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Radical 4‐ exo Cyclizations onto O ‐Alkyloxime Acceptors: Towards the Synthesis of Penicillin‐Containing Antibiotics
Author(s) -
Scanlan Eoin M.,
Walton John C.
Publication year - 2006
Publication title -
helvetica chimica acta
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.74
H-Index - 82
eISSN - 1522-2675
pISSN - 0018-019X
DOI - 10.1002/hlca.200690202
Subject(s) - chemistry , benzaldehyde , radical , ring (chemistry) , electron paramagnetic resonance , oxime , medicinal chemistry , thiazolidine , radical cyclization , stereochemistry , organic chemistry , catalysis , physics , nuclear magnetic resonance
The 4‐ exo cyclizations of two types of carbamoyl radicals onto O ‐alkyloxime acceptor groups were studied as potential routes to 3‐amino‐substituted azetidinones and hence to penicillins. A general synthetic route to ‘benzaldehyde oxime oxalate amides’ (= 2‐[(benzylideneamino)oxy]‐2‐oxoacetamides; see, e.g. , 10c ) of 2‐{[(benzyloxy)imino]methyl}‐substituted thiazolidine‐4‐carboxylic acid methyl esters 9 was developed ( Scheme 3 ). It was shown by EPR spectroscopy that these compounds underwent sensitized photodissociation to the corresponding carbamoyl radicals but that these did not ring close. An analogous open‐chain precursor, benzaldehyde O ‐(benzylaminoacetaldehyde‐ O‐ benzyloxalyl)oxime, 15 , lacking the 5‐membered thiazolidine ring, was shown by EPR spectroscopy to release the corresponding carbamoyl radical ( Scheme 4 ). The latter underwent 4‐ exo cyclization onto its CNOBn bond in non‐H‐atom donor solvents. The rate constant for this cyclization was determined by the steady‐state EPR method. Spectroscopic evidence indicated that the reverse ring‐opening process was slower than cyclization.