Computational Investigations of Bromine and Iodine Halogen Bonded Complexes and The Proline Catalyzed Direct Aldol Reaction

Halogen bonding is a non-covalent interaction that has significant impact in different sub-disciplines of chemistry. Until recently it has been largely ignored due to the greater prevalence of hydrogen bonding. Non-bonding interactions have long been a problem for density functional theory due to the theory’s local nature. This has lead to the creation of new functionals such as the M06 and M06-2X methods or the addition of an empirical correction to existing methods to accurately describe medium distance interactions. Examination of halogen bonds requires the use of a basis set that is optimized for all halogens such as def2-TZVP, which uses effective-core potentials for iodine for efficiency and is close enough to the basis set limit to ignore BSSE. These new methods and basis sets are judged against the CT7/04 database to determine their accuracy and efficiency. The M06-2X and ωB97XD exchange correlation functionals coupled with the def2-TZVP basis set produce the most accurate method/basis set combinations which are used to benchmark these methods and basis sets against the Hal77/12 database proposed in this work. Geometries of the Hal77/12 database are optimized using M06-2X/def2-TZVP, M06-2X/def2-QZVP, ωB97XD/def2-TZVP, ωB97XD/def2-TZVP, MP2/def2-TZVP, and CCSD(T)/def2-TZVP. The geometries optimized at the CCSD(T)/def2-TZVP level and their respective single point energies are used as the reference values for benchmarking. The best method/basis set combination was ωB97XD/def2-TZVP with a deviation 2.78 kJ/mol from the reference values. The proline catalyzed direct aldol reaction is an important example of a organocatalyst with the ability to form carbon carbon bonds. The computational assessment of the mechanisms energetics has long been difficult due to the size of the system. A new approach using parameterized coupled cluster theory, LPNO-CCSD and LPNO-pCCSD/IIa, is used to evaluate the energetics of the mechanism. The single point energies of the coupled cluster approach are compared to density functional theory results. The mechanism is evaluated in the gas phase, in water, and in DMSO to assess the utility of these newer approaches in solvents. The mechanism for the reaction is different in the gas phase than in water and DMSO. The single point energies evaluated in water and DMSO are nearly identical and suggest that the two solvents could be used interchangeably in a laboratory setting.