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

• Published in: Chemistry : a European journal Vol. 26; no. 40; pp. 8742 - 8748
• Main Authors: Dell'Aera, Marzia, Perna, Filippo Maria, Vitale, Paola, Altomare, Angela, Palmieri, Alessandro, Maddock, Lewis C. H., Bole, Leonie J., Kennedy, Alan R., Hevia, Eva, Capriati, Vito
• Format: Journal Article
• Language: English
• Published: Germany Wiley Subscription Services, Inc 17-07-2020
• Subjects: addition; Additives; Aliphatic compounds; arylation; Catalysts; Chelation; Chemistry; Conjugates; Disproportionation; Functional groups; Lithium; nitroolefins; Reaction time; Reagents; Transition metals; zincate; Zincates; Lithium; nitroolefins; addition; arylation; zincate
• ISSN: 0947-6539; 1521-3765
• DOI: 10.1002/chem.202001294

We report the first transition metal catalyst‐ and ligand‐free conjugate addition of lithium tetraorganozincates (R4ZnLi2) to nitroolefins. Displaying enhanced nucleophilicity combined with unique chemoselectivity and functional group tolerance, homoleptic aliphatic and aromatic R4ZnLi2 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 Et4ZnLi2 into equimolar amounts of solvent‐separated Et3ZnLi and EtLi.
The metamorphosis of organozinc reagents! Transforming neutral R2Zn into nucleophilic R4ZnLi2 zincate complexes enabled chemoselective alkylation/arylation of nitroolefins to give 1,4‐addition adducts in up to 98 % yield. Structural and spectroscopic investigations confirmed the dianionic‐type nature of these species and the key role of donor additives in their aggregation and structure.