Spring-loaded Compounds in Organic Synthesis

INTRODUCTION Ring strain is a property possessed by small molecules and is recognized by chemists as an exceptionally efficient and practical tool for attaining challenging transformations. Organic chemistry has witnessed tremendous progress towards this end with the development of a plethora of methods that can harvest the high energy of a strained system and direct it into productive pathways. Thus, the transition-metal catalyzed activation of a C–C sigma bond, a long-standing challenge, has been achieved utilizing the strain of four-membered rings. The energy stored in norbornadiene has been exploited in its use as an acceptor for group transfer, a relay tool for selective C–H activation, and a ligand scaffold for efficient catalysis. The use of overbred intermediates (intermediates en route to cyclic structures that have one or more excess C-C bonds) for realizing difficult disconnections has been proven to be a fruitful strategy in total synthesis. Extreme cases of strained molecules include propellanes, quadricyclanes, and bicyclobutane. These molecules were synthesized in the mid-20th century and were the subjects of intensive studies due to their peculiar chemical and physical properties. Recently, renewed interest from the organic community has begun to unveil new reactivity and utility of these unique motifs. OUTLINE In the mid-70s Gassman and co-workers demonstrated that bicyclobutanes can be fragmented to produce a variety of different products.1 The outcome is highly sensitive towards the substitution pattern of the substrate, choice of catalyst, concentration, and temperature. Due to the unpredictable nature of the process, this pioneering work has more theoretical significance than practical. Not until 2008 was this intriguing reactivity revisited by Wipf and co-workers, who reported a rhodium-catalyzed cycloisomerization of the bicyclobutanes 1.2 This process selectively leads to 7,3or 5,3-fused bicycles (2,3), depending on the ligand of choice (Scheme 1). Thus, fine tuning of the catalytic system results in controllable conversion of strain energy into polycyclic frameworks. R N Ts N