Cobalt-catalyzed addition reaction of organoboronic acids with aldehydes: highly enantioselective synthesis of diarylmethanols.

Transition-metal-catalyzed addition of organometallic reagents to aldehydes is a key method for the synthesis of substituted secondary alcohols. Various organometallic reagents, such as organomagnesium, -zinc, -lithium, -silane, -stannane and -boron, have been used in these addition reactions. Among them, organoboron reagents have gained much attention due to the advantages of air and moisture stability, low toxicity, and availability. Rhodium, palladium, platinum, and nickel complexes efficiently catalyzed the addition reaction of organoboronic acids to aldehydes. Recently, copperand iron-catalyzed addition reaction of organoboronic acid with aldehydes were also reported. However, the scope of aldehydes in these two addition reactions is rather limited. Only aromatic aldehydes with an electron-withdrawing substituent worked well. Despite the fact that various metal-catalyzed addition reactions of organoboronic acids with aldehydes are available in the literature, only a few reports on asymmetric reactions were discussed. In 2006, Zhou et al. reported a rhodium-catalyzed enantioselective addition reaction of aromatic boronic acids with aromatic aldehydes. In the reaction, enantiomeric excess (ee) values of 62–87 % for chiral biaryl methanols were observed. Recently, Miyaura and coworkers reported a ruthenium-catalyzed enantioselective addition reaction of aromatic boronic acids with aromatic aldehydes. In the reaction, the expected chiral biarylmethanols were observed in excellent enantiomeric excess. However, in these reactions specially designed chiral ligands and expensive ruthenium or rhodium catalysts were used. Chiral secondary alcohols are key structural units present in various biologically and pharmaceutically active compounds. The development of new, mild, and convenient methods using a low-cost catalyst for the synthesis of chiral secondary alcohols remains highly attractive.Recently, we have reported a cobalt-catalyzed hydroarylation of alkynes with organoboronic acids and other cobalt-catalyzed reactions. Our continuing interest in developing new reactions using less expensive cobalt complexes as catalysts prompted us to investigate the addition of organoboronic acids with aldehydes and the enantioselective version of this reaction. Herein, we wish to show that cobalt complexes very efficiently catalyze this addition reaction to give diarylmethanols in excellent yields and ee values. Treatment of phenylboronic acid (1 a) with 4-cyanobenzaldehyde (2 a) in the presence of Co ACHTUNGTRENNUNG(acac)2 (5 mol %), 1,2bis(diphenylphosphino)ethane (dppe; 5 mol %) in THF/ CH3CN (1/1) at 80 8C for 12 h gave addition product 3 aa in 96 % isolated yield (Table 1, entry 1). In the present reaction, no extra base was required and only 1.2 mmol of boronic acid was used. The use of binary solvent system THF/CH3CN (1:1) appears to improve the yield of product 3 aa. If the catalytic reaction was carried out in THF, product 3 aa was observed only in 75 % yield along with benzene, the protodeboronation product of 1 a, in 18 % yield. The catalytic reaction also worked equally well using CoI2 or CoCl2 (5 mol%), dppe (5 mol %) as the catalyst, and THF as solvent to afford 3 aa in 96–97 % yield, but base (K2CO3 (1.50 equiv)) was needed to activate the boronic acid. Under similar reaction conditions, a variety of substituted aromatic aldehydes, heterocyclic aldehydes, and aliphatic aldehydes were examined with phenylboronic acid (1 a) (Table 1). Thus, benzaldehydes with electron-withdrawing groups, such as 4-NO2 (2 b), 4-CHO (2 c), 4-CO2Me (2 d), and 4-CF3 (2 e) provided diarylmethanols 3 ab–3 ae in excellent yields (89–97 %; Table 1, entries 2–5). For these substrates, only the CHO group participated in the reaction, the other functional groups remained essentially intact. The reaction of dialdehyde 2 c with 1 a also proceeds selectively at one of the CHO groups. Halo-substituted benzaldehyde derivatives are compatible with the present catalytic reac[a] J. Karthikeyan, Dr. M. Jeganmohan, Prof. Dr. C.-H. Cheng Department of Chemistry, National Tsing Hua University Hsinchu, 30043 (Taiwan) Fax: (+886) 35724698 E-mail : chcheng@mx.nthu.edu.tw Supporting information for this article is available on the WWW under http://dx.doi.org/10.1002/chem.201001160.