Scope and Utility of a New Soluble Copper Catalyst [CuBr−LiSPh−LiBr−THF]:  A Comparison with Other Copper Catalysts in Their Ability to Couple One Equivalent of a Grignard Reagent with an Alkyl Sulfonate

Abstract

A mixture of equal amounts of CuBr−SMe2, LiBr, and LiSPh in THF at 0 °C furnished a new soluble copper catalyst that was highly efficient at coupling primary, secondary, tertiary, aryl, vinyl, and allylic Grignard reagents to primary tosylates and primary Grignard reagents to secondary tosylates and mesylates, all with the use of only 1 equiv of Grignard reagent. The new catalyst was shown to be much more reactive than copper catalysts CuBr and Li2CuCl4 and more efficient in the transference of secondary and tertiary alkyl groups than lower order cuprates (Gilman reagents) and demonstrated more reactivity than the lower order cuprates with its ability to couple primary Grignard reagents to secondary sulfonates. The Grignard reagent/catalyst system was compatible with an ester functionalized tosylate, thus proving to be more chemoselective than a Grignard reagent without the catalyst. The catalyst exhibited good reactivity below room temperature, and with the addition of 6% v/v of HMPA to the catalyst solution, excellent yields of coupled product were obtained within a 25−67 °C temperature range. 1H NMR demonstrated that the catalyst solution consisted of several species that most likely were composed of copper ligated with thiophenol, THF, and LiBr in aggregated forms.

Copper‐Catalyzed Cross‐Coupling Reaction of Organoboron Compounds with Primary Alkyl Halides and Pseudohalides

“…[2] This requirement causes serious waste of the precious organometallic species, in particular in the case of cuprate reagents (R 2 CuLi), which contain two transferable R groups. [3] To solve this problem, several research groups have developed copper-catalyzed alkylation reactions of Grignard reagents. [3][4][5] It was found that these catalytic reactions are much easier to carry out and considerably less expensive.…”

“…[3] To solve this problem, several research groups have developed copper-catalyzed alkylation reactions of Grignard reagents. [3][4][5] It was found that these catalytic reactions are much easier to carry out and considerably less expensive. Additives, such as 1-methyl-2-pyrrolidinone and 1-phenylpropyne, were originally used to promote the alkylation reactions, [4] and the slow addition of the Grignard reagent was found to provide similar results in a recent study.…”

“…[5] Although primary alkyl halides (as well as mesylates and tosylates) are mostly used in these catalytic alkylation reactions, some studies have indicated that secondary and even tertiary alkyl halides may also be possible coupling partners. [3,6] Our interest in copper-catalyzed cross-coupling [7] prompted us to consider the possibility of using organoboron compounds in such alkylation reactions. The advantages of replacing Grignard reagents with organoboron reagents are well-known, including the better commercial availability of the reagents and the higher functional-group tolerance.…”

“…This feature compares favorably with previous examples of the copper-catalyzed coupling of primary alkyl halides with Grignard reagents, in which nearly all reported alkyl groups were hydrocarbons. [3][4][5] Furthermore, for the synthesis of 5 ab, we changed the catalyst from CuI to CuOtBu generated in situ through the equimolar reaction of anhydrous CuI with LiOtBu in THF at room temperature under nitrogen. The yield with CuOtBu was 90 %, which is slightly higher than that observed with CuI (86 %).…”

“…However, when alkyl 9-BBN reagents (9-BBN = 9-borabicyclo[3.3.1]nonane) were used as nucleophiles, the copper-catalyzed coupling reaction also proceeded to form a sp 3 …”