Synthesis of Hexahydro-1H-isoindole Derivatives from Arylacyl Bromides via Homoallenic Bromohydrins

Abstract

A procedure has been developed for the concise synthesis of hexahydro-1H-isoindole derivatives starting from phenacyl bromides. The approach employs a sequence involving an initial indium-mediated allenylation reaction of an arylacyl bromide with propargyl bromide. This process is followed by FeBr3-mediated SN2'-type substitution reaction of the formed homoallenic bromohydrin to produce a 2,5-dibromo-4-aryl-1,3-pentadiene, which then is subjected to a sequential, one-pot N-alkylation reaction with N-allyl-N-(p-tosyl)amine and a highly diastereoselective intramolecular Diels-Alder reaction of the formed ene-diene to generate the target hexahydro-1H-isoindole.

Hypervalent Iodine(III)-Induced Domino Oxidative Cyclization for the Synthesis of Cyclopenta[b]furans

“…In the study described below, we have explored a method for the synthesis of cyclopenta[ b ]furans containing a stereogenic, quaternary, aryl-substituted bridgehead carbon. For the preparation of 2-aryl-1,4-dibromopenta-2,4-dienes 2 we used a literature procedure developed in our group [17]. The β-ketoesters linked with pentadiene tether 3 were prepared by C -alkylation of ethyl acetoacetate enolate with 2 ; however, the chromatographic purification of compounds 3 is difficult in most cases (Table 1).…”

Deciphering the Chameleonic Chemistry of Allenols: Breaking the Taboo of a Onetime Esoteric Functionality

“…Further one-pot N -alkylation/Diels-Alder reaction with tosyl-amines 194 provided products 195 bearing the hexahydro-1- H -isoindole skeleton with good yields and high diastereoselectivities ( Scheme 35 , reaction b). 199 …”

“…Following a similar idea, Lin and co-workers developed a FeBr 3 -mediated bromination/rearrangement reaction to yield related 2,5-dibromo-4-aryl-1,3-pentadienes 193 . Further one-pot N -alkylation/Diels-Alder reaction with tosyl-amines 194 provided products 195 bearing the hexahydro-1- H -isoindole skeleton with good yields and high diastereoselectivities (Scheme , reaction b) …”

“…Further onepot N-alkylation/Diels-Alder reaction with tosyl-amines 194 provided products 195 bearing the hexahydro-1-H-isoindole skeleton with good yields and high diastereoselectivities (Scheme 35, reaction b). 198 The ability of α-allenols to easily isomerize to dienes through 1,3-migration reactions was also illustrated during the attempts to oxidize allenyl vinyl alcohols to the corresponding allenyl vinyl ketones. Harmata and collaborators envisioned the synthesis of ketones 198 as starting materials for Nazarov cycloadditions using PCC as mild oxidant.…”