Unsaturated Four‐Membered Rings: Efficient Strategies for the Construction of Cyclobutenes and Alkylidenecyclobutanes

Abstract

Our recent studies of the diastereo- and enantioselective formation of strained alkylidenecycloalkanes drove us to more-thoroughly investigate the formation of four-membered rings for which only few efficient methods are described. We first developed a strategy to diversify the saturated part of the four-membered ring and applied it to a highly diastereoselective synthesis of more-elaborate alkylidenecyclobutanes, which completed our precedent studies. In parallel, cyclobutene structures were built employing simple organometallic methods and further functionalized to give a diverse range of new substitution patterns, which consequently enriched the pool of cyclobutene-based building blocks.

Stereoselective Sequence toward Biologically Active Fused Alkylidenecyclobutanes

“…However, the study of cyclobutenes (CBs) and alkylidenecyclobutanes (ACBs) has undeniably suffered from the restricted number of strategies allowing their preparation. Recently, we have demonstrated the great ability of in situ generated cyclobutenylmetal species to undergo a subsequent cross-coupling reaction toward the formation of decorated cyclobutenes . Alternatively, a stereoselective double boron homologation led to new embedded allylboron reagents that subsequently reacted with a variety of aldehydes to stereoselectively furnish enantioenriched ACBs in good to excellent yields .…”

“…Recently, we have demonstrated the great ability of in situ generated cyclobutenylmetal species to undergo a subsequent cross-coupling reaction toward the formation of decorated cyclobutenes. 3 Alternatively, a stereoselective double boron homologation led to new embedded allylboron reagents that subsequently reacted with a variety of aldehydes to stereoselectively furnish enantioenriched ACBs in good to excellent yields. 4 We envisioned that opening a new and straightforward access to vinylcyclobutenes could ultimately unravel a path toward the diastereoselective synthesis of fused ACBs via a simple [4 + 2]-cycloaddition, 5 starting from readily available building blocks (Scheme 1), and leading expediently to direct heterocyclic analogues of protoilludanes, a family of sesquiterpenoids.…”

Chemodivergent and Stereoselective Access to Fused Isoxazoline Azetidines and Thietanes through [3 + 2]-Cycloadditions

“…Above all, there is an urgent need to bring such groups directly and economically onto core scaffolds. Driven by the need to push the boundaries of unexplored structural libraries, we recently reported the synthesis of new building blocks containing cyclobutenes, azetines, and thietes . These allowed us to develop new methodologies toward the stereocontrolled formation of alkylidenecyclobutanes, alkylideneazetidines, and cyclopropylketones formed by oxidative ring contraction of cyclobutenes.…”

Parallel Approaches for the Functionalization of Thietes: α-Metalation versus C–H Activation

“…Most recent examples reported by the groups of Carreira and Baran demonstrate the importance of small, strained bioisosteres, such as oxetanes, azetidines, or propellanes, in the modulation of bioactivities. In this context, we have recently assembled strategies to broadly and selectively access cyclobutenes and azetines, constituting a large library of building blocks. These allowed us to open unprecedented routes toward the stereocontrolled formation of alkylidenecyclobutanes, alkylideneazetidines, and fused systems thereof .…”