Reductive Heck Reaction Research Articles

ChemInform Abstract: Synthesis of Heterocycles via Transition‐Metal‐Catalyzed Hydroarylation of Alkynes

AbstractReview: 102 refs.

Synthesis of heterocycles via transition-metal-catalyzed hydroarylation of alkynes

Transition-metal (TM)-catalyzed hydroarylation reactions of alkynes have received much attention, because they enable the net insertion of alkyne C-C triple bonds into C-H bonds of aromatic precursors, resulting in regio- and stereo-selective formation of synthetically useful arylalkenes. Taking advantage of this feature, TM-catalyzed alkyne hydroarylations have been successfully used for the synthesis of heterocycles. TM-catalyzed alkyne hydroarylations can be classified into three major categories depending on the type of reaction and precursors involved: (1) palladium-catalyzed reductive Heck reactions of alkynes with aryl halides, (2) TM-catalyzed conjugate arylation reactions of activated alkynes with arylboronic acids, and (3) TM-catalyzed aromatic C-H alkenylations with alkynes. This review surveys heterocycle synthesis via TM-catalyzed hydroarylation of alkynes according to the above classification, with an emphasis on the scope and limitations, as well as the underlying mechanisms.

Progress in Reductive Heck Reaction

Progress in Reductive Heck Reaction

A Reductive-Heck Approach to the Hydroazulene Ring System: A Formal Synthesis of the Englerins

The reduction of a palladium enolate prior to β-hydride elimination provides a unique reaction for the synthesis of the hydroazulene ring system. When combined with a transannular epoxide rearrangement cascade, the reductive-Heck reaction allows rapid entry to the oxo-bridged guaiane core of the englerins.

ChemInform Abstract: Heck‐Type Hydroarylations and 1,3‐Dipolar Cycloaddition Reactions of New Tricyclic Hydrazones.

AbstractThe reductive Heck reaction of hydrazones (I) affords the tricyclic pyrolidinediones (III) as single exo‐diastereomers.

The Hydroarylation Reaction—Scope and Limitations

The synthetic potential of stereoselective, palladium-catalyzed hydro(het)arylation reactions of bi-, tri- and tetracyclic (hetero)alkenes in the presence of phospines and arsines as highly efficient ligands was studied. The mechanism of this reductive Heck reaction becomes more complex in the case of benzonorbornenes. Hydroarylation of diazabicyclo-[2.2.1]heptenes provides a stereoselective access to aryldiaminocyclopentanes. Electron-deficient arylpalladium complexes shift the reaction towards the product of a formal 1,2-hydrazidoarylation reaction of 1,3-cyclopentadiene by a stereoselective C-N cleavage. Due to steric reasons, rigid bicyclo[2.2.2]octenes react slower in hydroarylation reactions than the corresponding bicyclo[2.2.1]heptenes. The more flexible bicyclo[4.2.2]decene system already tends to undergo domino-Heck reactions, even under reductive conditions. When a tetracyclic cis-allylcyclopropane is carbopalladated in the presence of formates, the neighboring cyclopropane ring is attacked in the first reported example of a π,σ domino-Heck reaction.

Reductive Heck Reactions of N-Methyl-substituted Tricyclic Imides

The palladium-catalyzed hydroarylation of N-methyl-substituted tricyclic imides was studied in order to find a new stereoselective access to a series of new exo-aryl(hetaryl)-substituted tricyclic N-methylimides.

ChemInform Abstract: Synthesis of Chiral 3‐Substituted Indanones via an Enantioselective Reductive Heck Reaction.

AbstractChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.

Efficient Synthesis of the 3‐Benzazepine Framework via Intramolecular Heck Reductive Cyclization.

AbstractChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract, please click on HTML or PDF.

Synthesis of Chiral 3-Substituted Indanones via an Enantioselective Reductive-Heck Reaction

An efficient intramolecular palladium-catalyzed, asymmetric reductive-Heck reaction has been developed, which allowed for the synthesis of either enantiomerically enriched 3-substituted indanones or alpha-exo-methylene indanones depending on the base used.

Efficient Synthesis of the 3-Benzazepine Framework via Intramolecular Heck Reductive Cyclization

A microwave-assisted protocol based on reductive Heck reaction was developed for regio- and stereoselective construction of the 3-benzazepine core.

Cyclic sulfamidates as versatile lactam precursors. An evaluation of synthetic strategies towards (−)-aphanorphine

A full account of studies which led to the efficient asymmetric synthesis of (-)-aphanorphine is reported. Two routes to the key cyclic sulfamidate intermediate are described, the first was based on a chiral auxiliary approach and the second utilised asymmetric hydrogenation methodology. A range of C(3)-substituted lactams (, and ) were synthesised and evaluated as precursors for Pd(0) catalysed entries (based on (i) alpha-arylation of a lactam enolate and (ii) reductive Heck reaction) to the 3-benzazepine core of . These approaches were less effective than an aryl radical cyclisation which allowed the completion of a synthesis of in 12 steps from anisaldehyde.

“Reductive Heck Reaction” of 6‐Halopurines.

AbstractFor Abstract see ChemInform Abstract in Full Text.

‘Reductive Heck reaction’ of 6-halopurines

Alkenylation of 9-benzyl-6-halopurines with alkenes does not proceed under conventional Heck conditions. However, in the presence of triethylammonium formate a mixture of the corresponding saturated products was obtained. In contrast to the classical Heck reaction, the regioselectivity of this process is low giving a mixture of both α- and β-products regardless of the electronic nature of the substituent on the double bond of the alkene.

DYKAT of Baylis-Hillman adducts: concise total synthesis of furaquinocin E.

Baylis-Hillman adducts are easily accessible building blocks; the lack of asymmetric versions of the Baylis-Hillman reaction has however precluded their widespread use in asymmetric synthesis. A Pd-catalyzed DYKAT on carbonates derived from Baylis-Hillman adducts, followed by a reductive Heck reaction, allows the enantio- and diastereoselective construction of dihydrobenzofurans in a very efficient manner. These synthons represent the core structure of the furaquinocins. Introduction of different side chains and use of different squaric acid derivatives for the construction of the naphthoquinone allow the flexible synthesis of this class of natural products. This new approach is successfully applied to the synthesis of furaquinocin E and an analogue.

A double ring closing metathesis reaction in the rapid, enantioselective synthesis of NK-1 receptor antagonists.

[structure: see text]. The NK-1 receptor antagonist 1 has been prepared in seven steps from phenylglycine methyl ester. The key steps are a double ring closing metathesis reaction of tetraene 7 to prepare spirocycle 6 and a reductive Heck reaction to introduce the aryl moiety. This latter reaction discriminates the olefins of compound 6 and proceeds in a highly regio- and stereoselective manner.

Stereoselective dihydropyrido(2,1- a)isoindolone synthesis via diastereodivergent Heck cyclisations on chiral 1,4-dihydropyridines

A stereoselective dihydropyrido(2,1- a)isoindolone synthesis is described via diastereodivergent cyclisations by using reductive or non-reductive Heck reactions on chiral 1,4-dihydropyridines.

Total Synthesis of (-)-Strychnine via the Wieland-Gumlich Aldehyde.

Fifteen steps suffice for an enantioselective total synthesis of (-)-strychnine (1) from 1,3-cyclohexanedione. The key steps are the easy generation of the enantiopure intermediate 2, the closure of the piperidine ring by a reductive Heck reaction, and the elaboration of the indoline nucleus in an advanced synthetic stage. TBDMS=tert-butyldimethylsilyl.