Sodium Methyl Carbonate as an Effective C1 Synthon. Synthesis of Carboxylic Acids, Benzophenones, and Unsymmetrical Ketones

Abstract

Reported is the synthesis of carboxylic acids, symmetrical ketones, and unsymmetrical ketones with selectivity achieved by exploiting the differential reactivity of sodium methyl carbonate with Grignard and organolithium reagents.

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

“…As expected, when these conditions were employed, the yield of the desired tertiary alcohol 3 b decreased considerably and ketone 2 b appeared as by-product (Table 1, entry 17). A similar scenario was observed when MeLi was used as alkylating reagent (entries [18][19], obtaining better results when 2-MeTHF was employed as solvent. Finally, when 5 equivalents of the aromatic lithium reagent PhLi were employed, either in 2-MeTHF or in the absence of external solvents, none of the expected products were observed but the corresponding homo-coupling product PhÀ Ph.…”

“…Interestingly, it is important to note that under our experimental conditions, we never observed the formation of ketone 2 a as the main product of the reaction, in contrast with the previous studies reported by Jessop and Snieckus, in which sodium methyl carbonate was employed as C1 feedstock. [19] Next, and to expand further the scope of our study, the reactivity of carbonate 1 a with other organolithium reagents (RLi) under the optimized reaction conditions (5 equivalents, ambient temperature, under air) was also investigated by using 2-MeTHF as reaction medium or in the absence of any additional VOC solvent. Astonishing, in the case of EtLi and when 2-MeTHF was used as solvent, a near-quantitative yield of 3 b was observed (90 %), being the unique product of the reaction, as ketone 2 b was not detected (Table 1, entry 16).…”

“…These results indicate that the carbonyl carbon in 1 a-f, coming from the CO 2 , is more accessible than in the high stable free CO 2 molecule and even more than in the acyclic carbonates (like sodium methyl carbonate). [19] To probe the scope of our methodology in terms of the nature of the polar organometallic reagent employed and bearing in mind the previous work reported by Profs. Jessop and Snieckus in the addition of Grignard compounds to methyl carbonate, [19] we then decided to study the reactivity of cyclic carbonates (derived from CO 2 as sustainable C1 synthon) with RMgX reagents.…”

“…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.…”

Reactive capture using metal looping: the effect of oxygen

“…The production of benzophenone from carboxylic acid salts using Grignard reagents has been observed recently where the Grignard intermediate product benzoate salt was then reacted with organolithium reagents to form a variety of benzophenones. 21 While the previous report required the organolithium reagent to produce the benzophenone product, this process may occur with Grignards alone at the low yields observed in this study. Correspondingly this would involve the reaction of the magnesium benzoate salt with a second molecule of phenylmagnesium bromide followed by elimination of magnesium oxide.…”