Insertion of [1.1.1]propellane into aromatic disulfides

Area of Science:

• Organic Chemistry
• Synthetic Methodology

Background:

• Bicyclo[1.1.1]pentanes (BCPs) are increasingly recognized for their utility as rigid linkers and bioisosteres of para-substituted benzene and alkyne groups.
• The synthesis of BCPs is challenging, with limited established methods, driving the need for novel synthetic routes.
• The [1.1.1]propellane molecule is a key precursor for BCP synthesis, but its reactivity with disulfide bonds remains underexplored.

Purpose of the Study:

• To develop a novel and efficient method for synthesizing symmetrically and unsymmetrically substituted 1,3-bissulfanylbicyclo[1.1.1]pentanes.
• To investigate the UV-initiated radical reaction between [1.1.1]propellane and various disulfides.
• To explore the scope and limitations of this new synthetic approach, including functional group tolerance and product selectivity.

Main Methods:

• UV-initiated radical reaction between [1.1.1]propellane and disulfides.
• Optimization of reactant ratios to control product formation (BCP vs. [2]staffane).
• Purification techniques including column chromatography and preparative TLC.
• Structural confirmation using single crystal X-ray diffraction.

Main Results:

• Successful synthesis of symmetrically and unsymmetrically substituted BCP sulfides with yields up to 98%.
• Demonstrated control over product distribution by adjusting the ratio of [1.1.1]propellane to disulfide, yielding either BCPs or a mixture of BCPs and [2]staffanes.
• The reaction tolerates a range of functional groups, including halogens, alkyl, and methoxy substituents.
• Challenging but achievable separation of BCP and [2]staffane products via chromatography.
• X-ray diffraction confirmed the characteristic rod-like structure of the [2]staffane products.

Conclusions:

• A novel UV-initiated radical reaction provides an efficient route to functionalized 1,3-bissulfanylbicyclo[1.1.1]pentanes.
• The method offers control over product selectivity and demonstrates broad functional group compatibility.
• This work expands the synthetic toolbox for accessing valuable BCP scaffolds and related [2]staffanes for diverse applications.