Highly chemoselective conjugate addition of lithium tetraorganozincates to coumarin derivatives and functionalization with electrophiles

The nucleophilic addition (alkylation/arylation) of lithium tetraorganozincate species (R4ZnLi2) to coumarin derivatives takes place cleanly, with a short reaction time (30 min) and with high chemoselectivity, when working under mild conditions (0 °C) and with no additional solvents. Particularly remarkable is the diastereoselectivity of the reaction (up to 96:4), after trapping the resulting intermediates with external electrophiles. The stereochemistry of the major trisubstituted stereoisomer was assigned by combining 2D NOESY experiments with DFT calculations

12th International School of Organometallic Chemistry, Camerino, Italy (ISOC 2019)

The conjugate addition of organometallics to nitroalkenes provides a useful method for nitro-alkylation. This type of addition is much pursued in organic synthesis as the nitro group can be easily transformed into various functional groups including carbonyl derivatives by the Nef reaction, amines by reduction, nitriles and imines by other transformations. While the 1,4-conjugated addition of organozinc reagents (R2Zn and RZnX) has been extensively studied, applications of alkali-metal zincates in fundamental organic transformations are still in their infancy. These type of reagents show unique, synergistic chemical characteristics which cannot be replicated by their monometallic (organolithium/organozinc) counterparts. Furthermore, the replacement of the vinylic nitro group by an alkyl group remains a complication encountered when nitrostyrenes are reacted with dialkylzinc compounds in the absence of a Lewis acid. In this Communication, we compare the kinetic reactivity of two different alkali-metal zincates, namely triorgano- and tetraorganozincates, in Deep Eutectic Solvents and under neat conditions, towards variously substituted nitroalkenes. Under optimised reaction conditions (0 °C and with no additional solvents), Michael additions promoted by aliphatic and aromatic lithium organozincates take place with high regio- and chemoselectivity, thereby providing the expected nitroalkanes in yields up to >98% without replacement of the vinylic nitro group by the alkyl group (Scheme 1). Isolation of key intermediates and structural aspects will be discussed as well

Boosting Conjugate Addition to Nitroolefins Using Lithium Tetraorganozincates: Synthetic Strategies and Structural Insights

We report the first transition metal catalyst- and ligand-free conjugate addition of lithium tetraorganozincates (R 4ZnLi 2) to nitroolefins. Displaying enhanced nucleophilicity combined with unique chemoselectivity and functional group tolerance, homoleptic aliphatic and aromatic R 4ZnLi 2 provide access to valuable nitroalkanes in up to 98 % yield under mild conditions (0 °C) and short reaction time (30 min). This is particularly remarkable when employing β-nitroacrylates and β-nitroenones, where despite the presence of other electrophilic groups, selective 1,4 addition to the C=C is preferred. Structural and spectroscopic studies confirmed the formation of tetraorganozincate species in solution, the nature of which has been a long debated issue, and allowed to unveil the key role played by donor additives on the aggregation and structure of these reagents. Thus, while chelating N,N,N',N'-tetramethylethylenediamine (TMEDA) and (R,R)-N,N,N',N'-tetramethyl-1,2-diaminocyclohexane (TMCDA) favour the formation of contacted-ion pair zincates, macrocyclic Lewis donor 12-crown-4 triggers an immediate disproportionation process of Et 4ZnLi 2 into equimolar amounts of solvent-separated Et 3ZnLi and EtLi

1,3‐Dipolar Cycloaddition of Alkanone Enolates with Azides in Deep Eutectic Solvents for the Metal‐Free Regioselective Synthesis of Densely Functionalized 1,2,3‐Triazoles

The 1,3-dipolar cycloaddition reaction between alkanone enolates and azides proceeds smoothly and regioselectively in eco-friendly eutectic mixtures to yield densely functionalized 1,2,3-triazoles. Pharmacologically active triazoles have also been targeted directly in DESs via telescoped, one-pot cycloaddition/reduction processes

Function of the photosynthetic reaction center from Rhodobacter sphaeroides in deep eutectic solvents

Deep eutectic solvents (DESs) are emerging as a new class of green solvents, with the potentiality of replacing organic solvents in many applications both at industrial and laboratory scale. The intriguing possibility of carrying out bio-catalytic reactions has been recently explored using hydrolases with promising results [1]. In this work we aim to offer a complete characterization of the behavior of the bacterial photosynthetic reaction center (RC) from Rhodobacter sphaeroides in a series of choline chloride-based DESs. The stable charge-separated state of RC, attained under illumination, represents the first step of light energy conversion into chemical energy in phototrophic organisms and a number of reports have recently enlightened the possibility of effectively exploiting RC photo-activity in bio-devices. The employment of non-aqueous solvents would then open the way to a wider range of technological applications. Moreover, the fully characterized RC is the ideal model for carrying out basic studies of protein-solvent interactions, due to its information-rich optical spectrum and its light-triggered enzymatic activity. Herein we report that RC (a) is stable in all the DESs tested, (b) is able to generate the charge-separated state under illumination, and (c) even to perform its natural photocycle. We have indeed demonstrated in DES environment that RC can effectively promote under light the reduction of quinone molecules by withdrawing electrons from cytochrome c. Finally, as an example of biotechnological application, a photo-electrochemical cell based on DES-dissolved RC has been designed and successfully employed to generate photocurrents arising from the reduction of the electron-donor ferrocene-methanol