This journal is c The Royal Society of Chemistry 2013 Chem. Commun., 2013, 49, 10947--10949 10947 Cite this: Chem. Commun., 2013, 49, 10947 A multicomponent cascade reaction for the synthesis of novel chromenopyranpyrazole scaffolds†‡ Manickam Bakthadoss,* ab Damodharan Kannan a and Raman Selvakumar a A catalyst, solvent, work-up and column free synthesis of chromeno- pyranpyrazoles via multicomponent cascade reaction has been achieved with high stereoselectivity. This novel reaction creates two N–C, two C–C and one O–C bonds through a domino process for the construction of three new rings and three contiguous stereogenic centers. An efficient and elegant assembly of complex structures with multiple stereocenters has become an important topic in organic chemistry. Heterocyclic rings are present as fundamental compo- nents in the skeleton of more than half of the biologically active compounds produced by nature. 1 Among them, benzopyran and pyrazole heterocyclic ring systems are present in a vast number of natural products and bioactive substances, with a wide application range. 2 These heterocycles are privileged structures, constituting pivotal drug-like scaffolds in medicinal chemistry, and have received much attention. 3 An interesting aspect in the field of heterocyclic synthesis is in the use of domino reactions. During the past decade, domino reactions have emerged as powerful and efficient methods for the construction of heterocyclic compounds. Amongst such reactions, the domino Knoevenagel-hetero-Diels–Alder reaction has proven to be a useful tool for the synthesis of polyheterocyclic compounds. 4 The progression of new methodologies with the improvement of synthetic efficiency is an important objective in modern organic synthesis. 5 Multicomponent reactions (MCR), which encompass numerous bond-forming reactions in a one-pot operation, represent appealing strategies for the facile construction of novel molecular architecture. These reactions are venerable to create wide libraries of diverse molecules in a facile manner by virtue of their convergent nature. Therefore, the development of new multicomponent protocols for the rapid construction of fused molecular frameworks represents one of the frontiers of preparative chemistry. Pyrazole derivatives display a broad spectrum of biological activ- ities and represent an important structural class in pharmaceuticals and agrochemicals. They are present in leading drugs such as viagra and celebrex, and therefore synthesis of pyrazole motifs is considered very important in pharmaceutical industries. 6 In parti- cular, 3-methyl-1-phenyl-1H-pyrazol-5-one (edaravone 4), which is a free radical scavenger, has interesting medicinal applications, such as a potential neuroprotective agent for recovery of acute brain ischemia and subsequent cerebral infarction. 7 The compounds containing a pyrano[2,3- c]pyrazole unit have shown antimicrobial, insecticidal, anti-inflammatory, and molluscicidal activities. On the other hand, photochromic compounds having a benzopyran nucleus have practical applications in data storage, optical filters, displays, sensor protection, waveguides, and ophthalmic plastic lenses. 8 Representative members of pyrazoles and benzopyran structural motif containing natural products and biologically active molecules 9 such as pyrano[2,3-c]pyrazole (I), 9a chromenopyrazolylsulfon- amide (II), 9b suksdorfin (III), 9c deguelin (IV), tephrosin (V) 9d and edaravone (4) 7 are shown in Fig. 1. The Baylis–Hillman adducts have become a valuable source for various organic transformations and have been transformed into a number of carbocycles and heterocyclic frameworks of medicinal importance. In fact, due to the close proximity of functional groups the B–H adducts and their derivatives have become attractive sources/substrates for a number of organic transformations often leading to the synthesis of several bioactive compounds and important frameworks of medicinal relevance. 10 In continuation of our ongoing research program in the field of heterocyclic chemistry, 11 we herein report a convenient, Fig. 1 Representative examples of natural products and bioactive molecules containing pyrazoles and benzopyran motifs. a Department of Organic Chemistry, University of Madras, Guindy Campus, Chennai – 600 025, Tamilnadu, India. Fax: +91-44-22352494 b Department of Chemistry, Pondicherry University, R. V. Nagar, Pondicherry – 605 014, India. E-mail: bhakthadoss@yahoo.com † This paper is dedicated to Professor Mariappan Periasamy, University of Hyderabad, on the occasion of his 60th birthday. ‡ Electronic supplementary information (ESI) available: Copies of 1 H and 13 C spectra of all the new compounds. CCDC 780638 and 780639. For ESI and crystallographic data in CIF or other electronic format see DOI: 10.1039/c3cc45502e Received 19th July 2013, Accepted 19th September 2013 DOI: 10.1039/c3cc45502e www.rsc.org/chemcomm ChemComm COMMUNICATION Published on 19 September 2013. Downloaded by University of Madras on 06/01/2014 12:16:03. View Article Online View Journal | View Issue