Synthesis And Application Of Chiral Six-membered N-heterocyclic Carbene Precursors

The five-membered N-heterocyclic carbenes(NHCs) have been rapidly developed and become a novel organocatalyst due to their stability and high catalytic property in recent years. The bond angles of the 6-membered N-heterocyclic carbenes are larger than them of five-membered N-heterocyclic carbenes. This makes it have a stronger electron-donating and nucleophilic ability. Six-membered N-heterocyclic carbene may have wider applications than five-membered N-heterocyclic carbenes in the field of organic catalysis. However, their applications were limited because of complex design and synthesis. Only a limited number of reported NHCs were based on six-membered rings.Therefore, synthesis of additional types of six-membered N-heterocyclic carbene precursors, especially chiral precursors, would be very valuable for expanding the repertoire of NHCs for organic transformation. Here, we would proceed to the synthesis of a series of chiral NHC precursors based on a 3, 4-dihydro-quinazoline core.The substituted benzophenone compounds as starting material, after condensation reaction, we got compound 1a, 1b and 1c in the condition of a chiral R(+)-t-butyl sulfonamide auxiliary group. The compound 1a, 1b and 1c were reduced by Dibal-H at-78℃ and gave the product 2a, 2b and 2c. Their enantiomeric excess was up to96%. After removal of the sulfinyl group(>95% yield), additional(identical)N-substitutions can be introduced to the two free amines of 3a 、 3b and 3c using palladium-catalyzed reactions for aryl groups to generate compound 4a1-a4, 4b1-b4,4c1-c4. Finally, condensation of compound 4a1-a4, 4b1-b4, 4c1-c4 with trimethyl-orthoformate produces the desired quinazolinium as NHC precursor compound5a1-a4, 5b1-b4, 5c1-c4 for all the examples. The total yield was 54% to 62%. Their structure was characterized by NMR, MS and HRMS.Subsequently, we studied the catalytic applications of chiral six-membered N-heterocyclic carbene precursors. We screened the activity of the catalysts with α, β-unsaturated esters and B2Pin2. Under alkaline conditions(Na OtBu), the chiral sixmembered N-heterocyclic carbenes were deprotonated. The carbene copper complexes were obtained by carbene precursors and cuprous chloride. We found that the catalytic activity of compound 5c2 was best at room temperature and the enantiomeric excess of product reached 72%. At-55℃, the enantiomeric excess was 93%. Therefore, we chose compound 5c2 to catalize application and acquired good results.