Highly Regio‐ and Enantioselective Synthesis of N‐Substituted 2‐Pyridones: Iridium‐Catalyzed Intermolecular Asymmetric Allylic Amination

The first iridium‐catalyzed intermolecular asymmetric allylic amination reaction with 2‐hydroxypyridines has been developed, thus providing a highly efficient synthesis of enantioenriched N‐substituted 2‐pyridone derivatives from readily available starting materials. This protocol features a good tolerance of functional groups in both the allylic carbonates and 2‐hydroxypyridines, thereby delivering multifunctionalized heterocyclic products with up to 98 % yield and 99 % ee.     

Copper‐Catalyzed Enantioselective Allyl–Allyl Coupling between Allylic Boronates and Phosphates with a Phenol/N‐Heterocyclic Carbene Chiral Ligand

Copper‐catalyzed enantioselective allyl–allyl coupling between allylboronates and either Z‐acyclic or cyclic allylic phosphates using a new chiral N‐heterocyclic carbene ligand, bearing a phenolic hydroxy, is reported. This reaction occurs with exceptional S_N2′‐type regioselectivities and high enantioselectivities to deliver chiral 1,5‐diene derivatives with a tertiary stereogenic center at the allylic/homoallylic position.     

Iridium‐Catalyzed Regio‐ and Enantioselective Allylic Substitution of Silyl Dienolates Derived from Dioxinones

Reported herein is the iridium‐catalyzed regio‐ and enantioselective allylic substitution reactions of unstabilized silyl dienolates derived from dioxinones. Asymmetric allylic substitution of a variety of allylic trichloroethyl carbonates with these silyl dienolates gave γ‐allylated products selectively in 60–84 % yield and 90–98 % ee.     

Enantioselective intramolecular crossed Rauhut-Currier reactions through cooperative nucleophilic activation and hydrogen-bonding catalysis: scope and mechanistic insight

A highly efficient and enantioselective intramolecular crossed Rauhut-Currier (RC) reaction of nitroolefins with tethered enonates has been developed through cooperative nucleophilic activation and a hydrogen-bonding catalytic strategy (≤98% ee and 98% yield). The reaction features simple experimental procedures and is completely chemoselective and atom-economic in character. The potential synthetic applications have been demonstrated by the conversion of the RC reaction products into biologically and pharmaceutically valuable compounds with highly diastereoselectivity. In addition, computational investigations were employed to support the proposed mechanism and to obtain a good understanding of the origin of the stereoselectivity in RC reactions.     

Enantioselective and diastereoselective Tsuji-Trost allylic alkylation of lactones: an experimental and computational study

The Tsuji-Trost protocol has been successfully employed for the allylic alkylation of preformed lactone enolates. It has been demonstrated that this Pd-catalyzed reaction can be carried out in an enantio- and diastereoselective manner. The use of additives, such as LiCl, was found to be crucial for reaching high levels of product selectivity. For one particular pair of reactants, density functional theory was used to investigate the mechanism of the nucleophilic addition. Among the five pathways considered, the reaction between an (allyl)Pd(BINAP) complex and a LiCl-lithium enolate adduct is predicted to be the most likely route for C-C bond formation. LiCl plays a key role as the connecting link between the noble metal and the enolate in the kinetically favored transition state. The computed diastereoselectivity ratio is in good agreement with the experimentally observed value.     

Ir‐Catalysed Asymmetric Allylic Substitutions with Cyclometalated (Phosphoramidite)Ir Complexes—Resting States,Catalytically Active (π‐Allyl)Ir Complexes and Computational Exploration

Mechanistic aspects of allylic substitutions with iridium catalysts derived from phosphoramidites by cyclometalation were investigated. The determination of resting states by ³¹P NMR spectroscopy led to the conclusion that the cyclometalation process is reversible. A novel, one‐pot procedure for the preparation of (π‐ allyl)Ir complexes was developed, and these complexes were characterised by X‐ray crystal structure analyses and spectral data. They are fully active catalysts of the allylic substitution reaction. DFT calculations on the allyl complexes, transition states of the allylic substitution and product olefin complexes gave further mechanistic insight.     

Enantioselective palladium-catalyzed addition of 1,3-dicarbonyl compounds to an allene derivative

Enhancing atom economy of the metal‐catalyzed asymmetric allylic alkylation (AAA) shifts from the usual nucleophilic displacement of a leaving group to an addition of a pronucleophile to a double bond. Using 1‐alkoxyallenes as proelectrophiles, the palladium‐catalyzed AAA proceeds with 1,3‐dicarbonyl compounds as pronucleophiles with excellent regioselectivity and enantiomeric excess under optimized conditions. The pH of the medium proved crucial for reactivity/selectivity. By using the more acidic Meldrum's acids, the reactions required a co‐catalytic amount of Brønsted acid, such as trifluoroacetic acid. Single regioisomeric products of 82–99 % ee were obtained. On the other hand, the less acidic 1,3‐diketones failed to react under such conditions. The fact that a less acidic acid like benzoic acid sufficed, suggested the need for general base catalysis as well. Thus, a mixture of triethylamine and benzoic acid proved optimal (ee's 93–99). Employment of the (R,R)‐phenyl Trost ligand gave a product with S configuration. A model to rationalize the results has been developed.     

Organocatalytic Enantioselective Cross‐Vinylogous Rauhut–Currier Reaction of Methyl Coumalate with Enals

The organocatalytic enantioselective intermolecular cross‐vinylogous Rauhut–Currier (RC) reaction of methyl coumalate with α,β‐unsaturated aldehydes is reported, and the enals are activated by iminium catalysis to serve as the Michael acceptors and methyl coumalate is used as an activated diene to generate a latent enolate. The excellent selectivity is driven by the aromaticity of methyl coumalate, and the post transformation of this heterocyclic structure into other electron‐deficient arenes and heterocycles have addressed, in part, the challenging selectivity issues of the intermolecular cross‐RC reactions and the limited scope of iminium catalysis.     

Synthetic scope of Ru(OH)x/Al2O3-catalyzed hydrogen-transfer reactions: an application to reduction of allylic alcohols by a sequential process of isomerization/Meerwein-Ponndorf-Verley-type reduction

Reduction of allylic alcohols can be promoted efficiently by the supported ruthenium catalyst Ru(OH)x/Al2O3. Various allylic alcohols were converted to saturated alcohols in excellent yields by using 2-propanol without any additives. This Ru(OH)x/Al2O3-catalyzed reduction of a dienol proceeds only at the allylic double bond to afford the corresponding enol, and chemoselective isomerization and reduction can be realized under similar conditions. The catalysis is truly heterogeneous and the high catalytic performance can be maintained during at least three recycles of the Ru(OH)x/Al2O3 catalyst. The transformation of allylic alcohols to saturated alcohols consists of three sequential reactions: oxidation of allylic alcohols to alpha,beta-unsaturated carbonyl compounds; reduction of alpha,beta-unsaturated carbonyl compounds to saturated carbonyl compounds; and reduction of saturated carbonyl compounds to saturated alcohols.     

Nickel‐Catalyzed Allylic Alkylation with Diarylmethane Pronucleophiles: Reaction Development and Mechanistic Insights

Palladium‐catalyzed allylic substitution reactions are among the most efficient methods to construct C?C bonds between sp³‐hybridized carbon atoms. In contrast, much less work has been done with nickel catalysts, perhaps because of the different mechanisms of the allylic substitution reactions. Palladium catalysts generally undergo substitution by a “soft”‐nucleophile pathway, wherein the nucleophile attacks the allyl group externally. Nickel catalysts are usually paired with “hard” nucleophiles, which attack the metal before C?C bond formation. Introduced herein is a rare nickel‐based catalyst which promotes substitution with diarylmethane pronucleophiles by the soft‐nucleophile pathway. Preliminary studies on the asymmetric allylic alkylation are promising.