Generation, structure and reactivity of tertiary organolithium reagents

Abstract

Tertiary alkyllithium reagents are very useful intermediates in synthesis. Alkyllithium reagents with adjacent heteroatoms may be formed stereoselectively or may react stereoselectively, and have been used in the synthesis of alkaloids, C-glycosides and spirocycles. An overview of the generation, reactivity and stereochemistry of tertiary alkyllithium reagents will be presented, as well as examples of their use in organic synthesis. The discussion will be focused on a conceptual understanding of the generation and reactivity of these intermediates. The reactions described herein generate fully substituted carbon atoms, and the forces driving stereoselectivity will be discussed in detail. Where appropriate, computational results will be introduced to provide a better understanding for the structure and reactivity of tertiary alkyllithium reagents.

The reductive decyanation reaction: an overview and recent developments

“…Because of the mechanism described in Scheme 1 , the nature of the medium and the substrate strongly influence the course of the reaction. Then, in the absence of a proton source, the organolithium intermediate can cyclize or react with an electrophile giving the expected coupling products [ 23 – 27 ]. Metal dissolving conditions allow the reduction of various other functional groups [ 28 ].…”

“…Recent reviews demonstrated the richness of this chemistry and emphasized synthetic applications particularly in heterocyclic chemistry [ 41 – 44 ]. The reductive decyanation of α-aminonitriles under metal dissolving conditions is a common procedure that proceeds through a two-electron-transfer pathway ( Scheme 1 ) [ 23 , 44 ]. In the ionic pathway, the loss of the cyanide ion yields an iminium cation that can be reduced by various hydride donors ( Scheme 6 ).…”

Continuous synthesis of 1‐ethoxy‐2,3‐difluoro‐4‐iodo‐benzene in a microreactor system and the Gaussian and computational fluid dynamics simulations

“…Among these side reactions, the decomposition of ED-Li and the reaction of n-BuLi/ED-Li with solvent occupied the majority, and both reactions are highly exothermic. 2,4,6 Because of the instability and high reactivity of organolithium compounds, these reactions must be carried out at low temperatures, with isolation from various electrophiles, which renders them small-scale syntheses. [7][8][9][10][11][12] Currently, there is an increasing demand for the development of an efficient and economical method to produce P on a large scale.…”

Stereochemical Outcomes in Reductive Cyclizations To Form Spirocyclic Heterocycles

“…8 However, there are very few reactions reported with tertiary, unactivated N-Boc α-aminoalkyllithium reagents. 9 The investigations of a variety of spirocyclizations based on NBoc α-aminonitiles are described herein.The substrates for reductive cyclization were prepared through our previously described method. 7 Formation of the first ring proceeded through a double-alkylation reaction of an N-Boc α-aminonitrile 4 with dibromides 5 to give cyclic aminonitriles 6 as shown in Table 1.…”