A New Strategy for Designing Non‐C₂‐Symmetric Monometallic Bifunctional Catalysts and Their Application in Enantioselective Cyanation of Aldehydes

Abstract

A monometallic bifunctional catalyst, in which only one imidazolyl moiety is directly attached at the 3-position of a binaphthol moiety, has been developed. The ligand (R)-1, which lacks C2-symmetry and flexible linkers, in combination with Ti(OiPr)4, has been demonstrated to promote the enantioselective cyanation of aldehydes with trimethylsilylcyanide (TMSCN), giving excellent enantioselectivities of up to 98 % ee and high yields of up to 99 %. The use of this bifunctional catalytic system obviates the need for additives and is extremely simple as the reagents are added in one portion at the beginning of the reaction. The protocol has been found to tolerate a relatively wide range of aldehydes when 10 mol % of the (R)-1/Ti(OiPr)4 complex is deployed in CH2Cl2 at -40 degrees C, the conditions which proved most practical and effective. The asymmetric cyanations also proceeded with lower catalyst loadings (5 mol %, or even 2 mol %), still giving satisfactory enantiomeric excesses and yields. Interestingly, the use of freshly distilled TMSCN dried over CaH2 gave a low enantioselectivity and only a moderate yield of the adduct as compared with direct use of the commercial reagent. The results of 13C NMR spectroscopic studies implicate HCN as the actual reactive nucleophile.

Copper‐Catalyzed Direct C Arylation of Heterocycles with Aryl Bromides: Discovery of Fluorescent Core Frameworks

“…Our investigation started with the coupling of caffeine (1) with p-bromotoluene (2 a) using copper(I) iodide as the catalyst. After screening a variety of ligands, solvents, and bases ( Table 1, entries [1][2][3][4][5][6][7][8][9][10][11][12][13][14][15], the best results were obtained in DMF/xylene (1:1) at 140 8C for 36 h using two equivalents of K 3 PO 4 as the base in the presence of a catalyst system that was generated in situ from CuI (20 mol %) and 1,20 mol %). An attempt to lower the amount of CuI to 10 mol % resulted in the incomplete consumption of caffeine, in spite of extended reaction time (Table 1,entry 16).…”

Synthesis and application of 3‐substituted (S)‐BINOL as chiral ligands for the asymmetric ethylation of aldehydes

“…of n ‐BuLi at 0°C for 4 h, followed by the addition of B(OCH 3 ) 3 at −78°C, and subsequently quenching with saturated NH 4 Cl aqueous solution generated ( S )‐3‐dihydroxyborane‐2,2′‐bis(methoxymethoxy)‐1,1′‐binaphthyl ( S )‐2 in 89% yield, and the unreacted ( S )‐1 could be recovered and reused. According to the procedure reported by Gau and co‐workers,47 N‐arylation reaction of ( S )‐2 with imidazole and benzimidazole successfully produced the cross‐coupling products ( S )‐3 and ( S )‐4 nearly quantitatively. After deprotection, ligands Ligand‐ 1 and Ligand‐ 2 were obtained in 80% and 82% overall yields, respectively, starting from ( S )‐BINOL.…”

“…Ligand‐ 3 –Ligand‐ 6 and their precursors were synthesized according to the similar procedure described by Gau and co‐workers 47…”

“…In connection with our interest in the design and preparation of a set of novel chiral ligands, for example, the BINOL ligands bearing sulfur or nitrogen‐containing heterocycles at 3 or 3,3′ positions, and their applications in the asymmetric ethylation of several kinds of aldehydes and α,β‐unsaturated ketones,40–46 herein, we report the synthesis of 3‐substituted BINOL bearing imidazole and triazole groups and their utilization in the asymmetric addition of diethylzinc to various aldehydes in the presence of titanium tetraisopropoxide. Although the ( R ) configuration of Ligand‐ 1 , Ligand‐ 3 , and Ligand‐ 6 have been prepared and used as chiral ligands in the enantioselective cyanation of aldehydes,47 their applications in the asymmetric ethylation of aldehydes have not been reported so far. What is more, benzimidazole, benzotriazole, and 5‐chlorobenzotriazole were also conveniently introduced at the 3 position of ( S )‐BINOL and tested in the reaction of diethylzinc with benzaldehyde.…”

Ultrasound‐mediated synthesis of camphoric acid‐based chiral salens for the enantioselective trimethylsilylcyanation of aldehydes

“…The studies of Belokon and North support the existence of a dimeric titanium species, with the two titanium atoms connected through two oxygen bridges. 5,15,[30][31][32] The involvement of a monomeric titanium species is suggested by others 10,[33][34][35][36] and is said to be favored when there are large substituents, such as t-butyl, on the aldehyde moiety. It has been referred that the catalyst structure (monomeric, dimeric, or a mixture of both) is probably related to some reaction conditions such as molar ratios, solvents, and ligand structures.…”