ABSTRACT
The palladium catalyzed alkoxycarbonylation and aminocarbonylation of vinyl tosylates are described. A variety of ketone and aldehyde derived vinyl tosylates may be carbonylated in the presence of primary, secondary, and tertiary alcohols, or primary and secondary amines, to provide the corresponding esters and amides in good yields. The alkoxycarbonylation was applied to a short synthesis of isoguvacine.
Subject(s)
Alcohols/chemistry , Palladium/chemistry , Vinyl Compounds/chemistry , Amination , Anions/chemistry , Catalysis , Free Radicals/chemistry , Ligands , Molecular StructureABSTRACT
A three-stage process for the synthesis of LFA-1 inhibitor 1 from amine 4 with an overall yield of 65% is described. The key stage involves a Ph(3)PCl(2)-induced dehydration/cyclization of urea 6 followed by a regioselective bromination to give 1H-imidazo[1,2-a]imidazol-2-one 9. Br/Mg exchange of 9 followed by addition to SO(2) in THF and subsequent oxidation produces a sulfonyl chloride which is directly reacted with L-alaninamide using K(2)CO(3) as base in aqueous DMF/THF to give 1 in a one-pot operation. The process was implemented for the production of 1 on a metric ton scale.
Subject(s)
Lymphocyte Function-Associated Antigen-1/metabolism , Molecular Structure , Oxidation-Reduction , Peptides/chemistry , Urea/chemical synthesisABSTRACT
The key Pd-catalyzed cross-coupling of aryl bromides or triflates and cyclopropylmagnesium bromide in the presence of substoichiometric amounts of zinc bromide produces cyclopropyl arenes in good to excellent yields. The cross-coupling of other alkyl, cycloalkyl, and aryl Grignard reagents with aryl bromides under the same conditions gives the corresponding substituted arenes in good yields.
Subject(s)
Bromides/chemistry , Calixarenes/chemical synthesis , Hydrocarbons, Brominated/chemistry , Organometallic Compounds/chemistry , Palladium/chemistry , Zinc Compounds/chemistry , Calixarenes/chemistry , Catalysis , Molecular Structure , StereoisomerismABSTRACT
The regioselective N-alkylation of 1,2,3-triazoles 1-6 was studied. Good to excellent N-2 selectivity and high chemical yields for N-2-substituted 4,5-dibromotriazoles 7 were obtained with 4,5-dibromo- and 4-bromo-5-trimethylsilyl-1,2,3-triazoles. These building blocks can be readily converted to 2-mono-, 2,4-di-, and 2,4,5-polysubstituted triazoles 10-15, providing a general, protective, group-free method for the synthesis of N-2-substituted triazoles. Observed regioselectivities can be rationalized by a combination of Frontier Molecular Orbital, steric, and electrostatic directing effects on the heterocyclic scaffolds.
Subject(s)
Triazoles/chemical synthesis , Alkylation , Models, Molecular , Molecular Structure , Static ElectricityABSTRACT
A series of structurally novel, operationally convenient, and efficient chiral 2-phosphino-2,3-dihydrobenzo[d][1,3]oxaphosphole ligands was developed. Applications of ligands 3a and 3b in rhodium-catalyzed asymmetric hydrogenation of alpha-(acylamino)acrylates and beta-(acylamino)acrylates provided excellent enantioselectivities (up to >99% ee) and reactivities (up to 10,000 TON).
Subject(s)
Phosphorus/chemistry , Rhodium/chemistry , Catalysis , Hydrogenation , Ligands , Models, Molecular , Molecular Conformation , Organometallic Compounds/chemistry , StereoisomerismABSTRACT
Reaction of 4-bromo-NH-1,2,3-triazoles 2 with alkyl halides in the presence of K(2)CO(3) in DMF produced the corresponding 2-substituted 4-bromo-1,2,3-triazoles 5 in a regioselective process. Subsequent Suzuki cross-coupling reaction of these bromides provided an efficient synthesis of 2,4,5-trisubstituted triazoles 3. In addition, reduction of the bromotriazoles by hydrogenation furnished an efficient synthesis of 2,4-disubstituted triazoles 8.
Subject(s)
Hydrocarbons, Brominated/chemistry , Triazoles/chemical synthesis , Alkylation , Catalysis , Combinatorial Chemistry Techniques , Molecular Structure , Stereoisomerism , Triazoles/chemistryABSTRACT
Reaction of 4,5-dibromo-1,2,3-triazole with electron-deficient aromatic halides in the presence of potassium carbonate in DMF produces the corresponding 2-aryl-4,5-dibromotriazoles with high regioselectivity. Subsequent debromination of these triazoles by hydrogenation furnishes 2-aryltriazoles in excellent yields. Overall, this two-step process provides an efficient access to 2-aryl-1,2,3-triazoles.
Subject(s)
Triazoles/chemical synthesis , Catalysis , Combinatorial Chemistry Techniques , Hydrocarbons, Brominated , Hydrogenation , Molecular Structure , Stereoisomerism , Triazoles/chemistryABSTRACT
[reaction: see text] Iodoaromatics bearing a reactive pyrimidine ring underwent a clean iodine-magnesium exchange with isopropylmagnesium chloride in the presence of bis[2-(N,N-dimethylamino)ethyl] ether to provide the corresponding Grignard reagents. The presence of bis[2-(N,N-dimethylamino)ethyl] ether prevented reduction of the pyrimidine ring and addition by isopropylmagnesium chloride. As a result, the newly formed reactive Grignard reagents were allowed to react with electrophiles in a highly selective manner to afford adducts in excellent yields.
ABSTRACT
[reaction: see text] Iodo- and bromoaromatics bearing sensitive carboxylic ester and cyano groups underwent a selective halide-magnesium exchange with isopropylmagnesium chloride at ambient temperature in the presence of bis[2-(N,N-dimethylamino)ethyl] ether to afford the corresponding Grignard reagents. The newly formed reactive Grignard reagents were allowed to react with electrophiles such as trimethylborate to afford arylboronic acids in good to excellent yields.
ABSTRACT
[chemical reaction: see text]. Direct addition of Grignard reagents to acid chlorides in the presence of bis[2-(N,N-dimethylamino)ethyl] ether proceeds selectively to provide aryl ketones in high yields. A possible tridentate interaction between Grignard reagents and bis[2-(N,N-dimethylamino)ethyl] ether moderates the reactivity of Grignard reagents, preventing the newly formed ketones from nucleophilic addition by Grignard reagents.
ABSTRACT
A highly diastereoselective addition of i-BuLi to a triethylmethylsulfinamide derived aldimine was used as the key step in the first asymmetric synthesis of (R)-didesmethylsibutramine, a metabolite of sibutramine for the potential treatment of CNS disorders. [reaction: see text]
Subject(s)
Cyclobutanes/chemical synthesis , Glycolipids/chemistry , Glycolipids/isolation & purification , Indicators and Reagents , Models, Molecular , Molecular Conformation , StereoisomerismABSTRACT
Simple and practical asymmetric synthesis of functionally differentiated aminoindanol based endo-N-sulfonyl 1,2,3-oxathiazolidine-2-oxide as sulfinyl transfer agents are developed. The importance of these new and unique sulfinyl transfer reagents are exemplified by the expedient production of several sulfinamide ligands, including either enantiomer of (R)-tert-butanesulfinamide in excellent yields and enantiopurities.