AlCl 3 ‑Promoted Selective Michael Addition with Allenoate and Methyleneindolinone: Synthesis of Spirocyclic Oxindole by Using Allenoate as a Four-Carbon Component Building Block Shibo Xu, † Chunju Li, † Xueshun Jia,* ,†,‡ and Jian Li* ,† † Department of Chemistry, Innovative Drug Research Center, Shanghai University, Shanghai 200444, China ‡ CAS Key Laboratory of Synthetic Chemistry of Natural Substances, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, 345 Lingling Road, Shanghai 200032, China * S Supporting Information ABSTRACT: The AlCl 3 -promoted cyclization of readily available allenoates with methyleneindolinone is disclosed. The present strategy provides a rapid access to spirocyclic oxindole-cyclohexenones in an efficient manner. Remarkably, the allenoate is implemented as a four-carbon (4C) component to form the ring, which shows high synthetic efficiency. Flexibility of this method allows quick synthesis of spirocyclic oxindole-dihydropyrans by varying one of the components. It is also noteworthy that AlCl 3 serves as the chlorine source as well as an effective catalyst to facilitate this interesting transformation. ■ INTRODUCTION Spirocyclic oxindole represents a privileged synthetic motif in a large family of clinical pharmaceuticals and natural products including welwitindolinone A, horsfiline, paraherquamide A, and citrinadin A (Scheme 1). 1 These compounds often showed a broad range of biological activities such as insecticidal, antitumor, and antibacterial properties. 2 Enormous efforts have been dedicated to the efficient and selective construction of this core skeleton. As such, transition metal-catalyzed synthesis involving a domino approach, as well as C-H activation, has been widely documented. 3 More recently, organocatalyzed reactions and Lewis acid-promoted annulation have emerged as attractive synthetic strategies. 4,5 Although considerable progress has been described toward their syntheses, developing a novel method to efficiently synthesize this core structure remains valuable. In recent decades, allenoate has received significant interests in organic synthesis due to its facile preparation and versatile reactivity. 6 For instance, nucleophilic addition and electrophilic addition reactions with a wide range of substances, as well as rearrangements, have been well-documented. 7,8 In particular, they were proven to be valuable building blocks in many types of cycloaddition reactions. 9 In this field, the phosphine- catalyzed cycloaddition reaction is of great interest due to simple reagents and structural diversity of the adduct (Scheme 2a). 10 The first example of phosphine-catalyzed [3 + 2] cycloaddition reaction could be dated back to the work of Zhang and Lu in 1995. 11 Following this pioneering work, Zhu et al. 12 reported another important variant [4 + 2] cyclo- addition. After that, a large number of asymmetric versions as Received: September 26, 2014 Published: October 27, 2014 Scheme 1. Natural Products Possessing Spirooxindole as a Core Structure Article pubs.acs.org/joc © 2014 American Chemical Society 11161 dx.doi.org/10.1021/jo502209f | J. Org. Chem. 2014, 79, 11161-11169