ABSTRACT
To date, effective nickel-catalyzed enantioselective cross-couplings of alkyl electrophiles that bear oxygen leaving groups have been limited to reactions of allylic alcohol derivatives with Grignard reagents. In this Communication, we establish that, in the presence of a nickel/pybox catalyst, a variety of racemic propargylic carbonates are suitable partners for asymmetric couplings with organozinc reagents. The method is compatible with an array of functional groups and utilizes commercially available catalyst components. The development of a versatile nickel-catalyzed enantioselective cross-coupling process for electrophiles that bear a leaving group other than a halide adds a significant new dimension to the scope of these reactions.
Subject(s)
Nickel/chemistry , Oxygen/chemistry , Alkynes/chemistry , Carbon/chemistry , Catalysis , Chemistry, Pharmaceutical/methods , Cross-Linking Reagents/chemistry , Drug Design , Electrochemistry/methods , Humans , Hypersensitivity/drug therapy , Inflammation/drug therapy , Models, Chemical , StereoisomerismABSTRACT
Since their first discovery in 1959, natural products containing the piperazic acid motif have been isolated from a variety of sources and exhibit diverse biological activity profiles. This review provides information about their isolation and biological activities, and presents an overview of recent total syntheses of these molecules.
Subject(s)
Biological Products , Pyridazines , Biological Products/chemical synthesis , Biological Products/isolation & purification , Biological Products/pharmacology , Molecular Structure , Pyridazines/chemical synthesis , Pyridazines/chemistry , Pyridazines/pharmacologyABSTRACT
Here we describe in full our investigations into the synthesis of the dimeric cyclohexapeptide chloptosin in 17 linear steps. Particularly, this work features an organocatalytic tandem process for the synthesis of the embedded piperazic acids, in which a differentially protected azodicarboxylate is used together with pyrrolidinyl tetrazole as the catalyst. The central biaryl bond is being formed by Stille coupling of two sterically demanding ortho-chloropyrroloindole fragments. The inherent flexibility of the synthetic strategy proved beneficial as the route could be adjusted smoothly during the progression of the synthesis programme.
Subject(s)
Peptides, Cyclic/chemical synthesis , Pyridazines/chemical synthesis , Catalysis , Molecular Structure , Peptides, Cyclic/chemistry , Pyridazines/chemistry , StereoisomerismABSTRACT
A sequential, organocatalysed asymmetric reaction to access chiral 1,2-oxazines and chiral pyridazines is reported, which proceeds in moderate to good yields and good to excellent enantioselectivities.
