4 Aryl 3 azetidin 2 ones

Vergely, I. Boggetto, N. Okochi, V. Golpayegani, S. Reboud-Ravaux, M. Kobaiter, R. Joyeau, R. Wakselman, M. Inhibition of human leucocyte elastase by functionalized V-aryl azetidin-2-ones substituent effects at C-3 and benzylic positions. Eur. J. Med. Chem. 1995, 30, 199-208. 

The palladium catalyzed hydrogenolysis of 3-amino 4-aryl azetidin-2-ones, Fig. 11, constitutes an excellent and reliable strategy to access a-amino acid derived peptides. The discovery, development, and synthetic opportunities of this approach have been reviewed by Ojima [145-148], and will not be covered here. Only the... 

The classical reaction with chlorosulfonyl isocyanate has been extended to it-vinyl sulfide 449 to give a 2.5 1 diastereomeric mixture of 4-(phenylthio)azetidin-2-ones 343 and 450 (Equation 180) <2000MI935>. The facial selectivity in the cycloaddition has been explained by the conformational preference of the allylic groups in the transition structure. A similar reaction with styrene resulted into synthesis of the racemic 4-aryl-azetidin-2-one (Equation 181) <2000TA2351>. The divinyl ether 451 reacted with acid-free chlorosulfonylisocyanate to form 4-vinyloxyazetidin-2-one 452 (Equation 182) <1996SL895, 1997TA2553, 1998TL8349>. Most of the results in the reactions of isocyanate with vinyl ethers could be rationalized by a -conformational preference of the ether in... 

Holton RA, Liu JH (1993) A Novel Asymmetric Synthesis of Cis-3-Hydroxy-4-Aryl Azetidin-2-Ones. Bioorg. Med Chem Lett 3 2475... 

N(4-hydroxycyclohexyl)-3-mercapto/cyano-4-aryl-azetidine-2-one has been synthesized fromN-(4-hydroxycyclohexyl)-arylaldimine byreacting with ethyl a-mercapto/a-cyanoacetate on basic alumina under microwaves (Scheme 54), wherein not only the reaction time were brought down from hours to minutes in comparison to conventional heating but also yields were improved. 

N-Inversion in azetidine and azetidin-2-one is rapid, even at —77 and -40 °C, respectively (B-73NMR144). Again, halo substituents on nitrogen drastically slow the inversion rate, so that Af-chloro-2-methylazetidine can be separated into two diastereomers (b-77SH(1)54). Substituent effects on N-inversion are much the same as in the aziridines Af-aryl and N- acyl... 

Azetidines, 7, 237-284, 238-246 addition compounds with trimethylboron, 7, 240 AT-alkylation, 7, 240 applications, 7, 246 AT-arylation, 7, 240 azetidin-2-ones from, 7, 263 bicyclic... 

Aminosilanes, 87-9 Artemisia ketone, 33 Aryl silyl ethers, 41 Arylsilanes, 39-43 Arylsulphonylhydrazones, 12 Aryltrimethylsilanes, 39, 42,43 Azetidin-2-ones, 70 Azetidin-2-one 4-carboxylic acids, 92... 

The synthesis of 4-aryl-3-(3-chloropropyl)azetidin-2-ones was reported to be performed by means of a Staudinger reaction between arylmethylideneamines and 5-chloropentanoyl chloride in the presence of 2,6-lutidine [123]. 

The carbonyl group at G-4 of the 3-aryl-4-benzoylazetidin-2-one is reduced with sodium borohydride to the corresponding hydroxyl group <2003T5259>. Treatment of azetidin-2-one 372 with sodium hydride gave a fused tricyclic azetidin-2-one 373 (Equation 140) as a result of an intramolecular nucleophilic substitution reaction of the alkoxide with an aromatic group at the C-3 position. 

Fused tetracyclic biaryl-2-azetidinones have been prepared by the radical cyclization of aryl /3-lactam-tethered haloarenes. Azetidin-2-one 504, having an extra radical acceptor on C-3, underwent radical cyclization with tributyltin hydride to give the biaryl-2-azetidinone 505 in a low yield, with debrominated 3-phcnoxyA-phcnyl-l -(/ -methoxy-phenyl)-2-azetidinone as the main product (60% yield) (Equation 82). But when the azetidinones 506 (Rz = R6 = H) bearing an extra link (O) on the radical precursor at C-3 or N-l of the /3-lactam ring were treated with tributyltin hydride, the expected cyclization products 507 were obtained. If azetidinones 506 (Rz = OMe, or Me R6 = H, OMe, or Me) were treated in the same way then the tetracyclic azetidinones 508 were produced (Equation 83) <2005T7894>. 

This microwave-accelerated double alkylation reaction was applicable to a variety of aniline derivatives and dihalides, furnishing N-aryl azacycloalkanes in good to excellent yields [89]. The reaction was applicable to alkyl chlorides, bromides and iodides and was extended to include hydrazines [90]. This improved synthetic methodology provided a simple and straightforward one-pot approach to the synthesis of a variety of heterocycles such as substituted azetidines, pyrrolidines, piperidines, azepanes, N-substituted-2,3-dihydro-Iff-isoindoles, 4,5-dihydro-pyrazoles, pyrazolidines, and 1,2-dihydro-phthalazines [91]. The mild reaction conditions tolerated a variety of functional groups such as hydroxyls, carbonyls, and esters. 

Not only aryl fluorides can be prepared from trimethylsilanes. Regioselective electrochemical fluorination of4-(trimethylsilyl)azetidin-2-ones 10 to give 11 has also been reported (Table 5). The electrolyses of compounds 10 are carried Out using acetonitrile as solvent. The best yields of fluorinated compounds (Table 5) are obtained when triethylamine trishydrofluoride is used as the fluorine source (with hydrogen fluoride/pyridine and triethylamine bishydro-fluoride lower yields are obtained). The stereochemistry of alkylidene side chains (Table 5, entries 3 and 4) is retained during the electrolyses. High stereoselectivity is observed in some cases (Table 5, entry 6). 

Not only aryl fluorides can be prepared from trimethylsilanes. Regioselective electrochemical fluorination of4-(trimethylsilyl)azetidin-2-ones 10 to give 11 has also been reported (Table 5).33... 

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