Studies On CuX₂-Promoted Halocyclization1,2-Allenyl Phosphonates And Suzuki Coupling Reaction

Organophosphic compounds have been widely used in transition metal-catalyzed reactions. asymmetric synthesis, materials science, medicine as well as pesticides. On the other hand. metal-catalyzed cyclization reactions of functionalized allenes have proven to be a highly efficient strategy lor the synthesis of cyclic compounds. This group has made some progress in this area in recent years.Previously, Dr. Yu in our group reported the transition metal-mediated cyclization reaction of monoethyl esters of1,2-allenyl phosphonic acids for the synthesis of vinylphosphonic acid lactone skeleton, which has been reported to show potential biological activity. The starting material monoethyl esters of1.2-allenyl phosphonic acids in this reaction were synthesized from alkynols and P(OEt)2Cl, affording the1,2-allenyl phosphonates. which were then hydrolyzed. However, he found that monoethyl esters of1.2-allenyl phosphonic acids with aryl substituent or without substituent at1-position are not available from hydrolysis of the corresponding1,2-allenyl phosphonates. Besides, the hydrolysis of1,2-allenyl phosphonates with a large substituent group at1-or3-position generally led to the recovery of a large amount of the starting material. To solve the above-mentioned problems, we wish to investigate the halocyclization of1,2-allenyl phosphonates.Firstly, we studied the CuX2(X=Br, Cl)-promoted halocylization of1.2-allenyl phosphonates. affording a series4-halo-2,5-dihydro[1.2]oxaphophole2-oxides in high yields. thereby nicely addressed the issue of hydrolysis of1,2-allenyl phosphonates with large substituents or without substituent at1-position.Secondly, by utilizing LB-Phos, a ligand recently developed in our group, combined with Pd(â…¡) as the catalyst, we successfully realized the activation of C-Cl bonds and subsequent Suzuki cross-coupling reactions of the4-halo-2,5-dihydro [1,2]-oxaphophole2-oxides. providing an easy access to [1,2]-oxaphophole cyclopentadiene compounds.Thirdly, starting from optically active alkynols, the central chirality can be transferred to the axial chirality of the1,2-allenyl phosphonates without obvious racemization. Under the standard conditions of halocyclization, the axial chirality of the1,2-allenyl phosphonates can be efficiently transferred to the central chirality in4-halo-2,5-dihydro-[1,2]-oxaphophole2-oxides. The subsequent C-CI bonds activation and Suzuki cross-coupling also proceeded smoothly without racemization.