A catalytic enantioselective and regiodivergent arylation of alkenes is described. Chiral copper(II)bisoxazoline complexes catalyze the addition diaryliodonium salts to allylic amides in excellent ee. Moreover, can be controlled by electronic nature salt enabling preparation nonracemic diaryloxazines or β,β′-diaryl enamides.

The copper-catalyzed conjugate addition of various Grignard reagents to polyconjugated enones (dienone and enynone derivatives) is reported. catalyst system, composed copper triflate an NHC ligand, led the unusual selective formation 1,4-addition products. This reaction allows for creation all-carbon chiral quaternary centers with enantiomeric excesses up 99%. remaining unsaturation on 1,4 adducts give access valuable synthetic transformations.

Chiral amines catalyze the enantioselective conjugate addition of aldehydes to vinyl phosphonates in high yields and with enantioselectivities up 97% ee. This novel process provides synthetically useful chiral γ-geminal phosphonate which can be easily converted a few steps into β-substituted conservation optical purity.

The first highly enantioselective and regiodivergent conjugate addition of trialkylaluminium reagents to nitrodienes nitroenynes is described. By a design the substrate fine-tuning reaction conditions, it possible selectively form 1,4- or 1,6-adduct. same combination catalyst, copper source, ferrocene-based phosphine ligand afforded enantioselectivities up 95% 91%, respectively.

Readily available alkenylalanes, arising from hydroalumination of unprotected terminal alkynes, have been directly employed for the copper-catalyzed asymmetric conjugate addition (ACA) to β-substituted cyclic enones. The desired products, containing a quaternary stereogenic center, are generally obtained in good yields and enantioselectivities.

In this letter we describe an unusual result in terms of regioselectivity with respect to copper-catalyzed conjugate additions various Grignard reagents cyclic enynones. The use Cu(OTf)2 and NHC ligand L1 as the catalyst combination CH2Cl2 led unique formation 1,4 adduct. This selectivity does not follow general trend previously observed literature using extended Michael acceptors. Moreover these reactions allowed for creation a quarternary stereogenic center enantioselectivities up 97% ee.

Abstract A gram‐scale catalytic enantioselective formal synthesis of morphine is described. The key steps the involve an ortho–para oxidative phenolic coupling and a highly diastereoselective “desymmetrization” resulting cyclohexadienone that generates three four morphinan ring junction stereocenters in one step. stereochemistry controlled from single carbinol center installed through hydrogenation. These transformations enabled preparation large quantities intermediates could support...

Abstract The copper‐catalysed conjugate addition of trialkylaluminium and dialkylzinc reagents to polyconjugated nitroolefins (nitrodiene nitroenyne derivatives) is reported. A reversed Josiphos ligand L7 allows for the selective 1,4‐ or 1,6‐addition with high enantioselectivities.

The formation of chiral and sterically congested cyclohexanone derivatives has been achieved through a multistep sequence with one single purification step. (n-Butoxymethyl)-diethylamine was identified as highly efficient reagent for the direct trapping aluminum enolates. Lewis acidic character suffices to activate α-aminoether form in situ an electrophilic iminium species. In return enolate is rendered more nucleophilic by coordination butoxy group aluminate.

Synthesis of 1,3-substituted cyclobutyls enabled by zinc insertion into functionalized iodocyclobutyl derivatives followed Negishi coupling with halo-heteroaromatics is reported. Two distinct sets conditions were developed; the first involved a two-step batch protocol using activated Rieke zinc, and second multistep continuous flow process. Both methods showed complementarity allowed for rapid access to these medicinally relevant motifs, possibility scaling up, automation library synthesis.

Abstract A gram‐scale catalytic enantioselective formal synthesis of morphine is described. The key steps the involve an ortho–para oxidative phenolic coupling and a highly diastereoselective “desymmetrization” resulting cyclohexadienone that generates three four morphinan ring junction stereocenters in one step. stereochemistry controlled from single carbinol center installed through hydrogenation. These transformations enabled preparation large quantities intermediates could support...

SimplePhos ligands proved to be very powerful in the generation of quaternary stereogenic centers by Michael addition alkenyl-aluminum reagents cyclic enones. Using commercially available and easily accessible alkenylbromides as alane precursors present procedure offers a facile access β-alkenyl-substituted cyclohexanones with high enantioselectivities up 96%.

Abstract The first catalytic enantioselective total synthesis of riccardiphenol B, a sesquiterpene derivative isolated from Japanese collection the liverwort Riccardia crassa , has been achieved. A copper‐catalyzed asymmetric conjugate addition trimethylaluminum was used at an early stage to generate quaternary stereogenic center with high enantiomeric excess. corresponding sterically encumbered aluminum enolate directly trapped α‐amino ether, allowing after oxidation, release key...

We report an amination of mesylated cyclobutanol enabled by a multistep continuous flow process. The sequence involved azidation followed Staudinger reduction which avoids the handling and isolation hazardous alkyl azide compound. process is stereospecific with step proceeding to complete stereochemical inversion.

Computational reaction prediction has become a ubiquitous task in chemistry due to the potential value accurate predictions can bring chemists. Boronic acids are widely used industry; however, understanding how avoid protodeboronation side remains challenge. We have developed an algorithm for silico of rate boronic acids. A general mechanistic model devised through kinetic studies was found literature and forms foundation on which presented this work is built. Protodeboronation proceeds 7...

Herein, we introduce the concept of pseudoisotope to describe particles which have similar chemistry but different masses. Examples include ligands with substituents or metal ions identical charges and coordination properties. Mixtures pseudoisotopes may be used establish rapidly nuclearity polynuclear species by electrospray ionization-mass spectrometry. Pseudoisotope exchange allows study dynamics complexes, shows these reactions surprisingly slow. The evolution mass spectra indicates...

We report a large-scale carboxylation of N-Boc-4,4-difluoropiperidine (1) enabled by continuous flow process. The process involved N-Boc-directed α-deprotonation using s-BuLi in THF and subsequent trapping with CO2 gas. Flow chemistry the safe scalable preparation 400 g carboxylic acid 2 over course day to support our medicinal research program.

Abstract 3‐Aryl substituted (2Z)‐prop‐2‐en‐1‐ylamides are transformed in the presence of a chiral copper‐bisoxazoline catalyst with diaryliodonium salts.

Abstract The reaction of (I) and (VII) with Grignard reagents results in regio‐ enantioselective formation 1,4‐adducts.

Abstract A variety of alkenylalanes is applied in cyclopentenone, cyclohexenone and cycloheptenone derivatives using SimplePhos monodentate ligands.

Abstract The copper‐catalyzed addition of trialkylaluminum reagents to polyconjugated olefins using a ferrocene‐based phosphine ligand affords selectively 1,4‐addition products with high enantioselectivity.