ABSTRACT
The synthesis of bicyclic ureas and sulfamides via palladium-catalyzed alkene carboamination reactions between aryl/alkenyl halides/triflates and alkenes bearing pendant cyclic sulfamides and ureas is described. The substrates for these reactions are generated in 3-5 steps from commercially available materials, and products are obtained in good yield with up to >20:1 diastereoselectivity. The stereochemical outcome of the sulfamide alkene addition is consistent with a mechanism involving anti-aminopalladation of the alkene, whereas the stereochemical outcome of the urea alkene addition is consistent with a syn-aminopalladation mechanism.
ABSTRACT
A new method for the synthesis of 2-aminoimidazole products is described. The heterocyclic products are generated in good yields via Pd-catalyzed carboamination reactions of N-propargyl guanidines and aryl triflates. This methodology generates both a C-N and C-C bond during the annulation step and facilitates the rapid construction of 2-aminoimidazole products with different aryl groups. The utility of this methodology was demonstrated in the total synthesis of preclathridine A, preclathridine B, and dorimidazole B from a single intermediate.
Subject(s)
Alkaloids/chemical synthesis , Biological Products/chemical synthesis , Imidazoles/chemical synthesis , Palladium/chemistry , Alkaloids/chemistry , Biological Products/chemistry , Combinatorial Chemistry Techniques , Guanidines/chemistry , Imidazoles/chemistry , Molecular StructureABSTRACT
A new annulation strategy for the synthesis of trans-bicyclic sulfamides is described. The Pd-catalyzed alkene carboamination reactions of 2-allyl and cis-2,5-diallyl pyrrolidinyl sulfamides with aryl and alkenyl triflates afford the fused bicyclic compounds in good yields and with good diastereoselectivity (up to 13:1 dr). Importantly, by employing reaction conditions that favor an anti-aminopalladation mechanism, the relative stereochemistry between the C3 and C4a stereocenters of the products is reversed relative to related Pd-catalyzed carboamination reactions that proceed via syn-aminopalladation.
Subject(s)
Alkenes/chemistry , Palladium/chemistry , Pyrrolidines/chemical synthesis , Sulfonamides/chemical synthesis , Amination , Catalysis , Molecular Structure , Pyrrolidines/chemistry , Stereoisomerism , Sulfonamides/chemistryABSTRACT
A new approach to the synthesis of substituted 5-membered cyclic guanidines is described. Palladium-catalyzed alkene carboamination reactions between acyclic N-allyl guanidines and aryl or alkenyl halides provide these products in good yield. This method allows access to a number of different cyclic guanidine derivatives in only two steps from readily available allylic amines.
