Enantioselective Alkenylation Research Articles

Synthesis of Chiral Allylic Alcohols by Enantioselective Alkenylation of Aldehydes Under Cobalt Catalysis

Synthesis of Chiral Allylic Alcohols by Enantioselective Alkenylation of Aldehydes Under Cobalt Catalysis

Cobalt-Catalyzed Enantioselective Alkenylation of Aldehydes.

Catalytic enantioselective alkenylation of aldehydes with easily accessible alkenyl halides promoted by a chiral cobalt complex derived from a newly developed tridentate bisoxazolinephosphine is presented. Such processes represent an unprecedented reaction pathway for cobalt catalysis and a general approach that enable rapid construction of highly diversified enantioenriched allylic alcohols containing a 1,1-, 1,2-disubstituted and trisubstituted alkene as well as axial stereogenicity in up to 99 % yield and 99 : 1 er without the need of preformation of alkenyl-metal reagents. DFT calculations revealed the origin of enantioselectivity.

Cobalt‐Catalyzed Enantioselective Alkenylation of Aldehydes

AbstractCatalytic enantioselective alkenylation of aldehydes with easily accessible alkenyl halides promoted by a chiral cobalt complex derived from a newly developed tridentate bisoxazolinephosphine is presented. Such processes represent an unprecedented reaction pathway for cobalt catalysis and a general approach that enable rapid construction of highly diversified enantioenriched allylic alcohols containing a 1,1‐, 1,2‐disubstituted and trisubstituted alkene as well as axial stereogenicity in up to 99 % yield and 99 : 1 er without the need of preformation of alkenyl–metal reagents. DFT calculations revealed the origin of enantioselectivity.

Palladium-Catalyzed Enantioselective Directed C(sp3)-H Functionalization Using C5-Substituted 8-Aminoquinoline Auxiliaries.

8-Aminoquinoline (AQ) has proven to be a highly effective bidentate directing group for palladium-catalyzed C-H functionalization reactions. However, enantiocontrol of AQ-directed C(sp3)-H functionalization reactions has been challenging. Herein, a new protocol is presented for the Pd-catalyzed enantioselective arylation of unactivated β C(sp3)-H bonds of alkyl carboxamides with aryl iodides using a C5-iodinated 8-aminoquinolines (IQ) auxiliary in conjugation with a BINOL ligand. Additionally, a C5-aryl substituted 8-aminoquinoline auxiliary can facilitate enantioselective alkenylation and alkynylation of benzylic C(sp3)-H bonds of 3-arylpropanamides with the corresponding bromide reagents under similar conditions.

Enantioselective Alkenylation of o-Carboranes via Ir-Catalyzed Asymmetric B–H Activation

Enantioselective Alkenylation of <i>o</i>-Carboranes via Ir-Catalyzed Asymmetric B–H Activation

Asymmetric alkenylation reaction of benzoxazinones with diarylethylenes catalyzed by B(C6F5)3/chiral phosphoric acid

Catalytic enantioselective alkenylation is an efficient method to construct chiral alkene molecules, but the asymmetric alkenylation of simple alkenes catalyzed by metal-free catalysts remains an elusive challenge. Herein, we reported an asymmetric alkenylation of benzoxazinones with diarylethylenes by utilizing a B(C6F5)3/chiral phosphoric acid catalyst. A broad of benzoxazinones and diarylethylenes with electron-withdrawing and electron-donating groups were tolerated (up to 95% yield and 97.5:2.5 e.r.) in the methodology under mild reaction conditions. Moreover, the synthetic utility was confirmed by the scaled-up reaction and transformations of the products. The mechanism was preliminarily explored by control reactions, nonlinear effect experiment and DFT calculations.

Catalytic enantioselective alkenylation-heteroarylation of olefins: stereoselective syntheses of 5-7 membered azacycles and oxacycles.

Catalytic enantioselective domino alkenylation-heteroarylation of nonconjugated iododienes proceeded with excellent stereoselectivity and broad scope of substrates. The reaction enables stereoselective syntheses of substituted azacycles such as piperidine, pyrrolidine azepine and dihydropyrans carrying new quaternary stereocenters. Mechanistically, C-H bonds of heterocycles were activated by lithium alkoxides via reversible deprotonation, rather than conventional palladium(ii)-assisted metalation processes. Many types of heteroarenes can be used, including not only azoles (such as thiazoles, oxazoles, imidazoles and oxadiazoles), but also nonazoles (thiophene, furan and azine N-oxides).

Rhodium-Catalyzed Highly Enantio- and Diastereoselective Alkenylation of β,γ-Unsaturated Butenolides via Dynamic Kinetic Resolution.

A rhodium-catalyzed highly enantio- and diastereoselective alkenylation of β,γ-unsaturated butenolides is reported. The use of a chiral diene ligand, (S,S)-Ph-bod, enables the facile synthesis of chiral butyrolactones in high yields with extremely high enantioselectivities (>99% ee in all cases) and high diastereoselectivities (up to >20:1 dr). The key process of the reaction involves the isomerization of β,γ-unsaturated butenolides to racemic α,β-unsaturated butenolides and the subsequent dynamic kinetic resolution through ligand-controlled, enantioselective alkenylation with an alkenylrhodium species that is generated in situ via 1,4-rhodium migration.

Three-component enantioselective alkenylation of organophosphonates via nickel metallaphotoredox catalysis

•Highly enantioselective synthesis of structurally complex chiral phosphonates •Modular and stereodivergent access to chiral trans- and cis-alkenyl moieties •Asymmetric radical multicomponent reaction via metallaphotoredox catalysis •Enantioselective control of alkyl radicals by guiding the trajectory of radical metalation The development of efficient catalytic multicomponent reactions (MCRs) is highly sought-after in chemical synthesis. However, catalytic asymmetric MCRs, particularly involving radical species, remain largely underdeveloped due to the exceptionally high reactivity of open-shell radical species. Herein, we report a metallaphotoredox-catalyzed asymmetric three-component method to access a diverse array of enantio-enriched α-alkenyl phosphonates from readily available vinyl phosphonates, alkenyl halides, and alkyl trifluoroborates under mild conditions. This operationally simple and redox-neutral protocol exhibits broad substrate scope and excellent chemo-, regio-, stereo-, and enantioselectivity. Furthermore, by simple modification of the triplet energy of the photocatalyst employed, both enantio-enriched trans and cis α-alkenyl phosphonates can be divergently accessed. Detailed computational and experimental studies were undertaken to elucidate the mechanism and origin of the observed reactivity and selectivity, which support a radical cascade sequence with α-phosphonate controlling the trajectory of radical capture by a chiral tetrahedral alkenyl nickel(II) species in the enantioselectivity-determining step. The development of efficient catalytic multicomponent reactions (MCRs) is highly sought-after in chemical synthesis. However, catalytic asymmetric MCRs, particularly involving radical species, remain largely underdeveloped due to the exceptionally high reactivity of open-shell radical species. Herein, we report a metallaphotoredox-catalyzed asymmetric three-component method to access a diverse array of enantio-enriched α-alkenyl phosphonates from readily available vinyl phosphonates, alkenyl halides, and alkyl trifluoroborates under mild conditions. This operationally simple and redox-neutral protocol exhibits broad substrate scope and excellent chemo-, regio-, stereo-, and enantioselectivity. Furthermore, by simple modification of the triplet energy of the photocatalyst employed, both enantio-enriched trans and cis α-alkenyl phosphonates can be divergently accessed. Detailed computational and experimental studies were undertaken to elucidate the mechanism and origin of the observed reactivity and selectivity, which support a radical cascade sequence with α-phosphonate controlling the trajectory of radical capture by a chiral tetrahedral alkenyl nickel(II) species in the enantioselectivity-determining step.

A relay catalysis strategy for enantioselective nickel-catalyzed migratory hydroarylation forming chiral α-aryl alkylboronates

A relay catalysis strategy for enantioselective nickel-catalyzed migratory hydroarylation forming chiral α-aryl alkylboronates

Enantioselective Alkenylation of Aldehydes with Protected Propargylic Alcohols in the Presence of a Crown Ether as an Additive

AbstractThe enantioselective alkenylation of aldehydes with protected propargylic alcohols catalyzed by chiral amino thiol has been developed. The best results were obtained for the hydrozirconation‐transmetallation to zinc protocol. The key element of the method is the use of crown ethers as an additive. The enantioselectivity of the reaction performed in the presence of the crown ether was substantially higher than in the absence of this additive and the enantiomer ratio reached 98:2.magnified image

Asymmetric Synthesis of Chiral 1,4-Enynes through Organocatalytic Alkenylation of Propargyl Alcohols with Trialkenylboroxines.

A highly enantioselective synthesis of 1,4-enynes is described that proceeds through an organocatalytic reaction between propargyl alcohols and trialkenylboroxines. Our strategy relies on acid-mediated generation of the carbocationic intermediate from propargyl alcohols followed by enantioselective alkenylation with trialkenylboroxines. A range of chiral 1,4-enynes were obtained in moderate to good yields with high levels of enantioselectivity. Use of a highly acidic chiral N-triflyl phosphoramide catalyst, which has two distant Lewis basic oxygen atoms, was found to be crucial for both high reactivity and selectivity in the present reaction.

Asymmetric Synthesis of Chiral 1,4‐Enynes through Organocatalytic Alkenylation of Propargyl Alcohols with Trialkenylboroxines

AbstractA highly enantioselective synthesis of 1,4‐enynes is described that proceeds through an organocatalytic reaction between propargyl alcohols and trialkenylboroxines. Our strategy relies on acid‐mediated generation of the carbocationic intermediate from propargyl alcohols followed by enantioselective alkenylation with trialkenylboroxines. A range of chiral 1,4‐enynes were obtained in moderate to good yields with high levels of enantioselectivity. Use of a highly acidic chiral N‐triflyl phosphoramide catalyst, which has two distant Lewis basic oxygen atoms, was found to be crucial for both high reactivity and selectivity in the present reaction.

Palladium-Catalyzed Enantioselective Alkenylation of Sulfenate Anions.

A novel approach to synthesize enantio-enriched alkenyl/aryl sulfoxides is achieved by using CsF to generate sulfenate anions and conducting the catalytic enantioselective alkenylation with [Pd(allyl)Cl]2/(2 R)-1-[(1 R)-1-[bis(1,1-dimethylethyl)phosphino]ethyl]-2-(diphenylphosphino)ferrocene (SL-J002-1). A wide variety of sulfoxides bearing sensitive functional groups are produced with high yields (up to 94%) and enantioselectivities (up to 92%).

Palladium-catalyzed enantioselective alkenylation of alkenylbenzene derivatives.

A regioselective and enantioselective palladium-catalyzed relay Heck alkenylation of alkenylbenzene derivatives to construct remote stereocenters is disclosed. Various β-substituted styrenes were readily obtained in moderate yields with good to excellent levels of enantioselectivity. This strategy provides rapid access to enantioenriched δ, ε, ζ, and η-alkenyl aryl compounds from simple starting materials. Mechanistic studies suggest that termination of the relay reaction is controlled by affinity of the arene for the Pd complex during migration.

Enantioselective Alkenylation of Acyclic Enol Ethers

Enantioselective Alkenylation of Acyclic Enol Ethers

Rhodium-Catalyzed Enantioselective Alkenylation of Cyclic Ketimines

Key words rhodium catalysis - asymmetric addition - ketimines - α,α-disubstituted allylic amines

Rhodium-Catalyzed Enantioselective Alkenylation of Cyclic Ketimines: Synthesis of Multifunctional Chiral α,α-Disubstituted Allylic Amine Derivatives.

By employing a simple open-chain chiral phosphite-olefin ligand, a highly enantioselective rhodium-catalyzed alkenylation of 1,2,5-thiadiazole 1,1-dioxide-type cyclic ketimines with diverse vinylboronic acids was achieved under mild conditions at room temperature. This protocol provides an efficient and practical access to multifunctional α,α-disubstituted chiral allylic amines bearing quaternary stereocenters in high yields (up to 99%) with good to excellent ee's (up to 99%).

A Rapid Synthesis of Chiral Allylic Amines via Microwave‐assisted Asymmetric Alkenylation of N‐Tosyl Aldimines Catalyzed by Rhodium/Chiral Diene Complexes

A method providing expeditious access to chiral allylic amines via a Rh(I)/bicyclo[2.2.1]heptadiene‐catalyzed enantioselective alkenylation of N‐tosyl aldimines with potassium alkenyltrifluoroborates under microwave irradiation is described. The rate of the asymmetric 1,2‐addition reaction, conducted in the presence of 1 mol % of the catalyst, was significantly enhanced as compared to when the standard heating method was applied while still providing the corresponding products without decrease in enantioselectivity.

Asymmetric total synthesis of (−)-perforanoid A

Asymmetric total synthesis of (−)-perforanoid A, a novel limonoid isolated from the leaves of Harrisonia perforata, has been achieved. The key features of our total synthesis include the Rh-catalyzed intramolecular Pauson–Khand reaction of an allene and an alkene, the Pd-catalyzed lactonization of an allylic alcohol with a vinyl ether, and the enantioselective alkenylation of 3-furaldehyde.