Enynes palladium acetate

Yet another palladium-catalyzed transformation leading to 1,2-dialkyl-idenecycloalkanes was established by Trost et al. when investigating a catalytic Alder-ene reaction (path D in Scheme 12). They showed that two different catalyst systems are capable of cycloisomerizing enynes 92 to either cyclic 1,4-dienes 96—the products of regular Alder-ene reactions— or the 1,3-dienes 95 (Scheme 15) [66-68]. Starting from palladium acetate, the reaction presumably occurs by coordination of both unsaturated moieties (intermediate 93) and subsequent cycloisomerization to the ring-... 

The last and key step in the total synthesis of mvxalamide A by C.H. Heathcock et al. was a Suzuki cross-coupling between an ( )-vinylborane and a (Z)-iodotriene. The (E)-vinylborane was prepared prior to the coupling by reacting the precursor enyne with 2 equivalents of cathecholborane. Upon completion of the hydroboration, it was combined with the (Z)-iodotriene and catalytic amounts of palladium acetate. 

Hydridopalladative entry into the reaction cycle is also practical, hi a total synthesis of picrotoxinin 197, enyne 195 was converted into tricycle 196 in the presence of palladium acetate, dbpp, and dpba (Scheme The unusual catalyst system was necessary to... 

Terminal alkynes react to form l-en-3-ynes in a process catalyzed by palladium acetate and tris(2,6-dimethoxyphenyl)phosphine. A number of functional groups such as internal alkenes, esters, and alcohols are tolerated, and good yields of homo- (eq 25) as well as hetero-coupled enynes (eq 26) are obtained. ... 

Alder-ene cyclizations involve enyne substrates with an aUylic hydrogen at the olefinic termini. The pioneering work of Trost initially demonstrated that palladium acetate efficiently promote intramolecular Alder-ene type reactions of 1,6- and 1,7-enynes, leading to 5- or 6-membered rings with exocyclic methylene bonds (Fig. 10.2) [16]. These processes generate a tetrahedral stereogenic centre from a planar sp -carbon in the starting material. Therefore, asymmetric variants... 

Another useful class of palladium-catalyzed cycloisomerizations is based on the general mechanistic pathway shown in Scheme 13. In this chemistry, a hydridopalladium acetate complex is regarded as the catalytically active species.27b-29 According to this pathway, coordination of a generic enyne such as 59 to the palladium metal center facilitates a hydropalladation reaction to give intermediate 60. With a pendant alkene, 60 can then participate in a ring-form-... 

Palladium complexes are effective catalysts for the reductive cydization of enyne substrates [53,54], The first report of catalytic cydization of 1,6- and 1,7-enynes 115a,b to cyclopentane 116a and cyclohexane 116b derivatives appeared in 1987 (Eq. 19) [70]. The authors proposed that the Pd(II) species 117 forms by oxidative addition of acetic acid to Pd(0) (Scheme 25). Complex 117 hydrometallates the alkyne to give 118, which cyclizes to provide... 

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. 

To probe the reaction mechanism of the silane-mediated reaction, EtjSiD was substituted for PMHS in the cyclization of 1,6-enyne 34a.5 The mono-deuterated reductive cyclization product 34b was obtained as a single diastereomer. This result is consistent with entry of palladium into the catalytic cycle as the hydride derived from its reaction with acetic acid. Alkyne hydrometallation provides intermediate A-7, which upon cw-carbopalladation gives rise to cyclic intermediate B-6. Delivery of deuterium to the palladium center provides C-2, which upon reductive elimination provides the mono-deuterated product 34b, along with palladium(O) to close the catalytic cycle. The relative stereochemistry of 34b was not determined but was inferred on the basis of the aforementioned mechanism (Scheme 24). 

In analogy to the mechanism of the palladium-catalyzed enyne cyclization, it is postulated that exposure of palladium(O) to acetic acid promotes in situ generation of hydridopalladium acetate LnPd"(H)(OAc). Alkyne hydrometallation affords the vinylpalladium complex A-10, which upon r-carbopalladation of the appendant alkyne provides intermediate B-7. Silane-mediated cleavage of carbon-palladium bond liberates the cyclized product along palladium(O), which reacts with acetic acid to regenerate hydridopalladium acetate to close the cycle (Scheme 33). 

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... 

Blechert reported a skillful method of cross-enyne metathesis. Solid-supported alkyne 139 is reacted with alkene in the presence of Ic to give 140. For cleavage of 1,3-diene from solid-supported product 140 having an allyl acetate moiety, palladium-catalyzed allylic substitution is used. Thus, 140 is treated with Pd(PPh3)4 in the presence of methyl malonate to afford three-component coupling product 141 in good yield ... 

One conceivable pathway for the 1,6-enyne cyclization is a cyclo-pal ladation via complex 42 to cyclic palladium compound 43, which contains Pdlv, followed by cleavage of the latter to intermediate 44 that subsequently releases hydridopalIndium acetate and product 14-/. An alternative route proceeds by way of hydropalla-dation of the C-C triple bond to intermediate 45, which after addition to the C-C double bond gives bicyclic system 46. This leads to product L4-Z following a p-hydride elimination. The appearance of double-bond isomeric compound 15-Z is explained by another addition of the palladium species to the cyclic C-C double bond in 14-Z and subsequent p-hydride elimination. 

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... 

Jeong et al. demonstrated that the tandem allylic alkylation/Pauson—Khand reaction of the propargylic amines 96 with allyl acetate 97 and CO took place in the presence of a mixture of palladium and rhodium catalysts to give the bicyclopentenones 98 in high yields (Scheme 33).112 Most probably, the allylation of 96 with allyl acetate 97 occurs in the presence of palladium catalyst to give the corresponding enyne, which undergoes the Pauson—... 

Equation 26 illustrates the rare enyne cycloisomerization process which is feasible under relatively mild conditions (in acetic acid at 80 °C for 6 h) in the presence of a palladium (0) catalyst. In the presence of EtAlCl2, alkenes undergo ene reactions with 2-(dialkoxyphosphinoyl)propenoic esters (equation 27 " ) the same catalyst, and other Lewis acids, catalysed the intramolecular reactions of 385 and 386 ( = 0 or 1), which are exemplified by reaction 28 . 

Terminal acetylenes dimerize to conjugated enynes in the presence of catalytic amounts of palladium(II) acetate and the hindered phosphine tris(2,6-dimethoxyphenyl)phosphine. 1-Octyne, for instance, affords the enyne 36 5. Palladium-catalysed condensations of 1-alkynes RC=CH (R=Ph or CH2OH) with vinyl bromide, ( )-2-bromostyrene, iodobenzene and 2-bromopyridine to yield 37, 38, 39, and 40, respectively (Scheme 1), have been reported (see also References 27 and 28). The palladium[tetrakis(triphenylphosphine)]-catalysed alkynylation of 1,1-dichloroethene with terminal alkynes 41 (R = pentyl, 3-chloropropyl, Ph or SiMes) results in the eneynes 42. ... 

The Pd(II)-catalyzed carbocyclization reactions of 1,6-enynes have generally been performed by Pd(OAc)2 or by combined use of Pd(0) species, [Pd2(dba)3] CHCI3, and a weak acid such as acetic acid or trifluoroacetic acid. However, these typical palladium catalysts were ineffective for the 1,6-enyne system (8) in the presence of a chiral bidentate phosphine ligand, such as BINAP, exhibit-... 

A range of cyclization and cycloisomerization reactions of enynes, including enynes with heteroatoms in the skeleton, have been reported for which the possibility of Pd(IV) intermediates has been canvassedJ f t t A typical example is shown in Scheme 16, where supporting ligands at palladium include palladacyclopentadienes, acetate, acetate/PPhj, and acetate/P(o-tol)3. An alternative pathway involving a Pd(0)-Pd(II) cycle has been acknowledged (Scheme 16), and different reaction conditions may favor each pathwayJ Alkylidene complexes as intermediates have also been proposed for some reactions of enynes... 

A highly efficient synthesis of a wide range of 2,5-disubstituted furans from enyne acetates was described. The reactions were conducted by using Lewis acid and palladium catalysts, and provided symmetrical and unsym-metrical products in good-to-excellent yields, with broad substrate scope, including with a variety of aromatic and aliphatic substituents at the 2- and 5-positions of the furan (14SL2341). 

Conjugated enynes were the major products obtained from palladium-catalysed reaction of vinyl bromides such as (32) with acetylenes (Scheme 53). Again the yields of simple enyne acetates are variable, with starting material and other products such as dienynes being isolated. The reaction demonstrates that when a substrate has a choice of undergoing either vinylic coupling or substitution (via a -allyl complex) the former process appears to be favoured. 

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