Insertion of [1.1.1]propellane into aromatic disulfides

Herein we present the synthesis of symmetrically and unsymmetrically substituted 1,3-bissulfanylbicyclo[1.1.1]pentanes from disulfides and [1.1.1]propellane. Bicyclo[1.1.1]pentanes (BCPs) recently gained interest as rigid linkers and as bioisosters of para-substituted benzene and alkyne moieties. The most promising precursor for BCPs is [1.1.1]propellane (1). The available methods to synthesize BCPs are quite limited and many groups contribute to the development of novel methods. The insertion of 1 into disulfide bonds is known, but has never been thoroughly investigated. In this study, we show that an UV initiated radical reaction can be used to synthesize symmetrically and unsymmetrically substituted BCP sulfides by reaction of [1.1.1]propellane (1) with disulfides. Depending on the ratio of 1 to the disulfide, only the BCP product (with up to 98% yield) or a mixture of BCP and [2]staffane can be obtained. The reaction tolerates functional groups such as halogens, alkyl and methoxy groups. The separation of the corresponding BCP and [2]staffane products is challenging but possible by column chromatography and preparative TLC in most cases. Single crystal X-ray diffraction analysis confirms the rod-like structure of the [2]staffanes that is often required in material applications.


Optimization experiments
For the optimization experiment, the following reaction was set up under different conditions and a sample was taken with a syringe after different times. The samples were diluted with ethyl acetate (1.5 mL) and checked by GC-MS. The relative conversion was calculated based on the integrals of the signals of 10a, 6a and 11a, respectively. There were no additional peaks visible in the spectrum.
The propellane solution {B|1} (0.0345 g, 0.522 mmol, 1.00 equiv) was added to a solution of diphenyl disulfide {A|10a} (0.114 g, 0.523 mmol, 1.00 equiv) in THF {S1} (1.0 mL) under argon atmosphere in a quartz flask and the mixture was irradiated with different light sources for 2 h. The propellane solution (1.00 equiv in Et 2 O) was added to a solution of the disulfide (3.00 equiv) in THF under argon atmosphere in a quartz flask and the mixture was irradiated with UV light (500 W) for 20 min. After evaporation of the solvent, the crude residue was purified via column chromatography or preparative TLC.

General procedure b
The propellane solution (2.00 equiv in Et 2 O) was added to a solution of the disulfide (1.00 equiv) in THF under argon atmosphere in a quartz flask and the mixture was irradiated with UV light (500 W) for 20 min. After evaporation of the solvent, the crude residue was purified via preparative TLC.  (1): In a flame-dried round-bottomed flask that has been purged with argon 1,1-dibromo-2,2-bis(chloromethyl)cyclopropane (4.04 g, 12 mmol, 1.00 equiv) was dissolved in diethyl ether (17.0 mL) and cooled to −40 °C. 1.9 M Phenyllithium solution (2.06 g, 12.9 mL, 25 mmol, 2.00 equiv) in dibutyl ether was added dropwise under vigorous stirring. After complete addition the mixture was allowed to warm to 0 °C and stirred at this temperature for further 2 h. The reaction flask was attached to an argon purged rotavap with dry ice condenser. The receiving flask was cooled to −78 °C and the product was distilled together with diethyl ether. The water bath was set to 20 °C and the pressure was reduced from 500 mbar to 20 mbar slowly. A solution of 1 in diethyl ether was obtained and stored at −78 °C.
The conditions for this reaction were deposited at Chemotion-repository:

Crystal structure determination of 14
Single crystal X-ray diffraction data of 14 were collected on a STOE STADI VARI diffractometer with monochromated Ga K (1.34143 Å) radiation at 200 K. Using Olex2 [1], the structure was solved with the ShelXS [2] structure solution program using Direct Methods and refined with the ShelXL [3] refinement package using Least Squares minimization. Refinement was performed with anisotropic temperature factors for all non-hydrogen atoms; hydrogen atoms were calculated on idealized positions.