Application of Metathesis Protocols to the Stereocontrolled Synthesis of some Functionalized β‐Amino Esters and Azaheterocycles

Abstract

In this account our aim was to give an insight into the application of metathesis protocols (ROM, RCM, RCEYM, CM, RRM) for the synthesis of various azaheterocyclic frameworks. Due to the high biological potential and importance in peptide chemistry and drug design of β‐amino acids our intention is to give a highlight on the synthetic procedures and transformation of these class of compounds with the above‐mentioned metathesis strategies with emphasis on selectivity, stereocontrol, substrate‐directing effect or functional group tolerance.

Selective Transformation of 1,3‐Cyclooctadiene into Novel Functionalized Azaheterocycles, β‐Amino Esters, and Lactams by Means of Ring‐Rearrangement Metathesis

“…Similar findings were observed earlier. [33,34,37] Note, however, that the reason of this observation is currently unknown.…”

“…Based on our previous research endeavours, [30][31][32][33][34] we accomplished the ROM/RCM and ROM/RCEYM protocols of 1,3-cyclo-octadiene-based amino esters in ethylene atmosphere. We systematically explored each reaction using four common, commercially available Ru-based catalysts illustrated in Figure 2.…”

“…Earlier work: synthesis of diverse azaheterocyclic β-amino esters via ring-rearrangement metathesis; X = O, CH 2 ; Y = O, N; Pg = Boc, Ts. [30][31][32][33][34][35] Scheme 2. Current goal: synthesis of novel azaheterocyclic β-amino esters, β-amino lactones, and β-amino lactams through ring-rearrangement metathesis; X = O, NH.…”

“…Earlier, our research group applied RRM of easily accessible strained carbocyclic β-amino esters to obtain various azaheterocyclic β-amino esters in a stereocontrolled fashion. [30][31][32][33][34] This synthetic approach is particularly noteworthy, because it allows an accurate control of the configurations of the stereocenters within the resulting azaheterocyclic compounds. In addition, it opened up new avenues for the synthesis of diverse and structurally intricate β-amino acids, paving the way for potential applications in pharmaceutical and medicinal chemistry.…”

“…Diversity-oriented syntheses have used the easily available norbornadiene-, oxanorbornadiene-, and 1,3-cyclooctadiene-derived starting compounds to form the corresponding azaheterocyclic β-amino esters (Scheme 1). [30][31][32][33][34][35] To extend and demonstrate the versatility and reliability of the method, the aim of the current work was the application of RRM to access other azaheterocyclic β-amino esters, β-amino lactones, and β-amino lactams, which might be considered to be highly valuable building blocks in organic synthesis. The starting compounds for this investigation comprised either allyl/propargyl cyclooctene β-lactams or β-amino esters or the analogous N-allylated/N-propargylated amides or esters derived from 1,3-cyclooctadiene, showcasing our commitment to explore future diverse structural motifs (Scheme 2).…”