The “principle of vinylogy” instructed by Fuson in 1935 allows transmission of electronic properties of a
functional group in a molecules via interposed conjugated multiple bonds and thereby facilitates
functionalization at a distal position which is not apparent from other reaction modalities.1 A major challenge
associated with this powerful strategy is how to control chemo-, regio-, and stereoselectivities of vinylogous
species as they often possess more than two reactive sites.1 Situation becomes more cumbersome when a
catalytic reaction condition is in concern. Nevertheless, this concept was judicially explored to assemble
molecular complexities including total synthesis of valuable natural products and pharmaceuticals.1,2 In this
regime, alkylidene malononitriles are highly appealing. While the presence of two strong electron-withdrawing
nitrile moieties makes -C–H bond labile under mild conditions, the nitrile functionality can also serve as
nucleophile acceptor, effectively constituting a major avenue for cascade annulations.1,2 This thesis works
focused on the development of stereoselective cascade annulation reactions of alkylidene malononitriles to
access polycyclic carbocycles (Chapter 2), carbospirocycles with multiple stereocenters (Chapter 3), and fused
N-heterocycles (Chapter 4).3 Further exploration of cascade annulation led to concise synthesis of clausenamide
analogoues (Chapter 5).3b In this seminar, the journey toward these findings will be discussed.
Scheme 1: Stereoselective vinylogous annulation cascade reactions of alkylidine malononitriles.
References:
1. (a) R. C. Fuson, Chem. Rev. 1935, 16, 1. (b) S. E. Denmark, J. R. Heemstra, Jr., G. L. Beutner, Angew.
Chem. Int. Ed. 2005, 44, 4682. (c) C. Curti, L. Battistini, A. Sartori, F. Zanardi, Chem. Rev. 2020, 120,
2448. (d) H. -L. Cui, Y. -C. Chen, Chem. Commun. 2009, 4479.
2. (a) B. Mao, M. Fañanás-Mastral, B. L. Feringa, Chem. Rev. 2017, 117, 10502. (b) R. Chinchilla, C,
Nájera, Chemical Reviews, 2000, 100, 1891.
3. (a) V. Bhajammanavar, S. Mallik, M. Baidya, Adv. Synth. Catal. 2019, 361, 5472. (b) V.
Bhajammanavar, S. Mallik, M. Baidya, Org. Biomol. Chem., 2019, 17, 1740. (c) I. Ramakrishna, V.
Bhajammanavar, S. Mallik, M. Baidya, Org. Lett. 2017, 19, 516.