理論計算の有機合成への活用

抄録

Utilization of ab initio and DFT calculations for the development of organic synthesis is described here. The first topic is the base-mediated intramolecular amination of bromoallens having an axial chirality. The treatment of both (4S,aR)- and (4S,aS)-bromoallenes with NaH in DMF affords cis-ethynylaziridines in 92:8-99:1 and 79:21-91:9 selectivity, respectively. These experimental results were rationalized by DFT calculations with Onsager solvation model. The calculations also predicted that a less polar solvent gives higher cis selectivity for the (4S,aS) isomers. In fact, improvement of the cis selectivity to >99:1 has been realized by using a less polar THF solvent. The second topic is the intramolecular in-plane S_N2 reaction of haloalkenes with inversion of configuration at the sp² carbon, which was predicted to be a facile process for the first time by DFT calculations (ΔG=14.4 kcal/mol). This prediction was confirmed experimentally and the intramolecular in-plane S_N2 reaction was utilized for the preparations of various four- and five-membered cyclic compounds. The third topic is the origin of π-facial stereoselectivity in the alkylation of enolates derived from 4-substituted γ-butyrolactones. The main source of the anti-selectivity is eclipsing strain in the syn-transition structures. The fourth topic is the mechanistic study on the gold catalyzed C-S bond formation of α-thioallenes to form 2,5-dihydrothiophenes. The proton transfer is the rate-limiting step with very high activation energy in a gas phase. In the presence of one water molecule, activation energy was lowered by as much as 19.9 kcal/mol. This prediction was also confirmed experimentally.