Ring expansion azetidines

Azetidine N-oxides produce isoxazolidines by a thermal ring expansion (77AHC(21)207, 75GEP2365391), and nitrosobenzenes react with alkenes to provide isoxazolidines (77AHC(21)207, 79IZV1059). 

A number of examples of acid catalyzed ring expansion of acyl and thioacyl azetidines to sbc-membered rings have been reported (B-73MI50903). This type of rearrangement (Scheme 2) is similar to the more general vinylaziridine to pyrroline ring expansion. 

Ring expansion of activated aziridines (43) with sulfur ylides also provides a synthesis of azetidines (75JOC2990, 58BSF345, 81CC417). The highly reactive sulfonium methylide (44 R = R = H) undergoes further reaction with the azetidines (46), but the reaction is satisfactory for substituted methylides. The less reactive sulfoxonium methylide (45 R = R = H)... 

A number of 2-acylazetidines have been prepared by reaction of 1,3-dihaloacyl compounds with amino derivatives (Section 5.09.2.3.l(m)). This is illustrated for azetidine 2-carboxylic acid (56), the only known naturally occurring azetidine. Ring expansion of activated aziridines (43) and contraction of 4-oxazolines (55) has also found limited use (Section 5.09.2.3.2(f) and Hi)). 

Ring expansion of haloalkyloxiranes provides a simple two-step procedure for the preparation of azetidin-3-ols (Section 5.09.2.3.2(f)) which can be extended to include 3-substituted ethers and O-esters (79CRV331 p. 341). The availability of 3-hydroxyazetidines provides access to a variety of 3-substituted azetidines, including halogeno, amino and alkylthio derivatives, by further substitution reactions (Section 5.09.2.2.4). Photolysis of phenylacylamines has also found application in the formation of azetidin-3-ols (33). Not surprisingly, few 2-0-substituted azetidines are known. The 2-methoxyazetidine (57) has been produced by an internal displacement, where the internal amide ion is generated by nucleophilic addition to an imine. 

Ring expansions of suitable /3-lactams can also be achieved on treatment with base rearrangement of the Af-substituted azetidin-2-ones (133) occurs in the presence of LDA to give (134) (72JA9261). Aminolysis of the /3-lactam epoxide (135) and the aldehyde (137) affords (136) and (138) respectively (81JHC1239). 

Azetidine, 7V-bromo-, 7, 240 Azetidine, AT-r-butyl- N NMR, 7, 11 Azetidine, AT-t-butyl-3-chloro-transannular nucleophilic attack, 7, 25 Azetidine, 3-chloro-isomerization, 7, 42 Azetidine, AT-chloro-, 7, 240 dehydrohalogenation, 7, 275 Azetidine, 7V-chloro-2-methyl-inversion, 7, 7 Azetidine, 3-halo-synthesis, 7, 246 Azetidine, AT-halo-synthesis, 7, 246 Azetidine, AT-hydroxy-synthesis, 7, 271 Azetidine, 2-imino-stability, 7, 256 Azetidine, 2-methoxy-synthesis, 7, 246 Azetidine, 2-methyl-circular dichroism, 7, 239 optical rotatory dispersion, 7, 239 Azetidine, AT-nitroso-deoxygenation, 7, 241 oxidation, 7, 240 synthesis, 7, 246 Azetidine, thioacyl-ring expansion, 7, 241 Azetidine-4-carboxylic acid, 2-oxo-oxidative decarboxylation, 7, 251 Azetidine-2-carboxylic acids absolute configuration, 7, 239 azetidin-2-ones from, 7, 263 synthesis, 7, 246... 

Corey s ylide (1), as the methylene transfer reagent, has been utilized in ring expansion of epoxide 75 and arizidine 77 to provide the corresponding oxetane 76 and azetidine 78, respectively. 

The oxetane tertiary amides 15 on treatment with methyl triflate in anhydrous nitrobenzene at 150 °C undergo ring expansion to the cyclic acetals 16 and, if the groups R and R2 are sufficiently bulky, the acetals undergo a ring contraction to form the azetidines 17 . 

Thermal isomerization of certain cis-l,3,4-trisubstituted azetidin-2-ones 76 provided the trans isomer in good yield . Bases caused the isomerization of cis-3-substituted-4-formylazetidin-2-ones and of sulfonic acid derivatives of 3-aminoazetidin-2-ones during the formation of a Schiff base <00T3985>. 4-Acyloxy-iV-o-azidobenzoyl-P-lactams underwent ring expansion to produce l,3-oxazin-6-ones 77 . 

Azetidin-2-one can be synthesized by treating 1-ethoxy-1-hydroxycy-clopropane with aqueous sodium azide at pH 5.5 (Scheme 8.7a). This type of construction has wider applications and A-substituted derivatives are formed from 1-amino-1-hydroxycyclopropanes in two steps first A-chlorination with tert- miy hypochlorite [2-methylpropan-2-yl chlo-rate(I)], and then treatment with silver ion in acetonitrile (ethanenitrile) to release chloride ion and trigger ring expansion of the tricycle (Scheme 8.7b). 

Tetrabutylammonium cyanide catalyses ring expansion of 4-(arylimino)methyl-azetidin-2-ones to 5-aryliminopyrrolidin-2-ones through a novel N(l)-C(4) bond cleavage of the /3-lactam nucleus and provides for an efficient one-pot protocol to enantiopure succinimide derivatives (Scheme 20).36... 

Ammonium ylides derived from azetidine-2-carboxylates undergo efficient ring expansion via the Stevens [l,2]-shift (Scheme 77).11... 

The oxetane /-amides 222 undergo a ring expansion-contraction sequence in the presence of a Lewis acid to azetidine derivatives 223 (Equation 60) <2000JOC2253>. The overall reaction sequence has been described as double isomerization . The four-membered oxetane ring first enlarged to a [2.2.2]-dioxazabicycle, which in turn rearranged to the final azetidine derivatives. 

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