Azabicycloalkenes as Synthetic Intermediates − Synthesis of Azabicyclo[X.3.0]alkane Scaffolds

Abstract

A general method to synthesize functionalized azabicyclo[X.3.0]alkane scaffolds 5 is reported. Key intermediates are azabicycloalkenes such as 1 and 2, which are acylated with unsaturated carboxylic acids and subsequently submitted to tandem olefin metathesis. The resulting bicyclic heterocycles are versatile intermediates for different dipeptide mimetics and can be used as intermediates for natural products with indolizidine scaffolds or analogues thereof. [reaction: see text].

Mild, Selective Sulfoxidation with Molybdenum(VI) cis-Dioxo Catalysts

“…A more specific application of sulfoxidation is in the synthesis of chiral vinylglycine from methionine. Rapoport and Afzali-Ardakani reported a synthesis of ( l )-vinylglycine in 1980 with an overall yield of 54%, which stands so far as the highest reported overall yield and therefore the most widely used method for the synthesis of vinylglycine. − Chiral vinylglycine is useful as an enzyme inhibitor , and as a derivative for amide functionality within enantiopure target organic molecules. As such, vinylglycine is produced on industrial scale.…”

Metal-Free [3 + 2 + 1]/[2 + 2 + 1] Biscyclization: Stereospecific Construction with Concomitant Functionalization of Indolizin-5(1H)-one

“…In the meantime, indolizin-5(1 H )-one bicyclic scaffolds have been proven to be key building block for the total synthesis of various indolizidine alkaloids . Several approaches to bicyclic motifs have been developed, including the Schmidt reaction, ring-closing metathesis reaction, metal-catalyzed cycloaddition, and Rh-catalyzed cyclization . However, most of these approaches suffer from several noticeable drawbacks, such as the use of costly and toxic metal catalysts, multistep procedures, inaccessible substrates, and lack of effective derivation from the target skeleton.…”

Desymmetrization of 7-azabicycloalkenes by tandem olefin metathesis for the preparation of natural product scaffolds

“…As a part of a general synthetic concept using azabicycloalkenes as masked analogs of functionalized pyrrolidines or piperidines [ 32 - 39 ] we have previously applied the concept of intramolecular ring-opening/ring-closing metathesis (RORCM) [ 40 - 54 ] to N -acylated 2-azabicycloalkenes 4 as precursors for azabicyclo [X.3.0]alkanes like 6 (Scheme 1 ). [ 55 ] Various other strained heterocycles have also been used for ring opening metathesis or other tandem metathesis sequences. [ 56 - 61 ]…”