Asymmetric counteranion-directed photoredox catalysis.

Photoredox catalysis enables distinctive and broadly applicable chemical reactions, but controlling their selectivity has proven to be difficult. The pursuit of enantioselectivity is a particularly daunting challenge, arguably because of the high energy of the activated radical (ion) intermediates, and previous approaches have invariably required pairing of the photoredox catalytic cycle with an additional activation mode for asymmetric induction. A potential solution for photoredox reactions proceeding via radical ions would be catalytic pairing with enantiopure counterions.

Organocatalytic stereoselective cyanosilylation of small ketones.

Enzymatic stereoselectivity has typically been unrivalled by most chemical catalysts, especially in the conversion of small substrates. According to the 'lock-and-key theory', enzymes have confined active sites to accommodate their specific reacting substrates, a feature that is typically absent from chemical catalysts. An interesting case in this context is the formation of cyanohydrins from ketones and HCN, as this reaction can be catalysed by various classes of catalysts, including biological, inorganic and organic ones.

Unified Approach to Imidodiphosphate-Type Brønsted Acids with Tunable Confinement and Acidity.

We have designed and realized an efficient and operationally simple single-flask synthesis of imidodiphosphate-based Brønsted acids. The methodology proceeds consecutive chloride substitutions of hexachlorobisphosphazonium salts, providing rapid access to imidodiphosphates (IDP), iminoimidodiphosphates (IDP), and imidodiphosphorimidates (IDPi). These privileged acid catalysts feature a broad acidity range (p from ∼11 to <2 in MeCN) and a readily tunable confined active site.

The Smelling Principle of Vetiver Oil, Unveiled by Chemical Synthesis.

Vetiver oil, produced on a multiton-scale from the roots of vetiver grass, is one of the finest and most popular perfumery materials, appearing in over a third of all fragrances. It is a complex mixture of hundreds of molecules and the specific odorant, responsible for its characteristic suave and sweet transparent, woody-ambery smell, has remained a mystery until today. Herein, we prove by an eleven-step chemical synthesis, employing a novel asymmetric organocatalytic Mukaiyama-Michael addition, that (+)-2-epi-ziza-6(13)en-3-one is the active smelling principle of vetiver oil.

Catalytic enantiocontrol over a non-classical carbocation.

Carbocations can be categorized into classical carbenium ions and non-classical carbonium ions. These intermediates are ubiquitous in reactions of both fundamental and practical relevance, finding application in the petroleum industry as well as the discovery of new drugs and materials. Conveying stereochemical information to carbocations is therefore of interest to a range of chemical fields.

Homologation of the Fischer Indolization: A Quinoline Synthesis via Homo-Diaza-Cope Rearrangement.

We disclose a new Brønsted acid promoted quinoline synthesis, proceeding via homo-diaza-Cope rearrangement of N-aryl-N'-cyclopropyl hydrazines. Our strategy can be considered a homologation of Fischer's classical indole synthesis and delivers 6-membered N-heterocycles, including previously inaccessible pyridine derivatives. This approach can also be used as a pyridannulation methodology toward constructing polycyclic polyheteroaromatics.

Strong and Confined Acids Control Five Stereogenic Centers in Catalytic Asymmetric Diels-Alder Reactions of Cyclohexadienones with Cyclopentadiene.

We describe a highly enantioselective Diels-Alder reaction of cross-conjugated cyclohexadienones with cyclopentadiene, in which five stereocenters are effectively controlled by a strongly acidic and confined imidodiphosphorimidate catalyst. Our approach provides tricyclic products in excellent stereoselectivity. We also report methods to convert the obtained products into useful intermediates and a computational study that aids in gaining deeper insight into the reaction mechanism and origin of stereoselectivity.

Strong and Confined Acids Enable a Catalytic Asymmetric Nazarov Cyclization of Simple Divinyl Ketones.

We report a catalytic asymmetric Nazarov cyclization of simple, acylic, alkyl-substituted divinyl ketones using our recently disclosed strong and confined imidodiphosphorimidate Brønsted acids. The corresponding monocyclic cyclopentenones are formed in good yields and excellent regio-, diastereo-, and enantioselectivities. Further, the chemical utility of the obtained enantiopure cyclopentenones is demonstrated.

Approaching sub-ppm-level asymmetric organocatalysis of a highly challenging and scalable carbon-carbon bond forming reaction.

The chemical synthesis of organic molecules involves, at its very essence, the creation of carbon-carbon bonds. In this context, the aldol reaction is among the most important synthetic methods, and a wide variety of catalytic and stereoselective versions have been reported. However, aldolizations yielding tertiary aldols, which result from the reaction of an enolate with a ketone, are challenging and only a few catalytic asymmetric Mukaiyama aldol reactions with ketones as electrophiles have been described.

Asymmetric Catalysis of the Carbonyl-Amine Condensation: Kinetic Resolution of Primary Amines.

A Brønsted acid catalyzed kinetic resolution of primary amines is described that is based on the condensation between an amine and a carbonyl compound. 1,3-Diketones react with racemic α-branched amines to furnish the corresponding enantioenriched enaminone and recovered starting material. Good to excellent enantioselectivity was observed with both aromatic and aliphatic primary amines.

Nitrated Confined Imidodiphosphates Enable a Catalytic Asymmetric Oxa-Pictet-Spengler Reaction.

The development of a highly enantioselective catalytic oxa-Pictet-Spengler reaction has proven a great challenge for chemical synthesis. We now report the first example of such a process, which was realized by utilizing a nitrated confined imidodiphosphoric acid catalyst. Our approach provides substituted isochroman derivatives from both aliphatic and aromatic aldehydes with high yields and excellent enantioselectivities.

A Dual-Catalysis Anion-Binding Approach to the Kinetic Resolution of Amines: Insights into the Mechanism via a Combined Experimental and Computational Study.

Racemic benzylic amines undergo kinetic resolution via benzoylation with benzoic anhydride in the presence of a dual catalyst system consisting of a readily available amide-thiourea catalyst and 4-dimethylaminopyridine (DMAP). An evaluation of various experimental parameters was performed in order to derive a more detailed understanding of what renders this process selective. The catalyst's aggregation behavior and anion-binding ability were evaluated in regard to their relevance for the catalytic process.

Catalytic asymmetric dearomatizing redox cross coupling of ketones with aryl hydrazines giving 1,4-diketones.

An asymmetric Brønsted acid catalyzed dearomatizing redox cross coupling reaction has been realized, in which aryl hydrazines react with ketones to deliver 1,4-diketones, bearing an all-carbon quarternary stereocenter in high enantiopurity.

A dual-catalysis approach to the kinetic resolution of 1,2-diaryl-1,2-diaminoethanes.

The kinetic resolution of racemic C(2)-symmetric 1,2-diaryl-1,2-diaminoethanes was accomplished for the first time through application of a dual-catalysis approach.

A dual-catalysis approach to the asymmetric Steglich rearrangement and catalytic enantioselective addition of O-acylated azlactones to isoquinolines.

A dual-catalysis approach, namely the combination of an achiral nucleophilic catalyst and a chiral anion-binding catalyst, was applied to the Steglich rearrangement to provide α,α-disubstituted amino acid derivatives in a highly enantioselective fashion. Replacement of the nucleophilic co-catalyst for isoquinoline resulted in a divergent reaction pathway and an unprecedented transformation of O-acylated azlactones. This strategy provided highly substituted α,β-diamino acid derivatives with excellent levels of stereocontrol.

Catalytic enantioselective desymmetrization of meso-diamines: a dual small-molecule catalysis approach.

The desymmetrization of meso-diamines was accomplished via enantioselective monobenzoylation facilitated by the cooperative action of two small-molecule catalysts. A chiral acyl-transfer reagent is formed in situ through the interplay of benzoic anhydride, 4-(dimethylamino)pyridine as a nucleophilic catalyst, and a chiral amide-thiourea cocatalyst.

Redox-neutral indole annulation cascades.

Aminobenzaldehydes react with indoles in an unprecedented cascade reaction. This acid-catalyzed redox-neutral annulation proceeds via a condensation/1,5-hydride shift/ring-closure sequence. Polycyclic azepinoindoles and related compounds are obtained in a single step with good to excellent yields.

Merging nucleophilic and hydrogen bonding catalysis: an anion binding approach to the kinetic resolution of propargylic amines.

An efficient kinetic resolution of primary propargylic amines with s-factors of up to 56 is reported. The strategy is based on a dual catalytic approach, namely the use of a newly developed and easy-to-make thiourea-amide anion binding catalyst in combination with 4-(dimethylamino)pyridine (DMAP), both employed at a 5 mol % catalyst loading. Benzylic amines are also resolved with s-factors of up to 38.

Merging nucleophilic and hydrogen bonding catalysis: an anion binding approach to the kinetic resolution of amines.

A new concept for asymmetric nucleophilic catalysis is presented. Acyl pyridinium salts derived from 4-(dimethylamino)pyridine (DMAP) and benzoic anhydride are rendered chiral via interaction with a chiral thiourea anion receptor. The power of this concept is demonstrated in the context of kinetic amine resolution.