Enantioselective α-Alkylation of Aldehydes by Photoredox Organocatalysis: Rapid Access to Pharmacophore Fragments from ß-Cyanoaldehydes.

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.

A general and enantioselective approach to pentoses: a rapid synthesis of PSI-6130, the nucleoside core of sofosbuvir.

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.

Enantioselective organocatalytic α-fluorination of cyclic ketones.

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.

Enantioselective alpha-arylation of aldehydes via organo-SOMO catalysis. An ortho-selective arylation reaction based on an open-shell pathway.

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.

A Ru-isocyanate initiator for fast, living, precisely controlled ring-opening metathesis polymerization at ambient temperatures.

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.

Highly efficient Ru-pseudohalide catalysts for olefin metathesis.

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.