Reactions of SmI₂ with Alkyl Halides and Ketones:  Inner-Sphere vs Outer-Sphere Electron Transfer in Reactions of Sm(II) Reductants

Abstract

This paper presents the effect of additives on the mechanism and selectivity of the SmI2-mediated coupling of alkyl halides and ketones. The reaction of 1-iodobutane and 2-octanone was carried out with SmI2 in the absence of cosolvent and in the presence of HMPA, LiBr, and LiCl. The experiments using cosolvent free SmI2 and SmI2−HMPA reductants gave the Barbier product, 5-methyl-5-undecanol predominantly. The same procedure carried out with LiBr as an additive produced the pinacol product, 7,8-dimethyl-7,8-tetradecanediol, exclusively. A careful product analysis of the SmI2-mediated coupling of 1-iodododecane and 2-octanone in the presence of LiBr, LiCl, and HMPA was also performed. The combination of SmI2 and LiBr again produced the pinacol coupling product exclusively and left the 1-iodododecane unreduced. In contrast, the SmI2−HMPA combination gave only the Barbier product. Analysis of the Sm(II) reductants employing cyclic voltammetry and UV−vis spectroscopy coupled with reaction protocol changes and mechanistic studies led to the conclusion that the SmI2-mediated coupling of alkyl halides and carbonyls in the presence of HMPA gives the Barbier product through an outer-sphere electron-transfer process, while the reaction utilizing SmI2 with LiBr or LiCl gives the pinacol product through an inner-sphere reductive coupling of ketones. The results presented herein show that it is possible to alter the reactivity and selectivity of Sm(II) reagents through the choice of additives or cosolvents, primarily by changing the steric bulk around the reductant.

Beyond Samarium Diiodide: Vistas in Reductive Chemistry Mediated by Lanthanides(II)

“…[14] Flowers and co-workers have investigated the use of SmBr 2 in C À C bond-forming reactions of alkyl halides and carbonyl compounds, and observed complete selectivity for pinacol coupling in the presence of reactive alkyl iodides (Scheme 3). [10] With SmBr 2 as a reductant, complete selectivity for pinacol coupling in the presence of reactive alkyl iodides was observed. Interestingly, mixtures of products were detected in reactions mediated by SmI 2 or SmCl 2 (see Section 2.2 for a discussion of the characteristics of SmCl 2 ), while SmI 2 /HMPA [15] (SmI 2 /HMPA: À1.75 V vs SCE in THF) exclusively afforded the Barbier products 4.…”

“…Although SmBr 2 is a powerful reductant (SmBr 2 : À1.55 V vs SCE in THF; SmI 2 : À0.98 V vs SCE in THF), [10] remarkable levels of selectivity are possible with this reagent. It was shown by Kagan and co-workers that SmBr 2 can be conveniently prepared by the reduction of SmBr 3 with metallic lithium, [11] while Namy and co-workers reported another straightforward synthesis of SmBr 2 from samarium metal and tetrabromoethane.…”

“…Chemoselective SmBr 2 -mediated reductive coupling of alkyl ketones by Flowers and co-workers. [10] SET = single-electron transfer.…”

Preparation and Use of Samarium Diiodide (SmI₂) in Organic Synthesis: The Mechanistic Role of HMPA and Ni(II) Salts in the Samarium Barbier Reaction

“…of HMPA the reaction is nearly quantitative and complete within a few minutes. 15,23 With the addition of 1 mol% Ni(acac) 2 , the reaction is complete within 15 min, with a 97% yield.…”

“…The Sm-Barbier reaction is similar to the traditional Grignard reaction with the only difference being that the alkyl halide, carbonyl, and Sm reductant are mixed simultaneously in one pot. 1,15 Examples of Sm-mediated Barbier reactions with a range of coupling partners have been reported, 1,3,7,10,12 and have been utilized in key steps of the synthesis of large natural products. 16,17 Previous studies on the effect of additives on SmI 2 reactions have shown that HMPA enhances the reduction potential of SmI 2 by coordinating to the samarium metal center, producing a more powerful, [13][14]18 sterically encumbered reductant [19][20][21] and in some cases playing an integral role in post electrontransfer steps facilitating subsequent bond-forming events.…”