Rh(II)-Catalyzed C–N Bond Formation Using Enynones and N–H Imines: An Approach to Diarylmethylamines

A Rh(II)-catalyzed furyl carbene N–H insertion reaction involving an N-sp2-hybridized imine is described, which represents an atom-economical route by which to access diarylmethylamine derivatives with high efficiency and broad substrate scope. An unusual reaction mechanism is proposed, in which the rhodium catalyst plays a dual role in facilitating enynone cyclization via activation and enhancement of the nucleophilicity of the NH imine

Rh(II)-Catalyzed C–N Bond Formation Using Enynones and N–H Imines: An Approach to Diarylmethylamines

A Rh(II)-catalyzed furyl carbene N–H insertion reaction involving an N-sp2-hybridized imine is described, which represents an atom-economical route by which to access diarylmethylamine derivatives with high efficiency and broad substrate scope. An unusual reaction mechanism is proposed, in which the rhodium catalyst plays a dual role in facilitating enynone cyclization via activation and enhancement of the nucleophilicity of the NH imine

Tandem Blaise/Palladium-Catalyzed Ullmann Coupling for the One-Pot Synthesis of Enamino Ester-Functionalized Biaryls from Nitriles

A novel Pd-catalyzed Ullmann-type homocoupling reaction of the Blaise reaction intermediate generated by the reaction of 2-bromo arylnitriles and a Reformatsky reagent has been developed for one-pot synthesis of enamino ester-functionalized biaryls <b>2</b> in good yields. The 2,2′-substituted enamine moieties of the coupling products could be cyclized under acidic conditions through the conjugate addition/deamination cascade to afford the seven-membered <i>N</i>-heterocyclics <b>3</b> with biaryl backbone in excellent yields

Rhodium-Catalyzed Intermolecular Carbonylative [2 + 2 + 1] Cycloaddition of Alkynes Using Alcohol as the Carbon Monoxide Source for the Formation of Cyclopentenones

A highly regioselective rhodium-catalyzed intermolecular carbonylative [2 + 2 + 1] cycloaddition of alkynes using alcohol as a CO surrogate to access 4-methylene-2-cyclopenten-1-ones has been developed. In this transformation, the alcohol performs multiple roles, including generating the Rh–H intermediate, functioning as the CO source, and assisting in the isomerization of the alkyne. Alkynes can act as both the olefin and the alkyne partner in the cyclopentenone core

Chemoselective Intramolecular Alkylation of the Blaise Reaction Intermediates: Tandem One-Pot Synthesis of <i>exo</i>-Cyclic Enaminoesters and Their Applications toward the Synthesis of <i>N</i>-Heterocyclic Compounds

The intramolecular alkylative reactivity and N/C selectivity of the various Blaise reaction intermediates, which are formed from the reaction of the Reformatsky reagents with ω-chloroalkyl nitriles, did not reach the synthetic potential as an entry to <i>exo</i>-cyclic enaminoesters. To circumvent this issue, various additives were investigated, among which the addition of NaHMDS dramatically enhanced the reactivity and N/C selectivity. This modification provided a highly efficient route for the synthesis of various <i>N</i>-fused heterocyclic compounds, as it requires only two steps from nitriles

Tandem Blaise/Palladium-Catalyzed Ullmann Coupling for the One-Pot Synthesis of Enamino Ester-Functionalized Biaryls from Nitriles

A novel Pd-catalyzed Ullmann-type homocoupling reaction of the Blaise reaction intermediate generated by the reaction of 2-bromo arylnitriles and a Reformatsky reagent has been developed for one-pot synthesis of enamino ester-functionalized biaryls <b>2</b> in good yields. The 2,2′-substituted enamine moieties of the coupling products could be cyclized under acidic conditions through the conjugate addition/deamination cascade to afford the seven-membered <i>N</i>-heterocyclics <b>3</b> with biaryl backbone in excellent yields

DMF as a Source of Oxygen and Aminomethine: Stereoselective 1,2-Insertion of Rhodium(II) Azavinyl Carbenes into the CO Bond of Formamides for the Synthesis of <i>cis</i>-Diamino Enones

A new catalytic reaction in which all the atoms of a formamide are incorporated into the product through a formal stereoselective 1,2-insertion of rhodium­(II) azavinyl carbenes, generated in situ from readily available <i>N</i>-sulfonylated 1,2,3-triazoles, into the CO bond of DMF and other <i>N</i>,<i>N</i>-disubstituted formamides to afford <i>cis</i>-diamino enones is described

An Expedient and Divergent Tandem One-Pot Synthesis of Pyrimidin-2,4-diones Using the Blaise Reaction Intermediate

A novel divergent tandem one-pot method for the synthesis of 3,5,6-trisubstituted 1<i>H</i>-pyrimidin-2,4-dione derivatives is developed. In the presence of 10 mol % of Cu(OAc)₂, the α-substituted Blaise reaction intermediates (R² ≠ H) reacted with isocyanates chemoselectively to afford pyrimidin-2,4-diones, whereas the α-unsubstituted Blaise reaction intermediate (R² = H) showed a propensity to be a C-nucleophile toward electrophiles, permitting the installation of different functionalities at the 5-position through sequential tandem reactions

An Expedient and Divergent Tandem One-Pot Synthesis of Pyrimidin-2,4-diones Using the Blaise Reaction Intermediate

A novel divergent tandem one-pot method for the synthesis of 3,5,6-trisubstituted 1<i>H</i>-pyrimidin-2,4-dione derivatives is developed. In the presence of 10 mol % of Cu(OAc)₂, the α-substituted Blaise reaction intermediates (R² ≠ H) reacted with isocyanates chemoselectively to afford pyrimidin-2,4-diones, whereas the α-unsubstituted Blaise reaction intermediate (R² = H) showed a propensity to be a C-nucleophile toward electrophiles, permitting the installation of different functionalities at the 5-position through sequential tandem reactions

Tandem One-Pot Synthesis of Polysubstituted NH-Pyrroles Involving the Palladium-Catalyzed Intramolecular Oxidative Amination of the Zinc Bromide Complex of β‑Enamino Esters

The Pd-catalyzed oxidative olefin amination of the zinc bromide complex intermediate, formed by the sequential reaction of nitriles with a Reformatsky reagent and 1-alkynes, affords pyrrole derivatives in good to excellent yields. This tandem protocol provides a simple, efficient, and atom- and pot-economical way to quickly build polysubstituted NH-pyrroles starting from readily available reagents in a regiocontrolled manner with a broad substrate scope and high functional group tolerance. In contrast, the Pd-catalyzed oxidative olefin amination of an isolated α-vinyl-β-enamino ester did not proceed effectively, but the reaction efficiency can be restored by addition of <i>n</i>-BuZnBr or Zn­(OAc)₂, indicating the crucial role of the zinc complex in this transformation. The synthetic utility of this protocol is exemplified by the rapid synthesis of pyrrolophenanthrenes and pyranopyrrolones through selective Pd- and Cu-catalyzed C–C and C–O bond-forming reactions