ABSTRACT
A study of the reactivity pattern associated with zwitterionic allenolates "on water" is reported. This study establishes the chemical basis for two organocatalyzed allenolate-driven reaction networks operating "on water". The first one is a chemodifferentiating three building block (ABB') three-component reaction (ABB' 3CR) manifold comprising terminal alkynoates and aldehydes. The manifold produces propargylic enol ethers 3 with higher average efficiency than their homologues in organic solvents. The second one is a novel organocatalytic system elicited by the reaction of alkynoates and nitrones in the presence of tertiary amines or phosphines. While terminal alkynoates afford 2,3,5-trisubstituted 2,3-dihydroisoxazoles 5 and propargylic N-hydroxylamines 6, internal alkynoates selectively afford the 2,3,4,5-tetrasusbstituted 2,3-dihydroisoxazaole 10. Importantly, in both cases, the 2,3-dihydroisoxazole ring is obtained as a sole regioisomer.
Subject(s)
Naphthalenes/chemistry , Water/chemistry , Alkynes/chemistry , Catalysis , Nitrogen Oxides/chemistry , StereoisomerismABSTRACT
The first example of a regioselective and organocatalyzed 1,3-dipolar cycloaddition reaction between conjugated alkynoates and nitrones "on water" is described.
Subject(s)
Naphthalenes/chemistry , Nitrogen Oxides/chemistry , Water/chemistry , Amines/chemistry , Catalysis , Molecular Structure , Phosphines/chemistry , StereoisomerismABSTRACT
The organocatalytic generation of a strong base by the action of a good nucleophile is the base for the in situ catalytic generation of conjugated acetylides in the presence of aldehydes or activated ketones. The method is affordable in a multicomponent, domino format able to generate a chemically diverse set of multifunctionalized adducts that are very well suited for diversity-oriented molecular construction. The domino process involves a nucleophile as catalyst and a terminal conjugated alkyne (H-C[triple chemical bond]C-Z) and an aldehyde or activated ketone as building blocks. The chemical outcome of this process changes dramatically as a function of the nucleophile (tertiary amine or phosphine), temperature, stoichiometry, and solvent. These multicomponent domino processes achieve molecular construction with good atom economy and, very importantly, with an exquisite chemo-differentiating incorporation of identical starting units into the products (nondegenerated chemical output). These properties convert the H-C[triple chemical bond]C-Z unit into a specific building block for diversity-oriented molecular construction. Applications to the modular and diversity-oriented synthesis of relevant heterocycles are discussed. A protocol involving two coupled domino processes linked in a one-pot manner will be discussed as an efficient synthetic manifold for the modular and diversity-oriented construction of multisubstituted nitrogen-containing heterocycles.
Subject(s)
Alkynes/chemical synthesis , Aldehydes/chemistry , Alkynes/chemistry , Catalysis , Ketones/chemistry , Molecular Structure , Oxidation-ReductionABSTRACT
A modular, one-pot, two-step, four-component synthesis of polysubstituted 1,3-oxzolidines is described. The method comprises two linked domino processes: an organocatalyzed domino reaction of alkyl propiolate and an aliphatic aldehydes and a microwave-assisted amine addition cyclization domino process. An alternative modular, one-pot, three-step, four-component synthesis has also been developed by linking the organocatalyzed domino process to a sequential amine addition/Yb(OTf)(3)-catalyzed enamine cyclization reaction.
Subject(s)
Oxazoles/chemical synthesis , Oxazoles/chemistry , Prodrugs/chemistryABSTRACT
A new microwave-assisted rearrangement of 1,3-oxazolidines scaffolds is the basis for a new, metal-free, direct, and modular construction of tetrasubstituted pyrroles from terminal-conjugated alkynes, aldehydes, and primary amines. This new reaction manifold entails two linked domino processes in a one-pot manner with both atom- and bond-efficiency and under very simple and environment-friendly experimental conditions.
