Catalytic Enantioselective Synthesis of Indanes via Cation-Directed 5-Endo-Trig Cyclization

2015-01-13T17:41:50Z (GMT) by Robert Paton
<p>Supporting DFT Structures (PDB formatted) for “Catalytic Enantioselective Synthesis of Indanes via Cation-Directed 5-Endo-Trig Cyclization” Nature Chemistry (2015) doi:10.1038/nchem.2150</p> <p>Craig P. Johnston, Abhishek Kothari, Tetiana Sergeieva, Sergiy I. Okovytyy, Kelvin E. Jackson, Robert S. Paton & Martin D. Smith</p> <p><br></p> <p>Abstract: 5-<em>Endo</em>-<em>trig</em> cyclizations are generally considered to be kinetically unfavourable, as described by Baldwin's rules. Consequently, observation of this mode of reaction under kinetic control is rare. This is usually ascribed to challenges in achieving appropriate approach trajectories for orbital overlap in the transition state. Here, we describe a highly enantio- and diastereoselective route to complex indanes bearing all-carbon quaternary stereogenic centres via a 5-<em>endo</em>-<em>trig</em> cyclization catalysed by a chiral ammonium salt. Through computation, the preference for the formally disfavoured 5-<em>endo</em>-<em>trig</em>Michael reaction over the formally favoured 5-<em>exo</em>-<em>trig</em> Dieckmann reaction is shown to result from thermodynamic contributions to the innate selectivity of the nucleophilic group, which outweigh the importance of the approach trajectory as embodied by Baldwin's rules. Our experimental and theoretical findings demonstrate that geometric and stereoelectronic constraints may not be decisive in the observed outcome of irreversible ring-closing reactions. </p> <p> </p> <p></p>