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Flexible Synthesis of Planar Chiral Azoninones and Optically Active Indolizidinones
Author(s) -
Bohland Frank,
Erlin Irina,
Platte Lukas,
Schröder Maike,
Schollmeyer Dieter,
Nubbemeyer Udo
Publication year - 2014
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.201402720
Subject(s) - stereocenter , chemistry , stereochemistry , electrophile , antipodal point , proline , double bond , enantioselective synthesis , ring (chemistry) , optically active , natural product , combinatorial chemistry , amino acid , organic chemistry , catalysis , biochemistry , geometry , mathematics
The flexible synthesis of defined substituted optically active indolizidinones starting from chiral pool ( S )‐proline and trans 4‐hydroxy‐( S )‐proline is described. Several defined 2‐vinylpyrrolidines were generated in short sequences. The aza‐Claisen rearrangement using chloro and phenylketene equivalents delivered nine‐membered‐ring lactams with up to three stereogenic centres and pS ‐arranged E olefins. Depending on the substitution pattern, certain azoninones had a flexible conformation and showed pS / pR double‐bond flipping. Treatment of the unsaturated lactams with the soft electrophile iodine induced diastereoselective transannular ring contractions. Here, the planar chiral arrangement of the azoninone double bond predetermined the bridgehead configuration of the product indolizidinones. Thus, the ( S )‐proline starting materials could be used to gain access to either one of the two antipodal series of indolizidinone products. The indolizidinone scaffolds should serve as versatile key intermediates in the synthesis of natural products and pharmaceutically important molecules.