Recent Advances in the Synthesis and Medicinal Chemistry of SF5 and SF4Cl Compounds

Abstract

This Short Review covers the most important advances published in the literature during the last five years, concerning the synthesis, chemical modification and applications of SF5- and SF4Cl-compounds in medicinal/bioorganic chemistry and materials science.

Regio‐ and Stereoselective Hydroelementation of SF5‐Alkynes and Further Functionalizations.

“…[3] On the other hand, fluorinated enamines are also of great interest and can be readily prepared by fluoroalkylation, [4] fluorination of ynamides, [5] dehaloamination of haloalkenes, [6] Michael addition, [7] hydroamination of alkynes, [8] and other methods. [9] Nowadays, the pentafluorosulfanyl group (SF 5 ) [10] is growing in interest in many fields such as heterocyclic synthesis, [11] material science, [12] and medicinal chemistry, [13] and drug development are in progress. [14] However, synthetic routes to SF 5 compounds with structural diversity remain highly challenging and rely mainly on two general methods: the direct radical pentafluorosulfanylation of alkenes, alkynes, diazo ketones or [1.1.1]propellane, [15] or the oxidative fluorination of aromatic thiols, disulfide or derivatives.…”

Moving out of CF3‐Land: Synthesis, Receptor Affinity, and in silico Studies of NK1 Receptor Ligands Containing a Pentafluorosulfanyl (SF5) Group

“…[23] Despite being known for many years, the SF 5 group had not enjoyed much interest except in the specialized subareas of sulphur/fluorine chemistry. However, recent years have witnessed a revived interest in this moiety enabled by significant progress in synthetic methodologies that made SF 5 -containing building blocks more accessible (reviewed recently [23,24,28,29] ). SF 5 -containing compounds have been now actively considered in materials chemistry, [30] catalysis, [31] structural chemistry, [31][32][33] agrochemistry [34] and in medicinal chemistry.…”

“…[35] In the latter, SF 5 moiety was applied in antibacterials, [36] antivirals, [37] antischistosomal agents, [38] farnesoid X receptor/epoxide hydrolase modulators, [39] modulators [40] and full antagonists [41,42] of the androgen receptor, benzodiazepine analogues, [43] P2Y6 receptor ligands [44] or dopamine receptor ligands. [45] This list contains only several very recent applications and is not intended to be comprehensive (more examples can be found in the reviews [23,24,28,29,35] ).…”

“…building blocks more accessible (reviewed recently [23,24,28,29] ). SF 5 ‐containing compounds have been now actively considered in materials chemistry, [30] catalysis, [31] structural chemistry, [31–33] agrochemistry [34] and in medicinal chemistry [35] .…”

Rhodium-Catalyzed Intramolecular Cyclopropanation of Trifluoromethyl- and Pentafluorosulfanyl-Substituted Allylic Cyanodiazoacetates

“…Among the various fluorinated substituents, the trifluoromethyl group (CF 3 ) is the most common, but other fluorinated motifs are emerging, such as the trifluoromethoxy (OCF 3 ), trifluoromethylthio (SCF 3 ), and pentafluorosulfanyl (SF 5 ) groups. The latter is often called “super CF 3 ” due to its increased electronegativity, higher lipophilicity, steric demand, and unique octahedral geometry . In the past decade, methods have been developed predominantly for the synthesis of SF 5 -substituted (hetero)­aromatics, and only a few accounts of aliphatic derivatives are described .…”