Carbonylation of Aziridines as a Powerful Tool for the Synthesis of Functionalized β‐Lactams

Abstract

Within heterocyclic chemistry, β‐lactams comprise an extraordinary class of strained compounds, recognized for their biological importance as potent antibiotics and their chemical value as flexible building blocks for the construction of diverse nitrogen‐containing structures. Among the synthetic routes available to access this interesting scaffold, the carbonylation of aziridines, in which carbon monoxide is inserted into one of the ring carbon–nitrogen bonds, is praised for its efficiency and remarkable regio‐ and stereoselectivity. This review provides a comprehensive overview of aziridine‐to‐azetidin‐2‐one carbonylation studies. The protocols are categorized according to the different transition metals (i.e. rhodium, palladium, nickel, iron, and cobalt) that have been employed (in a catalytic or stoichiometric amount) to effect this transformation.

No Making Without Breaking: Nitrogen-Centered Carbonylation Reactions

“…This Review consists of two parts: nitrogen-center-directed carbonylation reactions (Scheme bonds or simply using amines as nucleophiles are beyond the scope of this Review. Since the carbonylation of aziridines has been summarized, 24 this topic is specifically excluded here. We hope that this Review can arouse increasing interest and promote further developments in this interesting area.…”

Intermolecular [3+3] ring expansion of aziridines to dehydropiperi-dines through the intermediacy of aziridinium ylides

“…An attractive feature of aziridines is their~26 kcal mol −1 of ring strain, ensuring a favorable thermodynamic driving force for ring-opening. Figure 1 illustrates a selection of transition metalcatalyzed aziridine expansions that furnish 4-7 membered Nheterocycles [37][38][39][40][41][42][43][44][45][46][47][48] . For example, Alper and others have achieved metal-catalyzed carbonylations of aziridines to yield valuable β-lactams, although good regioselectivity depends on the substitution pattern of the three-membered ring 45 .…”

“…Figure 1 illustrates a selection of transition metalcatalyzed aziridine expansions that furnish 4-7 membered Nheterocycles [37][38][39][40][41][42][43][44][45][46][47][48] . For example, Alper and others have achieved metal-catalyzed carbonylations of aziridines to yield valuable β-lactams, although good regioselectivity depends on the substitution pattern of the three-membered ring 45 . Njardarson has described a series of Cu-catalyzed transformations of aziridines to pyrrolidines and related rings; while these reactions are often stereospecific, they are largely limited to intramolecular examples [40][41][42] .…”

Synthesis of β-Lactams through Carbonylation of Diazo Compounds Followed by the [2 + 2] Cycloaddition Reaction

“…Quantitative studies are available where IR spectroscopy is utilized to detect ketene formed by the carbonylation of diazo compounds by non-gaseous metal carbonyl [Co 2 (CO) 8 ] . [Co 2 (CO) 8 ] is known to catalyze carbonylation reactions, − aza-Pauson-Khand-type reaction, , condensation and intra-molecular carbonylative cyclization, , ring-opening carbonylations, − ring-opening carbonylative polymerizations, , and ring-expansion carbonylations . Hence, the use of metal carbonyl is a superior option for carbonylation of diazo compounds at mild reaction conditions.…”