Stereoselective Allylation Research Articles

Facile synthesis of homoallylamines via α-regioselectivity in ultrasonic mediation and γ-adduct syn-stereoselective allylation with AlCl3-catalysis

The allylation reaction of aldimines with allyl metal reagents is an important synthetic method for the preparation of homoallylamines. Therefore, we wish to report a highly regioselective and stereoselective allylation reaction under sonochemical Barbier-type reaction conditions. The high yields of regioselective α-adducts were achieved by reacting cinnamyl bromide, zinc, 1,2-dibromoethane, and aldimine in THF under sonochemical Barbier-type conditions. Highly regioselective and stereoselective allylation reactions were also achieved under Lewis acid-promoted Barbier-type reaction conditions.

Synthesis of C21‐C41 fragment of the reported structure of Neaumycin B

AbstractStereoselective synthesis of the C21‐C41 fragment 4 of the reported structure of Neaumycin B(1), a 28‐membered macrolide compound with 19‐chiral centers and 6,6‐spiroketal structure, has been described. C21‐C27 fragment 5 was synthesized from the commercially available (S)‐Roche ester 7 using stereoselective allylation and Brown anti‐crotylation as key steps. C28‐C41 fragment 6 was constructed from chiral oxazolidinone auxiliary 13 using Evans syn‐aldol reaction, diastereoselective epoxidation, and (S)‐CBS reduction as key steps. Finally, boron‐mediated acetate aldol reaction of 5 and 6 led to the synthesis of C21‐C41 fragment 4 for the reported structure of Neaumycin B (1).

Discovery and Bioinspired Synthesis of Salpratone A.

Salpratone A (1), a novel abietane diterpenoid containing a unique cis-fused A/B ring, was isolated from Salvia prattii. Bioactivity studies showed that 1 has potent activity in inhibiting platelet aggregation induced by multiple agonists as well as antithrombotic efficacy in the FeCl3-induced rat in vivo thrombosis model. Furthermore, a bioinspired synthesis of 1 from the abundant natural product ferruginol was achieved in 6 steps with a 22% overall yield. The key steps include a stereoselective allyl oxidation and a subsequent regioselective Meinwald rearrangement.

Synthesis of a Propellane-Type 5/5/6-Tricyclic System by Tandem-Metathesis: A New Approach to a Quadranoid Skeleton

AbstractWe disclose a useful synthetic method for preparing the propellane-type 5/5/6-tricyclic system that is present in diquinane-based natural products such as quadrone, terrecyclic acid A, or terrecyclol. The method involves an LDA-mediated regio- and stereoselective allylation and a tandem metathesis as key steps. The target molecules were assembled in just two steps starting from a readily available building block, a 3β-vinyl tricyclic ketone prepared from endo-dicyclopentadiene-1-one. All the compounds prepared were characterized by NMR analyses and/or chemical methods. The synthetic methods demonstrated here are useful in syntheses of quadranoid-type natural products.

Enantioselective Palladium-Catalyzed Directed Migratory Allylation of Remote Dienes.

Chain walking has been an efficient route to realize the functionalization of inert C(sp3 )-H bonds, but this strategy is limited to mono-olefin migration and functionalization. Herein, we demonstrate the feasibility of tandem directed simultaneous migrations of remote olefins and stereoselective allylation for the first time. The adoption of palladium hydride catalysis and secondary amine morpholine as solvent is critical for achieving high substrate compatibility and stereochemical control with this method. The protocol is also applicable to the functionalization of three vicinal C(sp3 )-H bonds and thus construct three continuous stereocenters along a propylidene moiety via a short synthetic process. Preliminary mechanistic experiments corroborated the design of simultaneous walking of remote dienes.

Enantioselective Palladium‐Catalyzed Directed Migratory Allylation of Remote Dienes

AbstractChain walking has been an efficient route to realize the functionalization of inert C(sp3)−H bonds, but this strategy is limited to mono‐olefin migration and functionalization. Herein, we demonstrate the feasibility of tandem directed simultaneous migrations of remote olefins and stereoselective allylation for the first time. The adoption of palladium hydride catalysis and secondary amine morpholine as solvent is critical for achieving high substrate compatibility and stereochemical control with this method. The protocol is also applicable to the functionalization of three vicinal C(sp3)−H bonds and thus construct three continuous stereocenters along a propylidene moiety via a short synthetic process. Preliminary mechanistic experiments corroborated the design of simultaneous walking of remote dienes.

Regio- and Stereoselective Allylation of Anilines with Aryl Allenes in Hexafluoroisopropanol Solvent.

A regio- and stereoselective allylation of N-unsubstituted anilines has been developed that explores aryl allenes as masked allyl synthons and a combination of Mg(OTf)2/HFIP as an effective proton source. The protocol is operationally simple and scalable and offers high yields of diverse p-allyl anilines bearing an olefin motif with exclusive E-geometry. The methodology was also suitable for the regioselective allylation of indole and can be advanced in a three-component reaction mode using NIS activator. The alteration of the catalytic system with TfOH resulted in the regioselective difunctionalization of allenes, which follows an allylation/hydroarylation cascade.

Design and Synthesis of Linearly Fused Triquinanes through Tandem‐Metathesis: Access to Basic Core of Cucumin, Capnellene, Chondrosterin, and Xeromphalinone

AbstractHerein, a short synthetic approach to linearly fused tricyclic enone 1 and cis‐anti‐cis type hydroxy‐triquinane 2 has been described in an efficient manner by employing tandem‐metathesis as a key step. The triquinane‐based enone 1 is prepared by a Babler–Dauben oxidation of hydroxy‐triquinane 2, which is assembled by following a three‐step sequence involving a regio‐ and stereoselective allylation, vinyl Grignard addition, and tandem‐metathesis. Our strategy relies on exo‐tricyclic ketone, which is derived from readily available exo‐dicyclopentadiene‐1‐one. The newly synthesized molecules were identified and characterized by nuclear magnetic resonance spectroscopy (NMR), and high‐resolution mass spectrometry (HRMS) data. It is worth mentioning that tricyclic enone 1 is present as a core unit of many naturally occurring polyquinanes, particularly xeromphalinone family members. Hence, our approach may be useful in the synthesis of such bioactive molecules.

Catalyst Controlled Site- and Stereoselective Rhodium(II) Carbene C(sp3)-H Functionalization of Allyl Boronates.

Rhodium(II) catalyst-controlled site- and stereoselective carbene insertion into the distal allylic C(sp3)-H bond of allyl boronates is reported. The optimum chiral catalyst for this reaction is Rh2(S-TPPTTL)4. The fidelity and asymmetric induction of this catalytic transformation allows for a highly diastereoselective and enantioselective C-C bond formation without interference from the allyl boronate functionality. The resulting functionalized allyl boronates are susceptible to stereoselective allylations, generating products with control of stereochemistry at four contiguous stereogenic centers.

Influence of Achiral Phosphine Ligands on a Synergistic Organo- and Palladium-Catalyzed Asymmetric Allylic Alkylation.

An unusual diastereodivergent stereoselective allylation reaction is presented. It consists of a palladium-catalyzed allylation reaction of an organocatalytically generated amino isobenzofulvene, where the diastereoselectivity is controlled by the electronic properties of a monodentate, achiral ligand on palladium. One major diastereoisomer is formed using triarylphosphines substituted with neutral or electron-donating substituents of the aryl group, while those with electron-withdrawing substituents favor the other diastereoisomer. The diastereoselectivity correlates with the Taft inductive parameter of substituents on the triarylphosphine ligand on palladium. The synergistic reaction involves both a catalytic secondary amine catalyst for the indene-aldehyde activation and the monodentate phosphine ligands on palladium, affording a highly enantioselective reaction with up to 98 % enantiomeric excess. Based on computational investigations, the role of the monodentate phosphine ligand on the diastereoselectivity is discussed.

Rhodium-Catalyzed Intermolecular Stereoselective Allylation of Indoles with Allenes

Rhodium-Catalyzed Intermolecular Stereoselective Allylation of Indoles with Allenes

Nickel‐Mediated Enantioselective Photoredox Allylation of Aldehydes with Visible Light

AbstractHere we report a practical, highly enantioselective photoredox allylation of aldehydes mediated by chiral nickel complexes with commercially available allyl acetate as the allylating agent. The methodology allows the clean stereoselective allylation of aldehydes in good to excellent yields and up to 93 % e.e. using a catalytic amount of NiCl2(glyme) in the presence of the chiral aminoindanol‐derived bis(oxazoline) as the chiral ligand. The photoredox system is constituted by the organic dye 3DPAFIPN and a Hantzsch's ester as the sacrificial reductant. The reaction proceeds under visible‐light irradiation (blue LEDs, 456 nm) at 8–12 °C. Compared to other published procedures, no metal reductants (such as Zn or Mn), additives (e.g. CuI) or air‐sensitive Ni(COD)2 are necessary for this reaction. Accurate DFT calculations and photophysical experiments have clarified the mechanistic picture of this stereoselective allylation reaction.

Nickel-Mediated Enantioselective Photoredox Allylation of Aldehydes with Visible Light.

Here we report a practical, highly enantioselective photoredox allylation of aldehydes mediated by chiral nickel complexes with commercially available allyl acetate as the allylating agent. The methodology allows the clean stereoselective allylation of aldehydes in good to excellent yields and up to 93 % e.e. using a catalytic amount of NiCl2 (glyme) in the presence of the chiral aminoindanol-derived bis(oxazoline) as the chiral ligand. The photoredox system is constituted by the organic dye 3DPAFIPN and a Hantzsch's ester as the sacrificial reductant. The reaction proceeds under visible-light irradiation (blue LEDs, 456 nm) at 8-12 °C. Compared to other published procedures, no metal reductants (such as Zn or Mn), additives (e.g. CuI) or air-sensitive Ni(COD)2 are necessary for this reaction. Accurate DFT calculations and photophysical experiments have clarified the mechanistic picture of this stereoselective allylation reaction.

Towards α,α-disubstituted amino acids containing vicinal stereocenters via stereoselective transition-metal catalyzed allylation

Towards α,α-disubstituted amino acids containing vicinal stereocenters via stereoselective transition-metal catalyzed allylation

Synergistic Pd/Cu catalysis for stereoselective allylation of vinylethylene carbonates with glycine iminoesters: Enantioselective access to diverse trisubstituted allylic amino acid derivatives

We reported a synergistic Pd/Cu catalyzed enantioselective decarboxylative allylation of vinylethylene carbonates with glycine iminoesters, which provides facile access to non-proteinogenic diverse trisubstituted allylic amino acid derivatives in high yields, exclusive regioselectivities and excellent stereoselectivities. This reaction tolerates a wide range of γ and β-aryl substituted vinylethylene carbonates with either electron-donating or electron-withdrawing groups. Significantly, this method was proven to be sufficient in the gram scale synthesis of chiral trisubstituted allylic amino acid while retaining the enantioselectivity and geometric control.

Stereoselective allylation of isatinimines with γ-substituted allylboronic acids

A highly efficient asymmetric allylboration of isatinimines with γ-substituted allylboronic acids under metal-free conditions was disclosed. Employing chiral amino alcohol as the chirality controller, the reaction proceeded with high efficiency and excellent stereoselectivity, providing a broad range of chiral 3-allyl-3-hydroxyethylamino oxindoles containing adjacent quaternary–tertiary stereocenters in high yields with excellent diastereoselectivities (up to 92% yield, >20:1 d.r.)

Chiral bipyridine-annulated bicyclo[3.3.1]nonane N-oxide organocatalysts for stereoselective allylation and hydrosilylation reactions

Abstract The synthesis of chiral C2-symmetric bis(bipyridine N,N′-dioxide) and bis(bipyridine N-monooxide) derivatives featuring bipyridine-annulated bicyclo[3.3.1]nonane framework is reported. The new Lewis basic bipyridine N,N′-dioxides exhibited good catalytic activity in the asymmetric allylation of aldehydes with allyltrichlorosilane, furnishing corresponding homoallylic alcohols in up to 75% ee. Reduction of ketimines and β-enamino esters with trichlorosilane catalyzed by bipyridine N,N′-dioxides proceeded in high yields but modest enantioselectivity (38–54% ee); good levels of asymmetric induction (up to 73% ee) were attained in the reduction of α-imino esters at room temperature.

Stereoselective Allylic Alkylations of Amino Ketones and Their Application in the Synthesis of Highly Functionalized Piperidines.

Chelated ketone enolates are excellent nucleophiles for allylic alkylations. Electron-withdrawing groups on the allyl moiety allow subsequent intramolecular Michael additions giving rise to piperidines with up to five stereogenic centers.

Internal Chelation within Functionalized Organoindium Reagents: Prospects for Regio- and Stereocontrol in the Allylation, Propargylation and Allenylation of Carbonyl Compounds

The low basicity, selective nucleophilicity, and mildness of organoindium compounds allow for the incorporation of many important yet sensitive functional groups into their structure, including examples capable of intramolecularly chelating the indium center within these reagents. The specific nature of such chelated organoindiums causes the reactions involving them to proceed in a unique manner, often with regio- and stereoselectivity inaccessible with simple organometallic reagents. This review covers the rare examples of regio- and stereoselective allylation, propargylation, and allenylation of carbonyl compounds with chelated organoindiums, including brief descriptions of the applications of the resulting adducts in the asymmetric synthesis of natural products and synthetic targets of biological and medicinal interest.1 Introduction2 Internal Chelation Control in the Allylation Processes2.1 Allylindiums with a Chelating Center at the γ-Position2.2 Allylindiums with a chelating Center at the δ-Position2.3 Allylindiums with a Chelating Center at ε- and ζ-Positions2.4 Allylindiums with a Chelating Center at γ′- and δ′-Positions3 Internal Chelation Control in Propargylation and Allenylation Processes­3.1 Additions of Chelated Allenylindiums3.2 Additions of Chelated Propargylindiums4 Conclusion

Engaging Aldehydes in CuH‐Catalyzed Reductive Coupling Reactions: Stereoselective Allylation with Unactivated 1,3‐Diene Pronucleophiles

AbstractRecently, CuH‐catalyzed reductive coupling processes involving carbonyl compounds and imines have become attractive alternatives to traditional methods for stereoselective addition because of their ability to use readily accessible and stable olefins as surrogates for organometallic nucleophiles. However, the inability to use aldehydes, which usually reduce too rapidly in the presence of copper hydride complexes to be viable substrates, has been a major limitation. Shown here is that by exploiting relative concentration effects through kinetic control, this intrinsic reactivity can be inverted and the reductive coupling of 1,3‐dienes with aldehydes achieved. Using this method, both aromatic and aliphatic aldehydes can be transformed into synthetically valuable homoallylic alcohols with high levels of diastereo‐ and enantioselectivities, and in the presence of many useful functional groups. Furthermore, using a combination of theoretical (DFT) and experimental methods, important mechanistic features of this reaction related to stereo‐ and chemoselectivities were uncovered.