Catalytic Regioselective Synthesis of Structurally Diverse Indene Derivatives from N-Benzylic Sulfonamides and Disubstituted Alkynes

Abstract

An unprecedented protocol has been developed for the regioselective synthesis of structurally diverse indene derivatives from readily accessible N-benzylic sulfonamides and disubstituted alkynes through FeCl(3)-catalyzed cleavage of sp(3) carbon-nitrogen bonds to generate benzyl cation intermediates. In the presence of 10 mol % of FeCl(3), a broad range of N-benzylic sulfonamides smoothly react with internal alkynes, alkynylcarbonyl compounds, alkynyl chalcogenides, or alkynyl halides to afford various functionalized indene derivatives with extremely high regioselectivity.

Iron Catalysis in Organic Synthesis

“…1603 The reaction includes CÀN cleavage under formation of a benzylic cation. Subsequent addition to the alkyne and electrophilic ring closure affords the indene skeleton.…”

Transition-Metal-Catalyzed Cleavage of C–N Single Bonds

“…18,[102][103][104][105] In these cases, the Lewis acids (ZnCl 2 or FeCl 3 ) accelerate the formation of carbocationic species from N-tosyl compounds. The formed carbocationic species would couple with carbon or sulfur nucleophiles in an S N 1 manner to afford various functional molecules, 54−57, via nucleophilic attack.…”

“…105 In the case of β-keto acids, the Fe-catalyzed reaction provides an effective decarboxylative alkylation of β-keto acids via sequential cleavage of C−N and C−C bonds. 104 In the case of alkynes 103 and arylallenes, 105 the two reactions proceed via the Friedel−Crafts cyclization of carbocations to afford polysubstituted indenes 55 and 57, respectively.…”

“…The process for the formation of indene derivatives 55 was taken as an example to elucidate the mechanism (Scheme 19). 103 Benzyl cation 58 would first be generated from N-benzylic sulfonamide in the presence of FeCl 3 . This cation would then be attacked by the disubstituted internal alkyne to give vinyl cation 59, followed by a cyclization and an aromatization to form the indene derivatives 55.…”

Recent Advances in the Synthesis of Indanes and Indenes

“…Depending on alkyne substituents and on reaction conditions, a second benzylation could take place with formation of indenes 232 (Scheme ) . In a similar way, substituted indenes were obtained in a highly regioselective fashion from the reaction between N ‐benzylic sulfonamides and disubstituted alkynes carried out in the presence of 10 mol % of FeCl 3 in MeNO 2 at 80 °C …”