A New Type Of Ferrocene-based Phosphine-tert-butylsulfinamide Ligands: Synthesis And Application In Asymmetric Catalysis

The phosphine and sulfonamide group are introduced in ferrocene skeleton which is the chiral ligand advantage framework. Therefore, the seven novel ferrocene-based phosphine-tert-butylsulfinamide ligands(L1-L7) were designed and synthesized, which contain planar chiral, carbon chiral, sulfur chiral and other chiral factors. And they are applied in the Palladium-catalyzed asymmetric allylic substitution reactions and Rhodium-catalyzed asymmetric arylation for testing their catalytic activity and enantioselectivity.The main contents are as followed:1. The seven novel ferrocene-based phosphine-tert-butylsulfinamide ligands were designed and synthesized from Uig’s amine as the original material. After four steps of reactions, the target ligands are obtained and confirmed their structures with NMR and HRMS.2. The chiral ligands(L1-L7) were firstly applied in the Palladium-catalyzed asymmetric allylic substitution reactions. The results indicated that the chiralities of ferrocenyl moiety in the ligands play the decisive role in this reactions. While the carbon-centred chirality and the planar chirality of ferrocene scaffold are the main governing factors, the sulfur-centred chirality of sulfinamide moiety is also important, and(RC,SFc,RS)-L1 are the ligands with the matched chiralities. To further improve the chemical yield and enantioselectivity, we optimized the reaction conditions, such as the proportion of catalyst, solvent, temperature, additive, base and Palladium source and so on. In the optimal catalytic conditions, the palladium complex derived from ligand L1 was an efficient catalyst in asymmetric allylic alkylation of symmetrical disubstituted linear substrates(up to 89% ee). For the asymmetric allylic amination, good stereoselectivities were also obtained(up to 87% ee).3. To further study the potential of ligand L1, it was tested it in the asymmetric allylic alkylation of more challenging unhindered cyclic substrate and unsymmetrical disubstituted linear substrates. Importantly, high enantioselectivity(91% ee) was obtained in the allylic alkylation of difficult substrate-2-cyclohexenyl acetate. For unsymmetrical disubstituted linear substrates, the catalytic system showed dissatisfactory regioselectivity, but ee value of each isomer were moderate to high(89% ee). This study of challenge substrates is the first reported.4. Then, four chiral ligands of a new type of ferrocene-based phosphinetert-butylsulfinamide applied in the Rhodium-catalyzed asymmetric arylation. The effects of configuration of sulfur chiral and the group of nitrogen atoms on the ligand were conducted by the catalytic activity and stereoselectivity.The results showed that the(RC,SFc,RS)-L1 is the best ligand. Through screening of solvent, temperature, base and their ratio, the optimum catalytic conditions is 0.024 mmol L1, 0.006 mmol [Pd Cl(C2H4)2]2, 0.42 mmol 1-Naphthaldehyde, 0.34 mmol phenylboroxine, 0.48 mmol t-Bu ONa, 1 m L Cl CH2CH2 Cl, 1 m L H2 O, 50 degrees and 24 hours. I In the optimal catalytic conditions, different substrates were tested, however, it is regrettable that it showed 62% yields and 55% enantioselectivities.