ABSTRACT
We describe highly enantioselective synthesis of beta-amino acid derivatives (1a-c) using asymmetric hydrogenation of alpha-aminomethylacrylates (2a-c), which contain a free basic N H group, as the key step. The alpha-aminomethylacrylates (2a-c) were prepared using the Baylis-Hillman reaction of an appropriate aldehyde with methyl acrylate followed by acetylation of the resulting allylic alcohols (4a-b) and S(N)2'-type amination of the allylic acetates (3a-b).
Subject(s)
Amino Acids/chemical synthesis , Methacrylates/chemistry , Methacrylates/chemical synthesis , Catalysis , Hydrogenation , StereoisomerismABSTRACT
A simple and efficient methodology for the synthesis of C(2),N(3)-disubstituted-4 quinazolones from anilines and N-acylanthranilic acids was developed. The new cyclization conditions are much milder than any other reported protocols and resulted in excellent yields (87-98%) without chromatography.
ABSTRACT
An efficient synthesis of 9H-xanthene-9-carboxaldehyde (3a), 9H-thioxanthene-9-carboxaldehyde (3b), and 9,10-dihydro-10-methyl-9-acridinecarboxaldehyde (3c) by a novel two-carbon homologation of xanthydrol (1a), thioxanthydrol (1b), and 9,10-dihydro-10-methyl-9-acridinol (1c), respectively, using N-vinylacetamides (2a,b) or ethyl vinyl ether (2c) as acetaldehyde anion equivalents, is described.
ABSTRACT
DABCO is an extremely active catalyst for the methylation of indoles in conjunction with dimethyl carbonate (DMC). This green chemistry is highly effective and produces N-methylindoles in nearly quantitative yields. The reaction sequence consists of competing alkylation and acylation pathways and involves 1,4-diazabicyclo[2.2.2]octane (DABCO) dually as a nucleophilic catalyst, ultimately resulting in a single product: the N-methylated indole.
ABSTRACT
An efficient palladium-catalyzed amination of aromatic bromides with hindered N-alkyl-substituted anilines is described, either using the combination of Pd(OAc)(2) and P(t-Bu)(3) or a palladium(I) tri-tert-butylphosphine bromide dimer, [Pd(mu-Br)(t-Bu(3)P)](2), a new, commercially available, and easily handled catalyst.
ABSTRACT
[reaction: see text] An efficient and practical N-methylation of amino acid derivatives with dimethyl sulfate in the presence of sodium hydride and a catalytic amount of water is described. Reaction of water with sodium hydride generated highly reactive dry sodium hydroxide, which led to much faster reaction rates than powdered sodium hydroxide itself.
Subject(s)
Amino Acids/chemical synthesis , Methylation , Sodium Hydroxide/chemistry , Sulfuric Acid Esters/chemistry , Water/chemistryABSTRACT
An efficient and large-scale enantioselective synthesis of PNP405 (1), a purine nucleoside phosphorylase inhibitor, is described. This synthesis of 1 involved eight steps starting from o-fluorophenylacetic acid with a 21.6% overall yield and >99.5% enantiopurity. The key stereogenic center with (R)-configuration was created using Evans' asymmetric alkylation methodology. This synthesis also features the racemization-free reductive removal of the chiral auxiliary in 5 using sodium borohydride, protection of the gamma-cyano alcohol 6 as the trityl ether by a new water-assisted tritylation with trityl chloride and triethylamine or with trityl alcohol and catalytic trifluoroacetic acid, and an efficient one-pot cyclo-guanidinylation of 10 using cyanamide as the guanidinylating agent.
Subject(s)
Combinatorial Chemistry Techniques/methods , Enzyme Inhibitors/chemical synthesis , Enzyme Inhibitors/pharmacology , Fluorobenzenes/chemical synthesis , Fluorobenzenes/pharmacology , Purine-Nucleoside Phosphorylase/antagonists & inhibitors , Pyrimidinones/chemical synthesis , Pyrimidinones/pharmacology , Catalysis , Enzyme Inhibitors/chemistry , Fluorobenzenes/chemistry , Molecular Structure , Pyrimidinones/chemistry , StereoisomerismABSTRACT
1,8-Diazabicyclo[5.4.0]undec-7-ene (DBU) is an effective nucleophilic catalyst for carboxylic acid esterification with dimethyl carbonate (DMC). The reaction pathway of this new class of nucleophilic catalysis has been studied. A plausible, multistep mechanism is proposed, which involves an initial N-acylation of DBU with DMC to form a carbamate intermediate. Subsequent O-alkylation of the carboxylate with this intermediate generates the corresponding methyl ester in excellent yield. In the absence of DBU or in the presence of other bases, such as ammonium hydroxide or N-methylmorpholine, the same reaction affords no desired product. This method is particularly valuable for the synthesis of methyl esters that contain acid-sensitive functionality.
