Brønsted Acid Catalyzed [3 + 2]-Cycloaddition of Cyclic Enamides with <i>in Situ</i> Generated 2‑Methide‑2<i>H</i>‑indoles: Enantioselective Synthesis of Indolo[1,2‑<i>a</i>]indoles

An efficient formal [3 + 2]-cycloaddition toward the highly diastereo- and enantioselective synthesis of indolo­[1,2-<i>a</i>]­indoles is disclosed. A chiral BINOL-derived phosphoric acid catalyzed the highly enantioselective conjugate addition of cyclic enamides to <i>in situ</i> generated 2-methide-2<i>H</i>-indoles and subsequent aminalization to give rise to acetamide-substituted indolo­[1,2-<i>a</i>]­indoles carrying three contiguous stereogenic centers. Importantly, these products were formed as single diastereomers and with excellent yields and enantioselectivities. Mild reaction conditions at ambient temperatures, the facile removal of the acetamido group, and the possibility of a scale-up highlight the practicality of this methodology

Quinine-Derived Thiourea and Squaramide Catalyzed Conjugate Addition of α‑Nitrophosphonates to Enones: Asymmetric Synthesis of Quaternary α‑Aminophosphonates

Conjugate addition of α-nitrophosphonates to enones was carried out in the presence of two sets of organocatalysts, viz. a quinine-thiourea and a quinine-squaramide. The quinine-thiourea provided the products possessing an α-quaternary chiral center in high enantioselectivities only in the case of electron rich enones. On the other hand, the quinine-squaramide was more efficient in that a wide variety of electron rich and electron poor enones underwent Michael addition of nitrophosphonates to afford the quaternary α-nitrophosphonates in excellent yields and enantioselectivities. The hydrogen bonding donor ability of the bifunctional catalyst, as shown in the proposed transition states, appears primarily responsible for the observed selectivity. However, a favorable π-stacking between the aryl groups of thiourea/squaramide and aryl vinyl ketone also appeared favorable. The reaction was amenable to scale up, and the enantioenriched quaternary α-nitrophosphonates could be easily transformed to synthetically and biologically useful quaternary α-aminophosphonates and other multifunctional molecules

Enantioselective Synthesis of Quaternary α-Aminophosphonates via Conjugate Addition of α-Nitrophosphonates to Enones

Enantioselective Michael addition of <b>α</b>-nitrophosphonates to enones for the synthesis of <b>α</b>-aminophosphonates is reported for the first time. The reaction proceeds in good to high yields and moderate to high selectivity in the presence of a new quinine thiourea catalyst. The quaternary nitrophosphonates were conveniently transformed to cyclic quaternary <b>α</b>-aminophosphonates via in situ reduction–intramolecular cyclization or Baeyer–Villiger oxidation followed by in situ reduction–intramolecular cyclization

Enantioselective Synthesis of Quaternary α-Aminophosphonates via Conjugate Addition of α-Nitrophosphonates to Enones

Enantioselective Michael addition of <b>α</b>-nitrophosphonates to enones for the synthesis of <b>α</b>-aminophosphonates is reported for the first time. The reaction proceeds in good to high yields and moderate to high selectivity in the presence of a new quinine thiourea catalyst. The quaternary nitrophosphonates were conveniently transformed to cyclic quaternary <b>α</b>-aminophosphonates via in situ reduction–intramolecular cyclization or Baeyer–Villiger oxidation followed by in situ reduction–intramolecular cyclization

Quinine-Derived Thiourea and Squaramide Catalyzed Conjugate Addition of α‑Nitrophosphonates to Enones: Asymmetric Synthesis of Quaternary α‑Aminophosphonates

Conjugate addition of α-nitrophosphonates to enones was carried out in the presence of two sets of organocatalysts, viz. a quinine-thiourea and a quinine-squaramide. The quinine-thiourea provided the products possessing an α-quaternary chiral center in high enantioselectivities only in the case of electron rich enones. On the other hand, the quinine-squaramide was more efficient in that a wide variety of electron rich and electron poor enones underwent Michael addition of nitrophosphonates to afford the quaternary α-nitrophosphonates in excellent yields and enantioselectivities. The hydrogen bonding donor ability of the bifunctional catalyst, as shown in the proposed transition states, appears primarily responsible for the observed selectivity. However, a favorable π-stacking between the aryl groups of thiourea/squaramide and aryl vinyl ketone also appeared favorable. The reaction was amenable to scale up, and the enantioenriched quaternary α-nitrophosphonates could be easily transformed to synthetically and biologically useful quaternary α-aminophosphonates and other multifunctional molecules

Enantioselective Synthesis of Quaternary α-Aminophosphonates via Conjugate Addition of α-Nitrophosphonates to Enones

Enantioselective Michael addition of <b>α</b>-nitrophosphonates to enones for the synthesis of <b>α</b>-aminophosphonates is reported for the first time. The reaction proceeds in good to high yields and moderate to high selectivity in the presence of a new quinine thiourea catalyst. The quaternary nitrophosphonates were conveniently transformed to cyclic quaternary <b>α</b>-aminophosphonates via in situ reduction–intramolecular cyclization or Baeyer–Villiger oxidation followed by in situ reduction–intramolecular cyclization

Quinine-Derived Thiourea and Squaramide Catalyzed Conjugate Addition of α‑Nitrophosphonates to Enones: Asymmetric Synthesis of Quaternary α‑Aminophosphonates

Conjugate addition of α-nitrophosphonates to enones was carried out in the presence of two sets of organocatalysts, viz. a quinine-thiourea and a quinine-squaramide. The quinine-thiourea provided the products possessing an α-quaternary chiral center in high enantioselectivities only in the case of electron rich enones. On the other hand, the quinine-squaramide was more efficient in that a wide variety of electron rich and electron poor enones underwent Michael addition of nitrophosphonates to afford the quaternary α-nitrophosphonates in excellent yields and enantioselectivities. The hydrogen bonding donor ability of the bifunctional catalyst, as shown in the proposed transition states, appears primarily responsible for the observed selectivity. However, a favorable π-stacking between the aryl groups of thiourea/squaramide and aryl vinyl ketone also appeared favorable. The reaction was amenable to scale up, and the enantioenriched quaternary α-nitrophosphonates could be easily transformed to synthetically and biologically useful quaternary α-aminophosphonates and other multifunctional molecules

Quinine-Derived Thiourea and Squaramide Catalyzed Conjugate Addition of α‑Nitrophosphonates to Enones: Asymmetric Synthesis of Quaternary α‑Aminophosphonates

Conjugate addition of α-nitrophosphonates to enones was carried out in the presence of two sets of organocatalysts, viz. a quinine-thiourea and a quinine-squaramide. The quinine-thiourea provided the products possessing an α-quaternary chiral center in high enantioselectivities only in the case of electron rich enones. On the other hand, the quinine-squaramide was more efficient in that a wide variety of electron rich and electron poor enones underwent Michael addition of nitrophosphonates to afford the quaternary α-nitrophosphonates in excellent yields and enantioselectivities. The hydrogen bonding donor ability of the bifunctional catalyst, as shown in the proposed transition states, appears primarily responsible for the observed selectivity. However, a favorable π-stacking between the aryl groups of thiourea/squaramide and aryl vinyl ketone also appeared favorable. The reaction was amenable to scale up, and the enantioenriched quaternary α-nitrophosphonates could be easily transformed to synthetically and biologically useful quaternary α-aminophosphonates and other multifunctional molecules