Heck reaction domino

Scheme 6/1.3. Allylsilane-terminated domino Heck reactions of 6/1-14a-f.

Scheme 6/1.27. Domino Heck reaction/CH-activation of a,(3-unsaturated sulfones and Phi.

A particularly elegant domino Heck reaction involving 4-bromoindole and bromo(indolyl)maleimide 251 to give N-methylarcyriacyanin A (252) in one operation was reported by Steglich [173]. This alkaloid could also be prepared from triflate 253 in higher yield in a heteroaryl Heck reaction. 

A domino Heck reaction of 137 has recently been used by Overman et al for the total synthesis of (+)-and (-)-scopaduldc add A139. The process leads to 138 which can be transformed into 139 (scheme 28).1741... 

Scheme 28. Domino Heck reaction for the total synthesis of (-)-scopadulcic acid A 129...

The transition metal-catalyzed domino reactions will undoubtedly have a splendid future which is underlined by the increasing number of publications in this area Steglich et al. presented an approach to arcyriacyanin A via a domino Heck reaction between a bromo(indolyl)maleiimide and 4-bromoindole.1811 The synthesis of 33 -bifurans by Ling et al. was achieved using a novel palladium-catalyzed domino dimerization and subsequent cyclization of acetylenic ketones.1821 Other applications of a combination of Heck reactions for domino processes are the syntheses of aza-heterocydes developed by our group.1831... 

We recently focused on processes involving the reductive Heck and Domino-Heck reactions [3] in a single synthetic operation by treating aryl iodides in conjimction with this work. 

Scheme 37.1 Domino-Heck reactions of compound 1 with trimethylsilylacetylene and aromatic...

Scheme 37.2 Domino-Heck reaction of compound 1 with phenylacetylene and aromatic iodides...

Domino-Heck Reactions-General Procedure 5.6 mg (25 pmol) of palladium(II) acetate and 55 pmol of the arsine ligand were dissolved in 3 ml of dry dimethyl formamide and the solution was stirred at 65°C (40°C for trimethylsilylacetylene) for 15 mitt Then, 127 mg (1.35 mmol) N-Benzoyl-2-azabicyclo[2.2.1]hept-5-en-3-one, 1 mmol of the aryl compound. Four hundred and eighty-eight microliters (3.50 mmol) of triethylamine, and 3.00 mmol of the phenylacetylene (or silylmethyl-acetylene) were added rapidly in one portion. The mixture was heated at the same temperature for 24 h. After cooling down to room temperature 50 ml of brine were added, the reaction mixture was extracted with ethyl acetate and dried over MgSO. The solvent was evaporated, the residue purified by column chromatography (n-Hexan-Ethyl acetate 4 1). 

Abstract New epibatidine analogues were synthesized by palladium catalyzed reductive Heck and Domino-Heck reactions and regioselective results were obtained. 

Keywords Epibatidine analogues, Epipedobates tricolor, Domino Heck reaction, frog, synthesis... 

We continued our work with the reductive Heck and Domino-Heck reactions [1, 7J of new bicyclic compound (3) by treating it with different aryl- and hetaryl-iodides, as a result a series of new epibatidine analogues were synthesized, continuously separated and purificated by column chromatography on silica gel. Treatment of 3 with iodobenzene, 2-iodothiophene, 1-iodonapthalene and 2-chloro-5-iodopy-ridine under reductive Heck conditions gave new compounds 4a-d and 5b, 5d as exo-regioisomers after chromatographic separations. The reactions with iodobenzene and 1-iodonapthalene gave only 5-exo- products. The use of trimethylsily-lacetylene under Domino-Heck conditions provided alkynic bicyclic systems 6e andf. 

For the exo-regioisomers of 6e and f resulting from the Domino-Heck reaction were also identified from the HMBC spectra. In the spectrum of 6f, the interaction of the acetylene carbon (at 103.5 ppm) with the H proton (at 4.24 ppm) was obvious in the isomer 6e, an interaction between the phei rl gronp qnatemaiy carbon (at 139.0 ppm) with the H proton (at 4.40 ppm) was apparent, bnt inboth cases similar effects were not seen in the other isomers. 

A ir,o domino-Heck reaction under concomitant rearrangement of the tetracyclic allylcyclopropane endo,exo-bishomobarrelene has been reported 138 the stereoselective reaction proceeds via an intramolecular insertion of a primarily formed carbopallada-tion intermediate into a strained cyclopropane C-C cr-bond (Scheme 96). 

For domino Heck reactions the initial carbometallation step must lead to intermediates that do not readily undergo /1-hydride elimination and can thus serve as starting points for additional Pd-mediated transformations [7]. Such processes, as exemplified in Scheme 6, have been used extensively by de Meijere, Grigg, Overman and others for assembly of complex carbon skeletons. 

Cinnamic esters 691 react with aryl halides via a domino Heck reaction-lactonization process in molten //-Iki () c///-B111 hr to yield 4-arylcoumarins (Scheme 170) <2005ASC308>. Likewise, the palladium(n)-cata-lyzed reaction of cinnamic esters with vinyl triflates yields 4-vinyl coumarins <1996SL568>. 

Scheme 25 A domino Heck-reaction-67T-electrocyclization-elimination sequence [93]...

A particularly elegant domino Heck reaction involving 4-bromoindole and... 

Scheme 38. Preparation of the benzfe] pyrenes 75 and 76 by domino Heck reactions [131]...

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