Desulfurization of Thioketals into Methylene and Methyl Derivatives: Nickel or not Nickel?

Abstract

In this review, the desulfurization of thioacetals and thioketals leading to methyl and methylene derivatives is summarized through metal and metal-free methodologies. In the section concerning the use of metals for desulfurization reactions, we will be successively presenting and discussing all methods requiring Ni and Ni derivatives as reducing agents and other examples in which metals were used to generate solvating electrons as reducing species. The following section will concern the use of other desulfurizing agents as metal-hydrides (Bu 3 SnH, Et 3 SiH) and metal-free desulfurization reactions of thioketals. The functional group tolerance of the presented methods with functionalized and sensitive substrates will be discussed.[a] G.

Mild Deprotection of Dithioacetals by TMSCl/NaI Association in CH3CN

“…desulfurized at r.t. [17] in CH 2 Cl 2 using this metal-free process in a Mozingo-type reaction. [18] By replacing CH 2 Cl 2 by CH 3 CN as the reaction solvent, we surprisingly observed that dithianes derivatives were not reduced into methylene substrates but were totally and cleanly deprotected into ketones. It seemed interesting to study this method for the deprotection of thioacetals which does not use metal salts, oxidants, toxic or expensive reagents ( Figure 1).…”

Sulfones as Chemical Chameleons: Versatile Synthetic Equivalents of Small‐Molecule Synthons

“…Further elaborations, includingr emoval of the sulfones and inversion of the lactones tereocenter,a fforded epimeric constanolactones 98 and 99. [40] Ab is(sulfone) also figuredp rominently into Takahashi's synthesis of dimethylg loiosiphone A ( 104). Sequential Pd-catalyzed allylic alkylationso fB PSM 4 with allylic acetate 100 and allylic bromide 101 furnished triene 102,w hich was transformed intos pirocycle 103 by aP d-catalyzed cycloisomerization reaction (Scheme23).…”

“…Sequential Pd-catalyzed allylic alkylationso fB PSM 4 with allylic acetate 100 and allylic bromide 101 furnished triene 102,w hich was transformed intos pirocycle 103 by aP d-catalyzed cycloisomerization reaction (Scheme23). After reductive cleavageo ft he sulfonyl groups, further elaboration of the core carbon skeleton in 103 eventually gave rise to dimethyl gloiosiphoneA (104). [41] Bis(sulfones)c an also be used to disconnect complexm olecules in the middle of an alkyl chain.…”

“…[103] Furthermore, like bis(sulfones), thioketals can be easily desulfurized under a variety of conditions. [104] Although bis(sulfones)a re better suited for use as methylene dianionsb ecause they are easier to unmask, malonates hold ad istinct edge if an isopropyl dianion is desired. The conversion of disubstitutedm alonates into gem-dimethyl-bearing quaternary centers is well-known, and generally proceeds by reduction of the malonate to the diol followed by tosylation and deoxygenation with ah ydride reducing agent (Scheme 65).…”

“…Whereas the latter are well‐suited for additions to soft electrophiles, such as π‐allyl complexes and Michael acceptors, dithiane anions are more reactive and can attack epoxides, aziridines, and carbonyl compounds . Furthermore, like bis(sulfones), thioketals can be easily desulfurized under a variety of conditions …”