Vinylpalladium Species Research Articles

Enantioselective Total Synthesis of (-)-Himalensine A via a Palladium and 4-Hydroxyproline Co-catalyzed Desymmetrization of Vinyl-bromide-tethered Cyclohexanones.

Herein, we describe the convergent enantioselective total synthesis of himalensine A in 18 steps, enabled by a highly enantio- and diastereoselective construction of the morphan core via a palladium/hydroxy proline co-catalyzed desymmetrization of vinyl-bromide-tethered cyclohexanones. The reaction pathway was illuminated by density functional theory calculations, which support an intramolecular Heck reaction of an in situ-generated enamine intermediate, where exquisite enantioselectivity arises from intramolecular carboxylate coordination to the vinyl palladium species in the rate- and enantio-determining carbopalladation steps. The reaction tolerates diverse N-derivatives, all-carbon quaternary centers, and trisubstituted olefins, providing access to molecular scaffolds found in a range of complex natural products. Following large-scale preparation of a key substrate and installation of a β-substituted enone moiety, the rapid construction of himalensine A was achieved using a highly convergent strategy based on an amide coupling/Michael addition/allylation/ring-closing metathesis sequence which allowed the introduction of three of the five rings in only three synthetic steps (after telescoping). Moreover, our strategy provides a new enantioselective access to a known tetracyclic late-stage intermediate that has been used previously in the synthesis of many Daphniphyllum alkaloids.

Rearrangement of a carboxy-substituted spiro[4.4]nonatriene to annulated fulvenes through a Pd(ii)-mediated 1,5-vinyl shift.

A novel synthesis of aryl-substituted, enantioenriched fulvenes from an oxidative Heck cascade and rearrangement of a carboxy-substituted spiro[4.4]nonatriene is disclosed. Mechanistic investigations with density functional theory (DFT) calculations and empirical results support the net transformation occurring through a novel Pd(ii)-mediated 1,5-vinyl shift from a vinyl-palladium intermediate that terminates with protodepalladation. This spiro-to-fused bicycle conversion tolerates a range of electron-rich and deficient arylboronic acids to give a range of mono- and diaryl substituted annulated fulvenes in moderate to good yields and enantiomeric ratios. Overall, this work connects two classes of molecules with a rich history in physical organic chemistry.

Palladium-Catalyzed Regioselective Arylalkenylation of Ynamides.

A cationic palladium-catalyzed arylalkenylation of ynamides is presented. The putative keteniminium arylpalladium intermediate likely dictates the regioselective carbopalladation of the ynamide to form a vinylpalladium species. The capture of this complex by the olefin yields linear conjugated β-alkenyl aminodienes (especially with trans selectivity). The transformation features a broad scope with labile functional group tolerance and makes 42 unusual molecular scaffolds with structural diversity. DFT studies provide valuable insights into the reaction mechanism.

Palladium-Catalyzed Amide-Directed Hydrocarbofunctionalization of 3-Alkenamides with Alkynes

A Pd-catalyzed carboxamide-directed hydrocarbofunctionalization reaction of unactivated alkenes with different alkynes has been developed. An 8-aminoquinoline auxiliary was utilized to increase the reactivity of the alkene and control the regioselectivity via the formation of thermodynamically favored five-membered palladacycle intermediate. 3-Alkene carboxamides bearing a C4-substituted alkene group reacted with a variety of terminal alkynes in the presence of an ortho-phenyl benzoic acid promoter, yielding γ-alkynylated products with high yields and regioselectivity. 3-Butenamide underwent a three-component coupling reaction with internal alkynes and carboxylic acids to give vinyl ester products. Preliminary mechanistic studies indicate that the intramolecular migratory insertion of alkynyl or vinyl palladium species into the C═C bond is responsible for the γ-selective alkynylation or alkenylation of the alkene group.

Palladium-Catalyzed Cycloaromatization/Alkylation of o-(Alkynyl)styrenes.

A Pd(II)-catalyzed mild and highly regioselective 6-endo cyclization/alkylation reaction of o-(alkynyl)styrenes with simple allylic alcohols has been developed. Under mild reaction conditions, the vinyl palladium species generated in situ after cyclization could insert a C-C double bond of allylic alcohol through a cross-coupling reaction and led to the formation of (alkyl)naphthalenes. This cascade cross-coupling reaction represents a direct and atom economic method for the construction of functionalized naphthalene derivatives in moderate to good yields.

Palladium-Catalyzed Cascade Intramolecular Cyclization and Allylation of Enynoates with Allylic Alcohols.

A Pd(II)-catalyzed mild and highly regioselective 6- endo cyclization/allylation reaction of enynoates with simple allylic alcohols has been developed. Under mild reaction conditions, the vinyl palladium species generated in situ after cyclization could insert C-C double bond of allylic alcohol through cross-coupling reaction and lead to the formation of allyl pyrone via β-OH elimination. This cascade cross-coupling reaction represents a direct and atom economic methodology for the construction of novel allyl pyrones in moderate to good yields.

Palladium-Catalyzed One-Pot Highly Regioselective 6- Endo Cyclization and Alkylation of Enynoates: Synthesis of 2-Alkanone Pyrones.

The Pd(II)-catalyzed one-pot tandem cyclization/alkylation reactions of enynoates with allylic alcohols have been demonstrated. In this reaction, an innovative protocol proceeded well through Pd-catalyzed intramolecular selective 6- endo cyclization, insertion of allylic alcohols into the Pd-C bond of vinylpalladium species generated in situ, and β-hydrogen elimination processes. This conversion provides a convenient and efficient methodology for the synthesis of 2-alkanone pyrones in moderate to good yields.

Palladium‐Catalyzed Carbocyclization of Alkynyl Ketones Proceeding through a Carbopalladation Pathway

Palladium‐Catalyzed Carbocyclization of Alkynyl Ketones Proceeding through a Carbopalladation Pathway

Synthesis and characterization of a cyclic vinylpalladium(ii) complex: vinylpalladium species as the possible intermediate in the catalytic direct olefination reaction of enamide

A six-membered cyclic vinylpalladium complex was synthesized via alkenyl C–H bond direct palladation, which was probed in detail by 1H NMR spectroscopy and characterized by X-ray analysis. The cyclic vinylpalladium complex was propounded to be the intermediate during the olefination reaction of enamides. An efficient catalytic system for oxidative cross-coupling reaction of enamides with electron-deficient olefins catalyzed by palladium(II) acetate and 1 atm oxygen as sole oxidant was developed. The corresponding products were obtained in moderate to good yields under mild conditions.

Pd(II)-catalyzed annulation of N-benzyl- N-aroylmethyl-2-alkynamides with arylboronic acids: an efficient synthesis of highly substituted α-alkylidene-β-hydroxy-γ-lactams

A simple palladium(II)-catalyzed intramolecular addition of vinylpalladium species to ketones initiated by the carbopalladation of alkynamides under mild conditions without a Pd(II)/Pd(0) redox system was developed. This cascade reaction provides a new approach for the synthesis of highly substituted α-alkylidene-β-hydroxy-γ-lactams.

Pd-Catalyzed Synthesis of Dihydrocoumarins

The authors describe a general ­tandem palladium-catalyzed process leading to 3-substituted coumarins (2) and optically active 3,4-dihydrocoumarins (3), chemoselectively and in good yields from the same starting material by selecting one of the catalysts. Compounds 3 can be obtained from two different conditions using [Pd(dppp)(H2O)2]²+(BF4 -)2 or Pd(S,S-bdpp)-(H2O)2 ²+(BF4 -)2] in dioxane at r.t. On the other hand, for the synthesis of 2 the procedure described uses [Pd(dppp)(H2O)2]²+(OTf-)2. The catalytic reaction worked well with a variety of aryl­boronic acids and 2-formylarylbut-2-ynoates (1). A possible mechanism involving tandem reaction by transmetalation of ArB(OH)2 with the palladium catalyst, carbopalladation of alkynoates, and the addition of a vinylpalladium species to the aldehyde was proposed.

Stereoselective synthesis of dibenzoxapine containing tetrasubstituted exocyclic alkenes via cascade methylboronic acid coupling reactions

A stereoselective method for the preparation of dibenzoxapine containing tetrasubstituted exocyclic E-alkenes has been developed. The key reaction involves an intramolecular cyclocarbopalladation of alkynes to form a vinylpalladium species and subsequently coupling the vinylpalladium with methylboronic acid. The approach provides a straightforward method for the synthesis of tetrasubstituted exocyclic E-alkenes.

Cationic Palladium‐Catalyzed [5+2] Annulation: Synthesis of 1‐Benzoxepines from 2‐Aroylmethoxyarylboronic Acids

AbstractThe synthesis of 1‐benzoxepines from 2‐aroylmethoxyarylboronic acids and alkynes in the presence of a catalytic amount of [Pd(dppp)(H2O)2]2+(TfO−)2 was developed. This [5+2] annulation involves the intramolecular nucleophilic addition of a vinylpalladium species to ketones.

Cationic Pd(II)-Catalyzed Enantioselective Cyclization of Aroylmethyl 2-Alkynoates Initiated by Carbopalladation of Alkynes with Arylboronic Acids

A cationic palladium(II)-catalyzed enantioselective intramolecular addition of vinylpalladium species to ketones initiated by the carbopalladation of alkynoates under mild conditions without a Pd(II)/Pd(0) redox system was developed with high yield and enantioselectivity. This cascade reaction provides an efficient method for the construction of optically active hydroxylactones.

Sequential Aminodiene Diels−Alder Approach to the Ergoline Skeleton

Through a novel sequence of aminodiene Diels-Alder reactions, several substituted amidofurans were readily converted to tricyclic ketones in good yield. The formation of the tricyclic ketone system is the result of a ring opening and dehydration of a transient oxabicyclic adduct formed by an intramolecular Diels-Alder cycloaddition of an amidofuran with a cyclohexenone moiety tethered such that it participates in the cycloaddition as the 2pi component. A convenient way to construct the cyclohexenone is to make use of some aminodiene chemistry developed by Rawal. An angular carbomethoxy group is required in order to activate the olefin toward cycloaddition with Rawal's diene. The presence of this activating group not only prevents the isomerization of the advanced ergoline intermediate to a naphthalene but can also be leveraged for an oxidation to provide Uhle's ketone (13). The easily formed Kornfeld ketone analogue 25 was readily transformed into the corresponding triflate 41 by the action of triflic anhydride and a base. Oxidative addition of vinyl triflate 41 to Pd(0) and the ability of the resulting vinyl palladium species to undergo cross-coupling with terminal alkynes prompted us to devise an expeditious route to lysergic acid. Unfortunately, our inability to carry out a regioselective Heck reaction using vinyl triflate 41 and the methylene amino acrylate ester 48 thwarted the completion of the synthesis of lysergic acid.

Carbopalladation of Nitriles: Synthesis of 3,4‐Disubstituted 2‐Aminonaphthalenes and 1,3‐Benzoxazine Derivatives by the Palladium‐Catalyzed Annulation of Alkynes by (2‐Iodophenyl)acetonitrile.

AbstractFor Abstract see ChemInform Abstract in Full Text.

Carbopalladation of nitriles: synthesis of 3,4-disubstituted 2-aminonaphthalenes and 1,3-benzoxazine derivatives by the palladium-catalyzed annulation of alkynes by (2-Iodophenyl)acetonitrile.

Intramolecular carbopalladation of the cyano group has been employed for the synthesis of 3,4-disubstituted 2-aminonaphthalenes. (2-Iodophenyl)acetonitrile reacts with a variety of internal alkynes to afford 2-aminonaphthalenes in high yields with good regioselectivity. The scope and limitations of this process, which proceeds by the intramolecular addition of a vinylpalladium species to the triple bond of the cyano group, have been studied. The annulation of certain hindered propargylic alcohols affords 1,3-benzoxazine derivatives, rather than the expected 2-aminonaphthalenes. The involvement of trialkylamine bases in the formation of these heterocyclic compounds has been established. A proposed mechanism for the synthesis of 1,3-benzoxazine derivatives involves the formation of the expected 2-amino-3-(1-hydroxyalkyl)naphthalenes, followed by their condensation with an iminium ion species formed from the trialkylamine base used in the reaction.

Palladium(II)-catalyzed carbocyclization: Vinylpalladium in 1,4-oxidation of conjugated dienes

Palladium-catalyzed 1,4-oxidation of conjugated dienes involving carbon-carbon bond formation has been realized. The reaction is performed with both acyclic and cyclic dienes with a carbon chain containing a terminal or internal triple bond. A vinylpalladium species formed by chloropalladation of the alkyne inserts one of the double bonds of the diene in a Heck-type reaction. The addition of palladium and chloride over the triple bond is non-stereoselective while the overall 1,4-addition by carbon and chloride over the diene is highly stereoselective and occurs anti. The stereoselectivity of the chloropalladation is dependent on the chloride concentration and varies with the substrate.

ChemInform Abstract: Palladium‐Catalyzed Tandem Cyclization‐Anion Capture Processes. Hydride Ion Capture by Vinylpalladium Species.

AbstractN‐Alkynyl‐2‐iodoanilines such as (I) or (IV) undergo Pd‐mediated ring closure, forming indoles, e.g. (II) or (III), and isoquinoline derivatives, e.g. (V) or (VI), respectively.