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

Abstract

A facile, efficient, and gram‐scale method for the conversion of para‐anisic acid into 3,4,5‐triiodoanisole through a one‐pot C–H iodination/ipso‐iododecarboxylation reaction was investigated. Commercially available benzoic acid was used, which allowed the reaction to be performed on a multigram scale in good yield. This report discloses a practical method for the one‐pot synthesis of hitherto unknown 3,4,5‐triiodoanisole that is catalytic, scalable, efficient, and easy to work up and purify. Potential application of the target compound as a precursor for novel site‐selective metal–iodine exchange and Suzuki–Miyaura cross‐coupling reactions were also explored. 3,4,5‐Trisubstituted anisole derivatives were provided in a highly regioselective fashion; these compounds are useful building blocks in synthesis and indeed are hard to prepare by any other means.

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

“…When reacting tert-BuLi or sec-BuLi with 1,2,3-triiodobenzene 5 at the same temperature, the (2,6-diiodophenyl)(phenyl)methanol 5a was isolated in low yields along with unidentified products ( High product yield, good regioisomeric ratio and the use of commercially available isopropylmagnesium chloride in tetrahydrofuran (Table 1, entry 9) encouraged us to apply previously reported 1,2,3-triiodoarenes under the optimized reaction conditions with the aim of expanding their applications in synthesis and medicine. 20,43 A variety of 1,2,3-triiodoarene substrates were prepared following the literature procedures and subjected to the optimized reaction conditions with different aldehydes. Generally, all substrates underwent a highly regioselective metal-iodine exchange reaction.…”

“…26,41,42 Recently, we disclosed efficient and practical two methods for the synthesis of 1,2,3-triiodoarenes over two-step protocols from aromatic amines or aromatic carboxylic acids respectively. 20,43 Remarkably, 1,2,3-triiodoarenes are found to be crystalline and bench stable solids compare to other polyiodoarene compounds. Herein, we report the first synthesis of hitherto unknowns ortho-diiodobenzyl alcohol and 2,3-diiodobenzyl alcohol derivatives via regioselective metal-iodine exchange reaction of 1,2,3-triiodoarenes that is general in scope, regioselective and gives good yields.…”

Modern Transition-Metal-Catalyzed Carbon–Halogen Bond Formation

“…144 Al-Zoubi and co-workers reported a Pd-catalyzed conversion of 4-methoxy benzoic acid 69 to 3,4,5-triiodoanisole 70 (Scheme 54). 145 This reaction proceeds by a similar double Pd-catalyzed ortho C−H iodination to that of Yu 95 followed by a Pd-catalyzed ipso-iododecarboxylation.…”

“…This reaction offers a complementary method to those of Buchwald which are not capable of generating aryl iodides. 142,145 In 2013, Jeganmohan reported both the meta-and orthoselective Ru-catalyzed intramolecular halogenation of Omethylbenzohydroximoyl halides 148 using diphenylacetylene as an additive (Scheme 133). 261 In some instances, the meta halogenation products 149 were obtained, while in others, the ortho halogenated products 150 were obtained exclusively.…”

Simple, Efficient and Controllable Synthesis of Iodo/Di-iodoarenes via Ipsoiododecarboxylation/Consecutive Iodination Strategy

“…Al-Zoubi reported the palladium catalyzed C–H iodination/ipsoiododecarboxylation of para -anisic acid under illumination [Fig. 1(C)]49. The potential application of the target compound was thoroughly investigated.…”