RESUMO
(Diene)Rh(I) complexes catalyze the stereoselective three-component coupling of silyl glyoxylates, arylboronic acids, and aldehydes to give glycolate aldol products. The participation of Rh-alkoxides in the requisite Brook rearrangement was established through two component Rh-catalyzed couplings of silyl glyoxylates with ArB(OH)2 to give silyl-protected mandelate derivatives. The intermediacy of a chiral Rh-enolate was inferred through enantioselective protonation using a chiral Rh-catalyst. Diastereoselective three-component couplings with aldehydes as terminating electrophiles to give racemic products were best achieved with a bulky aryl ester on the silyl glyoxylate reagent. Optimal enantioselective couplings were carried out with the tert-butyl ester variant using an anisole-derived enantiopure tricyclo[3.2.2.02,4 ]nonadiene ligand.
RESUMO
The synthesis of the stereotriad core in the eastern portion of the Veratrum alkaloids jervine (1), cyclopamine (2), and veratramine (3) is reported. Starting from a known ß-methyltyrosine derivative (8), the route utilizes a diastereoselective substrate-controlled 1,2-reduction to establish the stereochemistry of the vicinal amino alcohol motif embedded within the targets. Oxidative dearomatization is demonstrated to be a viable approach for the synthesis of the spirocyclic DE ring junction found in jervine and cyclopamine.
Assuntos
Veratrum , Alcaloides de VeratrumRESUMO
A stereoselective intermolecular Diels-Alder cycloaddition of an intermediate pyrazinone with both achiral and chiral acrylate-derived dienophiles provides rapid access to the bicyclo[2.2.2]diazaoctane core shared among several prenylated indole alkaloids. The product derived from cycloaddition with 2-nitroacrylate required an additional five to six synthetic operations to intercept established precursors to premalbrancheamide and brevianamide B. The chemistry detailed in this manuscript constitutes a formal total synthesis (12 steps each) of these [2.2.2]diazabicyclic natural products from proline methyl ester.
Assuntos
Alcaloides/química , Alcaloides/síntese química , Compostos Aza/química , Compostos Aza/síntese química , Produtos Biológicos/química , Produtos Biológicos/síntese química , Compostos Bicíclicos com Pontes/química , Compostos Bicíclicos com Pontes/síntese química , Piperazinas/química , Piperazinas/síntese química , Prolina/química , Compostos de Espiro/química , Compostos de Espiro/síntese química , Reação de Cicloadição , Estrutura Molecular , Prolina/análogos & derivados , EstereoisomerismoRESUMO
This Account describes new reactions that have been developed in the Johnson laboratories at UNC Chapel Hill enabled by considerations of N-O bond cleavage. Three main case studies are highlighted: the metal-catalyzed electrophilic amination of O-acyl hydroxyl amines, multihetero-Cope rearrangements driven by O-N bond breakage, and merged dearomatization/N=O cycloadditions for the synthesis of complex 4-aminocyclohexanols such as those found in the natural product tetrodotoxin.
RESUMO
Progress toward a stereoselective synthesis of tetrodotoxin (TTX) is presented. Oxidative dearomatization of a tetrasubstituted guaiacol arene yielded a masked ortho-benzoquinone that intercepted an acyl nitroso species generated in situ by the copper-catalyzed aerobic oxidation of an acyl hydroxylamine. The subsequent alkene dihydroxylation and reduction of a bis-neopentylic ketone proceeded with perfect diastereoselectivity to reveal advanced intermediates toward the synthesis of TTX.