Catalytic, Enantioselective Syntheses of β-Lactones—Versatile Synthetic Building Blocks in Organic Chemistry

Abstract

Owing to their highly strained ring system and interesting functional group, β‐lactones possess significant synthetic potential. Recently, novel methods have been developed to synthesize these valuable building blocks very efficiently by catalytic, enantioselective reactions, such as [2+2] cycloadditions, starting from simple precursors. These processes also offer an attractive alternative for the synthesis of optically active β‐hydroxy and β‐amino acids (see scheme).

Heterogeneous Epoxide Carbonylation by Cooperative Ion-Pair Catalysis in Co(CO)4–-Incorporated Cr-MIL-101

“…β-Lactones have received considerable attention due to their prevalence as key intermediates in numerous synthetic pathways. , Their versatility stems from the inherent ring strain in the four-membered cycles, which renders β-lactones highly susceptible to a rich variety of ring-opening and ring-expanding transformations. The high commercial value of the resulting products, namely, β-hydroxy acids, biodegradable polyhydroxyalkanoates, and succinic anhydrides, further substantiates the industrial relevance of β-lactone chemistry.…”

Gold(I)-Catalyzed Cycloisomerization of β-Alkynylpropiolactones to Substituted α-Pyrones

“…As expected, higher temperatures sped up the reaction and often increased yields (e.g., entries 8 vs 10 and 9 vs 11). Heat could also favor the formation of side products, β-lactones usually leading to enynes resulting from retro-[2 + 2]-cycloaddition ( 4 in Scheme ) . However, the main side product formed in the presence of gold was the conjugated acid 3a and surprisingly not the retro-[2 + 2]-cycloaddition enyne product 4a (Scheme ).…”

“…β-Lactones can be conveniently prepared through the cyclocondensation of acyl halides and propargyl aldehydes using an achiral procedure derived from the reaction described by Nelson and co-workers . Despite the inherent fragility of these substrates, isolated yields were routinely higher than 60% (Scheme ).…”

Cooperative Al(Salen)-Pyridinium Catalysts for the Asymmetric Synthesis of trans-Configured β-Lactones by [2+2]-Cyclocondensation of Acylbromides and Aldehydes: Investigation of Pyridinium Substituent Effects

“…Instead an acyl halide is usually used to generate a ketene in situ as a reactive intermediate by dehydrohalogenation induced by a base [ 15 , 16 , 17 , 18 , 19 ]. The ketene then undergoes a cycloaddition with an aldehyde, either catalyzed by a Lewis acid [ 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 ] or by a Lewis base [ 30 , 31 , 32 , 33 , 34 , 35 , 36 , 37 ] or by a combination of both [ 38 , 39 , 40 , 41 , 42 ]. Particularly appealing appears the development of trans -selective catalytic asymmetric β-lactone formations as a surrogate for anti -aldol additions, since for the latter reaction type only few efficient catalytic asymmetric protocols exist to date [ 43 , 44 , 45 , 46 ].…”