Cp*Co(III)-Catalyzed Ketone-Directed ortho-CH Activation for the Synthesis of Indene Derivatives (original) (raw)

A weakly coordinating, carbonyl assisted C-H activation of aromatic systems with α, β-unsaturated ketone and subsequent aldol condensation has been developed using Cp*Co(CO)I2 catalyst. The developed method is first example of indene synthesis by cobalt catalysed C-H activation. In addition, the reaction requires mild reaction conditions, easily accessible starting materials, and it shows excellent functional group compatibility. Indenes are important class of carbocyclic derivatives and are often found as basic units in a variety of naturally occurring molecules. 1 Several methods have been developed for synthesis of indenes due to their synthetic and biological importance in organic chemistry and pharmaceutical science (e.g. antimicrobial, antiviral, antifungal and anticancer activities). 1,2 In addition, indenes possess diverse applications in the field of material science 3 and have also been used as ligands for transition metal complexes in polymerization techniques. 4 Due to synthetic and biological importance of such carbocylic system, indenes have drawn much attention of various research groups for developing novel synthetic methods and their applications to the natural product synthesis. 5-8 Our group has also described a convenient approach for synthesis of highly substituted indenes by Lewis acid catalysed cyclization. 5,9 From past two decades, directing group assisted transition metal catalysed C-H functionalization of aromatic compounds has been very well established and its synthetic utility in the organic chemistry is also well documented. 10 Initially, contribution of second and third-row transition metals such as Rh, Ru, Ir, and Pd to these transition metal-catalysed C-H bond functionalizations is enormous but also constitute severe drawbacks for streamlined applications due to their toxicity, low natural abundance and sky-rocketting prices. 11 In recent years, there is a momentum for developing similar reactions using first row transition metals due to their low toxicity, high natural abundance, easy availability and low cost. 12 Especially, cobalt catalysed C-H bond functionalization has been explored with a variety of N-heteroaryl directing groups as well as other directing groups such as ketones, esters, amides, etc. 13 Also, weakly coordinating carbonyl directed C-H activation reactions have enormously enhanced the application of ketones in synthetic chemistry. 14 As ofinterest, C-H alkylation of ketones has been well established since Murai's report 15 but metal catalysed ketone directed ortho C-H olefination of aromatic systems are very few. 16 Similarly, various methods have been developed for synthesis of indenes via transition metal catalysed ortho-C-H activation and subsequent tandem cyclization. 17 In 1999, Nicholson and Woodgate reported the synthesis of indene derivatives via stoichiometric cyclomanganation of aromatic ketones followed by olefination in the presence of Pd as a co-catalyst. 18 Similarly, Takai group demonstrated that indenes can be efficiently derived from annulation of aromatic ketones and α, β-unsaturated esters via rhenium catalysed C-H activation (scheme 1a). 19 A rhodium catalysed carbocyclization of aryl ketones and alkynes for the synthesis of indenols was described by Cheng et al (scheme 1b). 20 In 2013, Li and coworkers developed a rhodium-catalyzed cascade cyclization of aromatic ketones with α, β-unsaturated carbonyl compounds (scheme 1c). 21 Although, rhodium catalysed reactions are admirable due to their high catalytic activity, air and thermal stability and decent functional group compatibility but above reactions are associated with harsh reaction conditions (temperature 130-180 o C), use of precious metal with less natural abundance, high cost and are toxicity. Therefore, the development of sustainable, efficient and straightforward method for the synthesis of indene derivatives using earth abundant metal catalysts thus remains