Azetidines, hydroxylation

Hydroxylation of azetidine-l-carboxylates 33 with a biocatalyst, Sphingomonas sp. HXN-200, gave the corresponding 3-hydroxyazetidines 34 (Equation 7) <20020L1859>. 

Chiral azetidines have been synthesized by lipase-catalyzed selective acylation of the hydroxyl group in 2,4-bis(hydroxymethyl)azetidine 112 (Scheme 24) <2001TA605>. The resulting alcohol 113 was then transformed into an amino alcohol 114 (Equation 29), which represents an interesting precursor for the chiral catalyst 115. 

Reduction of an azide functionality at C-3 of azetidin-2-one 355 followed by acylation afforded 3-amidoazetidin-2-one 356 (Scheme 50). O-Debenzylation, followed by treatment with the Jones reagent, afforded a m-3,4-disubsti-tuted azetidin-2-one 357, which is a precursor of the antibiotic loracarbef <2001TL4519>. The reduction of an ethoxycarbonyl group and an acetoxy group at C-3 to a hydroxyl group has been accomplished by sodium borohydride (Equation 134) <2001T10155>. 

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. 

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. 

Azetidines and pyrrolidines. Base-promoted cyclization of epoxy tosylamides is sensitive to the structures of the substrates. Thus products having either a primary or a secondary hydroxyl group may be obtained. 

Azetidines. (12, 333) These cyclic t directly, but can be obtained by reduction of 5-lactams with cleavage of the 1,2-bond to al ut monochloroalane (AIH2CI) or dichlortnli a high yield (85-100%). Azido groups, i -Butyl ester groups are reduced to hydroxyl... 

CYP153A7 (P450pyr) Sphingopyxis macrogoltabida 3RWL Hydroxylation of N-substituted pyrrolidines, piperidines, azetidines, 2-pyr-rolidines and 2-piperidinones [785]... 

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