ChemInform Abstract: Substituent‐Dependent, Iron‐Mediated Tandem Cyclization of Diynes with Benzaldehyde Acetals to Form Highly Functionalized Indene Derivatives.

Abstract

The construction of functionalized carboand heterocycles from relatively simple and readily available starting materials in a convergent manner is always desired in organic synthesis. Diynes have been used as versatile building blocks for the preparation of carboand heterocycles through transition-metal catalyzed carbocyclization, cycloaddition, and cycloisomerization reactions. The indene backbone is frequently found in natural products, pharmaceuticals, functional materials, and metallocene complexes, and a variety of synthetic methods have been developed for their construction. Although enediynes have been documented for the synthesis of indenes, diynes have seldom been applied for this purpose. Recently, iron catalysis has emerged as a promising, environmentally benign alternative to traditional transition-metal catalysis due to the many advantages of utilizing iron-catalyst precursors, such as low cost, nontoxicity, good stability, and straightforward methods of handling. Very recently, we discovered that FeCl3 and FeCl3·6H2O can efficiently promote the intramolecular cyclization of monoalkynyl aldehyde acetals to generate solvent-dependent Prins-type products and a,b-unsaturated cyclic ketones, respectively (Scheme 1). Herein, we report the FeCl3and FeBr3-mediated tandem cyclization of simple diynes with benzaldehyde acetals for the synthesis of highly functionalized indenes. In our initial studies, the reaction of diyne 1a with diethyl benzaldehyde acetal 2a was investigated to screen the reaction conditions (Table 1). Under a nitrogen atmosphere, compound 1a was reacted with an equimolar amount of 2a in the presence of FeCl3 (1.0 equiv) in CH2Cl2 at ambient temperature, to give 3-chlorovinyl-2,3-trisubstituted 1Hindene 3a in 55% isolated yield (Table 1, entry 1). Although several other products could be seen in the TLC analysis of the reaction mixture, no isomers of 3a or other potential products were successfully isolated. At 10 8C, 3a was formed in a better yield (63%), although formation of 3a (66%) was further improved by performing the reaction at 0 8C (Table 1, entries 2 and 3). The reaction was less efficient