New Directing Groups for Metal-Catalyzed Asymmetric Carbon–Carbon Bond-Forming Processes: Stereoconvergent Alkyl–Alkyl Suzuki Cross-Couplings of Unactivated Electrophiles

Abstract

The ability of two common protected forms of amines (carbamates and sulfonamides) to serve as directing groups in nickel-catalyzed Suzuki reactions has been exploited in the development of catalytic asymmetric methods for cross-coupling unactivated alkyl electrophiles. Racemic secondary bromides and chlorides undergo carbon–carbon bond formation in a stereoconvergent process in good ee at room temperature in the presence of a commercially available nickel complex and chiral ligand. Structure-enantioselectivity studies designed to elucidate the site of binding to nickel (the oxygen of the carbamate and of the sulfonamide) led to the discovery that sulfones also serve as useful directing groups for asymmetric Suzuki cross-couplings of racemic alkyl halides. To the best of our knowledge, this investigation provides the first examples of the use of sulfonamides or sulfones as effective directing groups in metal-catalyzed asymmetric carbon–carbon bond-forming reactions. A mechanistic study established that transmetalation occurs with retention of stereochemistry and that the resulting nickel–carbon bond does not undergo homolysis in subsequent stages of the catalytic cycle.

Facile Access to Fluoromethylated Arenes by Nickel‐Catalyzed Cross‐Coupling between Arylboronic Acids and Fluoromethyl Bromide

“…On the basis of these results and previous reports, [17] ap lausible reaction mechanism involving aN i I /Ni III catalytic cycle is proposed (Scheme 5). Ther eaction begins with the transmetalation between arylboronic acids and [Ni I L n ]( I), which may be generated through the comproportionation of in situ generated Ni 0 and the remaining Ni II species.…”

“…Furthermore,adecrease of the loading of NiCl 2 ·DME from 10 mol % to 5mol %and the use of L5 (5 mol %), DMAP (10 mol %), and K 2 CO 3 (2.0 equiv) in as olvent mixture of DME/1,4-dioxane [12] at 70 8 8Cp rovided 3a in ac omparable yield (entry 14). No product formation was observed in the absence of the nickel catalyst or the ligand L5,b ut 3a could be obtained in 51 %y ield without DMAP,t hus demonstrating the essential roles of both the nickel catalyst and the ligand L5 for the catalytic cycle (entries [15][16][17].…”

Synthesis of chiral heterocycles by ligand-controlled regiodivergent and enantiospecific Suzuki Miyaura cross-coupling

“…When using chiral secondary alkylboron intermediates, these issues are compounded by the challenge of stereocontrol (control of the configuration of a stereogenic carbon). Indeed, although some progress has been realized in recent years [7][8][9][10][11][12][13][14][15][16][17][18][19][20] , control of stereoselectivity is viewed as one of the final frontiers in the Suzuki Miyaura reaction (Fig. 1b) 21 .…”

Nickel-Catalyzed C-Br/C-H Bis-phenylation of Methyl 4-Bromocrotonate: A Stereoselective Entry to Methyl (E)-3,4-Diphenylbut-2-enoate

“…[37][38][39] We also tried to examine the scope of this method with respect to the nucleophilic partner but unfortunately we determined that this protocol is not suitable when functionalized arylboronic acids are employed in the reaction because the corresponding bis-arylated compounds are recovered in very poor yields. However, bis-phenylated compound 3 is a very attractive synthon because of its high potential to be further elaborated.…”