Green chem.: borohydride reaction of carbonyl compounds mediated by triethyl lithium borohydride

In recent years, the hydroboration of unsaturated compounds has attracted many scientists' interest A variety of transition metal complexes, as well as S-region, P-region and F-region element species, have been proved to be efficient catalysts for the hydrogenation of carbonyl compounds, nitriles and imine borohydride Okuda and others have made pioneering work in this field The alkali metal complex [(L) M] [hbph] 3 (L = n (ch2ch2nme 2) 3) developed by them can efficiently catalyze the borohydride reaction of aldehydes and ketones In addition, commercial NaOH powder, sodium hydride, n-butyl lithium and other alkali metal reagents are also reported to be able to mediate the borohydride reaction of unsaturated compounds, but due to the reaction conditions are not mild enough, there are still great limitations in application (source: Green chem.) Professor Krzysztof kuci ńńńńńńńńńńńńńńń Although this method is very green, high temperature is still needed to ensure the conversion of aldehydes in a short time, and this condition is completely ineffective for ketones Even at high temperature, only trace of target borates can be obtained Recently, on the basis of previous work, the team has realized the borohydride reaction of hydroborane and carbonyl compounds under ambient temperature and air atmosphere using cheap and easily available lithium triethylborohydride (lihbet 3) as catalyst (Fig 1) Relevant research results were published in green chem (DOI: 10.1039/c9gc00216b) First of all, the author used the alkali metal triethylborohydride (M = Li, Na, K) as the catalyst, and explored the borohydride reaction conditions of acetophenone 1a and pinacol borane 2 under the solvent-free condition (Table 1) The results show that the most active catalyst is lithium triethylborohydride (Table 1, entry 3) Other triethylborohydride showed low catalytic activity in this process The control experiment confirmed that the reaction can also be carried out in THF The results of NMR analysis showed that diborane was formed in all the reactions (about 5-8%) Although the total removal of oxygen and water reduces the overall by-products, this will require additional inert atmosphere It is also very difficult to separate by-products by distillation Therefore, the author decided to directly hydrolyze the borate into corresponding alcohol in one pot (source: Green chem.) after optimizing the reaction conditions, the author evaluated the substrate range (Table 2) of dihydroboration of carbonyl compounds catalyzed by lihbet 3 After the borohydride step, the author added 1 M NaOH solution to the reaction system to hydrolyze the corresponding alcohol Ketones and aldehydes with electron donor or electron acceptor groups can react smoothly In the case of solid matrix, THF was used as solvent The derivatives containing potential reactive functional groups (1g, 1H, 1y) can also be chemically selectively converted to the desired alcohols (3G, 3h, 3Y) The reaction of acetophenone 1A with pinacol borane 2 can be well carried out on the scale of gram, and 1-phenylethanol (3a, 1.46 g) can be obtained in 97% yield (source: Green chem.) next, the author conducted a scheme 2 experiment 4-acetylbenzaldehyde (1z) is borohydride selectively on aldehydes, while ketone functional groups are retained This shows that the catalytic system allows the chemical selective conversion of aldehydes even in the presence of ketones (source: Green chem.) finally, the author proposed the possible mechanism of the reaction (Fig 2): first, lihbet 3 is used as a catalyst to add carbonyl group to form an intermediate; then, the obtained intermediate reacts with pinacol borane to form corresponding boron ether; finally, the boron ether hydrolyzes under alkaline conditions to obtain alcohol (source: Green chem.) conclusion: Krzysztof kuci ńńńńńńńńńńńńńńńńńńńń The method has mild reaction conditions (air atmosphere), extensive functional group tolerance and high selectivity for aldehydes This study highlights the great potential of lihbet 3 in chemical synthesis.