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Zwitterionic Aza‐Claisen Rearrangements Controlled by Pyrrolidine Auxiliaries – Useful Key Steps in Convergent Enantioselective Syntheses
Author(s) -
Friedemann Nora M.,
Härter Alice,
Brandes Sebastian,
Groß Steffen,
Gerlach Dorothea,
Münch Winfried,
Schollmeyer Dieter,
Nubbemeyer Udo
Publication year - 2012
Publication title -
european journal of organic chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.825
H-Index - 155
eISSN - 1099-0690
pISSN - 1434-193X
DOI - 10.1002/ejoc.201200073
Subject(s) - chemistry , pyrrolidine , enantioselective synthesis , ketene , claisen rearrangement , chiral auxiliary , amide , diastereomer , asymmetric induction , stereochemistry , enantiomer , organic chemistry , pyrroline , catalysis
Chiral pyrrolidine substituents served as efficient auxiliaries in diastereoselective zwitterionic ketene aza‐Claisen rearrangements. Palladium‐catalysed N ‐allylation starting from optically active proline and prolinol derivatives, as well as from (2 S ,5 S )‐2,5‐dimethoxymethylpyrrolidine, gave various allylamines bearing trisubstituted olefin moieties. Treatment with complex carboxylic acid fluorides in the presence of trimethylaluminium induced activated ketene addition to the nitrogen and subsequent [3,3] sigmatropic rearrangement to give γ,δ‐unsaturated amides with excellent simple diastereoselectivities and up to 11:1 auxiliary‐induced diastereomeric ratios. Cleavage of the pyrrolidine amide was achieved through iodolactonization, with the option for recovery of the auxiliary pyrrolidine. The stereochemical outcomes of the rearrangements and the iodocyclizations were established by X‐ray and NOEDS analyses of suitable amides and lactones. Overall, both enantiomers were accessible selectively. The optically active amides and lactones of defined configurations formed in this way should be useful as key intermediates in convergent steroidal natural and pharmaceutically important product synthesis.