Lewis-Acid-Catalyzed Tandem Cyclization by Ring Expansion of Tertiary Cycloalkanols with Propargyl Alcohols

Abstract

A new method for the efficient synthesis of hexahydro-1H-fluorene and octahydrobenzo[a]azulene derivatives through a ring-expansion strategy is reported. With an appropriate combination of thulium(III) trifluoromethanesulfonate and 13X molecular sieves, a range of unsaturated polycyclic compounds were obtained in good yields. Mechanism studies reveal that the reaction is more likely to undergo Meyer−Schuster rearrangement, ring expansion, and Friedel−Crafts-type pathways, which provide a conceptually different strategy for the ring opening of tertiary cycloalkanols.

Recent Progress in Application of Propargylic Alcohols in Organic Syntheses

“…In 2021, after treatment of 15 mol% of Tm(OTf) 3 (thulium(III) trifluoromethanesulfonate) in the mixture of propargyl alcohols 1 and cycloalkanols 137, including cyclobutanols, cyclopentanols and cyclohexanols, a broad spectrum of hexahydro-1H-fluorene and octahydrobenzo[a]azulene structures 138 were obtained (Scheme 58). [57] ). [58] C 6 F 5 B(OH) 2 Lewis acid could catalyze the cycloaddition of a wide range of heteroareneboronic acids 91 as nucleophiles with tertiary propargylic alcohols.…”

Strained cycloalkanols in C–C bond formation reactions: a boon in disguise!

“…In this regard, Liang and co-workers utilized small, strained cycloalkanol derivatives as feedstocks for such polycycles via a Lewis acid-catalyzed cyclization and ring expansion with propargyl alcohols (Scheme 11). 20 The unprecedented cyclization was proposed to involve a conceptually novel strategy for cycloalkanol ring opening, involving a Meyer-Schuster rearrangement, ring expansion, and Friedel-Crafts-type pathways as the key steps in the mechanistic cycle.…”

“…In this regard, Liang and co-workers utilized small, strained cycloalkanol derivatives as feedstocks for such polycycles via a Lewis acid-catalyzed cyclization and ring expansion with propargyl alcohols (Scheme 11). 20…”

Synthesis of Hydroxylated Polycyclic Pyrrolo/Indolo[1,2-a]quinoxaline-Fused Lactam Derivatives via PhI(OAc)2-Promoted 1,2-Bond Migration and Solvent Insertion

“…Synthesis of several polyheterocycle-fused isoquinolinone and quinazolinone derivatives, mostly through transition-metal-catalyzed cyclization reactions are also reported . However, generation of fused heterocycles through the ring expansion of carbocyclic scaffolds by 1,2-migration of C–C σ-bond is limited due to difficulties in the cleavage of C–C bond . In recent times, hypervalent iodine­(III) reagents are being utilized in carrying out a number of Beckmann and Hoffman rearrangements and ring expansion as well as ring contraction reactions via oxidative 1,2-rearrangement, exploiting the intrinsic electrophilicity and excellent leaving aptitude of the hypercoordinated species .…”