Computational study of reaction mechanisms that enable carbon-carbon bond formation

Transition metal-catalyzed higher order [m+n+o] carbocyclization reactions are important C-C bond formation reactions that constitute an essential and efficient part in the design of natural products with multiple stereogenic centers. A critical feature in the development of these reactions is the ability to control the C-C bond formation in a chemo-, regio-, and stereoselective manner. Computational studies have been significantly useful in this area in the context of deriving insights and predicting the outcome of a specific transformation without having to revert to extensive experimentation. Mechanisms of a number of cycloaddition reactions have been investigated using Density Functional Theory, a standard quantum chemical method. Platinum and rhodium complexes with the chiral Me-DuPHOS backbone show enantioselective [4+1] cycloaddition of vinylallenes with CO to afford cyclopentenones. Interestingly, Pt and Rh give rise to different enantiomers of the cycloaddition product. Detailed study of the mechanisms probes the origin of this difference. In a different study, a broad-based investigation of iron-mediated [2+2+1] carbocyclization reactions of 1,1-disubstituted-allenylsilanes with alkynes and CO has been described. Computational investigation shows the origin of the regio-, and stereoselectivity of the reaction and identifies the reason for not having a catalytic turnover. These results will enable the rational design of an efficient iron-catalyst in future. In a third study, the theoretically inspired development of a Rh-catalyzed [3+2+1] carbocyclization of alkenylidenecyclopropanes with CO for the stereoselective construction of cis-fused bicyclohexenones is described. The experimental studies demonstrate the validity of the computational prediction. Theoretical study has proven to be useful in the investigation of the mechanism of cyclization of substituted porphyrins to synthesize light-harvesting macrocycles. The rate of cyclization has been found to be correlated to the nature of the substituent and subsequent structural deviation of the porphyrin core.