Transannular Rearrangement of Activated Lactams: Stereoselective Synthesis of Substituted Pyrrolidine‐2,4‐diones from Diketopiperazines

Oxidative radical cyclizations of diketopiperazines bearing an amidomalonate unit. Heterointermediate reaction sequences toward the asperparalines and stephacidins

“…DKPs upon deprotonation at higher temperatures [49][50][51], because the electron withdrawing carbamate protecting group renders the amide carbonyl group electrophilic enough toward intramolecular attack of the enolate. These results indicated that DKPs with electronaccepting protecting groups at the nitrogen atom are not suitable for oxidative SET-induced radical cyclizations because of competing rearrangements at higher temperatures, which are necessary to trigger the cyclizations.…”

Concise Pathway to New Multifunctionalized Constrained Pentacin Derivatives by Means of Two Stereospecific Tandem Reactions

“…The alkylating version of TRAL [32] is a useful ring-contraction reaction for the stereoselective construction of pyrrolidine-2,4-dione motifs from Boc-activated 2,5-diketopiperazines (DKPs) as precursors. [35] The challenge of this work was to combine and potentiate two methodologies, TRAL/alkylation and MIRC, for the stereoselective synthesis of multifunctionalized alicyclic β-amino esters, ideally to synthesize derivatives of cis-pentacin or trans-pentacin.…”

“…Aiming at the synthesis of rigid pentacin derivatives, we have applied this relevant reaction to a suitable chiral synthon fashioned from a regioselective and stereospecific tandem reaction: the transannular rearrangement of activated lactams (TRAL)/alkylation (Scheme 2). [32][33][34][35] Scheme 2. Chemical strategy involving two tandem reactions to access rigid pentacin derivatives, where Nu = -NHR and EWG = -COOR.…”

Stereoselective synthesis of original spirolactams displaying promising folded structures

“…Starting from N,N'-bis-Boc-activated diketopiperazines (DKP), the six-to five-membered ring-contraction yielded aminotetramate scaffolds with high stereoselectivity. 42 The broad interest of the reaction was previously demonstrated by the preparation of diverse scaffolds such as statins or pentacins analogues. [43][44][45] While a protonation in aqueous medium yielded TRAL product, addition in the reaction mixture of an alkylating agent allowed the formation and isolation of the 20 TRAL-alkylation product (Scheme 1).…”