Co-Catalyzed Cross-Coupling of Alkyl Halides with Tertiary Alkyl Grignard Reagents Using a 1,3-Butadiene Additive

Abstract

The cobalt-catalyzed cross-coupling of alkyl (pseudo)halides with alkyl Grignard reagents in the presence of 1,3-butadiene as a ligand precursor and LiI is described. Sterically congested quaternary carbon centers could be constructed by using tertiary alkyl Grignard reagents. This reaction proceeds via an ionic mechanism with inversion of stereochemistry at the reacting site of the alkyl halide and is compatible with various functional groups. The use of both 1,3-butadiene and LiI was essential for achieving high yields and high selectivities.

Low‐Valent Ate Complexes Formed in Cobalt‐Catalyzed Cross‐Coupling Reactions with 1,3‐Dienes as Additives

“… The formation of anionic cobaltate complexes as central intermediates of the title reaction, as suggested by Kambe and co‐workers …”

Nickel-Catalyzed Alkylative Cross-Coupling of Anisoles with Grignard Reagents via C–O Bond Activation

“…The Grignard reagents used in this study were purchased or prepared as diethyl ether (Et2O) solutions. [32][33][34][35] GC yield (%) Under these optimized conditions, the scope of Grignard reagents was investigated ( Figure 2). Initial ligand screening revealed that neither tricyclohexylphosphine (PCy3) nor 1,3dicyclohexylimidazol-2-ylidene (ICy), which are reported to be the most effective ligands for C(aryl)-O bond activation, 15,16 efficiently formed the desired cross-coupling product 1a with most of 1 being recovered (entries 1 and 2 in Table 1a).…”

The Cobalt-Catalyzed Cross-Coupling Reaction of Alkyl Halides with Alkyl Grignard Reagents: A New Route to Constructing Quaternary Carbon Centers­

“…Primary alkyl Grignard reagents gave the corresponding coupling products in good yields (Table 1, entries 11 and 12), but methylmagnesium chloride (MeMgCl) and phenylmagnesium bromide (PhMgBr) reacted sluggishly, due to difficulties in generating the active catalytic species (Table 1, entries 13 and 14). 5 The relative reactivity of n-, sec-and tertbutyl Grignard reagents was estimated to be roughly 1:4:0.6, by competitive experiments.…”

“…3 During the course our studies on transition-metal-catalyzed cross-couplings using unsaturated hydrocarbon additives, 3d,e,4 we found that cobalt salts, with the aid of lithium iodide (LiI) and conjugated diene additives such as 1,3-butadiene or isoprene, catalyze successfully cross-coupling reactions of alkyl (pseudo)halides with tertiary alkyl Grignard reagents giving rise to the formation of quaternary carbon centers, where esters, amides, carbamates and acetal functional groups were well tolerated. [5][6][7] It was also possible to couple primary and secondary alkyl Grignard reagents with alkyl halides using this catalyst system. The reactions Scheme 1 General procedures for the cobalt-catalyzed cross-coupling reaction of alkyl halides with alkyl Grignard reagents (Procedures 1 and 2), a reaction using 0.1 mol% of catalyst (Procedure 3) and a large-scale reaction (Procedure 4) + CoCl 2 (2 mol%), LiI (4 mol%)…”