Acyl Steglich rearrangements

In 1970, Steglich reported that DMAP catalyzed the rearrangement of O-acylated azlactones to their C-acylated isomers (the Steglich rearrangement) [166, 167]. This process effects C-C bond formation and concomitant construction of a qua-... 

The commonly accepted mechanism for the Steglich rearrangement, depicted in Scheme 40.2, involves a fast and reversible attack of the nucleophilic catalyst to the acyl of alkoxycarbonyl group, leading to an ion pair that in a slow irreversible step leads to the formation of the C4- or C2-substituted azlactone. If the nucleophile is chiral, the acyl cation can discriminate between the two enantiotopic faces of the azlactone enolate, affording enantiomerically enriched products. 

Scheme 40.16 Asymmetric acyl migration in the Steglich rearrangement.

In 2010, Ooi and coworkers proposed the use of chiral ammonium betaines as asymmetric ionic nucleophilic catalysts [29], They reasoned that an intramolecular alkoxonium salt could be an efficient catalyst for the Steglich rearrangement- since the alkoxide anion would displace the carbonyl substituent in the intermediate ion pair the ammonium cation would be engaged in an ionic interaction with the azlactone anion, enhancing both the rate and the stereoselectivity of the acyl transfer step (Scheme 40.22). 

In 1970 Steglich and Hofle reported that 4-dimethylaminopyridine (DMAP) and 4-(pyrrolidino)pyridine (PPY) are excellent catalysts for isomerization of O-acyl azlactones E to their C-acylated isomers F [79-81], In this rearrangement, a new quaternary stereocenter is generated (Scheme 13.41). Clearly, DMAP or PPY afford the rearrangement products F in the racemic form. 

Type I Asymmetric Acyl Addition to 7r-Nucleophiles Steglich and Related Rearrangements and Additions to Silyl Ketene Acetals/lmines... 

On this topic, several outstanding contributions were reported by Fu and coworkers,in which new asymmetric nucleophilic catalysts based on chiral ferrocene-type heterocycles were designed. To this end the planar-chiral PPY ferrocene complex (PPY = 4-(pyrrolidino)-pyridine (3.61) was prepared and resolved. Complex 3.61 catalysed the enantioselective rearrangement of A-acylated Azlactones to give C-acylated isomers with high yields and ee of 82-90%. The powerful effect of the chiral ferrocene scaffold was clearly evident if compared to the same reaction with the organic catalyst DMAP reported in 1970 by Steglich and Hofle where only racemic compounds were formed (Scheme 3.26). 

The rearrangement of O-aqflated azlactones (or of oxazolyl carbonates) to a C-acyl-(or to a C-carboxy) azlactone takes place easily at room temperature in the presence of catalytic amounts of 4-(dimethylarriino)pyridine (DMAP) or of 4-(l-pyrrolidinyl) pyridine (PPY), as first disclosed by Steglich and Hofle in 1969 (Scheme 40.1) [9]. Although the product is usuaUy a 4-acyl- (or a 4-alkoxycarbonyl)azlactone, if the R2 substituent is electron-donahng the rearrangement at C2 can take place. 

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