Fast and Chemoselective Addition of Highly Polarized Lithium Phosphides Generated in Deep Eutectic Solvents to Aldehydes and Epoxides

Abstract

Highly polarized lithium phosphides (LiPR 2) were synthesized, for the first time, in deep eutectic solvents as sustainable reaction media, at room temperature and in the absence of protecting atmosphere, through direct deprotonation of both aliphatic and aromatic secondary phosphines (HPR 2) by n-BuLi. The subsequent addition of in-situ generated LiPR 2 to aldehydes or epoxides proceeded quickly and chemoselectively, thereby allowing the straightforward access to the corresponding αor β-hydroxy phosphine oxides, respectively, under air and at room temperature (bench conditions), which are traditionally considered as textbook-prohibited conditions in the field of polar organometallic chemistry of s-block elements.

Fast Addition of s‐Block Organometallic Reagents to CO2‐Derived Cyclic Carbonates at Room Temperature, Under Air, and in 2‐Methyltetrahydrofuran

“…Having identified the best condition for the mono-addition of Grignard reagents (RMgX) as follows: 3 equivalents of nBuMgCl, at room temperature, under air and in 2-MeTHF as solvent; we next extended our studies to the previously assayed carbonates 1 a-f. For cyclic carbonates 1 a and 1 d, and due to their intrinsic symmetry, only one ring opening product can be formed, whereas with the asymmetric cyclic carbonates (1 b,c,e,f), two different openings of the cyclic carbonates can take place, thus giving rise to either primary (7,8,10,11) or secondary β-alcohol (7', 8', 10', 11'; Table 3). In general, these reactions gave moderated to low yields (63-16 %) of the monoaddition products as mixtures with the expected ketone 2 a and the tertiary alcohol 3 a.…”

“…[1] However, the synthetic work of various research groups worldwide has revealed the possibility to promote organic transformations that involve the use of these polar organometallics in unconventional solvents (like water or traditional ionic liquids). [3] Bearing this idea in mind, and trying to build new bridges between green chemistry [4] and s-block polar organometallic reagents, some of us recently reported the possibility to generate new CÀ C bonds [through the fast and chemoselective nucleophilic addition of organolithium (RLi) or organomagnesium (RMgX) reagents to different unsaturated organic electrophiles, such as ketones or esters, [5] imines or nitriles, [6] and alkenes [7] ]; or CÀ P bonds [by selective addition of lithium phosphides (LiPR 2 ) to aldehydes or epoxides], [8] working in all cases at room temperature and in the absence of protecting atmospheres, by using biorenewable deep eutectic solvents (DESs) based on choline chloride, water, or glycerol as sustainable reaction media. [9,10] Simultaneously, a huge amount of effort has been dedicated worldwide to try to convert CO 2 (an inexpensive, nontoxic and sustainable C1 feedstock) into value-added chemical products, and therefore this area is becoming nowadays a rapidly growing research field for the scientific community.…”

“…Thus, all these encouraging features clearly illustrate that cyclic carbonates are attractive alternatives to the direct use of carbon dioxide as a C1 building block. Therefore, taking into account our aforementioned studies on the fast and chemoselective addition of RMgX/RLi reagents to carbonyl compounds at room temperature and in the presence of air, [5][6][7][8] as well as the earlier elegant and illuminating method described by the research groups of Jessop and Snieckus for the conversion of other C1 feedstocks, such as sodium methyl carbonate, into carboxylic acids or ketones through direct addition of RMgX/RLi reagents, with dry organic solvents, under protecting atmosphere, and after 24 h of reaction, [19] we decided to study the use of cyclic carbonates (a CO 2 -derived sustainable feedstock) as biorenewable electrophiles capable of suffering the fast addition of RMgX/RLi reagents, at room temperature, under air and using 2-methyltetrahydrofuran (2-MeTHF) as a sustainable solvent or in the absence of external VOC solvents (we employed a stock solution of commercially available RLi/RMgX reagents containing various VOC solvents; Scheme 1). 2-MeTHF is considered a biorenewable biomass-derived solvent as it can be produced from furfural without the need of petrochemical protocols.…”

Deep eutectic solvents: alternative reaction media for organic oxidation reactions

“…Recently, Capriati and co-workers disclosed a onepot methodology to prepare α-and β-hydroxy-phosphine oxides in a very short reaction time (Scheme 17). 66 Scheme 17. α-and β-hydroxy-phosphine oxides synthesis through a one-pot two step protocol disclosed by Capriati. 66 The protocol consists of three steps.…”

“…66 Scheme 17. α-and β-hydroxy-phosphine oxides synthesis through a one-pot two step protocol disclosed by Capriati. 66 The protocol consists of three steps. Firstly, the reactive lithium phosphide is generated by adding 1 equivalent of n-BuLi to a solution of phosphine in DES (ChCl:Gly, 1:2); the electrophile (epoxy or aldehyde) is then added affording either the α-or β-hydroxy-phosphine analogue, which spontaneously undergoes the oxidation at the phosphorus centre in excellent yield (up to 95%).…”