Towards a Paradigm Shift in Polar Organometallic Chemistry

Abstract

Core tools of synthetic chemistry, polar organometallic reagents (typified by organolithium and Grignard reagents) are used worldwide for constructing compounds, especially aromatic compounds, which are ubiquitous in organic chemistry and thus in numerous commodities essential to everyday life. By isolation and characterisation of key organometallic intermediates, research in our group has led to the design of polar mixed-metal reagents imbued with synergistic effects that display chemical properties and reactivity profiles far exceeding the limits of traditional single-metal reagents. These studies have improved existing, or established new fundamentally important, synthetic methodologies based on either stoichiometric or catalytic reactions. Bimetallic cooperative effects have been demonstrated in an impressive array of important bond forming reactions including deprotonative metallation, transition metal-free C–C bond formation and metal–halogen exchange to name just a few. Towards greener, more sustainable, safer chemical transformations, our group has also pioneered the use of polar organometallic reagents under air and/or with water present using biorenewable solvents such as Deep Eutectic Solvents (DES) and 2-methyl THF. Herein we summarize some of our recent efforts in this intriguing area, which we believe can make inroads towards a step change in the practice and future scope of polar organometallic chemistry.

Sustainable and practical formation of carbon–carbon and carbon–heteroatom bonds employing organo-alkali metal reagents

“…As shown in Scheme 28 , the mixed-metal organometallic reagents were used in the C–H alkylation or arylation of heteroaromatics such as acridines or pyrazines by coordination of alkali metals adjacent to the anion activation site. 62 In 2020, efficient conjugated addition to nitroolefins employing lithium tetraorganozincates was reported under transition metal-free and ligand-free conditions ( Scheme 29 ). 63 This reaction allows highly chemo-selective access to nitromethane derivatives up to 98% isolated yields.…”

Recent Advancements in the Utilization of s-Block Organometallic Reagents in Organic Synthesis with Sustainable Solvents

“…Contrary to conventional wisdom, recent innovations in s-block polar organometallic chemistry [20][21][22][23][24][25][26][27] have challenged established norms. It has been demonstrated that polar organolithium (RLi) and Grignard (RMgX) reagents can be effectively used (i) in the presence of air; (ii) at room temperature, and (iii) in sustainable, protic, non-toxic and non-dried solvents, such as water or Deep Eutectic Solvents (DESs), which are eutectic mixtures of Lewis or Brønsted acids and bases strongly associated with each other, exhibiting a significant depression of freezing points far below that of ideal mixtures (each component has a higher melting point than the mixture) [28].…”

“…At this point, it is crucial to highlight that, beyond the sustainable perspective, the utilization of bench-type reaction conditions (presence of air/moisture at room temperature) in synergistic conjunction with the aforementioned unconventional, protic and polar reaction media (water and DES) or sustainable ethereal solvents (2-MeTHF/CPME) in polar organometallic chemistry has yielded significant advantages. This approach has, indeed, enabled (i) notable improvements in reaction times (on the scale of s/min); (ii) enhanced yields/selectivities in well-established chemical transformations and (iii) the discovery of novel reactions/mechanistic pathways that cannot be replicated in traditional, dry and toxic volatile organic compounds (VOCs) as solvents [20][21][22][23][24][25][26][27].…”

Reductive anti-dimagnesiation and dialumination of alkynes: Synthesis and reactions of trans-1,2-dimetalloalkenes

“…The preparation of such polar organometallics often depends on deprotonation at acidic C−H bonds or on metalation of organic halides via a reductive process or halogen−metal exchange (Figure 1a). [4][5][6] Although these methods are reliable, special classes of precursors, acidic hydrocarbons and halogenated compounds, are necessary. Unsaturated hydrocarbons such as alkenes and alkynes represent another important class of precursors (Figure 1b).…”