Synthesis of benzil-o-carboxylate derivatives and isocoumarins through neighboring ester-participating bromocyclizations of o-alkynylbenzoates

Abstract

Bromide mediated neighboring ester-participating bromocyclizations of o-alkynylbenzoates are described here for the synthesis of benzil-o-carboxylates. 4-bromoisocoumarins are also synthesized when phenyl o-alkynylbenzoate is used as the substrate. Mechanistic studies suggest that the whole process is composed of an electrophilic bromocyclization and a dibromohydration-based ring-opening, and the neighboring ester group participates in the bromocyclization. Interestingly, the two oxygen atoms of the keto carbonyls in benzil-o-carboxylates are both derived from water. The electrophilic bromo source is in situ generated from the oxidation of bromide.

Cu(i) catalysis for selective condensation/bicycloaromatization of two different arylalkynes: direct and general construction of functionalized C–N axial biaryl compounds

“…o -Amino arylkynes can easily undergo a series of reactions, such as hydration, intramolecular cyclization and di/polymerizations, which produce amino aryl ketones, 18 indoles, 19 2-(2-aminophenyl)quinoline, 20 etc. Meanwhile, more types of reactions for o -carbonyl arylalkynes, such as hydration, intramolecular cyclizations, aldol condensation, and di/polymerizations, could take place, producing diketones, 21 triketones, 22 1-indanones, 23 indenones, 24 1-naphthols, 23 chalocones, 25 1 H -isochromene 26 and chrysene, 27 etc. (2) Low reactivity of the condensation between arylamino and arylcarbonyl groups.…”

The α,α‐Dihalocarbonyl Building Blocks: An Avenue for New Reaction Development in Organic Synthesis

“…This is the first report, where ortho ‐ester‐assisted halogenation of alkynes 184 provides α,α‐dihaloketone 185 without terminating the reaction at isocoumarin 186 or isochromenol stage. Two similar protocols were also developed by the research groups of Qiu and Liu et al., for the oxidative dibromination followed by water addition across the alkyne 184 to generate 1,2‐diketones 185 (Scheme ). Tetrabutylammonium bromide (TBAB) and oxone found to be the best combination for ester‐directed bromocyclization of o ‐alkynylbenzoates 184 .…”

“…Two similar protocols were also developed by the research groups of Qiu and Liu et al., for the oxidative dibromination followed by water addition across the alkyne 184 to generate 1,2‐diketones 185 (Scheme ). Tetrabutylammonium bromide (TBAB) and oxone found to be the best combination for ester‐directed bromocyclization of o ‐alkynylbenzoates 184 . This strategy not only applicable for ester but also useful for aldehyde and ketone assisted reactions.…”

Synthesis of 4-Chloroisocoumarins via Intramolecular Halolactonization of o-Alkynylbenzoates: PhICl2-Mediated C–O/C–Cl Bond Formation

“…45 However, these methods are applicable only to the preparation of 4-iodo/bromoisocoumarins, and the synthesis of 4-chloroisocoumarins relies predominantly on the application of transition metal-mediated approaches. 33,35,[38][39][40]44 For example, Lisowski described a Cy 2 NH•HCl-promoted cyclization of o-alkynylbenzoates with CuCl 2 to give 4-chloroisocoumarins (Scheme 1, method a). 35 Similarly, Miyata reported the halocyclization of o-alkynylbenzoates using CuCl 2 /NCS (Scheme 1, method b).…”

“…Among the synthetic approaches, the synthesis of 4-haloisocoumarins has received considerable attention as these molecules possess interesting biological activities and the presence of a halogen atom at position 4 allows for further functionalization. − The predominant synthetic method used for the generation of 4-haloisocoumarins is the electrophilic cyclization of o -alkynylbenzoates using various electrophiles, including Br 2 , , I 2 , ,− ICl, − , NBS, and NIS . However, these methods are applicable only to the preparation of 4-iodo/bromoisocoumarins, and the synthesis of 4-chloroisocoumarins relies predominantly on the application of transition metal-mediated approaches. ,,− , For example, Lisowski described a Cy 2 NH·HCl-promoted cyclization of o- alkynylbenzoates with CuCl 2 to give 4-chloroisocoumarins (Scheme , method a) . Similarly, Miyata reported the halocyclization of o -alkynylbenzoates using CuCl 2 /NCS (Scheme , method b) .…”