Computational study of the stereoselectivity in the alkylation of cyclic silyl enol ethers by diarylmethylium salts.

This thesis is the computational integration to Barbero's work on the alkylation of silyl enol ethers with benzhydrylium ions and has a twofold goal: to obtain in silico the diastereomeric ratios found experimentally and to explain the reasons of the observed selectivity, seeking the possibility of predicting the diastereomeric ratios for compounds other than the ones considered here. We focus our attention on the alkylation (which is an addition reaction) of silyl enol ether 1-trimethylsiloxycyclohexene with (5-methylfuran-2-yl)(2-methylindol-3-yl)methylium ion: the product of the reaction, obtained as solid and fully characterized by X-Ray diffraction, is the subject of this work. It is obtained as a mixture of the SR/RS and RR/SS diastereoisomers in 87:13 and 57:43 ratios considering respectively o-benzenedisulfonimide and tetrafluoroborate as counterions. We make use of density functional theory (DFT) with functional M06-2X and basis set cc-pVDZ; PCM is also used with dichloromethane as solvent. We focus our attention on 24 transition structures (TSs) for the addition step of the reaction: this number arises taking into account two cyclohexene conformations, three geometries of attack and two positions of the trimethylsilyl group for each of the diastereoisomers. In the subsequent analysis, we take into account the previous stereochemical issues and two additional (forming C-C bond distances, electronic energies of TSs and adducts) and we try to seek a correlation between these data and the calculated electronic energies in order to individuate the factors that could be useful in order to understand the selectivity and to extend the model to other reactions. Unluckily, we have to conclude that we cannot establish such correlation: in order to give reliable results, one should know the complete picture of the stereochemistry of the reaction. Moreover, we take into account tetrafluoroborate as counterion and we concluded that, although it is surely involved in the stabilization, it is not responsible for the diastereoselectivity of the reaction, which is justified only on the basis of geometry of attacks and stereochemical issues analyzed before. Despite this, the diastereomeric ratios are well represented: the result is of 76 SR:24 RR, which is in great accord with both the experimental results reported above.