II. Radical Formation

A. Reaction Mechanism

Radical formation begins when SmI₂ coordinates with a substituent in a carbohydrate der­iv­ative (Scheme 1), that is, when a carbohydrate derivative replaces a solvent molecule within the coor­dination sphere of samarium(II) iodide. Within this new complex an electron is trans­ferred from SmI₂ to the carbo­hydrate derivative to produce a radical anion. This radical anion disso­ciates rapidly to give a carbohydrate radical and an anion complexed with SmI₂. It is pos­sible in some instances that the radical anion never actually forms; instead, the bond between the carbo­hy­drate and the functional group breaks during elec­tron transfer.³ [Section II.C.3 of Chapter 3 in Volume I contains addi­tional information about samarium(II) iodide and the complexes it forms.]

B. Effect of HMPA

Reaction with SmI₂ typically is conducted in tetrahydrofuran (THF). Adding the cosolvent hexamethylphosphoramide (HMPA) to the reaction mix­ture dramatically increases the rate con­stant for samarium(II) iodide reac­tion.^10,11 Since the redox potential (E^o) of Sm²⁺/Sm³⁺ increases from -1.33 V to -2.05 V with the addition of four equiv of HMPA to a THF solution of SmI₂,¹² the rate enhancement brought about by added HMPA can be attri­buted to the substantially increased ability of SmI₂ to donate an electron. (Addition of HMPA beyond four equivalents does not further increase reaction rates.¹⁰)

One explanation for the effect of HMPA on the reactivity of SmI₂ is based on the energies of the highest occupied (HOMO) and lowest unoccupied (LUMO) molecular orbitals pictured in Figure 1.¹³ (In the reac­tion represented in this diagram it is assumed that the substrate is a phenyl sulfone.) When HMPA complexes with SmI₂, it raises the HOMO energy of the resulting complex and, in so doing, reduces the energy required for elec­tron transfer to the σ* orbital (LUMO) of the sulfone (Figure 1). This energy reduction translates into a larger rate constant for reaction. HMPA also increases the rate of reaction of SmI₂ with halogenated compounds by elong­ating the carbon–halogen bond.^11b

Radical formation by reaction of samarium(II) iodide with carbo­hy­drate derivatives has been conducted under a variety of conditions.^14–18 In addi­tion to HMPA, other additives used are DMPU (1),¹⁴ ethylene glycol,¹⁹ and visible light.¹⁷ Alternative conditions also include reaction with HMPA in the presence of a proton donor^14–18 or a catalytic amount of nickel(II) halide.^9,17 Motivation for trying new reaction conditions comes from the possibilities of gaining greater understanding of the reaction mechanism, improving product yields, develop­ing greater stereo­selectivity, and finding a promoter for SmI₂ reaction that is safer than HMPA.