Semipinacol-Type Rearrangements of [3-(Arylsulfonyl)bicyclo[1.1.0]butan-1-yl]alkanols

Abstract

Selective lithiation of arylsulfonylbicyclo[1.1.0]butanes at the bridgehead methine and addition to carbonyl compounds yield tertiary bicyclobutyl alcohols that form spiro[3.4]octanes and related heteroatom-containing spirocycles via an acid-or halogen-mediated semipinacol rearrangement. Further synthetic transformations at the carbonyl or arylsulfone positions, in general in high yield and good chemoselectivity, allow access to acetals, difluorides, amides, and methylenecyclobutene building blocks.

Bicyclobutanes as unusual building blocks for complexity generation in organic synthesis

“…Replacing the acrylate moiety of 143 with a pendant propargyl alcohol led to spirocycle 145, and an α,β-unsaturated aldehyde provided spirocycle 146, which was used as an intermediate en-route to the tricyclic core of daphniglaucin natural products. Recently, Wipf and co-workers disclosed an alternative approach to spirocycles from BCBs, preparing a range of [4.3] spirocyclic compounds 94 . Exploiting the acidity of the bridgehead C-H bond, they were able to deprotonate BCB 21 with nBuLi, and add the formed organolithium species into cyclobutanone to give alcohol 147.…”

Bicyclobutanes: from curiosities to versatile reagents and covalent warheads

“…Recently, Kerner and Wipf reported an alternative BCB activation strategy that involves a semi-pinacol rearrangement. 75 In their approach, rearrangement of the BCB bridgehead group is triggered by a Brønsted or Lewis acid. This allowed the authors to generate ketones from BCB-alcohols.…”

Synthesis of Dihydropyridine Spirocycles by Semi-Pinacol-Driven Dearomatization of Pyridines

“…We envisaged a more general and straightforward approach in which easy-to-access hydroxycyclobutylpyridines ( 1 ) could undergo an electrophile-induced dearomatizing semi-pinacol ring expansion to deliver dihydropyridine spirocycles ( Figure 1 c, 2 ). 20 We predicted that employing N-acylation activators should render these compounds isolable, giving the potential to either directly access these atypical structures or perform hydrogenation to the corresponding piperidine spirocycles. 19 Herein, we report the successful synthesis of a broad range of dihydropyridine spirocycles through a dearomatizing semi-pinacol rearrangement, driven by the selective N-acylation of hydroxycyclobutylpyridines.…”