Regioselective Palladium-Catalyzed Phosphonation of Coumarins with Dialkyl H-Phosphonates via C–H Functionalization

Abstract

A novel Pd(II)-catalyzed dehydrogenative cross-coupling reaction between coumarins and H-phosphonates has been developed to give the corresponding 3-phosphonated products in moderate to good yields with high selectivity.

Phosphorylation of C–H bonds of aromatic compounds using metals and metal complexes

“…The authors started optimization of the reaction conditions for coumarin (2H-chromen-2-one, 81) and diethyl H-phosphonate (1) using 10 mol.% Pd(OAc) 2 and K 2 S 2 O 8 in MeCN at 100 8C for 24 h. 155 Phosphonation occurred in position 3 of the coumarin nucleus with high regioselectivity and in a relatively low but encouraging isolated yield (21%) ( Table 10, run 1). When 2,2 H -bipyridine (L2) was introduced into the reaction system as a ligand, the yield increased up to 46% (run 2).…”

Recent Advances in H-Phosphonate Chemistry. Part 2. Synthesis of C-Phosphonate Derivatives

“…The method consists of an oxidative cleavage of the C-H and P-H bonds and proceeds probably via a Pd(II)/Pd(IV) catalytic cycle. An analogous catalyst system was used for direct phosphonylation (C-H activation) of coumarins with dialkyl H-phosphonates to produce the corresponding 3-phosphonylated coumarin derivatives in a highly regioselective manner, with moderate to good yields [123]. Although Pd(II)-catalyzed reactions typically proceed via a Pd(II)/Pd(0) catalytic cycle (Scheme 17), a Pd(IV) species [124] was postulated as an intermediate [122,123].…”

Progress in the Synthesis of Arylated Coumarin Derivatives

“…由于其分子内有 C＝C 双键、C＝O 双键及內酯 结构, 该类化合物具有很强的荧光, 因此该类化合物在 荧光探针、染料和光学材料方面具有重要的应用 [4] . 近 年来, 为了进一步提高香豆素的应用范围和价值, 人们 对香豆素进行了多种功能化修饰, 包括膦酰化 [5,6] 、硝 化 [7,8] 、卤化 [9,10] 、芳甲酰化 [11～14] 、磺酰化 [15] 、亚磺酰胺 化 [16] 、烷基化 [17,18] 和芳基化 [19] 等. 其中, 芳基化香豆素 衍生物是一类重要的具有较高生物活性的药物分子, 通 过其衍生得到大量的目标药物分子可以作为单胺氧化 酶 B (MAO-B)抑制剂、辣根过氧化物酶(HRP)抑制剂和 艾滋病病毒 I (HIV-I)转录酶抑制剂, 都具有较好的效 果 [19] ; 此外, 芳基化香豆素衍生物具有较强的荧光, 在 …”