Azetidinium

In aqueous solution, azetidine (p/sTa 11.29) is slightly more basic than pyrrolidine and larger-ring cyclic amines and appreciably more basic than aziridine. It forms an addition compound (m.p. - 9 to -6 °C) with trimethylboron which is more stable than that formed by pyrrolidine (50JA2926, 64HC(l9-2)885). Azetidinium salts are well known (Section 5.09.2.2.7). 

The Cu(acac)2-promoted transformation 368 - 369 represents an intramolecular carbenoid insertion into the penicillin C5—S bond 347). The original report did not mention the low-yield formation of a second product to which the tricyclic structure 370 was assigned 348,349 >. In both 369 and 370, the original stereochemistry at C-5 of 368 has been inverted this is seen as a consequence of intramolecular nucleophilic a-face attack in a presumed azetidinium enolate intermediate. Attempts to realize a more flexible intermediate which then would have a chance to undergo p-face attack centered on the chain-extended diazoketone 371. Its catalytic decomposition led to the tricycle 372 exclusively, however, C7/N rather than C5/S insertion having taken place 349). 

P-Lactams have been used as a synthon for the preparation of a vast array of compounds. It has been reported that the reduction of 4-(haloalkyl)azetidin-2-ones with LiAlhL is a powerful method for the synthesis of stereodefined aziridines and azetidines <06OL1101>. However, reduction of 4-(haloalkyl)azetidin-2-ones with chloroalane afforded 2-(haloalkyl)azetidines, which were rearranged to 3,4-cw-disubstituted pyrrolidines and piperidines 32 <060L1105>. During these rearrangements, bicyclic azetidinium intermediates were formed which were ring opened by halides. The synthesis of a peptide-... 

A novel route to 3,4-disubstituted piperidines 206 via ring transformation of 2-(haloalkyl)azetidines 207 is shown below. During these reactions, bicyclic azetidinium intermediates are formed and then ring opened by a variety of nucleophiles generating stereospecific substituted piperidines in excellent yields <06OLl 105>. 

More recently, Naidu and West have utilized a ring expansion reaction of spiro azetidinium ylide 167 in the synthesis of pyrrolizidine alkaloids. Spiro azetidinium ylide 167 is generated through a Cu(acac)2-catalyzed intramolecular reaction of a copper carbene complex with a pendant amino moiety. Subsequent [l,2]-shift gives fused bicyclic products 168 and 169 as a diastereomeric mixture. Each diastereomer was further converted to naturally occurring pyrrolizidines ( )-turneforcidine and ( )-platynecine, respectively (Scheme 18). ... 

Like their monocyclic analogs (see Section 5.09.2.2.7) bicyclic azetidinium salts are subject to nucleophilic ring opening. Quaternary salt (27) can react with a nucleophile either at C-5 or C-7 producing the ring expansion (28) or direct substitution products (29), respectively (64HCA745, 69AG(E)962. ... 

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