ABSTRACT
The scope and limitations of the platinum catalyzed 7-endo cyclization of internal alkynyl amides were investigated. Substitution of the alkyne with an aryl group gave better results, presumably because it stabilized the transition state. Applying the reaction to a secondary amide, the caprazamycin core was successfully synthesized from commercially available material in eight steps.
Subject(s)
Alkynes/chemistry , Amides/chemistry , Azepines/chemistry , Azepines/chemical synthesis , Platinum/chemistry , Catalysis , Chemistry Techniques, Synthetic , CyclizationSubject(s)
Amides/chemistry , Bismuth/chemistry , Platinum/chemistry , Azepines/chemistry , Catalysis , Cyclization , Piperazines/chemistry , StereoisomerismABSTRACT
Synthesis of the pentacyclic core of ecteinascidin 743 is described. This synthesis features concise construction of the diazabicyclo[3.3.1]nonane skeleton using gold(I)-catalyzed one-pot keto amide formation, acid-promoted enamide formation, and oxidative Friedel-Crafts cyclization as the key steps.
Subject(s)
Biological Products/chemistry , Bridged Bicyclo Compounds, Heterocyclic/chemical synthesis , Phenylalanine/chemical synthesis , Polycyclic Aromatic Hydrocarbons/chemistry , Tetrahydroisoquinolines/chemistry , Bridged Bicyclo Compounds, Heterocyclic/chemistry , Catalysis , Cyclization , Molecular Structure , Oxidation-Reduction , Phenylalanine/chemistry , StereoisomerismABSTRACT
As a convenient and direct synthesis of 1,2-dihydroisoquinolines, the gold(I)-catalyzed intramolecular hydroamination of (2-alkynyl)benzyl carbamates has been developed. The reaction with cationic gold(I) complex [AuCl(PPh(3))/AgNTf(2)] proceeded at room temperature, giving the desired 6-endo adducts. The addition of alcohol efficiently promoted the reaction, and the amount of the catalyst could be reduced to 1 mol %. However, the alkynes bearing either an electron-deficient aryl group or an alkyl group resulted in predominant production of 5-exo adducts. In such cases, use of a bulky gold catalyst, AuCl[(o-biPh)((t)Bu)(2)P]Cl/AgNTf(2), improved the regioselectivity, giving the 6-endo adducts in better yields. Furthermore, the hydroamination of alkynyl carbamates bearing an acetal or enone was successfully applied to the concise synthesis of tetracyclic heterocycles such as nitidine via the single catalyst-mediated tandem cyclization which consists of a condensation or a Michael addition of the resulting enecarbamates.
