Allenyl‐β‐lactams: versatile scaffolds for the synthesis of heterocycles

Abstract

The hybrid allenic β-lactam moiety represents an excellent building block for carbo- and heterocyclization reactions, affording a large number of cyclic structures containing different sized skeletons in a single step. This strategy has been studied under thermal and radical-induced conditions. More recently, the use of transition-metal catalysis has been introduced as an alternative that relies on the activation of the allenic component. On the other hand, the intramolecular version has attracted much attention as a strategy for the synthesis of bi- and tricyclic compounds in a regio- and stereoselective manner. This overview focuses on the most recently developed cyclizations on 2-azetidinone-tethered allenes along with remarkable early works accounting for the mechanism, as well as for the regio- and diastereoselectivities of the cyclizations.

Palladium-catalyzed approach to the synthesis of five-membered O-heterocycles

“…A mild, palladium(II)-catalyzed reaction of α-allenols and α-allenic esters in a heterocyclization/cross-coupling sequence that is applicable to a wide range of substitution patterns has been developed for the preparation of 2,3,4-trifunctionalized 2,5-dihydrofurans, including β-lactam derivatives. The heterocyclizative cross-coupling between 2-azetidinone-tethered allenols and α-allenic acetates resulted in the achievement of β-lactam-dihydrofuran hybrids in good yields (Scheme 82) [170][171][172]60].…”

“…The transformation of allenols into spirocyclic disubstituted dihydrofuran β-lactams was readily achieved in moderate yields by treatment with BH acetates in the presence of palladium(II) acetate (Scheme 17) [60].…”

“…When (trimethylsilyl)acetylene or tolylboronic acid was used as the cross-coupling agent under the optimized conditions, the corresponding domino Sonogashira or Suzuki-Miyaura adducts were obtained (Schemes 15-16). Thus, the same catalytic system is able to promote two different but sequential catalytic cycles, allowing different transformations in a single reaction flask [60].…”

Gold-catalyzed bis-cyclization of 1,2-diol- or acetonide-tethered alkynes. Synthesis of ?-lactam-bridged acetals: a combined experimental and theoretical study

“…4 These biological activities, combined with the use of these products as starting materials to prepare α-and β-amino acids, alkaloids, heterocycles, taxoids, and other types of compounds of biological and medicinal interest, 5 provide the motivation to explore new methodologies for the synthesis of substances based on the β-lactam core. In addition, bridged acetals are structural units that are extensively encountered in a number of biologically active natural products such as attenol, brevicomin, cyclodidemniserinol, frontalin, multistriatin, and pinnatoxin A, 6 and therefore, their stereocontrolled synthesis remains an intensive research area.…”

New Chemotherapeutic Strategies Against Malaria, Leishmaniasis and Trypanosomiases

“…A great number of natural molecules with antimalarial activity have been and are being identified, and all of them, in the words of their discoverers, are worthy of "further investigation" as antiplasmodial agents. By way of example here we mention β-lactams, which besides their antibacterial activity acquired a prominent place in organic chemistry as synthetic building blocks (synthons) for further elaboration [118]. Following the initial observation that 1-aminopropan-2-ols are active against P. falciparum in the micromolar range [119], a library of gamma-aminoalchools was produced through the ring opening of cis-3-alkoxy-4-aryl-β-lactams [120].…”