ABSTRACT
An efficient SNAr approach for generating a wide array of 2-aryl and 2-alkyl pyrimidines in good to high yields was developed. This methodology does not require precious metal catalysts and is compatible with aryl, heteroaryl, and alkyl magnesium halides as nucleophiles. This process is scalable and performed at room temperature well below the temperature of the competing decomposition of the activated 2-tert-butyl sulfonyl pyrimidine electrophile.
ABSTRACT
Nucleophilic ring opening of methyl 1-nitrocyclopropanecarboxylates by phenol derivatives in the presence of Cs2CO3 is described. The reaction tolerates a variety of substituents on both the aromatic alcohol and the cyclopropane and affords the products in good yields (53-84%) and with complete preservation of the enantiomeric excess at C-4. The methodology was applied in an enantioselective synthesis of the norepinephrine reuptake inhibitor atomoxetine (Strattera).
Subject(s)
Adrenergic Uptake Inhibitors/chemical synthesis , Cyclopropanes/chemical synthesis , Nitro Compounds/chemical synthesis , Phenols/chemistry , Propylamines/chemical synthesis , Atomoxetine Hydrochloride , Carbonates/chemistry , Cesium/chemistry , Methylation , Models, Chemical , StereoisomerismABSTRACT
A norbornene-mediated palladium-catalyzed sequence is described in which an alkyl-aryl bond and an aryl-heteroaryl bond are formed in one reaction vessel. The aryl-heteroaryl bond-forming step occurs via a direct arylation reaction. A number of six-, seven-, and eight-membered ring-annulated indoles, pyrroles, pyrazoles, and azaindoles were synthesized from the corresponding bromoalkyl azole and an aryl iodide.
Subject(s)
Heterocyclic Compounds/chemical synthesis , Nitrogen/chemistry , Palladium/chemistry , Alkylation , Catalysis , Heterocyclic Compounds/chemistrySubject(s)
Hydrocarbons, Aromatic/chemical synthesis , Transition Elements/chemistry , Catalysis , Cyclization , Heterocyclic Compounds/chemical synthesis , Heterocyclic Compounds/chemistry , Hydrocarbons, Aromatic/chemistry , Metals/chemistry , Molecular Structure , Organometallic Compounds/chemistry , Polycyclic Aromatic Hydrocarbons/chemical synthesis , Polycyclic Aromatic Hydrocarbons/chemistryABSTRACT
A stereoselective synthesis of coronafacic acid, a natural component of the phytotoxin coronatin, was achieved using an intramolecular Diels-Alder reaction as the key step. The triene precursor bearing a substituted diene and a vinylketone as dienophile was synthesized and then tested in the thermal intramolecular cyclization. We have devised a new strategy to assemble the E,Z-diene through the stereoselective aldol reaction of an ester enolate followed by a stereoselective dehydration. Following the thermal cyclization, the corresponding hydrindanone thereby obtained with the desired relative stereochemistry could easily be converted into the natural product. The synthesis of the coronafacic acid was accomplished in six steps in 29% overall yield.
ABSTRACT
A norbornene-mediated palladium-catalyzed sequence is described in which two alkyl-aryl bonds and one alkenyl-aryl bond are formed in one pot with use of microwave irradiation. A variety of symmetrical and unsymmetrical oxygen-, nitrogen-, silicon-, and sulfur-containing tricyclic heterocycles were synthesized from a Heck acceptor and an aryl iodide containing two tethered alkyl halides. This approach was further applied to the synthesis of a tricyclic mescaline analogue.
Subject(s)
Heterocyclic Compounds, 3-Ring/chemical synthesis , Norbornanes/chemistry , Palladium/chemistry , Alkylation , Catalysis , Cyclization , Hydrocarbons, Halogenated/chemistry , Iodine/chemistry , Models, Chemical , Nitrogen/chemistry , Organosilicon Compounds/chemical synthesis , Oxygen/chemistry , Sulfur/chemistryABSTRACT
A norbornene-mediated palladium-catalyzed tandem alkylation/cyanation sequence is described in which an alkyl-aryl bond and a nitrile-aryl bond are formed in one pot. A variety of sterically hindered, five-, six-, and seven-membered ring benzonitriles were synthesized in good yields from easily accessible starting materials.
ABSTRACT
[reaction: see text] Polycyclic thiophenes and furans were synthesized using a one-pot ortho alkylation/direct heteroarylation reaction sequence. Under the optimized reaction conditions, aryl iodides were coupled with 3-(bromoalkyl)thiophenes or -furans, affording six- and seven-membered annulated ring products via formation of two C-C bonds from two aryl C-H bonds.
ABSTRACT
The synthesis of a variety of alkylidene benzoxacycles via a domino palladium-catalyzed ortho-alkylation/intramolecular Heck reaction is described. Under the optimized conditions [Pd(OAc)2 (10 mol %), P(2-Furyl)3 (20 mol %), norbornene (4 equiv), Cs2CO3 (2 equiv), CH3CN, 80 degrees C], aryl iodides with oxygen-tethered Heck acceptors are coupled with alkyl bromides (5 equiv) to generate a variety of six- and seven-membered-ring benzoxacyclic products.
Subject(s)
Benzoxazines/chemical synthesis , Alkylation , Benzoxazines/chemistry , Catalysis , Cyclization , Molecular Structure , Palladium/chemistry , StereoisomerismABSTRACT
[reaction: see text] A palladium-catalyzed/norbornene-mediated sequential coupling reaction involving an aromatic sp(2) C-H functionalization as the key step is described, in which an alkyl-aryl bond and an aryl-heteroaryl bond are formed in one pot. A variety of highly substituted six- and seven-membered annulated pyrroles and pyrazoles were synthesized in a one-step process in good yields from readily accessible N-bromoalkyl pyrroles or pyrazoles and aryl iodides.
ABSTRACT
A norbornene-mediated palladium-catalyzed tandem alkylation/C-H functionalization sequence is described, in which an alkyl-aryl bond and a heteroaryl-aryl bond are formed in one pot. A variety of highly substituted six- and seven-membered ring annulated indoles were synthesized in good yields from bromoalkyl indoles and aryl iodides.
