Organophosphorus reagents in organocatalysis: synthesis of optically active α-methylene-δ-lactones and δ-lactams.
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.
Center for Catalysis, Department of Chemistry, Aarhus University, 8000 Aarhus C, Denmark.
Anna
A
Albrecht
Fabio
F
Morana
Alberto
A
Fraile
Karl Anker
KA
Jørgensen
D002384:Catalysis; D007202:Indicators and Reagents / Q000737:chemistry*; D007769:Lactams / Q000138:chemical synthesis* / Q000737:chemistry; D007783:Lactones / Q000138:chemical synthesis*; D015394:Molecular Structure; D009943:Organophosphorus Compounds / Q000737:chemistry*; D013237:Stereoisomerism
D007202:Indicators and Reagents; D007769:Lactams; D007783:Lactones; D009943:Organophosphorus Compounds; C416683:methylene-lactone