Alkylation of secondary alcohols with primary alcohols in the presence of iridium N-heterocyclic carbene complexes via catalytic hydrogen autotransfer
Project no. 20384 · Status: Kapanmış · 2019
Summary
Alcohols are one of the most important intermediates that have been widely used in organic synthesis and chemical industry. Traditional routes to access ß-alkylated alcohols from secondary alcohols usually require a multistep process that involves oxidation of secondary alcohols, alkylation with toxic and expensive alkyl halides, and reduction of ß-alkylated ketones. This procedure generates stoichiometric amounts of salts as waste. Considering the demand of environmentally benign processes, transition-metal catalyzed direct ß-alkylation of secondary alcohols with primary alcohols has been widely studied as a greener route through a hydrogen borrowing or hydrogen autotransfer strategy in recent years. This alternative method involves a dehydrogenation of alcohol to ketone or aldehyde, followed by aldol reaction, generating the corresponding enone intermediate and subsequent hydrogenation of the enone to afford ß-alkylated alcohols with high atom economy by producing water as the only byproduct. But in most cases reaction requires high catalyst loadings (0.5-2.5 mol%) and equivalent or excess amount (100-200 mol%) of strong bases. We found that iridium(I) complexes bearing benzylic N-heterocyclic carbene (NHC) ligands catalyze hydrogen transfer reactions efficiently (Genç et. al., 2018). During our ongoing exploration of iridium(I) catalyzed acceptorless dehydrogenation of alcohols, we reasonably envisioned that the NHC-iridium complexes might be used as the catalyst for ß-alkylation of secondary alcohols with primary alcohols. Our preliminary results showed that by using very low amount of complexes with as catalyst (0.001 mol%) effectively catalyze ß-alkylation of secondary alcohols with primary alcohols through a hydrogen borrowing pathway with the lowest amount of strong base (20 mol% NaOH) in literature (Genç et. al., 2019).