Pentafluorosulfanyltrimethylsilane: A Nonexistent Molecule?

From a medicinal chemistry standpoint, the pentafluorosulfanyl (SF 5 ) group is justifiably viewed as a “super‐trifluoromethyl” group. Unfortunately, synthetic routes to this remarkable, strongly electron‐withdrawing, highly lipophilic substituent are limited. In this study, DFT calculations with large basis sets indicate that reagents of the form MSF 5 , where M = Me 3 Si, Li, Cu, MeZn, MeCd, and MeHg, are both thermodynamically and kinetically unstable. Attempts to synthesize reagents such as pentafluorosulfanyltrimethylsilane (TMSSF5) and pentafluorosulfanylcopper (CuSF 5 ) are therefore likely to fail.