Abstract
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 products come 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 almost quantitatively after 1h as a mixture of the syn- and anti- isomers. The relationship observed by 1H-RMN 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 1H-NMR 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 low-energy conformations for the syn-diastereomer and six low-energy conformations for the anti-diastereomer. On the other hand, we have carried out NMR experiments such as 1H, 13C, HSQC, to assign 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.
Highlights
In the last few years we have been working on the indium-mediated allylation of carbonyl compounds with allyl bromides as an interesting and convenient method to obtain homoallylic alcohols, significant building blocks in organic synthesis
In order to assess the syn-anti selectivity of the indium nanoparticles (InNPs)-mediated allylation of carbonyl compounds, we investigated the reaction of a series of ortho-substituted benzaldehydes bearing either electron-donating or electronwithdrawing groups with crotyl bromide
To simplify the reactive system and considering results reported by other authors, we evaluated the potential energy surfaces (PES) for the mentioned process by considering the formation of an initial complex between the carbonyl compound and the allyl-indium intermediate, a six-member cyclic chair-like transition state (TS) and a final complex, as can be seen in Scheme 1 for a representative compound
Summary
In the last few years we have been working on the indium-mediated allylation of carbonyl compounds with allyl bromides as an interesting and convenient method to obtain homoallylic alcohols, significant building blocks in organic synthesis. The diastereoselectivity in the addition of an allyl-metal to a carbonyl compound is a fundamental parameter to consider, and could be explained by steric and stereoelectronic or chelating effects [1] In this sense, previously we report [2] a series of reactions of carbonyl compounds and allylic. Substituted allyl bromides allowed us to establish that the reaction products come from a γ-coupling, via a sixmembered cyclic transition state, type Zimmerman–Traxler On another hand, in order to assess the syn-anti selectivity of the InNPs-mediated allylation of carbonyl compounds, we investigated the reaction of a series of ortho-substituted benzaldehydes bearing either electron-donating or electronwithdrawing groups with crotyl bromide. Considering that the homoallylic alcohol 1-(2-isopropoxyphenyl)-2methylbut-3-en-1-ol was not reported in the scientific literature, we apply different DFT and NMR methodologies that could allow us to assign each diastereomer, the discussion about these topics is included below
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