Chemoselective and Regioselective Synthesis of Spiroisoindolinone Indenes via an Intercepted Meyer–Schuster Rearrangement/Intramolecular Friedel–Crafts Alkylation Relay

Abstract

A Brønsted acid-catalyzed reaction between isoindolinone-derived propargylic alcohols and external aromatic nucleophiles for the construction of spiroisoindolinone indenes is described. The reaction proceeds rapidly with a broad range of substrates to generate spiroindenes chemoselectively and regioselectively in moderate to high yields. Key to the success of this transformation is an intercepted Meyer–Schuster rearrangement/intramolecular Friedel–Crafts alkylation relay that offers a modular approach in the synthesis of target compounds.

Substrate‐Controlled Product Divergence in Iron(III)‐Catalyzed Reactions of Propargylic Alcohols: Easy Access to Spiro‐indenyl 1,4‐Benzoxazines and 2‐(2,2‐Diarylvinyl)quinoxalines

“…In path I (X=O), FeCl 3 acting like a Lewis acid [20,21b] affords a benzylic carbocation intermediate D which isomerizes into bicyclo[3.1.0]epoxonium ion E through intramolecular nucleophilic addition of oxygen onto the transient carbenium ion adjacent to the NTs group [23] . Species E is now poised to undergo intramolecular Fridel–Crafts (IMFC)‐type cyclization [20a,24] preferably by 5‐ exo epoxide‐ring opening (as depicted in Scheme 2) which is consistent with Baldwin's rule [23b] and the prediction made in a recent study [23a] following experimental and computational evidences. Next, aromatization by deprotonation followed by demetalation [20b–c] affords the product 3 along with regeneration of FeCl 3 which enters into the catalytic cycle.…”

Bro̷nsted Acid-Catalyzed [5+1] and [4+1] Annulation of Cyclic Anhydrides with o-Alkynylanilines to Construct Fused-N-Heterocycles

“…We extended this strategy for [5+1] annulation with nonconjugated six membered cyclic (Scheme ) glutaric anhydride ( 9a ). It was reacted with our prime substrate 2-phenylethnylaniline ( 2a ) in the presence of methylsulfonic acid (30 mol % MsOH, p K a −2.0) instead of p -TsOH (p K a −2.8) to produce the desired 5-phenyl-3,4-dihydro-1 H -pyrido­[1,2- a ]­quinoline-1,6­(2 H )-dione ( 10a ) in excellent yield (84%). Similarly, electron-donating and mild withdrawing groups (Me, iPr, and Br) at the para position of aniline ring furnished ( 10b–d ) with excellent (82–86%).…”

Enantioselective intramolecular tandem cyclization of o-alkynylbenzamides: generation of enantioenriched CF3-containing spiro-isoindolinone-indoles

“…Therefore, development of efficient synthetic strategies for the construction of novel spiro-isoindolinones has attracted much attention and many efforts have been devoted to the preparation of diverse spiro-isoindolinones. [2][3][4] Recently, several groups have developed strategies for the construction of chiral spiro-isoindolinone-indolines by asymmetric cyclization of a dielectrophile with a dinucleophile. Singh 3a and Li 3b reported the chiral phosphoric acid catalyzed enantioselective synthesis of spiro-isoindolinone-indolines via formal [3 + 2] cycloaddition of 3-alkynyl-3-hydroxyisoindolinones with 3-substituted indoles independently (Scheme 1a).…”