Development of Asymmetric Nickel-Catalyzed Arylation of Aromatic Aldehydes with Arylboron Reagents

Abstract

A s y m m e t r i c N i c k e l -C a t a l y z e d A r y l a t i o n Abstract: The development of the nickel-catalyzed 1,2-addition of triarylboroxins to aromatic aldehydes in the presence of a phosphine ligand is described. This development allowed the asymmetric nickel-catalyzed 1,2-addition of arylboron reagents to aromatic aldehydes. The enantioselectivity is synthetically acceptable (up to 81% ee) using 1-naphthaldehyde and 2-substituted aromatic aldehydes as substrates. The results have enantioselectivity comparable to the best results reported by us for the rhodium-catalyzed arylation of aromatic aldehydes.The asymmetric arylation of aromatic aldehydes is one of the most important C-C bond-forming reactions, because optically active diarylmethanols are important intermediates for the synthesis of biologically active compounds. 1 Among various arylmetal reagents used, arylboron reagents are desirable due to the recent demand for safe and sustainable organic synthesis, as their reagents are less toxic and they are air-stable. Miyaura's group has reported that rhodium(I) complexes catalyze the 1,2-addition of arylboronic acids to aldehydes giving the corresponding products with 41% ee. 2 Although, later attention focused on asymmetric arylation with the combination of a rhodium catalyst and an arylboronic acid, 3 our method, exhibiting up to 85% enantioselectivity, gave the best results. 3c,f Recently, Ohta and Ito, 4a our group, 4b and others 4c-e reported the use of a less expensive palladium catalyst for the 1,2-addition of arylboronic acids to aromatic aldehydes. However, our method using a palladium catalyst gave no enantioselectivity. From the viewpoint of cost and practical convenience, the use of a more economical and naturally abundant metal catalyst such as nickel, rather than rhodium or palladium, is desirable. 5 To date, only one successful example of the nickel-catalyzed arylation of aldehydes with arylboron reagents has been reported by Shirakawa. 5a However, according to Shirakawa's report, 5a in the presence of a phosphine ligand, the arylation does not proceed at all, hence the extension to an asymmetric version of the nickel-catalyzed arylation seemed to be very difficult. Herein, we would like to report the development of an asymmetric nickel-catalyzed 1,2-addition of arylboron reagents to aromatic aldehydes. 6Initially our studies focused on the determination of the conditions for Ni(cod) 2 -catalyzed phenylation using various phosphine ligands, phenylboronic acid, and triphenylboroxin. As can be seen in Table 1, the dramatic effect of the boron reagent and ligand was observed. When phenylboronic acid was used as the boron reagent, the results for phenylation were not promising ( Table 1, entries 1 and 2). Next, the use of triphenylboroxin as the boron reagent was examined. After intensive screening of ligands, we found that the chemical yield was brought to an acceptable level by using (±)-Et-Duphos (6b) (Table 1, entry 10). Very interestingly, other five-membered chelating ligands such a...