Azetidinones reduction

Azetidin-2-one, l-benzyl-3,3,4-triphenyl-, 7, 249 Azetidin-2-one, l-(2-bromophenyl)-X-ray crystallography, 7, 247 Azetidin-2-one, 3-carboxy-synthesis, 7, 262 Azetidin-2-one, 3-halo-synthesis, 7, 77 ring contraction, 7, 81-82 Azetidin-2-one, 4-imino-IR spectroscopy, 7, 248 Azetidin-2-one, 1-phenyl-irradiation, 7, 255 Azetidin-2-one, 4-phenyl-reductive ring cleavage, 7, 252 Azetidin-2-one, 4-thio-IR spectroscopy, 7, 248 Azetidinones bicyclic, 7, 348-356 C NMR, 7, 348 H NMR, 7, 348 reactivity, 7, 356-358 spectroscopy, 7, 357 structure, 7, 349 synthesis, 7, 358-359 fused ring... 

Aryl vinyl sulphones, reactions of 646 Aryl vinyl sulphoxides 620 optical resolution of 287 reactions of 354, 355, 360, 361, 621 Asscher-Vofsi reaction 189 Asymmetric induction 625 Asymmetric oxidation 72-78 Asymmetric reduction 78, 79 Asymmetric synthesis 824-846 Atomic orbitals 2, 3 Azetidinones 790, 791 ot-Azidoaldehydes, synthesis of 811 Azidosulphones, photolysis of 883, 884 Azosulphones, photolysis of 879 Azoxysulphones, photolysis of 879 1-Azulyl sulphoxides, synthesis of 265... 

The p-thiolactams 50 are obtained by the action of Lawesson s or Davy s reagent on 3-substituted 1-methoxy- or 1-benzyloxy-azetidinones followed by reductive N-deprotection. The simple P-thiolactam can be modified to give the thiolactam analogues of monobactams <96LA141>. 

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... 

Reduction of hydroxamic acids. Buffered TiC lj can reduce simple hydroxamic acids (equation I). Yields are high when R1 is an alkyl group when it is hydrogen, aldehydes are obtained as by-products. The reagent also reduces substituted N-hydroxy-2-azetidinones to /Mactams (equation 11). 

Lactams.1 The ketene derived from (S)-phenyloxazolidylacetyl chloride (1), prepared from (S)-phenylglycine, undergoes cycloaddition with N-benzyl al-dimines to give two as-azetidinones with high stereochemical control (equation I). The chiral auxiliary and the benzyl group are cleaved by Birch reduction to provide enantiomerically pure azetidinones (3). 

The reductive opening of epoxy-p-lactam 97 with titanocene(III) chloride gives rise to a benzyl radical that can be trapped by intramolecular n systems to give the tricyclic 2-azetidinone 98 (Scheme 32) [78]. 

Apart from alanes [108-110], and monochloroalanes ([111] for use of mono-chloroalanes in the reduction of 2-azetidinones to azetidines, see [112]), boranes have also been employed for the (3-lactams N -C2 bond cleavage. Baldwin had reported the sodium borohydride promoted ring opening of A-Cbz (3-lactams... 

Oxidative methanolysis of azetidinone 176 followed by hydrogenolysis of compound 177 afforded /3-lactam 178, which was protected to obtain the protected amine 179. The best conditions for rearrangement of 179 were found using TFA. Conversion of compound 180 to carbacephem 183 was accomplished by ketone reduction, alcohol protection, and elimination of methanol. Synthesis of carbacephem derivative 186 has been performed by rhodium(n)-catalyzed cycliza-tion of iodonium ylide 185 <1997TL6981> (Scheme 33). The iodonium ylide 185 was easily prepared from the corresponding /3-keto ester 184 and [(diacetoxy)iodo]benzene in good yield. 

Sulopenem (CP-70429 see Tables 1 and 7) has been prepared via this reaction as the key step (G=0/C=S reductive coupling). The total synthesis utilizes L-aspartic acid to generate the chiral precursor 78 of the C-2 side chain, a modified chiron 76 (X = C1) to improve the preparation of the trithiocarbonate intermediate 79, a chemoselective oxalofluoride-based azetidinone N-acylation to give 80 (a procedure that avoids sulfoxide O-acylation), and mild final deprotection conditions of hydroxyl and carboxyl functions. In particular, the chloroallyl ester 81 has been selected, owing to its smooth cleavage by a palladium-mediated transesterification procedure (Scheme 42) <1992JOC4352>. 

Alcaide s group has reported further work on the radical cyclization of alkenyl or alkynyl substituted 4-allenynol-/)-lactams (see Section 2.04.9.6) <2007JOC1604>. Titanocene monochloride mediated reductive radical cyclization of l-cyanoalkyl-4-(epoxy-2-phenylethyl)-2-azetidinones yielded bi- or tri-cyclic /3-lactams, the latter having an aryl group fused to a seven membered ring <2007T3017>. 

Carbapenem antibiotics (29) can be manufactured from intermediates obtained by Ru(BINAP)-catalyzed reduction of a-substituted P-keto esters by a dynamic kinetic resolution (Scheme 12.8). 4-Acetoxy azetidinone (30) is prepared by a regioselective RuCl3-catalyzed acetoxylation reaction of 31 with peracetic acid 46 This process has been successful in the industrial preparation of the azetidinone 30 in a scale of 120 tons per year.47 The current process has changed ligands to 3,5-Xyl-BINAP (3c), and 31 is obtained in 98% ee and >94% de (substrate-to-catalyst ratio, or S/C ratio = 1,000).23... 

A synthesis of 2-aryl-3,3-dichloroazetidines 2, a relatively unexplored class of azaheterocycles, was accomplished by reduction of the corresponding 4-aryl-3,3-dichloro-2-azetidinones with monochloroalane. Reacting these 3,3-dichloroazetidines with sodium hydride in DMSO, followed by aqueous work up, afforded l-alkyl-2-aroylaziridines, by hydrolysis of the intermediate 2-azetines <02JOC2075>. 

The reductive opening of epoxyimonobactams with titanocene(ni) chloride gives rise to radicals that can be trapped intramolecularly by n systems to give new tricyclic 2-azetidinones 38 <02JOC8243>. 

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