Sulfur‐Bearing Lithium Compounds in Modern Synthesis

Abstract

Sulfur functions have been widely used for the stabilization of lithium carbanions. Their different oxidation states determine a variety of mechanisms for such stabilization, mainly related with their electronic effects (−I and −M) and associative abilities and also with the relative position of sulfur with respect to the C-Li bond. As additional interest, the sulfur of some of these functions is a stable stereogenic center, and their interactions with prochiral lithium carbanions are able to control the stereochemical course of their reactions with electrophiles, which can be successfully used in asymmetric synthesis. Finally, the chemical versatility of the sulfur functions and their easy elimination under diverse conditions confer to the sulfur-stabilized lithium carbanions a very important role in modern synthetic chemistry. In this chapter, we have organized the information attending to the relative position of the carbanionic center with respect to the sulfur function (α-, β-, and γ-lithiation, see Figure 8.1). Each item has been subdivided according to the nature of the sulfur function stabilizing the carbanion. In this sense, sulfoxides, sulfones, and sulfoximines are the three main functions stabilizing any type of lithium-carbanions, but the thioethers have also been described as stabilizing in αand β-lithiation processes. The fragment connecting S and Li is always formed by carbon atoms, but N is present in some cases of γ-lithiation.This chapter covers the literature of the last 10-12 years concerning the preparation and main synthetic applications of the lithium carbanions stabilized by sulfur functions. In most of the cases, the information that appeared in this century helps understand the role of the sulfur functions in the stabilization of the lithium carbanions, and therefore we have only mentioned, as introduction, the seminal references in the field. However, in those cases where there are few references in the last decade and most of the information has been reported before 2000, we have included and briefly commented on the most significant contributions to be able to understand the interest of such stabilizing functions. During the last decade have appeared excellent revisions concerning the reactivity and structure of lithium carbanions [1], the use of different sulfur functions in asymmetric synthesis [2], as Lithium Compounds in Organic Synthesis: From Fundamentals to Applications, First Edition. Edited by Renzo Luisi and Vito Capriati.

Asymmetric Synthesis of Tertiary Alcohols and Thiols via Nonstabilized Tertiary α‐Oxy‐ and α‐Thio‐Substituted Organolithium Species

“…Chiral α‐heteroatom (O, N, and S)‐substituted organolithium compounds are a versatile class of nucleophiles that are useful in the asymmetric synthesis of chiral alcohols, amines, and thiols . Although the use of secondary and mesomerically stabilized (e.g., benzylic and allylic) tertiary α‐O‐ and α‐S‐substituted organolithium reagents in synthesis is well established,– the use of non‐mesomerically stabilized (i.e., dialkyl‐substituted) tertiary reagents is not. This discontinuity is due to contrasting problematic features governing α‐O‐ and α‐S‐substituted organolithium species.…”

“…Having demonstrated the broad applicability of tertiary nonstabilized chiral α‐O‐organolithium species, we then embarked on a study of the more challenging sulfur analogues . Pioneering work by Beak had revealed that while the α‐deprotonation of dialkyl‐substituted tertiary thiobenzoates (such as 4 ) was facile at low temperature, they were configurationally unstable even at −98 °C in THF (Scheme A) …”

Isolation and structure determination of a tetrameric sulfonyl dilithio methandiide in solution based on crystal structure analysis and 6Li/13C NMR spectroscopic data

“…Dilithio methandiides 2 are accessible from sulfonyl lithio methanides 1 [9] through α-deprotonation [1,2,4], and from arylsulfonyl dilithio methanides 3 [10,11] though ortho,α-transmetallation [10][11][12][13] (Scheme 1).…”

α‐Functionalisation of Cyclic Sulfides Enabled by Lithiation Trapping

“…In two different metalation routes, Mulvey et al prepared and characterised (X-ray crystallography/NMR spectroscopy) magnesiated [15] and aluminated tetrahydrothiophene [16] although electrophilic trapping proved challenging. Such metalation approaches [17] build on the pioneering work by Gilman, Wittig, Corey, Seebach and Peterson in the 1940-60s on the α-lithation of dimethylsulfide and thioanisole. [18] Allylic and cyclopropyl-containing acyclic sulfides have also been successfully lithiated and used in synthesis.…”