Palladium enyne synthesis

Bromoalkynes also couple with vinylstannanes readily to result in enynes. Synthesis of protected enynals via cross-coupling of vinylstannanes with 1-bromoalkynes in the presence of a catalytic amount of Pd(II) has been reported (equation 143)252. Hiyama and coworkers extended the Stille methodology for sequential three-component coupling of trimethylstannyl(trimethylsilyl)acetylene with a vinyl iodide in the first step and cross-coupling of the intermediate trimethylsilylethyne with another alkenyl iodide in the presence of tris(diethylamino)sulphonium trimethyldifluorosilicate in the second step to generate a dienyne (equation 144)253. Both steps occur under palladium catalysis, in one-pot, to result in stereodefined l,5-dien-3-ynes. 

The palladium-catalyzed enyne synthesis is achievable via the decarboxylative coupling of propiolic acids with alkenyl bromides (Scheme 4.62) [63]. Propiolic acids also couple with benzyl halides through decarboxylation and subsequent sp C-sp C bond formation (Scheme 4.63) [64]. 

Synthesis of Functionalized Enynes by Palladium/Copper-catalyzed Coupling Reactions of Acetylenes with (Z)-2,3-Dibromopropenoic Acid Ethyl Ester (Z)-2-Bromo-5-(trimethylsilyl)-2-penten-4-ynoic Acid Ethyl Ester. 

The addition of a carbonylation step extended a pyrrole synthesis to pyrrole-2-acetic acid derivatives <06ASC2212>. Treatment of enyne amine 1 with palladium diiodide in the presence of CO and methanol produced pyrrole-2-acetic ester 2 via a 5-exo-dig cyclization, oxidative carbonylation, and isomerization. 

Few other examples of such reaction sequences have been described to date. Oh has reported the palladium-catalyzed reductive cyclizations of 1,6-enynes in the presence of formic acid or triethylsilane via an alkylpalladium intermediate and its application to organic synthesis. Palladium complexes also catalyze the conversion of a range of enynes to cyclic 6,7-unsaturated carboxylic acids in the presence of CO.260... 

Kibayashi and co-workers103 implemented the palladium-catalyzed cycloisomerization reaction in a stereoselective total synthesis of enantiomerically pure (+)-streptazolin. The cycloisomerization of enyne 172 to provide diene 173 was remarkably selective when performed in the presence of A,Ar -bis(benzylidene)ethylenediamine (BBEDA) as a ligand and water as a proton source (Scheme 44). 

For the synthesis of heterocycles, an efficient strategy has been introduced utilizing the dual transition metal sequences (Scheme 6).11,lla The key issue is the compatibility of the two catalyst systems. Jeong et al. studied the one-pot preparation of bicyclopentenone 35 from propargylsulfonamide 33 and allylic acetate.11 This transformation includes two reactions the first palladium-catalyzed allylation of 33 generates an enyne 34 and the following Pauson-Khand type reaction (PKR) of 34 yields a bicyclopentenone 35. The success of this transformation reflects the right combination of catalysts which are compatible with each other because the allylic amination can be facilitated by the electron-rich palladium(O) catalyst and the PKR needs a Lewis-acidic catalyst. Trost et al. reported the one-pot enantioselective... 

A hydrosilylation/cyclization process forming a vinylsilane product need not begin with a diyne, and other unsaturation has been examined in a similar reaction. Alkynyl olefins and dienes have been employed,97 and since unlike diynes, enyne substrates generally produce a chiral center, these substrates have recently proved amenable to asymmetric synthesis (Scheme 27). The BINAP-based catalyst employed in the diyne work did not function in enyne systems, but the close relative 6,6 -dimethylbiphenyl-2,2 -diyl-bis(diphenylphosphine) (BIPHEMP) afforded modest yields of enantio-enriched methylene cyclopentane products.104 Other reported catalysts for silylative cyclization include cationic palladium complexes.105 10511 A report has also appeared employing cobalt-rhodium nanoparticles for a similar reaction to produce racemic product.46... 

In 1993, Hayashi and co-workers reported a catalytic asymmetric synthesis of alle-nylboranes 256 by palladium-catalyzed hydroboration of conjugated enynes 253 (Scheme 4.66) [105]. Reaction of but-l-en-3-ynes 253 with catecholborane 254 in the presence of a catalyst, prepared from Pd2(dba)3 CHC13 (1 mol%) and a chiral mono-dentate phosphine ligand (S)-MeO-MOP 255 (1 mol%), gave an allenylborane 256. The ee of 256 was determined by the reaction with benzaldehyde affording the corresponding optically active homopropargyl alcohols 257 with up to 61% ee (syn anti= 1 1—3 1). 

Wang s approach for the synthesis of enyne-allenes focused on ene-allenyl iodide 45 (Scheme 14.12) [24]. Palladium-catalyzed Sonogashira reaction of 45 with terminal alkynes 46 (R= Ph or CH2OH) proceeded smoothly under mild reaction conditions in the presence of the cocatalyst cuprous iodide and n-butylamine. The initially formed enyne-allene 47b with substituent R= CH2OH cyclized spontaneously to the corresponding a-methylstyrene derivative 48. 

SYNTHESIS OF FUNCTIONALIZED ENYNES BY PALLADIUM/COPPER-CATALYZED COUPLING REACTIONS OF ACETYLENES WITH (Z)-2,3-DIBROMOPROPENOIC ACID ETHYL ESTER (Z)-2-BROMO-5-(TRIMETHYLSILYL)-2-PENTEN-4-YNOIC... 

Dienes and l -enynes. Negishi et al have extended the synthesis of 1,3-enynes by palladium-catalyzed cross-coupling of alkynylzinc chlorides with an alkenyl halide (8, 472) to a similar stcrcospccific synthesis of 1,5-dienes or 1,5-enynes by coupling an alkenyl halide with a homoallyl- or homopropargylzinc chloride. An example is the synthesis of the 1,5-cnync I (equation 1). This reaction... 

Compounds 1 3 are distinctive for their striking bicy-clo[3.1 OJhexane skeleton, which was prepared in enantiomerieally pure form for the first time in the synthesis described here, a linear process involving a palladium-catalyzed domino enyne cych/ation2 as the key reaction. 

The key step in this synthesis is the palladium-catalyzed domino- 1.6-enyne cyclization. which creates the bicyclic skeleton of the natural product in a single diastereoselective step. 

A palladium(0)-catalysed cascade cyclization-Suzuki coupling reaction of various 1,6-enynes (72) with ArB(OH)2 has been developed as a new approach to the synthesis of stereodefined a-arylmethylene-y-butyrolactones, lactams, multifunctional tetrahy-drofurans, pyrrolidines, and cyclopentanes (73) (X = O, H2, Y = O, CH2, NR3). A 7r-allylpalladium intermediate and a chair-like transition state were suggested to account for the stereochemistry of this reaction.86... 

The synthesis of five-membered carbo- and hetero-cyclic compounds, including fused rings, has been reported using acetate as a nucleophile in the cyclization of 1,6-enynes under palladium(II) catalysis (Scheme 91). The reaction is initiated by trans-acetoxypalladation of the alkynes and quenched by either trans- or ra-deaceloxypal-ladation in the presence of 2,2/-bipyridine as the ligand.134... 

For mechanistic investigations on Pd/Ag-catalyzed enyne or arylyne synthesis, Pale et al. mixed various alkynylsilvers with vinyl Inflates or aryl iodides in the presence of palladium salts or complexes (Scheme 10.66).105 This reaction clearly demonstrated that organosilvers can be transmetalated to organopalladium species, even if no halide was present, as demonstrated when starting from vinyl triflates. 

Saito S, Yamamoto Y (2002) Palladium-Catalyzed Benzannulation Reactions of Conjugated Enynes and Diynes. In Negishi E, de Meijere A (eds) Handbook of Organopalladium Chemistry for Organic Synthesis. Wiley, New York, p 1635... 

A spectacular application allowed the synthesis of fenestranes by a three-step sequential action of cobalt nanoparticles and a palladium catalyst [131]. The cascade reaction started with a PKR of enyne 105, accomplished by the cobalt catalyst giving 106, followed by the formation of allyl-7r3 palladium complex 107 which reacted with a nucleophile derived from diethyl malonate, to give enyne 108. The final step was a second PKR that gave 109 in good yield. They used cobalt nanoparticles as with Co/charcoal the third step did not take place, apparently due to damage in this catalyst after the allylation step (Scheme 31). 

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