Intramolecular Hydroacylation Reaction Research Articles

Organocatalyzed Hydroacylation of Enones by Photosensitization of Acyl Silanes.

A mild protocol for hydroacylation of enones through photosensitization of acyl silanes with thioxanthone under blue light (455 nm) irradiation is reported. A Brønsted acid is used as a cocatalyst in the reaction. The versatility of the method is demonstrated through inter- and intramolecular hydroacylation reaction. The hydroacylation product is applied for synthesizing an anti-HCV agent. Mechanistic insights are also provided through control experiments.

NHC‐Organocatalysed Hydroacylation of Unactivated or Weakly Activated C−C Multiple Bonds and Ketones

AbstractN‐Heterocyclic Carbenes (NHCs) are versatile organocatalysts owing to their umpolung capability – i. e. the catalytic transformation of electrophilic aldehydes into nucleophilic species. Profoundly, aldehyde umpolungs were exploited in Benzoin and Stetter reactions, whereas hydroacylation of unactivated carbon‐carbon multiple bonds (alkenes and alkynes) are challenging and highly desired. Normally, catalytic hydroacylation of alkenes was achieved by transition metal catalysts based on rhodium, cobalt, nickel, ruthenium, and iridium. However, the metal‐catalyzed strategy is accompanied by undesired side reactions, such as decarbonylation of aldehydes, and thus demands installation of directing group in the aldehydes. In contrast, NHCs overcome these downsides and utilize the umpolung strategy beyond the Benzoin and Stetter reactions to implement catalytic hydroacylation of unpolarised and unactivated carbon‐carbon multiple bonds (alkenes and alkynes) under mild reaction conditions with step‐ and atom‐economy. In addition, this unconventional transformation is extended to catalytic asymmetric catalysis. This highlight covers the progress and practicality of NHC‐catalyzed hydroacylation of alkenes, alkynes, arynes, and ketones to access biologically relevant organics. Both inter‐and intramolecular hydroacylation reactions in combination with Stetter were presented and key mechanistic pathways were discussed.

NHC-catalyzed green synthesis of functionalized chromones: DFT mechanistic insights andin vitroactivities in cancer cells

A simple green protocol for the synthesis of 3-aminochromone derivatives using a NHC catalyzed intramolecular hydroacylation reaction was developed. Further functional 3-aminochromes were evaluated for their anticancer activity.

Catalytic, Enantioselective Synthesis of Polycyclic Nitrogen, Oxygen, and Sulfur Heterocycles via Rh-Catalyzed Alkene Hydroacylation.

Enantioselective synthesis of polycyclic nitrogen, oxygen, and sulfur heterocycles by rhodium-catalyzed intramolecular alkene hydroacylation is reported. The intramolecular hydroacylation reactions generate 1,4-dihydrocyclopenta[b]indol-3(2H)-ones and 3,4-dihydrocyclopenta[b]indol-1(2H)-one in moderate-to-high yields (65-99%) with good-to-excellent enantioselectivities (84-99% ee). The catalyst system also promotes alkene hydroacylation of 3-vinylfuran-, 3-vinylbenzothiophene-, and 3-vinylthiophene-2-carboxaldehydes to generate the corresponding ketone products in moderate-to-high yields (71-91% yield) with excellent enantioselectivities (97-99% ee).

DTBP/TBHP‐Promoted Hydroacylation of Unactivated Alkenes

AbstractDi‐tert‐butyl peroxide (DTBP)‐promoted intermolecular hydroacylation reaction of alkenes with aromatic aldehydes that provides ketones is described. In this study, 4‐chromanones were formed when 2‐(allyloxy)benzaldehydes were treated with tert‐butyl hydroperoxide (TBHP). The reactions were performed under solvent‐ and metal‐free conditions. Reactions proceeded through the generation of acyl radicals, followed by the reaction with alkenes. Remarkably, not only terminal alkenes but also internal alkenes could serve as the starting materials for intramolecular hydroacylation reaction.

ChemInform Abstract: Cobalt‐Catalyzed Enantioselective Intramolecular Hydroacylation of Ketones and Olefins.

Cobalt–chiral diphoshine catalytic systems promote intramolecular hydroacylation reactions of 2-acylbenzaldehydes and 2-alkenylbenzaldehydes to afford phthalide and indanone derivatives, respectively, in moderate to good yields with high enantioselectivities. The ketone hydroacylation did not exhibit a significant H/D kinetic isotope effect (KIE) with respect to the aldehyde C–H bond, indicating that C–H activation would not be involved in the rate-limiting step.

ChemInform Abstract: Enantioselective Synthesis of Polycyclic Nitrogen Heterocycles by Rh‐Catalyzed Alkene Hydroacylation: Constructing Six‐Membered Rings in the Absence of Chelation Assistance.

Catalytic, enantioselective hydroacylations of N-allylindole-2-carboxaldehydes and N-allylpyrrole-2-carboxaldehydes are reported. In contrast to many alkene hydroacylations that form six-membered rings, these annulative processes occur in the absence of ancillary functionality to stabilize the acylrhodium(III) hydride intermediate. The intramolecular hydroacylation reactions generate 7,8-dihydropyrido[1,2-a]indol-9(6H)ones and 6,7-dihydroindolizin-8(5H)-ones in moderate to high yields with excellent enantioselectivities.

Cobalt-catalyzed enantioselective intramolecular hydroacylation of ketones and olefins.

Cobalt-chiral diphoshine catalytic systems promote intramolecular hydroacylation reactions of 2-acylbenzaldehydes and 2-alkenylbenzaldehydes to afford phthalide and indanone derivatives, respectively, in moderate to good yields with high enantioselectivities. The ketone hydroacylation did not exhibit a significant H/D kinetic isotope effect (KIE) with respect to the aldehyde C-H bond, indicating that C-H activation would not be involved in the rate-limiting step.

Enantioselective synthesis of polycyclic nitrogen heterocycles by Rh-catalyzed alkene hydroacylation: constructing six-membered rings in the absence of chelation assistance.

Catalytic, enantioselective hydroacylations of N-allylindole-2-carboxaldehydes and N-allylpyrrole-2-carboxaldehydes are reported. In contrast to many alkene hydroacylations that form six-membered rings, these annulative processes occur in the absence of ancillary functionality to stabilize the acylrhodium(III) hydride intermediate. The intramolecular hydroacylation reactions generate 7,8-dihydropyrido[1,2-a]indol-9(6H)ones and 6,7-dihydroindolizin-8(5H)-ones in moderate to high yields with excellent enantioselectivities.

ChemInform Abstract: Inter‐ and Intramolecular Hydroacylation of Alkenes Employing a Bifunctional Catalyst System.

AbstractA novel bifunctional P,N‐ligand is synthesized and successfully used in rhodium‐catalyzed inter‐ and intramolecular hydroacylation reactions of alkenes.

A Theoretical Study on the trans-Addition Intramolecular Hydroacylation of 4-Alkynals Catalyzed by Cationic Rhodium Complexes

The mechanism of the intramolecular hydroacylation reaction of 4-alkynals is studied for a 4-pentynal-[Rh(PH2CH2CH2PH2)]+ model system using MP2 calculations. The endo-cyclization to form a rhodacyclohexenone intermediate is kinetically less favorable than the exo-cyclization to form a rhodacyclopentanone intermediate. The kinetic preference toward the endo-cyclization is found to be enhanced by complexation of donor ligands (H2CO, NCH, and HCCH). The formation of cyclopentenone product proceeds via reductive elimination from one of the two rhodacyclohexenone intermediates, whereas the formation of cyclobutanone product from the two rhodacyclopentanone intermediates requires high activation energy. Addition of an acetylene stabilizes the highly electron-poor rhodacyclopentanone intermediate generated from exo-cyclization and leads to an insertion to give [4 + 2] annulation product, cyclohexenone. The role of a coordinating acetone solvent in the formation of cyclopentenone product is also discussed.

Rhodium‐Catalyzed Intramolecular Hydroacylation of 4‐Alkynals

AbstractFor Abstract see ChemInform Abstract in Full Text.

ロジウム錯体触媒による４‐アルキナールの分子内ヒドロアシル化反応

A novel intramolecular trans-hydroacylation of 4-alkynals leading to cyclopentenones was accomplished by using a cationic rhodium (I) complex. We also developed three types of new reactions, 1) reaction of 4-alkynals with phenol to provide cis-4-alkenoates, 2) [4 + 2] cycloaddition of 4-alkynals with alkynes to provide cyclohexenones, and 3) isomerization of 4-alkynals to 1, 3-dienals, through five-membered rhodium metallacycles generated from 4-alkynals. The asymmetric variants of this intramolecular hydroacylation reaction were successfully developed by using 3-methoxy-4-alkynals as the substrates. The present method represents an attractive new route to highly functionalized cyclopentenones and cyclobutanones.

A readily prepared neutral heterobimetallic titanium(iv)–rhodium(i) catalyst for intramolecular hydroacylation

The combination of HOCMe2CH2PPh2, Ti(OiPr)4, and [Rh(cod)Cl]2 (3:1:1) in either benzene or dichloromethane produces a discrete species (tentatively formulated as complex) that is an active catalyst for intramolecular hydroacylation reactions of 3-substituted pentenals.

Unusual type of catalysis by paramagnetic cobalt(0) complexes. Isolation of catalytically active 17-electron intermediate, (Ph 3P) 2Co(CH 2CHCH 2CH 2CHO), in the 4-pentenal intramolecular hydroacylation

The kinetics and mechanism of intramolecular hydroacylation catalyzed by complexes Co 2(μ-N 2)(PPh 3) 6 (III) and (PPh 3) 2Co(dppe) (IV) (dppe-1,2-bis(di-phenylphosphino)ethane) were studied. The active monomeric 17-electron intermediate, (Ph 3P) 2Co(CH 2CHCH 2CH 2CHO) (Vb) was isolated in the cyclisation of 4-pentenal (I), catalyzed by complex III. Crystals of Vb are stable in an inert atmosphere at room temperature for a month. A well defined EPR spectrum of Vb in toluene glass at 77 K was obtained. According to the IR spectrum of complex Vb aldehyde I is bonded to the metal as a bidentate π,π-ligand. The ligand exchange reaction was found to proceed readily between Vb and dppe to form free I (85%) and Co(dppe) 2. The complex Vb is the first example of a cobalt(0) complex with a coordinated aidehyde group. The analogous intermediate, (dppe)Co(CH 2CHCH 2-CH 2CHO) (Va) was identified by EPR in solution during the 4-pentenal cyclization, catalyzed by complex IV. For the 4-pentenal hydroacylation reaction, catalyzed by complex Vb, zero and first order kinetic laws were found for the aldehyde I and the catalyst concentrations respectively in accordance with the equation: W 0 = k[Vb], k = (8.5 ± 0.5) × 10 −4 s −1 at 70°C. It is suggested that the reaction mechanism involves oxidative addition of coordinated I to cobalt(0) within the complex Vb to give an acyl hydride intermediate (rate-determining step). The subsequent rearrangement of the acyl hydride complex to the acylalkylcobalt derivative, followed by a reductive elimination reaction yields the ketone II and the parent cobalt(0) complex. Unlike well-known catalytic processes, in which diamagnetic Co I and Co III species are key intermediates, the catalytic cycle of the intramolecular hydroacylation reaction seems to involve only mononuclear paramagnetic Co 0 and Co II species. Chelation of the cobalt atom by an unsaturated aldehyde was found to be an important requirement for this reaction to occur.

Intramolecular hydroacylation reaction catalyzed by Co2(?-N2)(PPh3)6 in the presence of various ligands

1. The efficiency of the catalytic system containing Co(O) and various ligands (phosphines, diphosphines, phosphites, and diamines) in the intramolecular hydroacylation reaction is greatest when using chelating diphosphines 1,2-bis(diphenylphosphino)ethane and 1,2-bis(diphenylphosphino)propane (ligand:Co=1∶:1). 2. For monodentate phosphorus-containing ligands, the activity and selectivity of the catalytic system increase with increasing donor capacity and decreasing bulk of the ligands. 3. In the presence of the Co2(μ-N2)(PPh3)6 + 1,2-bis(diphenylphosphino)ethane catalytic system, 4-pentenal cyclizes to cyclopentanone in acetonitrile at 70°C with about 100% selectivity at complete conversion (20 moles per g-at Co).