New Uses for Indium(III) Chloride

Rosana Freitas was born in 1988 in Rio Grande do Sul, Brazil. She received her B.Sc. in Pharmacy (2011) from Estácio de Sá University (UNESA) and her M.Sc. degree in Chemistry (2013) from ­Federal University of Rio de Janeiro (UFRJ) under the guidance of Professor Carlos A. Manssour Fraga. She is currently a Ph.D. student under the guidance of Professor Carlos A. Manssour Fraga and Professor Edson F. Silva. Her research focuses on the synthesis and pharmacological evaluation of new prototypes of anti-Trypanosoma cruzi agents.

Introduction

Indium(III) chloride (InCl₃) is an inexpensive, commercially available, easy-to-handle, air- and water-stable Lewis acid with moderate toxicity. It shows a high tolerance to most functional groups including oxygen and ­nitrogen functionalities.[1] Additionally, InCl₃ is very attractive for green-chemistry reactions due to its recyclability.[2] Therefore, InCl₃ has been described as a catalyst for various reactions, especially multicomponent reactions (MCR),[3] as given below.

Abstracts

(A) Synthesis of Furans: Dey and co-workers reported a one-pot synthesis of polysubstituted furans (3) using but-2-ene-1,4-diones (1) and acetoacetates (2) under acid catalysis using InCl3. It is an efficient and easy way of obtaining polysubstituted furans in excellent yields.[4] In a similar manner, Suresh and co-workers reported a synthesis of various pyrroles from α-azido chalcones and 1,3-dicarbonyl compounds using acid catalysis with InCl3 in water.[5]
(B) Multicomponent Reaction: A new protocol described a solvent-free, three-component reaction to generate 8,10-dimethyl-12-aryl-12H-naphtho[1′,2′:5,6]pyrano-[2,3-d]pyrimidine-9,11-diones (7) using functionalized aldehydes (4), 2-naphthol (5), and 6-amino-1,3-dimethyluracil (6) with InCl3 as catalyst. The synthesis is conducted in the absence of a co-catalyst and the desired compounds were obtained in good yields and lower reaction times.[6] Several other multicomponent reactions using InCl3 have been described since then.[3]
(C) Nucleophilic Substitution: Lin and co-workers described a versatile and useful methodology for the synthesis of new C(sp3)–C(sp2), C(sp3)–N, C(sp3)–S and C(sp3)–O bonds via nucleophilic substitution of secondary alkyl-substituted propargyl acetates (8) in MeNO2 using InCl3. Over twenty substrates were tested and the substitution products were obtained in high yields.[7]
(D) Barbier–Grignard-type Reaction: A novel and efficient one-pot synthesis of propargylamines (11) via a Barbier–Grignard-type reaction was described for a variety of ald­imines (9) and phenylacetylenes (10) in a bicatalytic system using InCl3 and CuCl in water. The products were obtained in moderate to good yields, without formation of byproducts or hydrolysis of ald­imines.[8]
(E) Reductive Amination: InCl3 and Et3SiH in methanol were able to promote the highly chemoselective reductive amination of various carbonyl compounds. In this methodology, ketones and aldehydes, some of them α,β-unsaturated, and various amines were used, including amines with other functional groups. The proposed mechanism suggests that the reducing agent is formed in situ by a catalytic cycle to generate active indium hydride species [InHCl2(MeOH)x–1], which then transfers the hydride to an iminium ion intermediate to generate the corresponding amine.[9]
(F) 1,4-Hydrosilylation: A new chemo- and stereoselective method for 1,4-hydrosilylation of α,β-enone ester (12) to silylenol ether (13) was developed by using InCl3, Et3SiH and TFA in toluene. The products were obtained in moderate yields, and the double bond showed only Z configuration indicating the stereoselective course of the reaction.[10]
(G) Reduction of Nitriles: Nitriles were reduced to primary amines in excellent yields using InCl3 and NaBH4 in THF. Among the tested substrates were aromatic, heteroaromatic and aliphatic nitriles, indicating the versatility of this new methodology. Species which promote the reduction of ­nitriles, for example, HInCl2 and BH3 ·THF, are generated in situ by reaction with NaBH4 and InCl3.[11]
(H) Heck Reaction: Liu and co-workers reported the discovery of InCl3 as the only catalyst for a Heck reaction between aryl iodides and olefins in the presence of sodium acetate in DMF. The new method was validated by the use of various olefins and functionalized aryl iodides, resulting in the formation of functionalized styrenes or stilbenes in high yields.[12]
(I) Friedel–Crafts Alkylation: InCl3 was effective to catalyze the Friedel–Crafts alkylation of 1-bromo-adamantane and monosubstituted benzenes to generate 1-adamantyl benzenes. Good yields were obtained, and an excellent regioselectivity for the formation of the para isomer compared to the meta isomer was achieved.[13]

• References


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For examples see:
• 2a Kantam ML, Roy M, Roy S, Subhas MS, Sreedhar B, Choudary BM, De RL. J. Mol. Catal. A: Chem. 2007; 265: 244
• 2b Sun G, Sun H, Wang Z, Zhou M.-M. Synlett 2008; 1096

For examples see:
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