Regio- and Diastereoselective Synthesis of Dihydropyridopyrimidines via Cascade Reactions of 2‑Aminopyridines with Morita–Baylis–Hillman Bromides of Nitroalkenes

The Morita–Baylis–Hillman (MBH) bromides of nitroalkenes have been employed as bielectrophiles for the first time. The 1,3-bielectrophilic reactivity of the MBH bromides has been demonstrated in the synthesis of 3,4-dihydro-2<i>H</i>-pyrido­[1,2-<i>a</i>]­pyrimidines. The reaction of MBH bromides with 2-aminopyridines takes place in the absence of any reagent in a cascade S_N2′-6-endo-trig fashion and is completely regioselective and highly stereoselective. The products, in their hydrobromide salt form, could be conveniently isolated and purified by crystallization. The high stereoselectivity has been rationalized in terms of the greater stability of the transition state in which the Ar and NO₂ groups are anti to each other

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

Regio- and Diastereoselective Synthesis of Dihydropyridopyrimidines via Cascade Reactions of 2‑Aminopyridines with Morita–Baylis–Hillman Bromides of Nitroalkenes

The Morita–Baylis–Hillman (MBH) bromides of nitroalkenes have been employed as bielectrophiles for the first time. The 1,3-bielectrophilic reactivity of the MBH bromides has been demonstrated in the synthesis of 3,4-dihydro-2<i>H</i>-pyrido­[1,2-<i>a</i>]­pyrimidines. The reaction of MBH bromides with 2-aminopyridines takes place in the absence of any reagent in a cascade S_N2′-6-endo-trig fashion and is completely regioselective and highly stereoselective. The products, in their hydrobromide salt form, could be conveniently isolated and purified by crystallization. The high stereoselectivity has been rationalized in terms of the greater stability of the transition state in which the Ar and NO₂ groups are anti to each other

Synthesis of Fused Bromofurans via Mg-Mediated Dibromocyclopropanation of Cycloalkanone-Derived Chalcones and Cloke–Wilson Rearrangement

A convenient two-step sequence for the conversion of alkylidenecycloalkanones to bromofurans is reported. The steps involve Mg-mediated diastereoselective dibromocyclopropanation of alkylidenecycloalkanone followed by acidic alumina-mediated regioselective ring expansion of the cyclopropyl ketone. The scope of the reaction was investigated using alkylidenecycloalkanones derived from tetralone, indanone, and benzosuberone to afford 2-aryl-3-bromofurans fused to various benzocycloalkanes. Representative examples of stereoconvergent dibromocyclopropanation and total aromatization of the furobenzocycloalkane are also reported

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

(3 + 3) Annulation of Nitroallylic Acetates with Stabilized Sulfur Ylides for the Synthesis of 2‑Aryl Terephthalates

A novel (3 + 3) annulation approach has been developed for the synthesis of 2-aryl terephthalates from nitroallylic acetates and stabilized sulfur ylides. The 2-aryl terephthalates, which are also biaryls bearing a terephthalate moiety, are formed through a cascade of reactions such as a γ-selective S_N2′ reaction, γ-selective intramolecular Michael addition, and two eliminations in the presence of Cs₂CO₃ in CH₃CN at room temperature. The products are formal precursors of farnesyltransferase inhibitors and are also potential monomers in polymer chemistry

(3 + 3) Annulation of Nitroallylic Acetates with Stabilized Sulfur Ylides for the Synthesis of 2‑Aryl Terephthalates

A novel (3 + 3) annulation approach has been developed for the synthesis of 2-aryl terephthalates from nitroallylic acetates and stabilized sulfur ylides. The 2-aryl terephthalates, which are also biaryls bearing a terephthalate moiety, are formed through a cascade of reactions such as a γ-selective S_N2′ reaction, γ-selective intramolecular Michael addition, and two eliminations in the presence of Cs₂CO₃ in CH₃CN at room temperature. The products are formal precursors of farnesyltransferase inhibitors and are also potential monomers in polymer chemistry

Synthesis of Fused Bromofurans via Mg-Mediated Dibromocyclopropanation of Cycloalkanone-Derived Chalcones and Cloke–Wilson Rearrangement

A convenient two-step sequence for the conversion of alkylidenecycloalkanones to bromofurans is reported. The steps involve Mg-mediated diastereoselective dibromocyclopropanation of alkylidenecycloalkanone followed by acidic alumina-mediated regioselective ring expansion of the cyclopropyl ketone. The scope of the reaction was investigated using alkylidenecycloalkanones derived from tetralone, indanone, and benzosuberone to afford 2-aryl-3-bromofurans fused to various benzocycloalkanes. Representative examples of stereoconvergent dibromocyclopropanation and total aromatization of the furobenzocycloalkane are also reported