Intramolecular Mizoroki-Heck Reaction Research Articles

Mizoroki-Heck Macrocyclization Reactions at 1 M Concentration Catalyzed by Sub-nanometric Palladium Clusters.

The synthesis of cyclized organic compounds with more than ten atoms (macrocycles) is traditionally based on reversible reactions under highly diluted conditions, typically <0.05 M, in order to circumvent the formation of intermolecular products. These reaction conditions severely hamper industrial productivity and the use of solid catalysts. Herein, it is shown that the intramolecular Mizoroki-Heck reaction of ω-iodide cinnamates proceeds at 1 M concentration when catalyzed by few-atom Pd clusters, either in solution or supported on a solid, to give different macrocycles in good yields. This paradigmatic increase in reaction concentration not only opens the door for macrocycle production with high throughputs but also enables the use of solid catalysts for a macrocyclization reaction in flow.

Ni-Catalyzed Enantioselective Intramolecular Mizoroki-Heck Reaction for the Synthesis of Phenanthridinone Derivatives.

A Ni-catalyzed enantioselective intramolecular Mizoroki-Heck reaction has been developed to transform symmetrical 1,4-cyclohexadienes with attached aryl halides into phenanthridinone analogues containing quaternary stereocenters. Herein, we report important advances in reaction optimization enabling control of unwanted proto-dehalogenation and alkene reduction side products. Moreover, this approach provides direct access to six-membered ring heterocyclic systems bearing all-carbon quaternary stereocenters, which have been much more challenging to form enantioselectively with nickel-catalyzed Heck reactions. A wide range of substrates were demonstrated to work in good to excellent yields. Good enantioselectivity was demonstrated using a new synthesized chiral iQuinox-type bidentate ligand (L27). The sustainability, low price of nickel catalysts, and significantly faster reaction rate (1 h) versus that of a recently reported palladium-catalyzed reaction (20 h) make this process an attractive alternative.

Synthesis of the eight-membered carbocycle of brachialactone by intramolecular Mizoroki-Heck reaction

A synthesis of the BC ring moiety of brachialactone, a fusicoccane-type diterpene isolated from the tropical forage grass Brachiaria humidicola and found to inhibit nitrification by soil microbes, is described. Several precursors including the C ring were synthesized from a known chiral cyclopentane, and then subjected to the conditions for the Mizoroki-Heck reaction. Substrates incorporating vinyl (R = H) or enone (R = COCH3) moieties and incorporating an S configuration at C-2 successfully underwent intramolecular Mizoroki-Heck reaction, giving the BC ring structure of brachialactone.

Synthesis of guaipyridine alkaloids (±)-cananodine and (±)-rupestines D and G using an intramolecular Mizoroki-Heck reaction

The guaipyridine alkaloids cananodine, rupestine D and rupestine G were synthesized in six steps or less from readily available 3-(allyloxy)-2-(bromomethyl)-6-methylpyridine. Key steps in the synthesis include an enolate alkylation of the aforementioned substituted picolyl bromide and an intramolecular Mizoroki-Heck reaction to form the seven-membered carbocycle of the target compounds.

Competent Route to Unsymmetric Dimer Architectures: Total Syntheses of (-)-Lycodine and (-)-Complanadines A and B, and Evaluation of Their Neurite Outgrowth Activities.

Valuable synthetic routes to the Lycopodium alkaloid lycodine (1) and its unsymmetric dimers, complanadines A (4) and B (5), have been developed. Regioselective construction of the bicyclo[3.3.1]nonane core structure of lycodine was achieved by a remote functionality-controlled Diels-Alder reaction and subsequent intramolecular Mizoroki-Heck reaction. A key coupling reaction of the lycodine units, pyridine N-oxide (66) and aryl bromide (65), through C-H arylation at the C1 position of 66 provided the unsymmetric dimer structure at a late stage of the synthesis. This strategy greatly simplified the construction of the dimeric architecture and functionalization. Complanadines A (4) and B (5) were synthesized by adjusting the oxidation level of the bipyridine mono-N-oxide (67). The diverse utility of this common intermediate (67) suggests a possible biosynthetic pathway of complanadines in Nature. Both enantiomers of lycodine (1) and complanadines A (4) and B (5) were prepared in sufficient quantities for biological evaluation. The effect on neuron differentiation of PC-12 cells upon treatment with culture medium, in which human astrocytoma cells had been cultured in the presence of 1, 4, or 5 was evaluated.

Intramolecular Mizoroki–Heck Reaction of 2-Thiosubstituted Acrylates for the Synthesis of 3-Substituted Benzo[b]thiophene-2-carboxylates

3-Substituted 2-(phenylthio)acrylates prepared from aldol condensation using titanium tetrachloride were employed to synthesize benzo[<i>b</i>]thiophenes. The acrylates containing aryls and alkyls generated the desired benzo[<i>b</i>]thiophenes in reasonable yields under the optimized Heck condition, but acrylates having heteroaryls gave the desired products in poor yields or no products under the condition.

ChemInform Abstract: Synthesis of Jiadifenin Using Mizoroki—Heck and Tsuji—Trost Reactions.

Abstract The formal synthesis of jiadifenin, which has potent neurotrophic activity, was accomplished using intramolecular Mizoroki–Heck reaction and tandem Tsuji–Trost cyclization/lactonization reaction as key steps. Intramolecular Mizoroki–Heck reaction was employed for the construction of the A ring moiety accompanied with the formation of C9 quaternary center, which was dramatically promoted by protic solvent. Tandem Tsuji–Trost cyclization/lactonization reaction was applied to the successive cyclization of the BC ring system to elaborate under conditions, Pd(OAc)2, (±)-BINAP, and LiOAc in t-BuOH, leading to Theodorakis's intermediate followed by a few functionalizations.

Synthesis of jiadifenin using Mizoroki–Heck and Tsuji–Trost reactions

The formal synthesis of jiadifenin, which has potent neurotrophic activity, was accomplished using intramolecular Mizoroki–Heck reaction and tandem Tsuji–Trost cyclization/lactonization reaction as key steps. Intramolecular Mizoroki–Heck reaction was employed for the construction of the A ring moiety accompanied with the formation of C9 quaternary center, which was dramatically promoted by protic solvent. Tandem Tsuji–Trost cyclization/lactonization reaction was applied to the successive cyclization of the BC ring system to elaborate under conditions, Pd(OAc)2, (±)-BINAP, and LiOAc in t-BuOH, leading to Theodorakis's intermediate followed by a few functionalizations.

Aqueous intramolecular Mizoroki–Heck reaction of (2-iodophenyl)(3-methyl-1H-indol-1-yl)methanone: a model reaction for the in situ performance evaluation of Pd catalysts

The activity of Pd catalysts for C–C coupling reactions is evaluated by using UV-vis spectroscopy and a Heck model reaction.

ChemInform Abstract: Stereoselective Synthesis of Benzofulvenes via a Palladium‐Catalyzed Cyclization of 1,3‐Dienes Derived from Morita—Baylis—Hillman Adducts.

AbstractA facile synthesis of benzofulvenes is carried out via Pd‐catalyzed intramolecular Mizoroki—Heck reaction of 1,3‐dienes easily obtained from the Wittig reaction between Morita—Baylis—Hillman adducts and various aldehydes (not shown).

Stereoselective synthesis of benzofulvenes via a palladium-catalyzed cyclization of 1,3-dienes derived from Morita–Baylis–Hillman adducts

A facile synthesis of benzofulvenes was carried out starting from the Morita–Baylis–Hillman adducts of 2-bromobenzaldehyde. The synthesis was carried out via the sequential bromination, Wittig reaction with aldehyde, and Pd-catalyzed intramolecular Mizoroki–Heck reaction. The stereochemistry of benzofulvenes was dependent on the reaction condition, especially on the kinds of base and reaction time, and the substituent of starting materials.

Intramolecular Mizoroki–Heck Reaction in the Regioselective Synthesis of 4‐Alkylidene‐tetrahydroquinolines

AbstractThe Mizoroki–Heck reaction of N‐alkenyl‐substituted 2‐haloanilines is an effective protocol for the synthesis of substituted 4‐alkylidene‐tetrahydroquinoline derivatives, avoiding isomerization and oxidation. When non‐substituted alkenes are used, the regioselectivity of the reaction can be directed towards the formation of an exocyclic or endocyclic double bond by choosing an adequate catalytic system. When the double bond is substituted by an amide moiety, the exocyclic double bond of E geometry is obtained selectively. Thus, this protocol efficiently synthesizes a series of 2‐substituted tetrahydroquinolines with an exo α,β‐unsaturated amide moiety at the C‐4 position.

ChemInform Abstract: Construction of Benzosiloles, Six‐ and Eight‐Membered Silacyclic Skeletons, via a Pd‐Catalyzed Intramolecular Mizoroki—Heck Reaction of Vinylsilanes.

A variety of silacycles including benzosiloles, six- and eight-membered silacyclic skeletons, were efficiently synthesized via a Pd-catalyzed intramolecular Mizoroki–Heck reaction of vinylsilanes.

Construction of Benzosiloles, Six- and Eight-Membered Silacyclic Skeletons, via a Pd-Catalyzed Intramolecular Mizoroki–Heck Reaction of Vinylsilanes

A variety of silacycles including benzosiloles, six- and eight-membered silacyclic skeletons, were efficiently synthesized via a Pd-catalyzed intramolecular Mizoroki-Heck reaction of vinylsilanes.

Three-Step Synthesis of (Thio)xanthene and Dibenzothiepine/Dibenzoxepine by an Intramolecular Mizoroki-Heck Reaction of Diaryl (Thio)Ethers

We present a novel three-step protocol for preparing xanthene/thioxanthene and dibenzothiepine/dibenzoxepine from readily available starting materials. The Mizoroki-Heck cyclization as the final step was optimized to afford full conversion of the corresponding diaryl (thio)ethers and furthermore to achieve reasonably good selectivity between the 6-exo and the 7-endo products.

Catalyzed Asymmetric Induction of Planar Chirality: Palladium‐Catalyzed Intramolecular Mizoroki—Heck Reaction of Prochiral (Arene)chromium Complexes.

AbstractFor Abstract see ChemInform Abstract in Full Text.

Catalytic asymmetric induction of planar chirality: palladium catalyzed intramolecular Mizoroki–Heck reaction of prochiral (arene)chromium complexes

The asymmetric intramolecular Mizoroki–Heck reaction of prochiral tricarbonyl(2,6-dibutenylchlorobenzene)chromium in the presence of a chiral phosphine–palladium catalyst gave the corresponding bicyclic chromium complex up to 73% ee.

Synthetic studies on (+)-naphthyridinomycin: stereoselective synthesis of the tetracyclic core framework.

[reaction: see text] The stereoselective synthesis of the tetracyclic intermediate 21 for (+)-naphthyridinomycin (1) has been accomplished. The convergent synthesis used the Ugi 4CC reaction with the amine derivative 10. The key features of the stereoselective synthesis of 21 were the intramolecular Mizoroki-Heck reaction, an aromatic-aldehyde cyclization, and a stereoselective hydroboration.