Cyclobutenones and Benzocyclobutenones: Versatile Synthons in Organic Synthesis

Abstract

Cyclobutenones, four-membered ketones bearing an unsaturated carbon–carbon double bond, and their structural sibling benzocyclobutenones, possess unique reactivity. Owing to their inherent high ring strain, such structures readily undergo ring opening under a variety of conditions, including thermolysis, photolysis, and transition metal catalysis, to afford reactive intermediates that can be trapped with nucleophiles, dienophiles, and unsaturated bonds. Their electron-deficient enone moieties are good electrophiles for facile nucleophilic addition. Such properties render cyclobutenones versatile synthons, serving as excellent coupling partners in a vast array of synthetically valuable transformations.

Fused‐Ring Formation by an Intramolecular “Cut‐and‐Sew” Reaction between Cyclobutanones and Alkynes

“…In particular, oxidative addition of transition metals into C−C σ bonds followed by 2π insertion, namely a “cut‐and‐sew” process, has been demonstrated to be effective for the construction of complex ring scaffolds . Cyclobutanone derivatives are of special interest for this type of transformation because of their easy access from olefins and their high reactivity towards C−C activation ,,,,. To date, significant progress has been achieved for the synthesis of bridged rings by means of intramolecular “cut‐and‐sew” reactions, in which cyclobutanones are coupled with an unsaturated unit tethered at the C3 position (Scheme a) .…”

High‐Throughput Ligand Screening Enables the Enantioselective Conjugate Borylation of Cyclobutenones to Access Synthetically Versatile Tertiary Cyclobutylboronates

“…Considering the importance of methylation in medicinal chemistry [19] and the structural simplicity of am ethyl substituent, we were particularly interested in targeting the borylation of a-methyl-b-aryl/heteroaryl cyclobutenones using 1a as am odel substrate (Scheme 1). Although cyclo-butenones have proven to be useful substrates in various contexts, [20] preparative methods for unsymmetrically disubstituted alkene derivatives were lacking in the literature. Inspired by pioneering work of Ghosez and co-workers, [21] cyclobutenone 1a was prepared by a[ 2 + +2] cycloaddition between an amide-derived keteniminium intermediate and phenylacetylene,f ollowed by an isomerization to the thermodynamically favored alkene.…”

High‐Throughput Ligand Screening Enables the Enantioselective Conjugate Borylation of Cyclobutenones to Access Synthetically Versatile Tertiary Cyclobutylboronates

“…Considering the importance of methylation in medicinal chemistry and the structural simplicity of a methyl substituent, we were particularly interested in targeting the borylation of α‐methyl‐β‐aryl/heteroaryl cyclobutenones using 1 a as a model substrate (Scheme ). Although cyclobutenones have proven to be useful substrates in various contexts, preparative methods for unsymmetrically disubstituted alkene derivatives were lacking in the literature. Inspired by pioneering work of Ghosez and co‐workers, cyclobutenone 1 a was prepared by a [2+2] cycloaddition between an amide‐derived keteniminium intermediate and phenylacetylene, followed by an isomerization to the thermodynamically favored alkene .…”