Hypervalent Iodine transmetallations, a HIT Mechanism

Reactions that form carbon-carbon bonds are essential to synthetic organic chemistry. Many methods exist to form carbon-carbon bonds, but few can support coupling two sp³ hybridized carbons. The modern methods used for carbon-carbon bond formation typically require heavy metals (Pd, Rh, Ru, etc.) that are toxic, expensive, and limited by β-hydride elimination. An alternative to the heavy metals used for C-C bond-forming reactions is to employ hypervalent iodine (HVI) reagents to achieve the desired coupling. Hypervalent iodine’s unique metal-like properties can be explained by the “soft” and electrophilic nature of the highly polarizable iodine atom and by the symmetry of the 3-center-4-electron bond that governs ligand association and dissociation. Applying those principles by conceptualizing iodine as a “metal” capable of undergoing transmetallation spawns the creative disconnections that would otherwise not be realized, specifically, other methods that fail due to β-hydride elimination. Exploring the Hypervalent Iodine Transmetallation (HIT) mechanism is warranted through its potential as a new way to view making C-C bonds.
Results show that reacting monoaryl and diaryl HVI reagents with alkyllithium and alkylmagnesium reactants results in C(sp³)-C(sp³) bond formations without β-hydride elimination products. The challenge to overcome is the instability of alkylated HVI intermediates and the production of statistical mixtures. Previously, HVI transmetallations with organometalloids were assumed to require the inherent unsaturation of alkenes, alkynes, or aromatics, but our group has seen it occur with alkylmetalloids. The challenge is that the resulting alkylated-HVI is highly reactive and decomposes, but we wish to determine if it can react with itself. Using Hypervalent Iodine-Guided Electrophilic Substitution (HIGES) theory, we intend to develop a method that can synthesize macrocycles containing eight atoms or more, is functional group tolerant, and will select for a larger ring rather than one smaller than 8-members. This intramolecular Aim of exploring C(sp³)-C(sp³) bond formation via macrocyclization relies on the T-shape geometry and pseudorotation of dialkylated hypervalent iodine intermediates.