ABSTRACT
A predictive computational study was conducted in order to assess the efficiency of electrocyclization reactions of keteniminium salts, in an effort to form a variety of heterocyclic systems, namely, 3-amino(benzo)thiophenes, 3-amino(benzo)furans, 3-aminopyrroles, as well as 3-aminoindoles. A density functional theory (DFT) approach was utilized and the effect of heteroatoms (NMe, O, S) was thoroughly investigated by means of population analysis, QTAIM, NICS, ACID, and local reactivity descriptors (Parr and Fukui functions). The electrocyclization of enamines leading to 3-aminopyrroles was shown to be both kinetically and thermodynamically most favorable. Moreover, the pericyclic nature of the electrocyclizations was confirmed using FMO, QTAIM, NICS, and ACID methods. Additionally, substituent effects were investigated in order to give further insight on the reactivity of heteroatom containing keteniminium systems toward electrocyclization reactions. Finally, computational predictions were experimentally confirmed for a selection of keteniminium systems.
ABSTRACT
A novel class of experimental fungicides has been discovered, which consists of special N-thiazol-4-yl-salicylamides. They originated from amide reversion of lead structures from the patent literature and are highly active against important phytopathogens, such as Phytophthora infestans (potato and tomato late blight), Plasmopara viticola (grapevine downy mildew) and Pythium ultimum (damping-off disease). Structure-activity relationship studies revealed the importance of a phenolic or enolic hydroxy function in the ß-position of a carboxamide. An efficient synthesis route has been worked out, which for the first time employs the carbonyldiimidazole-mediated Lossen rearrangement in the field of thiazole carboxylic acids.
Subject(s)
Fungicides, Industrial/chemical synthesis , Fungicides, Industrial/pharmacology , Oomycetes/drug effects , Salicylamides/chemical synthesis , Salicylamides/pharmacology , Thiazoles/chemical synthesis , Thiazoles/pharmacology , Dose-Response Relationship, Drug , Fungicides, Industrial/chemistry , Microbial Sensitivity Tests , Molecular Structure , Salicylamides/chemistry , Structure-Activity Relationship , Thiazoles/chemistryABSTRACT
Chiral framework: Chiral amines with pyrrolidine frameworks catalyze the enantioselective conjugate addition of a wide range of aldehydes to various vinyl sulfones and vinyl phosphonates in high yields and with enantioselectivities up to >99 % ee (see scheme). The high versatility of the Michael adducts is exemplified by various functionalizations with conservation of the optical purity.Chiral amines with a pyrrolidine framework catalyze the enantioselective conjugate addition of a broad range of aldehydes to various vinyl sulfones and vinyl phosphonates in high yields and with enantioselectivities up to >99 % ee. This novel process provides synthetically useful chiral gamma-gem-sulfonyl or phosphonyl aldehydes which can be widely functionalized with retention of the enantiomeric excess. Mechanistic insights including DFT calculations are explored in detail.
Subject(s)
Aldehydes/chemistry , Combinatorial Chemistry Techniques , Organophosphonates/chemistry , Organophosphonates/chemical synthesis , Sulfones/chemistry , Sulfones/chemical synthesis , Vinyl Compounds/chemistry , Vinyl Compounds/chemical synthesis , Aldehydes/chemical synthesis , Amines/chemistry , Catalysis , Models, Chemical , Molecular Structure , Pyrrolidines/chemistry , StereoisomerismABSTRACT
The enantioselective organocatalytic conjugate addition of alpha-aminoketone to nitroolefins is reported.
Subject(s)
Alkenes/chemistry , Ketones/chemistry , Nitro Compounds/chemistry , Catalysis , Molecular Structure , Nitro Compounds/chemical synthesis , Pyrrolidinones/chemical synthesis , Pyrrolidinones/chemistry , Stereoisomerism , Styrenes/chemistryABSTRACT
Chiral amines catalyze the enantioselective conjugate addition of aldehydes to vinyl phosphonates in high yields and with enantioselectivities up to 97% ee. This novel process provides synthetically useful chiral gamma-geminal phosphonate aldehydes which can be easily converted in a few steps into chiral beta-substituted vinyl phosphonates with conservation of the optical purity.
Subject(s)
Aldehydes/chemistry , Organophosphonates/chemistry , Vinyl Compounds/chemistry , Catalysis , Imidazolidines/chemistry , Magnetic Resonance Spectroscopy , Molecular Structure , Stereoisomerism , Vinyl Compounds/chemical synthesisABSTRACT
Over the last decade the potential of organocatalysis has successfully been demonstrated. In particular, chiral amines such as pyrrolidine analogues have emerged as a broadly applicable class of organocatalyst for asymmetric conjugate addition via enamine activation. This Feature Article documents the development of these catalysts, emphasizing the design and mechanistic features that supply high selectivity in asymmetric Michael reactions.
