A Combination of Computational and Experimental Studies to Correlate Electronic Structure and Reactivity of Donor-Acceptor Singlet Carbenes

Most of the reactivities of donor-acceptor (D-A) singlet carbenes are similar to metal carbenoids. However, the lone pair at the carbenoid carbon, coordinated with metal, is free in D-A carbene thereby making it nucleophilic as well. Herein, DFT-optimized structural features of D-A carbene has been investigated and is compared with rhodium carbenoid. It was observed that, when a D-A carbene reacts with cyclic-1,3-diones in different ethereal solvents, it is the lone pair at the sp(2) orbital of the carbene that abstracts the proton from the enol form (of the cyclic-1,3-diones) to form a benzylic carbocation and an enolate. Subsequently, the carbocation undergoes nucleophilic attack by O of the ether solvents and then by the enolate to afford the desired ether-linked products. Accordingly, herein the reaction in THF, which otherwise had failed to work as a substrate in reported amino etherification reactions, worked well. DFT-calculated orbital energy levels and reaction profile support this reverse reactivity of singlet carbenes. Furthermore, HOMO-LUMO calculations indicated that electron-rich arenes in D-A carbene stabilizes the LUMO and destabilizes the HOMO which increases yield. Additionally, a library of 37 enol ether and 39 ether-linked compounds of potential medicinal relevance have been synthesized with good to excellent yields using numerous cyclic-1,3-di-ones.