Direct Asymmetric Michael Addition to Nitroalkenes: Vinylogous Nucleophilicity under Dinuclear Zinc Catalysis

Direct Asymmetric Michael Addition to Nitroalkenes: Vinylogous Nucleophilicity under Dinuclear Zinc Catalysi

Direct Asymmetric Michael Addition to Nitroalkenes: Vinylogous Nucleophilicity under Dinuclear Zinc Catalysis

Direct Asymmetric Michael Addition to Nitroalkenes: Vinylogous Nucleophilicity under Dinuclear Zinc Catalysi

Direct Asymmetric Michael Addition to Nitroalkenes: Vinylogous Nucleophilicity under Dinuclear Zinc Catalysis

Direct Asymmetric Michael Addition to Nitroalkenes: Vinylogous Nucleophilicity under Dinuclear Zinc Catalysi

Synthesis of Benzocyclobutenes by Palladium-Catalyzed C−H Activation of Methyl Groups: Method and Mechanistic Study

An efficient catalytic system has been developed for the synthesis of benzocyclobutenes by C−H activation of methyl groups. The optimal conditions employed a combination of Pd(OAc)2 and PtBu3 as catalyst, K2CO3 as the base, and DMF as solvent. A variety of substituted BCB were obtained under these conditions with yields in the 44−92% range, including molecules that are hardly accessible by other methods. The reaction was found limited to substrates bearing a quaternary benzylic carbon, but benzocyclobutenes bearing a tertiary benzylic carbon could be obtained indirectly from diesters by decarboxylation. Reaction substrates bearing a small substituent para to bromine gave an unexpected regioisomer that likely arose from a 1,4-palladium migration process. The formation of this “abnormal” regioisomer could be suppressed by introducing a larger subsituent para to bromine. DFT(B3PW91) calculations on the reaction of 2-bromo-tert-butylbenzene with Pd(PtBu3) with different bases (acetate, bicarbonate, carbonate) showed the critical influence of the coordination mode of the base to induce both an easy C−H activation and to allow for a pathway for 1,4-palladium migration. Carbonate is shown to be more efficient than the two other bases because it can abstract the proton easily and at the same time maintain κ1-coordination without extensive electronic reorganization

Synthesis of Benzocyclobutenes by Palladium-Catalyzed C−H Activation of Methyl Groups: Method and Mechanistic Study

An efficient catalytic system has been developed for the synthesis of benzocyclobutenes by C−H activation of methyl groups. The optimal conditions employed a combination of Pd(OAc)2 and PtBu3 as catalyst, K2CO3 as the base, and DMF as solvent. A variety of substituted BCB were obtained under these conditions with yields in the 44−92% range, including molecules that are hardly accessible by other methods. The reaction was found limited to substrates bearing a quaternary benzylic carbon, but benzocyclobutenes bearing a tertiary benzylic carbon could be obtained indirectly from diesters by decarboxylation. Reaction substrates bearing a small substituent para to bromine gave an unexpected regioisomer that likely arose from a 1,4-palladium migration process. The formation of this “abnormal” regioisomer could be suppressed by introducing a larger subsituent para to bromine. DFT(B3PW91) calculations on the reaction of 2-bromo-tert-butylbenzene with Pd(PtBu3) with different bases (acetate, bicarbonate, carbonate) showed the critical influence of the coordination mode of the base to induce both an easy C−H activation and to allow for a pathway for 1,4-palladium migration. Carbonate is shown to be more efficient than the two other bases because it can abstract the proton easily and at the same time maintain κ1-coordination without extensive electronic reorganization

Synthesis of Benzocyclobutenes by Palladium-Catalyzed C−H Activation of Methyl Groups: Method and Mechanistic Study

An efficient catalytic system has been developed for the synthesis of benzocyclobutenes by C−H activation of methyl groups. The optimal conditions employed a combination of Pd(OAc)2 and PtBu3 as catalyst, K2CO3 as the base, and DMF as solvent. A variety of substituted BCB were obtained under these conditions with yields in the 44−92% range, including molecules that are hardly accessible by other methods. The reaction was found limited to substrates bearing a quaternary benzylic carbon, but benzocyclobutenes bearing a tertiary benzylic carbon could be obtained indirectly from diesters by decarboxylation. Reaction substrates bearing a small substituent para to bromine gave an unexpected regioisomer that likely arose from a 1,4-palladium migration process. The formation of this “abnormal” regioisomer could be suppressed by introducing a larger subsituent para to bromine. DFT(B3PW91) calculations on the reaction of 2-bromo-tert-butylbenzene with Pd(PtBu3) with different bases (acetate, bicarbonate, carbonate) showed the critical influence of the coordination mode of the base to induce both an easy C−H activation and to allow for a pathway for 1,4-palladium migration. Carbonate is shown to be more efficient than the two other bases because it can abstract the proton easily and at the same time maintain κ1-coordination without extensive electronic reorganization

Synthesis of Benzocyclobutenes by Palladium-Catalyzed C−H Activation of Methyl Groups: Method and Mechanistic Study

An efficient catalytic system has been developed for the synthesis of benzocyclobutenes by C−H activation of methyl groups. The optimal conditions employed a combination of Pd(OAc)2 and PtBu3 as catalyst, K2CO3 as the base, and DMF as solvent. A variety of substituted BCB were obtained under these conditions with yields in the 44−92% range, including molecules that are hardly accessible by other methods. The reaction was found limited to substrates bearing a quaternary benzylic carbon, but benzocyclobutenes bearing a tertiary benzylic carbon could be obtained indirectly from diesters by decarboxylation. Reaction substrates bearing a small substituent para to bromine gave an unexpected regioisomer that likely arose from a 1,4-palladium migration process. The formation of this “abnormal” regioisomer could be suppressed by introducing a larger subsituent para to bromine. DFT(B3PW91) calculations on the reaction of 2-bromo-tert-butylbenzene with Pd(PtBu3) with different bases (acetate, bicarbonate, carbonate) showed the critical influence of the coordination mode of the base to induce both an easy C−H activation and to allow for a pathway for 1,4-palladium migration. Carbonate is shown to be more efficient than the two other bases because it can abstract the proton easily and at the same time maintain κ1-coordination without extensive electronic reorganization

Greener Methodology: An Aldol Condensation of an Unprotected C‑Glycoside with Solid Base Catalysts

The development of a new enamine-solid-base-catalyzed (ESBC) methodology for the aldol condensation reaction is reported. Solid base catalysts [nonactivated and activated magnesium oxide (MgO and MgO_act) and calcium oxide (CaO and CaO_act), a hydrotalcite (HT), and a porous metal oxide (PMO)] were investigated as safer and greener alternatives to previously reported catalytic systems. Multiple reaction parameters (temperature, solvent, time, and catalyst loading) were investigated todetermine optimal conditions for the practitioner to employ in the synthesis of C-glycosides. The optimized reaction conditions provided highly functionalized (<i>E</i>)­α,β-unsaturated ketones from unprotected C-glycosides in good to excellent yields. Moreover, the ESBC methodology is applicable to a wide range of aromatic aldehydes that feature electron-rich and electron-poor moieties, as well as sterically bulky groups. Lastly, the recyclability of the MgO catalyst was demonstrated

Exploration of a Novel, Enamine-Solid-Base Catalyzed Aldol Condensation with C‑Glycosidic Pyranoses and Furanoses

A variety of unprotected C-glycosidic ketones were employed in a novel enamine-solid-base catalyzed (ESBC) aldol condensation to expand the scope and scalability of a previously reported reaction. The starting ketones were obtained from unprotected pyranoses and furanoses following Lubineau’s method via a Knoevenagel condensation. The aldol condensation reaction of the C-glycosidic ketones was performed with a nontoxic and abundant amino acid, L-proline, along with magnesium oxide (MgO) as a recyclable and sustainable catalyst. The enamine-solid-base catalyzed aldol condensations provided the corresponding (E)-α,β-unsaturated ketones in excellent isolated yields (91–100%)