Visible-light mediated installation of halogen functionality into aromatic systems

IGNACIO D. LEMIR; SCHMIDT LUCIANA C.; ARGÜELLO, JUAN E.

Carlos Paz

Encuentro; XIII Encuentro Latinoamericano de Fotoquímica y Fotobiología; 2017

The development of new methods for introducing halogens into organic compounds has constantly attracted many research groups. Halogen substituted compounds are important building blocks in organic synthesis for conversion and introduction of more valuable functional groups by transition metal catalysis[1] and nucleophilic substitution.[2] Furthermore, the interaction of halogen bonds with proteins or small molecules provide modulated physical and chemical properties such as lipophilicity and thermal/oxidative stability. The introduction of halogen functionalities into an aromatic system is a well-established method in organic chemistry. Most commonly activated aromatic rings are converted directly through reaction with excess of the diatomic halogens. However, this method suffers from critical drawbacks with handling of highly hazardous and volatile halogens and poor regioselectivity. Up to date, the most used bromination procedures involves the use N-Bromosuccinimide, transition metals catalyst or solutions of molecular bromine (Br2), these methodologies carry a high economic cost, high toxicity and requires the use of heat sources. In order to solve the above mentioned problems, visible-light photoredox catalysis has arisen as alternative. In the present report, we propose the bromination of anilines using organic photocatalysts and carbon tetrabromide (CBr4) as a source of bromine. ?in situ? Elemental bromide formation is possible using photocatalysts (FCs) such as Ru(bpy3) Cl2 and Eosin Y (EY). [3] Under this contribution, several bromo anilines and brominated heterocycles from activated substrates could be obtained by electrophilic aromatic substitution (SEAr). This methodology provided an alternative synthetic path with an advantage of avoiding toxic, liquid bromine and expensive transition metal catalyst. [1] Hartwig JF. Recent advances in palladium- and nickel- catalyzed chemistry provide new ways to construct C-N and C- O bonds . Transition Metal Catalyzed Synthesis of Arylamines and Aryl Ethers. Angewandte Chemie Int Ed. 1998;37:2046-2067. [2] Bunnet J. F., Zahler R. E. Aromatic Nucleophilic Substitution Reactions. Chem. Rev. 1951; 49:273-412. [3] (a) Zhao Y, Li Z, Yang C, Lin R, Xia W. Visible-light photoredox catalysis enabled bromination of phenols and alkenes. Beilstein J Org Chem. 2014;10:622-627. (b) Kee CW, Chan M, Wong W, Tan C. Selective Bromination of sp3 C-H Bonds by Organophotoredox Catalysis. Asian J Org Chem. 2013:1-10.