Asymmetric Allylic Alkylation Research Articles

Palladium catalyzed asymmetric allylic alkylation of isoquinolinedione derivatives in the preparation of quaternary carbon stereocenters.

A highly enantioselective allylic alkylation of isoquinolinedione derivatives under palladium catalysis was developed in the preparation of quaternary carbon stereocenters. Under standard reaction conditions, excellent yields and enantioselectivities were realized and the products could be transformed into dihydroisoquinolone with vicinal chiral carbon centers or THIQ core structures in short steps with high yields.

Sequence-Dependent Stereodivergent Allylic Alkylation/Fluorination of Acyclic Ketones.

The stereodivergent iridium-catalyzed allylic alkylation and fluorination of acyclic ketones is described. α-Pyridyl-α-fluoroketones with vicinal tertiary and quaternary stereocenters were obtained in moderate to excellent yields and stereoselectivities. Distinct from known stereodivergent synthesis, for which two different chiral catalysts are required in general, herein we report a sequence-dependent stereodivergent synthesis. With only a single chiral Ir catalyst, all four possible stereoisomers of the products were prepared from the same starting materials by simply adjusting the sequence of asymmetric allylic alkylation and fluorination and varying the absolute configuration of the Ir catalyst.

Sequence‐Dependent Stereodivergent Allylic Alkylation/Fluorination of Acyclic Ketones

AbstractThe stereodivergent iridium‐catalyzed allylic alkylation and fluorination of acyclic ketones is described. α‐Pyridyl‐α‐fluoroketones with vicinal tertiary and quaternary stereocenters were obtained in moderate to excellent yields and stereoselectivities. Distinct from known stereodivergent synthesis, for which two different chiral catalysts are required in general, herein we report a sequence‐dependent stereodivergent synthesis. With only a single chiral Ir catalyst, all four possible stereoisomers of the products were prepared from the same starting materials by simply adjusting the sequence of asymmetric allylic alkylation and fluorination and varying the absolute configuration of the Ir catalyst.

Gold(III) π‐Allyl Complexes

AbstractGold(III) π‐complexes have been authenticated recently with alkenes, alkynes, and arenes. The key importance of PdII π‐allyl complexes in organometallic chemistry (Tsuji–Trost reaction) prompted us to explore gold(III) π‐allyl complexes, which have remained elusive so far. The (P,C)AuIII(allyl) and (methallyl) complexes 3 and 3′ were readily prepared and isolated as thermally and air‐stable solids. Spectroscopic and crystallographic analyses combined with detailed DFT calculations support tight quasi‐symmetric η3‐coordination of the allyl moiety. The π‐allyl gold(III) complexes are activated towards nucleophilic additions, as substantiated with β‐diketo enolates.

Gold(III) π-Allyl Complexes.

Gold(III) π-complexes have been authenticated recently with alkenes, alkynes, and arenes. The key importance of PdII π-allyl complexes in organometallic chemistry (Tsuji-Trost reaction) prompted us to explore gold(III) π-allyl complexes, which have remained elusive so far. The (P,C)AuIII (allyl) and (methallyl) complexes 3 and 3' were readily prepared and isolated as thermally and air-stable solids. Spectroscopic and crystallographic analyses combined with detailed DFT calculations support tight quasi-symmetric η3 -coordination of the allyl moiety. The π-allyl gold(III) complexes are activated towards nucleophilic additions, as substantiated with β-diketo enolates.

Functionalization and Post-Translational Modification of Cysteines by Tsuji–Trost Reaction

Functionalization and Post-Translational Modification of Cysteines by Tsuji–Trost Reaction

Kinetics and Inverse Temperature Dependence of a Tsuji–Trost Reaction in Aqueous Buffer

The palladium-catalyzed Tsuji–Trost reaction has been extensively studied under synthetically relevant conditions (millimolar concentrations of substrates and catalyst, aprotic solvents, no additiv...

Palladium-Catalyzed Decarboxylative Asymmetric Allylic Alkylation of 1,4-Diazepan-5-ones.

We report the palladium-catalyzed asymmetric allylic alkylation of 1,4-diazepan-5-ones. This reaction proceeds smoothly to give gem-disubstituted diazepanone heterocycles bearing various functional groups in up to >99% yield and up to 95% ee. An electron-rich p-anisoyl lactam protecting group and the use of a nonpolar solvent proved crucial to obtaining high enantioselectivity in most cases. Additionally, we demonstrate the use of our methodology in the synthesis of a gem-disubstituted analogue of the FDA-approved anti-insomnia drug suvorexant.

Development of a new ratiometric probe with near-infrared fluorescence and a large Stokes shift for detection of gasotransmitter CO in living cells.

A near-infrared (NIR) ratiometric fluorescent probe, NIR-Ratio-CO, was developed for rapid detection of carbon monoxide (CO) in both solution and living cells through the strategy of Pd0-mediated Tsuji-Trost reaction. This probe shows a rapid, highly specific and sensitive detection process for CO, accompanied by colorimetric and distinct ratiometric fluorescence changes at 655 and 592 nm with a large Stokes shift up to 195 nm. The detection limit for CO was measured to be about 61 nM by the fluorescence method. In addition, this probe was successfully applied for ratiometric imaging of both exogenous and endogenous CO in living cells, indicating that it can be used as a novel tool for ratiometric fluorescent detection of CO in living systems.

Rapid detection of CO in vitro and in vivo with a ratiometric probe showing near-infrared turn-on fluorescence, large Stokes shift, and high signal-to-noise ratio

A new near-infrared (NIR) fluorescent probe was developed for the detection of CO in living systems. This probe is based on a unique cyanine fluorophore and uses an allyl ether moiety as the reaction site. Optical studies in solution show that this probe has good water solubility and possesses desirable sensing properties for CO including rapid response, high selectivity and sensitivity, large Stokes shift (123 nm), distinct colorimetric changes, and significant turn-on NIR fluorescence changes at 715 nm with high signal-to-noise ratio. Ratiometric fluorescent detection of CO with this probe at 715 and 570 nm is also applicable. The sensing mechanism was proven to be a process of recovery of the fluorophore by removing the allyl group via Tsuji-Trost reaction. Furthermore, this probe was applied for detecting CO in living cells and animals with good bioimaging performance. Moreover, indicated by this probe, more CO could be produced under oxidative stress conditions. All the results indicate that this probe can be applied as a promising new tool for in vitro and in vivo detection of CO.

Novel Chiral Ligands for Palladium-catalyzed Asymmetric Allylic Alkylation/ Asymmetric Tsuji-Trost Reaction: A Review

Background: Asymmetric catalysis holds a prestigious role in organic syntheses since a long time and chiral inductors such as ligands have been used to achieve the utmost desired results at this pitch. The asymmetric version of Tsuji-Trost allylation has played a crucial role in enantioselective synthesis. Various chiral ligands have been known for Pdcatalyzed Asymmetric Allylic Alkylation (AAA) reactions and exhibited excellent catalytic potential. The use of chiral ligands as asymmetric inductors has widened the scope of Tsuji-Trost allylic alkylation reactions. Conclusion: Therefore, in this review article, a variety of chiral inductors or ligands have been focused for palladium catalyzed asymmetric allylic alkylation (Tsuji-Trost allylation) and in this regard, recently reported literature (2013-2017) has been described. The use of ligands causes the induction of enantiodiscrimination to the allylated products, therefore, the syntheses of various kinds of ligands have been targeted by many research groups to employ in Pd-catalyzed AAA reactions.

Catalytic Asymmetric Synthesis of Diketopiperazines by Intramolecular Tsuji-Trost Allylation.

We report the intramolecular Tsuji–Trost reaction of Ugi adducts to give spiro-diketopiperazines in high yield and with high enantioselectivity. This approach allows the catalytic asymmetric construction of a broad range of these medicinally important heterocycles under mild conditions, in two steps from cheap, commercially available starting materials.

Desymmetrization of Phosphinic Acids via Pd-Catalyzed Asymmetric Allylic Alkylation: Rapid Access to P-Chiral Phosphinates.

The synthesis of P-chiral compounds is challenging, especially since useful catalytic methods for preparing such molecules are scarce. Herein we disclose a desymmetrization that employs phosphinic acids as prochiral nucleophiles in a Pd-catalyzed asymmetric allylic alkylation reaction, furnishing phosphinates with high enantio- and diastereoselectivity. This new method has broad scope and is applied to the synthesis of an enantioenriched tertiary phosphine oxide.

Synthesis of β3-Amino Esters by Iridium-Catalyzed Asymmetric Allylic Alkylation Reaction

A method to prepare chiral β3-amino esters from methyl 3-aminopropanoate was described. This method capitalized on a sequence involving an Ir-catalyzed asymmetric allylation of 2-azaallyl anions an...

Development of Chemo‐ and Enantioselective Palladium‐Catalyzed Decarboxylative Asymmetric Allylic Alkylation of α‐Nitroesters

AbstractWe describe the development of a Pd‐catalyzed decarboxylative asymmetric allylic alkylation of α‐nitro allyl esters to afford acyclic tetrasubstituted nitroalkanes. Optimization of the reaction parameters revealed unique ligand and solvent combinations crucial for achieving chemo‐ and enantioselective C‐alkylation of electronically challenging benzylic nitronates and sterically encumbered 2‐allyl esters. Substrates were efficiently accessed in a combinatorial fashion by a cross‐Claisen/ α‐arylation sequence. The method provides functional group orthogonality that complements nucleophilic imine allylation strategies for α‐tertiary amine synthesis.

Development of Chemo- and Enantioselective Palladium-Catalyzed Decarboxylative Asymmetric Allylic Alkylation of α-Nitroesters.

We describe the development of a Pd-catalyzed decarboxylative asymmetric allylic alkylation of α-nitro allyl esters to afford acyclic tetrasubstituted nitroalkanes. Optimization of the reaction parameters revealed unique ligand and solvent combinations crucial for achieving chemo- and enantioselective C-alkylation of electronically challenging benzylic nitronates and sterically encumbered 2-allyl esters. Substrates were efficiently accessed in a combinatorial fashion by a cross-Claisen/ α-arylation sequence. The method provides functional group orthogonality that complements nucleophilic imine allylation strategies for α-tertiary amine synthesis.

A Near-infrared Fluorescent Probe of Dicyanoisophorone Derivatives for Selective Detection and Fluorescence Cellular Imaging of Palladium.

Palladium (Pd) has been acknowledged to be a rare inner transition metal, which plays a pivotal role in many fields. This article focuses on developing a safe and effective near-infrared fluorescent probe, MW-PD, which would make a great contribution to the detection of palladium residue in drugs, especially trace residues. The fluorescent probe was rationally designed by combining the dicyanoisophorone fluorophore with an allyloxycarbonyl group. Based on the Tsuji-Trost reaction, the probe exhibited high selectivity and sensitivity toward Pd (0) over other common metal ions with a low detection limit (8.0 nM). Moreover, MW-PD showed biocompatibility and was successfully applied to imaging Pd (0) in Hela cells.

Benzothiazole derived ratiometric fluorescent probe for selective detection of Pd(0) based on Tsuji-Trost reaction

A novel ratiometric fluorescent probe (emission shift 112 nm) BTP-Pd based on benzothiazole derivatives has been developed for the detection of Pd(0). The structure of the probe BTP-Pd was characterized by 1H/13C NMR spectra, high-resolution mass spectra (HRMS) and X-ray crystallography. The probe BTP-Pd displays rapid fluorescence response (about 10 min) and low saturation concentration (about 4 μM) toward Pd(0). Moreover, the probe BTP-Pd can be used to discriminate Pd(0) and Pd2+. Therefore, it would provide an approach for detecting not only Pd(0), but also Pd2+ through reductant reduction in environment system.

Asymmetric Allylic Alkylation of Alkanoic‐Acid Ester Enolates

A protocol for the direct palladium‐catalyzed asymmetric allylic alkylation of simple alkanoic‐acid esters through their lithium enolates has been developed. The method permits to create stereogenic centers in the homo‐allylic or allylic position. The configuration of the allylation products has been elucidated.

Dynamic Kinetic Resolution of Axially Chiral Naphthamides via Atroposelective Allylic Alkylation Reaction.

Axially chiral amides are usually found in many biologically active compounds and are useful ligands in asymmetric catalysis. Herein, by using the dynamic kinetic resolution approach, an asymmetric allylic alkylation reaction of racemic amide naphthols is disclosed, which leads to generation of the axially chiral naphthamides in good to excellent yields (up to 97%) and enantioselectivities (up to 96:4 e.r.). Density functional theory was used to gain a theoretical understanding of the enantioselectivities in this reaction.