Synthesis Of Mop-type Ligands And Their Applications In Palladium-catalyzed Amination Reactions

In this dissertation, bulky and electron-rich MOP-type ligands,2-dialkylphosphino-2’-alkoxy-1,1’-binaphthyl were synthesized. The ligands were applied to the palladium-catalyzed amination reactions of aryl halides with various functionalized nitrogen nucleophiles, good to excellent catalytic efficiency was obtained.The dissertation includes:1. A series of bulky and electron-rich MOP-type ligands,2-dialkylphosphino-2’-alkoxy-1,1’-binaphthyl, were synthesized following the procedure:1,1’-bi-2-nathtol was dehydrated by HY zeolite with high SiO2/Al2O3ratio (>16) to form dinaphthofuran, ring-opening reaction of dinaphthofuran by lithium, selective phosphorylation with chlorodialkyl phosphine, and then followed by alkylation. The key intermediates, chlorodialkyl phosphines were synthesized successfully under the optimized reaction conditions by treating of PC13with dialkyl phosphine oxides, which were obtained by alkyl Grignard reagents reacting with HP(OEt)2with a total yield up to70%. The efficient synthesis of chlorodialkyl phosphines provided a general protocol for MOP-type ligands.2. A general and useful catalytic system for palladium-catalyzed coupling reaction of amino acids or esters with inactive aryl halides under mild conditions was developed. In the catalytic system, Pd(dba)2was used as palladium source,2-di-tert-butylphosphino-2’-isopropoxy-1,1’-binaphthyl as ligand, tBuOH as the solvent, and KOH as the base. This combination showed high efficiency for the coupling reactions of amino acids and inactive aryl halides to give N-aryl amino acids. For aryl halides bearing a base-sensitive functional group, the coupling reaction was also accomplished in high yields by transforming the amino acid to amino ester and using Cs2CO3as the base and dioxane as the solvent. Under the catalytic conditions, not only a-amino acids, but also β-, γ, ε-amino acids and aromatic amino acids have been coupled with aryl halides in moderate to high yields. Furthermore, this method has been proven useful for preparing enantiopure N-aryl β-amino acids and N-aryl a-amino acids with a bulky alkyl group at a-carbon.3. Palladium-catalyzed intermolecular C-N bond-formations between aryl halides and amides were realized employing2-di-tert- butylphosphino-2’-isopropoxy-1,1’-binaphthyl as the ligand. A variety of amides, such as aliphatic and aromatic primary amides, lactams, and carbamates were viable substrates for the amidations, which exhibited good functional group compatibility.2-Bromo-2’-methoxy-1,1’-binaphthyl couples with tert-butyl carbamate to provide2-amino-2’-methoxy-1,1’-binaphthyl (NOBIN) in high yield employing2-di-cyclohexylphosphino-2’-methoxy-1,1’-binaphthyl as the ligand.4.2-Di-tert-butylphosphino-2’-isopropoxy-1,1’-binaphthyl was employed as the ligand for the synthesis of aryl hydrazines by Pd-catalyzed coupling of unreactive aryl halides bearing meta, para substituted group with BocNHNHBoc in high efficiency. For ortho substituted aryl halides, similar reactions can be realized by replacing of BocNHNHBoc with NH2NHBoc as the nucleophile, coupling reaction occurred at amino group selectively and good to excellent yields were also obtained. The reaction provided a useful method for the preparation of aryl-substituted hydrazides with good functionality tolerance.