Terminal versus Internal Diiodobenzyl Alcohol Derivatives via Regioselective Metal–Iodine Exchange of 1,2,3‐Triiodoarenes: Synthesis and Antibacterial Activity

Abstract

A wide range of unique diiodobenzyl alcohol building blocks have been synthesized by regioselective Metal-Iodine Exchange reaction (MIE) using isopropylmagnesium chloride is reported. Remarkably, the regioselectivity of the MIE reaction is easily controlled by both the aldehydes and the 1,2,3-triiodoarenes to provide either the internal or the terminal products in good yields and in high regioselective fashion. The synthesized diiodobenzyl alcohols were tested for in vitro antibacterial activity against two Gram positive Micrococcus luteus (ATCC 934) and Staphylococcus aureus (ATCC 29213) and two Gram negative Escherichia coli (ATCC 25922) and Serratia marcescens (ATCC 27117). The biological data clearly shows that all tested diiodobenzyl alcohols have selective antibacterial activity against Gram positive strains and no activity against Gram negative ones. This report discloses a facile protocol for the synthesis of hitherto unknowns ortho-diiodobenzyl alcohol and 2,3-diiodobenzyl alcohol derivatives in only one step that is quite general in scope, scalable and hard to make by any other means. AbstractA wide range of unique diiodobenzyl alcohol building blocks have been synthesized by regioselective Metal-Iodine Exchange reactions (MIE) using isopropylmagnesium chloride is reported. Remarkably, the regioselectivity of the MIE reaction is easily controlled by both the aldehydes and the 1,2,3-triiodoarenes to provide either the internal or the terminal products in good yields and in high regioselective fashion. The synthesized diiodobenzyl alcohols were tested for in vitro antibacterial activity against two Gram positive Micrococcus luteus (ATCC 934) and Staphylococcus aureus (ATCC 29213) and two Gram negative Escherichia coli (ATCC 25922) and Serratia marcescens (ATCC 27117). The biological data clearly shows that all tested diiodobenzyl alcohols have selective antibacterial activity against Gram positive strains and no activity against Gram negative ones. This report discloses a facile protocol for the synthesis of hitherto unknowns ortho-diiodobenzyl alcohol and 2,3-diiodobenzyl alcohol derivatives in only one step that is quite general in scope, scalable and hard to make by any other means.

Facile, One‐Pot, and Gram‐Scale Synthesis of 3,4,5‐Triiodoanisole through a C–H Iodination/ipso‐Iododecarboxylation Strategy: Potential Application towards 3,4,5‐Trisubstituted Anisoles

“…Having only two regiochemically different sites occupied with iodine, the metal–iodine exchange/functionalization reaction sequence can afford no more than two possible regioisomers in this transformation, internal H and terminal I . As we previously observed in the metalation and reaction with 1,2,3‐triiodobenzene and 3,4,5‐triiodotoluene as electrophiles,6a,6b,11a the nature of the electrophile has a great influence on the regioselectivity of the reaction. For instance, the use of aldehydes as electrophiles provided a mixture of internal and terminal benzyl alcohol products (Scheme ; see 8 – 10 ).…”