5-Alkylidene-3-pyrrolin-2-ones

Finally, a 5-endo radical cyclization approach to 5-alkylidene-3-pyrrolin-2-ones has been reported by Tang and Li (Scheme 53 2004OL3229). Treatment of 4-iodo-3-octenoamide 227 (R = Ph) with t-butyl hypochlorite gives 5-(butyhdene)-3-pyrrolin-2-one 228 the same reaction with the corresponding primary amide 227 (R = H) gives the iminoketone 229. 

Pattenden and coworkers employed a Homer—Wadsorth—Emmons reaction to transform maleimides into 5-alkylidene-3-pyrrolin-2-ones (Scheme 146 1993PT(1)2567). For example, treatment of3,4-dimethylma-leimide (522) with phosphoms yhde 523 gives the alkylidene ester 524 with high Z-stereoselectivity. 

Yoshida and coworkers used an ozonolysis of aniline derivative 81 to produce y-aminoester derivative 82 (2005H(65)1481 Scheme 9). Subsequent hydrolysis of trifluoroacetamide 82 led to the alkylidene-substituted 3-pyrrolin-2-one 83. 

A few type be intermolecular approaches to 3-pyrrolin-2-ones have appeared in the literature. Zhou, Li, and coworkers applied a Rh-catalyzed hydroamidation reaction in a synthesis of 5-alkylidene-3-pyrrohn-2-ones (e.g., 338) (Scheme 86 2013OL1814). Treatment of oxime 335 and the aryhsocyanate 336 with a Rh catalyst gives the 3-pyrrolin-2-one 338. The mechanism of the reaction probably includes the formation of the hydroamidation intermediate 337 and subsequent condensation and elimination of O-methyUiydroxylamine. 

As far as we can tell, there is only one intermolecular type cd approach to 3-pyrroUn-2-ones that has appeared in the hterature. Aoyama and Shiori investigated the use of hthium trimethylsilyldiazomethane 347 to generate alkylidenecarbenes from carbonyl compounds alkylidene carbenes are useful intermediates that can be used to form new rings including 3-pyrrolin-... 

Chatzimpaloglou and colleagues employed this approach for a total synthesis ofphaeosphaeride A, a natural antitumor compound (2012JOC9659). They stirred 5-alkylidene-substituted furan-2-one with methoxyamine hydrochloide and LiHMDS in dry THF at —78 °C for 2 h to give the resulting 3-pyrrolin-2-one. 

Starting from 3,4-disubstituted maleic anhydride, Klopfleisch and coworkers synthesized the bilirubin oxidation end-product BOX A and isomers in four or six steps (20130L4608). Within this synthesis they transformed 5-alkylidene-furan-2-ones to the corresponding substituted 3-pyrrolin-2-ones using ammonium acetate and glacial acetic acid. Seidel and coworkers employed a similar approach to BOX B analogs (2014TL6526). 

Pereira and colleagues found that isobutylamine and highly substituted 5-alkylidene-furan-2-ones in methylene chloride at 0 °C provided N-iso-butyl-3-pyrrolin-2-ones (2014EJMC127). Some of these products inhibited... 

Buehrdel has demonstrated that a rearrangement is possible from 2-imi-nolactone to form 5-alkylidene-substituted 3-pyrrolin-2-ones upon treatment with TFA (2008JHC845). 

Accordingly, the photochemical [4+1] cycloaddition of allenyl imines and carbon monoxide leads to 3-alkylidene-4-pyrrolin-2-ones (Scheme 4-305). ... 

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