There is increasing interest in replacement of the planar aromatic rings of drug candidates with three-dimensional caged scaffolds in order to improve the physical properties, but bioisosteres of meta-substituted benzenes have remained elusive. We focused on the bicyclo[3.1.1]­heptane (BCH) scaffold as a novel bioisostere of meta-substituted benzenes, anticipating that [3.1.1]­propellane (2) would be a versatile precursor of diversely functionalized BCHs. Here, we describe a practical preparative method for [3.1.1]­propellane from newly developed 1,5-diiodobicyclo[3.1.1]­heptane (1), as well as difunctionalization reactions of 2 leading to functionalized BCHs. We also report postfunctionalization reactions of these products.

The bicyclo[1.1.1]pentane (BCP) scaffold is useful in medicinal chemistry, and many protocols are available for synthesizing BCP derivatives from [1.1.1]propellane. Here, we report (1) the α‐cyclodextrin (α‐CD) encapsulation of BCP derivatives, affording a stable, readily storable material from which BCPs can be easily and quantitatively recovered and (2) new and simple protocols for deiodination reaction of 1,3‐diiodo BCP to afford [1.1.1]propellane in protic/aprotic/polar/non‐polar solvents. The combination of these methodologies enables simple, on‐demand preparation of [1.1.1]propellane in various solvents under mild conditions from α‐CD capsules containing 1,3‐diiodo BCP.

The palladium-catalyzed cross-coupling reaction of 1-aryltriazenes with aryl-and alkenyltrifluorosilanes occurs readily at room temperature to yield the corresponding biaryl and stilbene products in moderate to good yields. In contrast to the previous results for the reaction with areneboronic acids, in which an additional Lewis acid such as boron trifluoride is essential for the activation of the 1-aryltriazenes, the Lewis acidity of organotrifluorosilanes seems to be strong enough to directly activate the triazene moiety to enter into the palladium-catalyzed cross-coupling reaction without an extra Lewis acid.

The bicyclo[1.1.1]pentane (BCP) scaffold is useful in medicinal chemistry, and many protocols are available for synthesizing BCP derivatives from [1.1.1]propellane. Here, we report (1) the α‐cyclodextrin (α‐CD) encapsulation of BCP derivatives, affording a stable, readily storable material from which BCPs can be easily and quantitatively recovered and (2) new and simple protocols for deiodination reaction of 1,3‐diiodo BCP to afford [1.1.1]propellane in protic/aprotic/polar/non‐polar solvents. The combination of these methodologies enables simple, on‐demand preparation of [1.1.1]propellane in various solvents under mild conditions from α‐CD capsules containing 1,3‐diiodo BCP.

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