ABSTRACT
A one-pot multibond-forming process involving a thermally mediated Overman rearrangement and a ring closing metathesis reaction of allylic trichloroacetimidates bearing a 2-allyloxyaryl group has been developed for the synthesis of 5-amino-substituted 2,5-dihydro-1-benzoxepines. Chemoselective reduction and functionalization of these compounds allowed access to a range of pharmacologically active 5-amino-2,3,4,5-tetrahydro-1-benzoxepine scaffolds.
Subject(s)
Benzoxepins/chemical synthesis , Heterocyclic Compounds/chemical synthesis , Benzoxepins/chemistry , Cyclization , Heterocyclic Compounds/chemistry , Molecular StructureABSTRACT
Allylic trichloroacetimidates bearing a 2-vinyl or 2-allylaryl group have been designed as substrates for a one-pot, two-step multi-bond-forming process leading to the general preparation of aminoindenes and amino-substituted 1,4-dihydronaphthalenes. The synthetic utility of the privileged structures formed from this one-pot process was demonstrated with the total synthesis of four oxybenzo[c]phenanthridine alkaloids, oxychelerythrine, oxysanguinarine, oxynitidine, and oxyavicine. An intramolecular biaryl Heck coupling reaction, catalyzed using the Hermann-Beller palladacycle was used to effect the key step during the synthesis of the natural products.
Subject(s)
Alkaloids/chemical synthesis , Biological Products/chemistry , Biological Products/chemical synthesis , Indenes/chemistry , Indenes/chemical synthesis , Naphthalenes/chemistry , Phenanthridines/chemistry , Phenanthridines/chemical synthesis , Acetamides/chemistry , Alkaloids/chemistry , Cyclization , Molecular Structure , Stereoisomerism , Vinyl Compounds/chemistryABSTRACT
A one-pot, three-step tandem process has been developed for the direct synthesis of functionalised bicyclic [3.3.0], [4.3.0] and [5.3.0] gamma-lactams from simple allylic trichloroacetimidates. The process involves a palladium(ii) mediated Overman rearrangement followed by the use of Grubbs first generation complex which catalyzes both a ring closing metathesis reaction and a Kharasch cyclization. As well as exploring the scope of this process for the synthesis of a range of functionalised bicyclic gamma-lactams, the use of chiral palladium(ii) catalysts during the Overman rearrangement for the enantioselective synthesis of the bicyclic gamma-lactams is also demonstrated.
Subject(s)
Bridged Bicyclo Compounds, Heterocyclic/chemistry , Bridged Bicyclo Compounds, Heterocyclic/chemical synthesis , Lactams/chemistry , Lactams/chemical synthesis , Catalysis , Palladium/chemistry , Stereoisomerism , Substrate SpecificityABSTRACT
With the aim of developing new SPECT imaging agents for the translocator protein (TSPO), a small library of iodinated quinoline-2-carboxamides have been prepared and tested for binding affinity with TSPO. N,N-Diethyl-3-iodomethyl-4-phenylquinoline-2-carboxamide was found to have excellent affinity (K(i) 12.0 nM), comparable to that of the widely used TSPO imaging agent PK11195.
