Single-Pot Asymmetric Approach toward Enantioenriched Quaternary Stereocenter-Containing Alkylidenecyclobutanes

Abstract

Enantioenriched alkylidenecyclobutanes possessing a quaternary stereogenic center, usually difficult to access, have been synthesized by combining a double boron-homologation and an allylboration through a highly efficient and diastereoselective one-pot process. Starting from commercially available substrates, this protocol represents a simple way of accessing chiral unsaturated four-membered ring systems with excellent stereoisomeric ratios.

Stereoselective Sequence toward Biologically Active Fused Alkylidenecyclobutanes

“…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 . 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, starting from readily available building blocks (Scheme ), and leading expediently to direct heterocyclic analogues of protoilludanes, a family of sesquiterpenoids …”

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

“…Next, we developed an asymmetric version of the one‐pot sequence by using chiral diols as boron ligands, which allowed enantiomerically enriched ACBs to be prepared (Scheme ) …”

Uncommon Four‐Membered Building Blocks – Cyclobutenes, Azetines and Thietes

“…With a chiral diol as ligand on the starting boron reagent, high enantiomeric excess (up to 99 %) can be obtained, through a stereodeterminant boron‐homologation step [2,47] . In case B ( 26 ), the chiral input comes from the cyclobutenyl ring itself, which orientates the approach of the aldehyde from the opposite face, leading therefore to the formation of methylenecyclobutanes 28 with the all‐ syn configuration in up to 99 : 1 dr [69] …”