dimethyl analog (14b) is obtained by pyrolysis of an isolable intermediate <7-7r-allyl complex (13b). 

Treatment of a pentacyclic la, I I -(2-oxethano) thioketal steroid with excess Et3SiH/TFA causes reduction of the carbon-carbon double bonds as well as the 17-carbonyl group to give a single reaction product (Eq. 213).368 Other work utilizes trifluoroacetic acid, triethylsilane, and anisole in the presence of a catalytic amount of boron trifluoride etherate to reduce the acetyl carbonyl of a 3-acetyl-2-azetidinone derivative with a dr of 8 1 (Eq. 214).395... 

Enantiopure carbacepham derivatives 54 have been prepared in good yields via Lewis acid promoted carbonyl-ene cyclization of the corresponding 2-azetidinone-tethered alkenylaldehydes 53 (Scheme 18) [63]. 

In 2006, the palladium-catalyzed carbonylative [2+2] cycloaddition of allyl bromide with heteroaryliden anilines was reported to afford 2-azetidinones... 

Substituted 2-azetidinones are reduced with sodium borohydride in aqueous isopropanol giving 3-aminopropan-l,2-diols. The degree of conversion depends on the substitution pattern in the 3- and 4-positions of the 2-azetidinone ring and shows good correlation with carbonyl LUMO energies of starting material.322... 

The silver acetate-promoted 1,3-dipolar cycloaddition of nitrilimines with 3(/f )-pheny]-4(A )-cinnamoyl-2-azetidinone produced the major adduct, 4-(4,5-dihydro- (g) pyrazol-5-yl)carbonyl-2-azetidinones, with high stereoselectivity.70 The 1,3-dipolar cycloadditions of substituted 2,7-dime(liyl-3-thioxo-3,4,5,6-ici.rahydro-2//- 1,2,41 triazepin-5-one with iV-aryl-C-ethoxycarbonylnitrilimines are highly chemoselective, where the sulfur atom of the dipolarophile interacts with the carbon atom of the dipole.71 The enantioselective 1,3-dipolar cycloaddition of nitrile imines with electron deficient acceptors produces dihydropyrazoles in the presence of 10 mol% of chiral Lewis acid catalyst.72... 

Pauson-Khand cyclization of vic-enyne derivatives of /3-lactams gave good yields of fused tricyclic compounds. The 1,4-disubstituted 2-azetidinone 391 and cobalt octacarbonyl gave the alkyne-cobalt carbonyl complex, which on thermolysis gave the tricycle 392 in 95% yield (Equation 54). When the complexes of 393 with cobalt octacarbonyl were treated with TMANO, a lower yield (65%) of 394 was obtained (Equation 55). A single diastereoisomer was formed in each case <1996TL6901>. 

Carbodiimides are also used in the enantioselective synthesis of 3-substituted 4-(alkoxy-carbonyl)-2-azetidinones from malic acid. DCC is used in the the synthesis of nocardicin Penam, 4-thiazabicyclo[3.2.0]heptan-7-one, and 2,3-disubstituted derivatives utilize EDCCl in the cyclization steps. ... 

The first 2-azetidinone O-lactam) was obtained by Staudinger from the reaction of diphenylketene with benzylideneaniline (equation 13). Most of the -lactams prepared by this method have been made from imines derived from aromatic carbonyl compounds and ketoketenes. - The reaction of ketene itself with imines has been recently reinvestigated. Good yields of 3-lactams are obtained when a stream of ketene gas is passed through Ae imine in the absence of solvent (equations 14 and IS). No [4 + 2] cycloadduct is formed with N-cinnamylideneaniline. 

In order to study possible side reactions which may reduce the yield in the Woodward method of annulation of azetidin-2-ones (Scheme 31) similar reactions of ylides (214), which do not contain groups capable of conversion to carbonyl by DMSO-acetic anhydride treatment, have been investigated. 30 A range of products, e.g. (215) and (216), were obtained. A mild, four-carbon homologation of the 4-formyl-substituted azetidinone (217) involving reaction with the phosphonium ylide (218) has been used to synthesize (219), a useful intermediate in the synthesis of carbacephem antibiotics. 3 ... 

Cp2TiMe2 is a suitable reagent for the methylenation of heteroatom-substituted carbonyl compounds in the reactions with a- and /3-lactams (Scheme 522). It reacts with l-aryl-2-azetidinones with the formation of methylene azetidine compounds. Analogous reactions with aziridinines afford methylene aziridine compounds.1339... 

Na2S-H20, H2O, THF, 68-90% yield DCC(-H20), 67-97% yield hydrazine dil. HCl, 55-95% yield. This method is used to cleave A/-phthalimido penicillins hydrazine attacks an intermediate phthalisoimide instead of the azetidinone ring. With a 3-lactam the typical hydrazinolysis is not always usable because of the reactivity of the azetidinone carbonyl. The following scheme provides an example. ... 

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