Applications of Computational and NMR Methodologies to the Study of Homoallylic Alcohols Diastereomers

E. LORENZO MARTÍNEZ; V. DORN; G. RADIVOY

Proceedings

MDPI

Año: 2019 vol. 9 p. 12 - 18

2504-3900

Through reducing the system InCl3-Li-DTBB(cat.) in THF at room temperature and in the absence of any additives or anti-caking ligand, we have synthesized indium nanoparticles (InNPs) of about 4 nm. The catalyst was employed in the allylation of carbonyl compounds, giving excellent yields of the corresponding homoallylic alcohols. We have established that the reaction productscome from a γ-coupling via a six members cyclic transition state, type Zimmerman?Traxler. Relative to the selectivity, the allylation with crotyl bromide of ortho substituted benzaldehydes (e.g., o-NO2,o-OMe, o-Cl, o-CF3) showed syn selectivity. With the aim to improve the mentioned selectivity, we synthetized o-iPrO-benzaldehyde, and evaluated the reaction with crotyl bromide and InNPs. The homoallylic alcohol 1-(2-isopropoxyphenyl)-2-methylbut-3-en-1-ol was obtained almostquantitatively after 1h as a mixture of the syn- and anti- isomers. The relationship observed by 1HRMN was 75:25, but we did not know if the syn-isomer was the dominant because the product has not been reported in the scientific literature. Based on this, and in order to determinate which 1HNMR signals correspond to each isomer, we started computational theoretical and NMR studies.The initial conformational analysis was performed using the semiempirical PM3 method, then we work with the B3LYP functional, applying the 6-31+G* basis set and the solvent effect (chloroform) was evaluated with the PCM model as implemented in Gaussian09. So, we found thirteen lowenergy conformations for the syn-diastereomer and six low-energy conformations for the antidiastereomer. On the other hand, we have carried out NMR experiments such as 1H, 13C, HSQC, toassign the signals of each diastereomer; and experiments such as NOESY, selective NOE, JRes, homo- and hetero-nuclear J-coupled and J-decoupling, to be able to measure coupling constants and establish the structure of each diastereomer.