Catalytic Asymmetric Hydrogen Atom Transfer: Enantioselective Hydroamination of Alkenes.

We report a highly enantioselective radical-based hydroamination of enol esters with sulfonamides jointly catalyzed by an Ir photocatalyst, Brønsted base, and tetrapeptide thiol. This method is demonstrated for the formation of 23 protected ß-amino-alcohol products, achieving selectivities up to 97:3 er. The stereochemistry of the product is set through selective hydrogen atom transfer from the chiral thiol catalyst to a prochiral C-centered radical. Structure-selectivity relationships derived from structural variation of both the peptide catalyst and olefin substrate provide key insights into the development of an optimal catalyst. Experimental and computational mechanistic studies indicate that hydrogen-bonding, π-π stacking, and London dispersion interactions are contributing factors for substrate recognition and enantioinduction. These findings further the development of radical-based asymmetric catalysis and contribute to the understanding of the noncovalent interactions relevant to such transformations.

Enantioselective Synthesis of (-)-10-Hydroxyacutuminine.

An enantioselective synthesis of (-)-10-hydroxyacutuminine is reported. Central to our strategy is a photochemical [2+2] cycloaddition that forges two of the quaternary stereocenters present in the acutumine alkaloids. A subsequent retro-aldol/Dieckmann sequence furnishes the spirocyclic cyclopentenone. Efforts to chlorinate the acutumine scaffold at C10 under heterolytic or radical deoxychlorination conditions led to the synthesis of an unexpected cyclopropane-containing pentacycle.

Total Syntheses of the C19 Diterpenoid Alkaloids (-)-Talatisamine, (-)-Liljestrandisine, and (-)-Liljestrandinine by a Fragment Coupling Approach.

The C19 diterpenoid alkaloids (C19 DTAs) are a large family of natural products, many of which modulate the activity of ion channels in vivo and are therefore of interest for the study of neurological and cardiovascular diseases. The complex architectures of these molecules continue to challenge the state-of-the art in chemical synthesis, particularly with respect to efficient assembly of their polcyclic ring systems. Here, we report the total syntheses of (-)-talatisamine, (-)-liljestrandisine, and (-)-liljestrandinine, three aconitine-type C19 DTAs, using a fragment coupling strategy. Key to this approach is a 1,2-addition/semipinacol rearrangement sequence which efficiently joins two complex fragments and sets an all-carbon quaternary center.

Biphilic Organophosphorus Catalysis: Regioselective Reductive Transposition of Allylic Bromides via P(III)/P(V) Redox Cycling.

We report that a regioselective reductive transposition of primary allylic bromides is catalyzed by a biphilic organophosphorus (phosphetane) catalyst. Spectroscopic evidence supports the formation of a pentacoordinate (σ(5)-P) hydridophosphorane as a key reactive intermediate. Kinetics experiments and computational modeling are consistent with a unimolecular decomposition of the σ(5)-P hydridophosphorane via a concerted cyclic transition structure that delivers the observed allylic transposition and completes a novel P(III)/P(V) redox catalytic cycle. These results broaden the growing repertoire of reactions catalyzed within the P(III)/P(V) redox couple and suggest additional opportunities for organophosphorus catalysis in a biphilic mode.