Expeditious and practical synthesis of tertiary alcohols from esters enabled by highly polarized organometallic compounds under aerobic conditions in Deep Eutectic Solvents or bulk water

Advancing Air‐ and Moisture‐Compatible s‐Block Organometallic Chemistry Using Sustainable Solvents

“…More recently in collaboration with Capriati's group, we have also reported an efficient protocol for the synthesis of symmetric tertiary alcohols in excellent yields (up to 98 %) but using esters as organic electrophiles (Scheme 6). [11] In this case, the fast (20 sec) and chemoselective double addition of RLi/ RMgX reagents (intermediate ketones were not isolated) can be performed in the sustainable choline chloride/urea eutectic mixture (1ChCl/2Urea) or in bulk water. This double addition protocol tolerates a wide variety of esters and alkylating/ arylating reagents (RLi/RMgX) takes place straightforwardly at room temperature in the presence of air.…”

“…Some of these strategies involve the use of electron-withdrawing groups on the substituents on the nitrogen atom; or the activation of the imine group through the addition of Lewis acids to the reaction media. Thus, and bearing in mind the foreseen activation effect of ChCl-based eutectic mixtures in the addition of organolithium reagents to ketones and esters (Scheme 4, Scheme 5, Scheme 6), [9,11] some of us decided to test non-activated imines as new electrophilic partners (Scheme 7a). [10a] We found that the addition reaction of either aliphatic or aromatic RLi reagents into the selected nonactivated imines took place faster (only 3 sec) than their corresponding hydrolysis process with the protic eutectic reaction medium, giving rise to the desired secondary amines: i) with high selectivity (only the starting imines and/or the final secondary amines were observed in the NMR spectra of the reaction crudes); ii) at room temperature and under air; and iii) in good to almost quantitative yields (73-95 %).…”

“…While the use of organolithium and Grignard reagents in bulk water and other unconventional solvents (DESs, glycerol, etc) is a recent innovation, [9][10][11][12][13][14][15][16][17][18][19][20] some previous precedents in the literature have hinted at the influence of water on the reactivity of these commodity organometallic reagents. Thus, in 1975 Taylor reported the reaction of n-BuLi with bromoarenes using Na-dried solvent wetted with T 2 O at À 70°C as an efficient method to access tritiated arenes.…”

“…Specifically, the Minireview is divided in different sections, which showcase different type of reactivities. This includes: i) chemoselective nucleophilic addition of RLi/ RMgX to carbonyl compounds (like ketones, [9] imines, [10] esters, [11] amides [12] ) or nitriles; [13] ii) regioselective ortho-or lateral lithiation of aromatic amides [12a] and aryltetrahydrofurans, [14] respectively; iii) formation of new Cheteroatom bonds (CÀ X) by using lithium amides (LiNR 2 ) [15] or phosphides (LiPPh 2 ); [16] iv) the anionic polymerisation of styrenes; [17] and v) cross-coupling reactions of RLi with aryl halides. [18] In addition, a section is included summarising current efforts to design one-pot tandem protocols in which aerobic polar s-block organometallic chemistry in green solvents can be synergically amalgamated with either metal- [12a,19] or organocatalysed [20] synthetic processes.…”

Scalable Negishi Coupling between Organozinc Compounds and (Hetero)Aryl Bromides under Aerobic Conditions when using Bulk Water or Deep Eutectic Solvents with no Additional Ligands

“…The yield of the nitro derivative 48 could also be improved in DES from 65 to 78 %. As testified by the recent literature, although sharing some physicochemical properties (e.g., a strong H‐bonded network), water and DES have been proven to be not on the same ground as far as the reactivity of the organometallic compounds is concerned [5b,f, 12g, 20] . Thus, they can advantageously and complementarily be used in organometallic chemistry.…”