Morita Baylis Hillman Carbonates Research Articles

Synthesis of Bisspiro(oxindole)s by DMAP‐Catalyzed [3 + 2] Annulation of Isatin‐Derived Morita–Baylis–Hillman Carbonates

Synthesis of Bisspiro(oxindole)s by DMAP‐Catalyzed [3 + 2] Annulation of Isatin‐Derived Morita–Baylis–Hillman Carbonates

Cooperative Gold(I)/DMAP Catalysis Enabled (2 + 3) Cycloadditions of Yne-Enones with Oxindole-Derived MBH Carbonates.

A cooperative gold(I)/DMAP system catalyzes the (2 + 3) cycloadditions of yne-enones with oxindole-derived Morita-Baylis-Hillman (MBH) carbonates, yielding diverse bispiro-cyclopentene oxindole products. The mild, scalable protocol demonstrates broad substrate scope and excellent chemo- and diastereoselectivity. Mechanistic study reveals pivotal roles of both catalysts in the unique (2 + 3) cycloaddition. This strategy showcases superiority in achieving transformation with unique chemoselectivity and excellent diastereoselectivity, unattainable through traditional monocatalytic methodologies.

Phosphine‐Catalyzed Domino Annulation Reactions of o‐Aminotrifluoroacetophenone Derivatives with Morita–Baylis–Hillman Carbonates: Construction of Tetrahydrofuro[3,2‐b]indolines

AbstractThe domino annulation reactions of o‐aminotrifluoroacetophenone derivatives and MBH carbonates enabled by PPh3 have been reported, which provide a series of tetrahydrofuro[3,2‐b]indolines containing a CF3‐substituted tetrasubstituted carbon stereocenters in yields of 74 to 95% and >20:1 dr. In this process, MBH carbonates were used as C1/C3 synthons. The MTT assay shows that the products exhibit the activity of inhibitory effect on proliferation on Hela cancer cell line.

Chiral Phosphine Ligands of COAP and SKP Switched Regiodivergent Asymmetric Allylic Alkylation of MBH Adducts.

The palladium-catalyzed highly regioselective asymmetric allylic alkylation of 3'-indolyl-3-oxindole derivatives with Morita-Baylis-Hillman (MBH) carbonates was developed to facilely construct chiral 3,3'-bisindole derivatives under mild reaction conditions. The regioselectivity (α/γ) of MBH carbonates was efficiently switched in the presence of chiral oxalamide phosphine or spiroketal-based diphosphine/Pd(0) complexes as a chiral catalyst. A series of multifunctional 3,3'-bisindole derivatives with all-carbon quaternary stereogenic centers were obtained in high yields with good to excellent enantio-, diastereo-, and regioselectivity. The present process is endowed with some salient features such as broad substrate scope, N-protecting group-free, excellent stereoselectivity, as well as adjustable regioselectivity.

Phosphine‐Catalyzed [4+3] Annulation Reaction of Indole Derivatives with MBH Carbonates: A Facile Access to Indole‐1,2‐fused 1,4‐Diazepinones and Azepines

Comprehensive SummaryA phosphine‐catalyzed [4+3] annulation between dinucleophilic indole derivatives and Morita−Baylis−Hillman (MBH) carbonates was discovered by using the N1 and N4′/C4′ nucleophilicities of the indole precursors, in which indoles act as four atom synthons. This protocol provides an efficient and facile access to indole‐1,2‐fused 1,4‐diazepinones and azepines in good to high yields in one step, which illustrates potential synthetic utilities in drug discovery.

Phosphine-Catalyzed (3 + 2) Annulation of γ-Substituted Cinnamic Aldehyde-Derived Morita-Baylis-Hillman Carbonates through Remote Activation.

A series of γ-substituted Morita-Baylis-Hillman (MBH) carbonates were synthesized and subjected to phosphine-catalyzed annulations with electrophilic exocyclic alkenes, giving various valuable spirocyclopentenes in moderate to excellent yields with moderate to excellent diastereoselectivities. A large scope of MBH carbonates bearing γ-hydrogen, alkenyl, and alkynyl substituents was well tolerated. The annulation unprecedentedly involves β-, γ-, and δ-carbons of MBH carbonates.

An Efficient Route to Access Spirooxindole–Pyrazolone-Fused Cyclopentenes by a Diastereoselective [3+2] Annulation

AbstractA DMAP-catalyzed, highly diastereoselective, [3+2] cycloaddition of pyrazolone-derived Morita–Baylis–Hillman carbonates to 3-methyleneoxindoles has been developed. A variety of structurally diverse and complex spiropyrazolone-fused oxindoles bearing three contiguous chiral centers have been synthesized in high yields (up to 98%) and with excellent diastereoselectivities (up to 99:1). Moreover, the synthetic potential of this protocol has been demonstrated by performing a Suzuki coupling reaction.

Lewis-Base-Catalyzed Enantioselective Formal [4 + 2] Annulations of Morita–Baylis–Hillman Carbonates: Access to Tetrahydroquinolines Derivatives

The Lewis-base-catalyzed enantioselective formal [4 + 2] annulation reaction of o-acylamino-aryl MBH carbonates and electron-deficient olefins was developed. Tetrahydroquinolines with three sequential stereogenic centers containing a quaternary stereocenter were obtained in high yields with good enantioselectivity.

Divergent Synthesis of Highly Substituted Tetrahydroquinolines and Cyclopentenes via Lewis Base Catalyzed Switchable [4 + 2] and [3 + 2] Annulations of MBH-Carbonates with Activated Olefins

A highly selective and divergent synthesis which enabled access to various complex compounds is highly attractive in organic synthesis and medicinal chemistry. Herein, we developed an effective method for divergent synthesis of highly substituted tetrahydroquinolines via Lewis base catalyzed switchable annulations of Morita-Baylis-Hillman carbonates with activated olefins. The reaction displayed switchable [4 + 2] or [3 + 2] annulations via catalyst or substrate control, providing a diverse range of architectures which contained highly substituted tetrahydroquinolines or cyclopentenes with three contiguous stereocenters bearing a quaternary carbon center in high yields with excellent diastereoselectivities and regioselectivities. Furthermore, synthetic utility of this strategy was further highlighted by gram-scale experiments and simple transformations of the products.

Chiral Phosphine Catalyzed Allylic Alkylation of Benzylidene Succinimides with Morita–Baylis–Hillman Carbonates

Owing to their unique chemical properties, α-alkylidene succinimides generally act as versatile synthons in organic synthesis. Compared with well-established annulations, nucleophilic alkylations of α-alkylidene succinimides are very limited. Accordingly, an organocatalytic allylic alkylation of α-benzylidene succinimides with Morita-Baylis-Hillman (MBH) carbonates was established. In the presence of a chiral phosphine catalyst, α-benzylidene succinimides reacted smoothly with MBH carbonates under mild conditions to furnish a series of optical active succinimides in high yields and enantioselectivities. Different from the reported results, the organocatalytic enantioselective construction of pyrrolidine-2,5-dione frameworks bearing contiguous chiral tertiary carbon centers was achieved via this synthetic strategy. Scaling up the reaction indicated that it is a practical strategy for the organocatalytic enantioselective alkylation of α-alkylidene succinimides. A possible reaction mechanism was also proposed.

Catalyst-Free α-Allylation of Dihydroisoquinolines with Morita-Baylis-Hillman Carbonates and Its Applications in the Construction of Benzo[a]quinolizidines.

In this work, a mild and efficient catalyst-free α-allylation of 3,4-dihydroisoquinoline imines with Morita-Baylis-Hillman (MBH) carbonates was reported. The scopes of 3,4-dihydroisoquinolines and MBH carbonates as well as gram-scale synthesis were investigated, and densely functionalized adducts were obtained in moderate to good yields. The synthetic utility of these versatile synthons was further demonstrated by the facile synthesis of diverse benzo[a]quinolizidine skeletons.

One‐Pot Divergent Synthesis of Benzoxazines and Dihydroquinolines from Morita‐Baylis‐Hillman Alcohols

AbstractBenzoxazines and hydroquinolines have been prepared by a one‐pot process via catalyst‐controlled divergent annulations of Morita‐Baylis‐Hillman (MBH) alcohols. In the presence of diazabicyclo[2.2.2]octane, MBH alcohols reacted with Boc2O to form MBH carbonates, followed by intramolecular annulation to give 4H‐benzo[d][1,3]oxazines. Divergently, the combination of Bu4NBr and NaOH enabled the formation of 1,2‐dihydroquinolines from the same starting materials.

Asymmetric α-Regioselective [3 + 2] Annulation of Morita-Baylis-Hillman Carbonates: Construction of Three Contiguous Stereocenters with Vicinal Quaternary Carbon Centers.

Asymmetric α-regioselective annulation of MBH carbonates with 4-arylmethylisoxazol-5-ones has been developed to afford spirocyclic oxindole derivatives containing three contiguous stereogenic centers and vicinal all-carbon quaternary chiral centers. This reaction exhibits a broad substrate scope and excellent functional group tolerance. Excellent yields with high diastereo- and enantioselectivities were obtained in this efficient organocatalytic reaction.

Lewis base catalyzed allylation reaction of N-aryl amides with Morita–Baylis–Hillman carbonates

A Lewis base catalyzed allylation reaction of N-aryl amides with various Morita–Baylis–Hillman (MBH) carbonates was described. The substrate scope of MBH carbonates and amides were comprehensively explored. The broad substrate scope, mild condition, as well as scale-up synthesis made this approach useful for the synthesis of diverfied branched tertiary N-allylic amides.

Asymmetric Formal Nucleophilic o-Cresolylation with Morita–Baylis–Hillman Carbonates of 2-Cyclohexenones via Palladium Catalysis

Here we report an asymmetric formal nucleophilic o-cresolylation reaction with the Morita-Baylis-Hillman (MBH) carbonates from 2-cyclohexanones and diverse aldehydes under palladium catalysis, by in situ generation of electron-neutral and HOMO-raised η2-Pd(0)-dienone complexes via an oxidative insertion/π-σ-isomerization/β-H elimination activation sequence. The subsequent umpolung vinylogous addition to a variety of imines is realized upon Pd(0)-mediated π-Lewis base catalysis, finally furnishing o-cresolylated products followed by another cascade of a π-σ-isomerization/β-H elimination/aromatization process. Moderate to excellent diastereo- and enantioselectivity are achieved for substantial substrate assemblies by employing a newly designed bulky chiral phosphonamidite ligand, and the resultant multifunctional products can be facilely elaborated to access diverse enantioenriched architectures. In addition, the catalytic reaction pathway is finely illuminated by control experiments.

Cooperative Tertiary Phosphine/Palladium Catalyzed Nucleophilic Allylation between Morita‐Baylis‐Hillman Carbonates and Alkenes

AbstractIn this work, we report an unusual nucleophilic allylation reaction between isatin‐derived Morita–Baylis–Hillman carbonates and simple alkenes synergistically catalyzed by tertiary phosphines and palladium complexes, through chemoselective assemblies of in situ formed onium salts and η1‐allylpalladium species, respectively. A range of 3,3‐disubstituted oxindoles were easily constructed in moderate to good yields with exclusive linear regioselectivity. Moreover, a number of control and deuterium experiments have been conducted to elucidate the catalytic mechanism.

Direct access to spirooxindole dihydropyrrole fused pyrazolones and bis-spiropyrazolone derivatives

A highly regio- and diastereo-selective [3 + 2] annulation of Morita–Baylis–Hillman carbonates of isatins/pyrazolones with pyrazolone derived ketimines has been developed to access spiroheterocycles. The protocol worked effectively to construct spirooxindole dihydropyrrole fused pyrazolone and bis-spiropyrazolone dihydropyrrole derivatives bearing two vicinal quaternary spirocentres in good to excellent yields with very high diastereoselectivities under mild catalytic condition at room temperature. The protocol proved to be efficient with diverse MBH carbonates and ketimine derivatives. The method has successfully demonstrated the utility of DMAP as the commercially viable catalyst for this transformation.

Organocatalytic Regio- and Enantioselective [3 + 2]-Annulations of Ninhydrin-Derived Morita-Baylis-Hillman Carbonates with 3-Methyleneoxindoles.

A type of Morita-Baylis-Hillman (MBH) carbonates has been developed from ninhydrin. These MBH carbonates have been successfully employed as 3C-synthons in the organocatalytic asymmetric [3 + 2]-annulations of the isatin-derived electron-deficient olefins, affording structurally diverse spirooxindoles in high yield with excellent stereoselectivity. In particular, the regioselectivity of MBH carbonates was controlled by the reaction partner, 3-methyleneoxindoles with carbonyl groups (R = ArCO), affording β-selective products and 3-methyleneoxindoles with ester groups (R = CO2Me) furnishing γ-selective products. The representative scale-up reactions and transformation of product were examined. The reaction mechanism was expounded by control experiments.

4‐(Dimethylamino)pyridine‐Catalyzed (3+2) Annulation of Pyrazoledione‐Derived Morita–Baylis–Hillman Carbonates with 2‐Arylideneindane‐1,3‐Diones: An Access to Dispirocyclic Compounds

AbstractA 4‐(dimethylamino)pyridine‐catalyzed (3+2) annulation of pyrazoledione‐derived Morita–Baylis–Hillman (MBH) carbonates with 2‐arylideneindane‐1,3‐diones has been developed to afford various multifunctional spiropyrazole derivatives in 16–99% yields with 3:2–>20:1 diastereoselectivities. As a type of Lewis‐base receptor, the pyrazoledione‐derived MBH carbonates will function as a key substrate in organocatalyzed annulation reactions for diverse syntheses of pyrazolinone‐containing dispirocyclic compounds.magnified image

Lewis Base Catalyzed Allylation Reaction of N-Aryl Amides with Morita–Baylis–Hillman Carbonates

Lewis Base Catalyzed Allylation Reaction of N-Aryl Amides with Morita–Baylis–Hillman Carbonates