ACS catalyst: Zhang Junliang, Fudan University and Wu Haihong, Huashi University reported the palladium / WJ Phos catalyzed asymmetric Suzuki miyaara cross coupling reaction

Axial chiral diarylphosphonides and their oxides have been widely used as chiral ligands and catalysts in asymmetric catalytic reactions Therefore, the development of new methods for the synthesis of chiral phosphine oxides has attracted wide attention At present, researchers have developed several strategies For example, the classical strategy for the synthesis of such compounds requires the multi-step synthesis of chiral binaphthol (scheme 1a and 1b) A highly efficient palladium catalyzed asymmetric synthesis of axially chiral 1-vinylnaphthalene-2-ylphosphine oxide by aryl bromide and hydrazone was developed by our group The obtained product was further oxidized by DDQ to obtain an axially chiral biaryl compound (scheme 1c) In addition, Buchwald and Qi team realized the asymmetric Suzuki coupling (scheme 1D) of palladium catalyzed arylboric acid with 2-diarylphosphonyl-1-naphthyl bromide by using chiral monophosphonic or cyclophosphate ligands Considering the importance of phosphine containing compounds, it is still necessary to develop new catalytic systems to enlarge the range of substrates and to be used for large-scale preparation Recently, Zhang Junliang group of Fudan University and Wu Haihong group of East China Normal University reported the highly enantioselective palladium catalyzed Suzuki coupling reaction with wj-phos as the chiral ligand This method can easily obtain a variety of substituted hindered isomeric phosphine oxides with high yield and excellent EE value The related research results were published on ACS catalyst (DOI: 10.1021 / acscan 9b04354) (source: ACS catalyst.) using 2-diphenylphosphine-1-bromonaphthalene 1a and 1-naphthalenboronic acid 2A as model substrates, the author first investigated a series of chiral ligands (Figure 1) The efficiency of chiral diphosphonic ligand L1-L3 is low, and the product 3AA can be obtained with the yield of 42% and the EE of 32% by using single phosphine ligand (R) - mop (L4) Among the ferrocene ligands, WJ Phos, which was developed by our group independently, has a good catalytic effect The yield of the reaction is 50% and the EE of 89% is worth 3 AA Inspired by this, the author further developed a new route for the synthesis of wj-phos, and prepared a series of non enantiomers wj4-wj8, and then studied the activity of this series of new wj-phos in asymmetric Suzuki coupling reaction The results show that (SC, RFC, RS) - wj5 with 1-naphthyl is the best, the yield is 55% and EE is 90% (Table 1, entry 4) Then the author continued to screen the palladium catalyst, solvent, alkali and other conditions, and finally determined the best conditions for the reaction: PD (OAC) 2 as catalyst, (SC, RFC, RS) - wj5 as ligand, potassium carbonate as base, substrate 1a and 2A in PhMe / EtOH mixed solvent at 50 ℃ for 36 hours, 84% yield and 94% ee value to axial chiral coupling product 3AA 。
(source: ACS catalyst.) (source: ACS catalyst.), after determining the optimal conditions, the author investigated the scope of application of the reaction (scheme 3) Benzene ring can react smoothly with O -, M - and n-naphthalene bromide with electron donor group or electron acceptor group In 70-87% yield, 94-96% ee is worth to the corresponding product 3ba - 3ra Dimethyl 1-bromo-2-naphthylphosphonate and diethyl ester were also suitable substrates 3ta (90% ee) and 3ub (93% ee) were obtained in medium yields, respectively Methyl substituted naphthalene boric acid and a variety of condensed boric acid are also compatible In addition, phenylboronic acid with methyl, phenyl, methoxy and other ortho groups can also be used in the system, and the corresponding products (3bE - 3mh, 3af - 3AK) can be obtained with good yield and EE value (source: ACS catalyst.) in order to illustrate the practicability of the catalytic system, the author has carried out a large-scale synthesis of BAC Under the catalysis of 2.5 mol% PD (OAC) 2 / (SC, RFC, RS) - wj5, the yield of 142.5 g 1a and 2A is 62% and the EE value of 94% is 98.6 g 3AA (scheme 4) In order to further prove that product 3AA can be used as a "platform molecule", the author carried out a scheme 5 derivatization Firstly, 4A thiophosphate was obtained by reduction and oxidation of 3AA Secondly, the phosphonic compound 4B - 4E was obtained by Pd (II) - catalyzed pH 2 (o) p-directed C-H acetylation, hydroxylation and alkenylation of 3AA PH2 (o) P group can not only be used as a guiding group, but also be used to construct phosphine ligands Under the corresponding conditions, the product 4E can be converted into the product 4f - 4I with high enantioselectivity (source: ACS catalyst.) Summary: the palladium catalyzed Suzuki miyaara cross coupling reaction has been developed by using WJ Phos as chiral ligand The reaction is simple and has excellent enantioselectivity This method provides a convenient way for the synthesis of a variety of substituted axial chiral biaryl monophosphonic oxides.