RESUMEN
The combination of photoredox catalysis and enamine catalysis has enabled the development of an enantioselective α-cyanoalkylation of aldehydes. This synergistic catalysis protocol allows for the coupling of two highly versatile yet orthogonal functionalities, allowing rapid diversification of the oxonitrile products to a wide array of medicinally relevant derivatives and heterocycles. This methodology has also been applied to the total synthesis of the lignan natural product (-)-bursehernin.
Asunto(s)
Aldehídos/química , Productos Biológicos/síntesis química , Lactonas/síntesis química , Lignanos/síntesis química , Aldehídos/síntesis química , Alquilación , Catálisis , Modelos Moleculares , Oxidación-Reducción , Procesos Fotoquímicos , EstereoisomerismoRESUMEN
An efficient route towards biologically relevant pentose derivatives is described. The de novo synthetic strategy features an enantioselective α-oxidation reaction enabled by a chiral amine in conjunction with copper(II) catalysis. A subsequent Mukaiyama aldol coupling allows for the incorporation of a wide array of modular two-carbon fragments. Lactone intermediates accessed via this route provide a useful platform for elaboration, as demonstrated by the preparation of a variety of C-nucleosides and fluorinated pentoses. Finally, this work has facilitated expedient syntheses of pharmaceutically active compounds currently in clinical use.
Asunto(s)
Desoxicitidina/análogos & derivados , Pentosas/química , Pentosas/síntesis química , Uridina Monofosfato/análogos & derivados , Técnicas de Química Sintética , Desoxicitidina/síntesis química , Desoxicitidina/química , Cinética , Sofosbuvir , Estereoisomerismo , Especificidad por Sustrato , Uridina Monofosfato/químicaRESUMEN
The first highly enantioselective α-fluorination of ketones using organocatalysis has been accomplished. The long-standing problem of enantioselective ketone α-fluorination via enamine activation has been overcome via high-throughput evaluation of a new library of amine catalysts. The optimal system, a primary amine functionalized Cinchona alkaloid, allows the direct and asymmetric α-fluorination of a variety of carbo- and heterocyclic substrates. Furthermore, this protocol also provides diastereo-, regio-, and chemoselective catalyst control in fluorinations involving complex carbonyl systems.
Asunto(s)
Halogenación , Cetonas/química , Catálisis , Estereoisomerismo , Especificidad por SustratoRESUMEN
The intramolecular alpha-arylation of aldehydes has been accomplished using singly occupied molecular orbital (SOMO) catalysis. Selective oxidation of chiral enamines (formed by the condensation of an aldehyde and a secondary amine catalyst) leads to the formation of a 3pi-electron radical species. These chiral SOMO-activated radical cations undergo enantioselective reaction with an array of pendent electron-rich aromatics and heterocycles thus efficiently providing cyclic alpha-aryl aldehyde products (10 examples: > or = 70% yield and > or = 90% ee). In accordance with our radical mechanism, when there is a choice between arylation at the ortho or para position of anisole substrates, we find that arylation proceeds selectively at the ortho position.
Asunto(s)
Aldehídos/química , Catálisis , Indolizinas/síntesis química , Indolizinas/química , Estereoisomerismo , Especificidad por SustratoAsunto(s)
Cerio/química , Catálisis , Cinética , Conformación Molecular , Oxidación-Reducción , Transición de Fase , Teoría Cuántica , Agua/químicaRESUMEN
The new complex Ru(NCO)(2)(IMes)(py)(2)(=CHPh) is the first ruthenium metathesis initiator capable of fast, controlled living polymerization of functionalized norbornenes at room temperature, irrespective of monomer bulk.
RESUMEN
Ruthenium alkylidene complexes containing one aryloxide "pseudohalide" ligand catalyze ring-closing metathesis of diene and ene-yne substrates with exceptionally high efficiency. Chromatographic removal of Ru residues is unexpectedly facile, offering a convenient means of isolating pure organic products in high yields.