Synthesis of pentafluorosulfanyl bicyclo[1.1.1]pentyl (hetero)aryl ketones

<p indent="0mm">The highly strained 1,3-disubstituted bicyclo<inline-formula id="INLINE49"><mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" display="inline"><mml:mrow><mml:mo stretchy="false">[</mml:mo><mml:mn>1.1.1</mml:mn><mml:mo stretchy="false">]</mml:mo></mml:mrow></mml:math></inline-formula>pentane (BCP) was identified as a bioisostere of <italic>para</italic>-disubstituted aromatics due to its ability to enhance the solubility and metabolic stability of parent compounds. In addition, pentafluorosulfanyl (SF₅)-containing compounds have received great attention in medicinal chemistry, particularly for pentafluorosulfanylarenes (SF₅-Ar). Consequently, pentafluorosulfanyl bicyclo<inline-formula id="INLINE50"><mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" display="inline"><mml:mrow><mml:mo stretchy="false">[</mml:mo><mml:mn>1.1.1</mml:mn><mml:mo stretchy="false">]</mml:mo></mml:mrow></mml:math></inline-formula>pentane (F₅S-BCP) could be considered as the bioisostere of pentafluorosulfanyl phenyl and might have potential applications in drug discovery. Our group has reported the first F₅S-BCP radical precursor, pentafluorosulfanyliodobicyclo<inline-formula id="INLINE51"><mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" display="inline"><mml:mrow><mml:mo stretchy="false">[</mml:mo><mml:mn>1.1.1</mml:mn><mml:mo stretchy="false">]</mml:mo></mml:mrow></mml:math></inline-formula>pentane (F₅S-BCP-I), and its radical addition with alkenes and alkynes. Herein, we describe the synthesis of pentafluorosulfanyl bicyclo<inline-formula id="INLINE52"><mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" display="inline"><mml:mrow><mml:mo stretchy="false">[</mml:mo><mml:mn>1.1.1</mml:mn><mml:mo stretchy="false">]</mml:mo></mml:mrow></mml:math></inline-formula>pentyl (hetero)aryl ketones through an aryl diazonium salt initiated radical reaction of <italic>N</italic>-<italic>tert</italic>-butyl-α-phenylnitrone (PBN) with F₅S-BCP-I.