Substitution of Secondary Propargylic Phosphates Using Aryl-Lithium-Based Copper Reagents

Abstract

The substitution of secondary propargylic phosphates ROP(O)(OEt)2 where R = [Ph(CH2)2]C(H)(C≡CTMS)] Ph(CH2)2CH(OP(O)(OEt)2)(C≡CTMS) with copper reagents derived from PhLi and copper salts such as CuCl, CuCN, and Cu(acac)2 was studied to establish an ArLi-based reagent system. Among the reagents prepared, PhLi/CuCl (2:1) showed 98% α regioselectivity (rs), while PhLi/Cu(acac)2 was γ selective (>99% rs). PhLi prepared in situ from PhI and PhBr by Li-halogen exchange with t-BuLi was also used for the α selective substitution. A study using the (S)-phosphate disclosed 99% enantiospecificity (es) and the inversion of the stereochemistry. The substitution of five phosphates with substituted aryl reagents produced the corresponding propargylic products with high rs and es values. Similar reactivity and selectivity were observed with 2-furyl and 2-thienyl reagents, which were prepared via direct lithiation with n-BuLi.

Theme Issue in Memory to Professor Jiro Tsuji (1927–2022)

“…Ostrowska et al proposed the synthetic protocol for palladacycle complexes using a mild base and an environmentally desirable solvent [121]. Finally, the substitution of secondary propargylic phosphates has been carried out by Kobayashi et al with the use of aryl-lithium-based copper reagents [122].…”