ABSTRACT
Ring the changes: The cycloaddition of nitrones with 1-carboallyloxy-1-carbomethoxycyclopropanes yields tetrahydro-1,2-oxazines, which in turn undergo a Tsuji dehydrocarbonylation to give dihydro-1,2-oxazines (see scheme; dba = dibenzylideneacetone). Addition of base to this reaction mixture results in clean conversion to pyrroles. The result is a flexible three-component strategy for the synthesis of tetrasubstituted pyrroles.
Subject(s)
Cyclopropanes/chemistry , Organometallic Compounds/chemistry , Palladium/chemistry , Pyrroles/chemical synthesis , Catalysis , Dehydration , Molecular Structure , Pyrroles/chemistry , StereoisomerismABSTRACT
The asymmetric total synthesis of (+)-isatisine A has been accomplished commencing with a Lewis acid-catalyzed cyclization of homochiral (S)-vinylcyclopropane diester and N-tosylindole-2-carboxaldehyde to construct the tetrahydrofuran ring. A palladium-catalyzed oxidative decarboxylation was utilized to obtain the dihydrofuran required for the subsequent dihydroxylation reaction to install the diol present on the tetrahydrofuran ring. The total synthesis was completed by an indole oxidation and electrophilic aromatic substitution sequence to construct isatisine A acetonide, which was then carried forward to the antipode of the natural product. The absolute configuration of the natural enantiomer (-)-isatisine A was determined to be C2(S), C9(R), C10(S), C12(R), and C13(R).
Subject(s)
Indole Alkaloids/chemical synthesis , Isatin/analogs & derivatives , Indole Alkaloids/chemistry , Isatin/chemical synthesis , Isatin/chemistry , Molecular Structure , StereoisomerismABSTRACT
The intramolecular reaction of oxime ethers and cyclopropane diesters results in the diastereoselective formation of substituted pyrrolo-isoxazolidines which serve as precursors to the ubiquitous pyrrolidine motif. A simple reversal of addition order of catalyst and substrate results in formation of two discrete diastereomers in a highly selective and predictable manner. The adducts are prepared in excellent yields from either enantiomer of an alkoxyamino-tethered cyclopropanediester, allowing efficient access to highly substituted homochiral pyrrolidines.
Subject(s)
Pyrrolidines/chemical synthesis , Cyclopropanes/chemistry , Esters/chemistry , Ethers/chemistry , Molecular Conformation , Oximes/chemistry , Pyrrolidines/chemistry , StereoisomerismABSTRACT
The reaction of 2,3-disubstituted-1,1-cyclopropanediesters with nitrones under Lewis acid conditions produces tetrahydro-1,2-oxazines in which the cis/trans relationship of the cyclopropanes is not conserved. Reacting nitrones with 2,3-cis-disubstituted cyclopropanes lead to 5,6-trans-oxazines, and 2,3-trans-disubstituted cyclopropanes lead to 5,6-cis-oxazines. This observed stereochemical inversion provides evidence for a stepwise annulation mechanism in the preparation of tetrahydro-1,2-oxazines.
