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Organophosphorus Reagents in Organocatalysis: Synthesis of Optically Active α‐Methylene‐δ‐lactones and δ‐Lactams
Author(s) -
Albrecht Anna,
Morana Fabio,
Fraile Alberto,
Jørgensen Karl Anker
Publication year - 2012
Publication title -
chemistry – a european journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.687
H-Index - 242
eISSN - 1521-3765
pISSN - 0947-6539
DOI - 10.1002/chem.201201325
Subject(s) - chemistry , iminium , michael reaction , methylene , adduct , aldehyde , organocatalysis , organic chemistry , reagent , tryptamine , enantioselective synthesis , combinatorial chemistry , catalysis , biochemistry
In this paper we describe new asymmetric, catalytic strategies for the synthesis of biologically important α‐methylene‐δ‐lactones and δ‐lactams. The elaborated protocols utilize iminium‐ion‐mediated Michael addition of trimethyl phosphonoacetate to α,β‐unsaturated aldehydes catalyzed by ( S )‐(−)‐α,α‐diphenyl‐2‐pyrrolidinemethanol trimethylsilyl ether as the key step. Enantiomerically enriched Michael adducts are employed in three different reaction pathways. Transformation into α‐methylene‐δ‐lactones is realized by a sequence of reactions involving chemoselective reduction of the aldehyde, followed by a trifluoroacetic acid (TFA)‐mediated cyclization and Horner–Wadsworth–Emmons olefination of formaldehyde. On the other hand, indolo[2, 3‐ a ]quinolizine‐framework‐containing products can be accessed when enantiomerically enriched Michael adducts are employed in a Pictet–Spengler reaction with tryptamine, followed by Horner–Wadsworth–Emmons olefination. Finally, reductive amination of the Michael adducts by using methylamine and Horner–Wadsworth–Emmons olefination of formaldehyde is demonstrated to give α‐methylene‐δ‐lactams. The developed strategies can be realized without the purification of intermediates, thus greatly increasing their practicality.