Cycloisomerization of 1,5-enynes

Michael additions of 7r-allyl species to alkynes were employed for the synthesis of elaborated carbocycles as in the ruthenium-catalyzed cycloisomerization of 1,6-enynes (Equation (188)).1... 

Zhang54 published the first and only account of a non-asymmetric rhodium-catalyzed Alder-ene cycloisomerization of 1,6-enynes.55 The conditions developed by Zhang and co-workers are advantageous in that, similar to the ruthenium conditions developed by Trost, selectivity for 1,4-diene products is exhibited. The rhodium conditions are dissimilar from many other transition metal conditions in that only (Z)-olefins give cycloisomerization products. 

For selected examples of the cycloisomerization of 1,6-enynes catalyzed by metals other than palladium, see (a) Titanium ... 

Scheme 9.4 Cycloisomerization of 1,6-enynes via rhodium vinylidene intermediates.

When enyne cycloisomerization takes place in the presence of an unsaturated molecule an insertion reaction can occur. Thus, Ru3(CO)12 catalyzes the cycloisomerization of 1,6-enynes under a CO atmosphere to give an insertion of carbon monoxide and the formation of bicyclic cyclopentenones as a catalytic Pauson-Khand reaction [78] (Eq. 57). 

The cycloisomerization of 1,6-enynes can also be catalyzed enantioselectively using a Rh-BICP catalyst (eq 8). However, Rh-Me-DuPhos affords a significantly higher enantioselectivity than Rh-BICP for this process (Table 4). 

Trost, B.M. and Toste, F.D. (1999) Ruthenium-catalyzed cycloisomerization of 1,6-enynes initiated by C-H Activation. 

The Rh-catalyzed cycloisomerization of 1,6-enynes that occurs via rhodium vinylidene-mediated intermediates was first described in 1988 by Grigg et al. (471). Cyclization of 1,6-enynes (I, Scheme 57) with [RhCl(cod)]2/P(p-FC6H4)3, where cod=l,5-lyclooctadiene as the catalyst generates a metal-vinylidene that undergoes [2 + 2] cycloaddition and... 

Cycloisomerization of 1,6-enynes. In sterically difficult situations, such as those reactions proceeding via a transition state disfavored by developing 1,3-diaxial interactions, the catalyst system must be well designed. A case in point is the annulation of a bridged ring system en route to picrotoxinin. Thus, a failed reaction is revitalized when Pd(OAc), is combined with a tied-back ligand and an internal source of protons. 

The cycloisomerization of 1,6-enynes proceeds smoothly in the presence of AcOH or HCO2H and the reaction is explained by the following mechanism (hydridopalladium acetate mechanism) [45]. Most importantly, oxidative addition of AcOH to Pd(0) generates H-Pd-OAc 143, and the cyclization of 1,6-enynes starts by insertion of the triple bond to 143 to afford the alkenylpalladium 144. Subsequent intramolecular insertion of the double bond gives the alkylpalladium 145. The termination step is (i-R elimination and either the diene 136 or 138 is formed with regeneration of H-Pd-OAc. It should be noted that the alkenylpalladium 144 is a similar species formed in a Heck reaction by oxidative addition of alkenyl halide to Pd(0). Based on this reaction, alkyne is a useful starter in domino cyclization of polyenynes. 

Transition-metal-catalyzed intramolecular cycloisomerization is one of the most useful carbocyclization reactions, and specifically, the Rh-catalyzed cycloisomerization of 1,6-enynes provides a powerful tool in organic synthesis. Cyclization of l,6-en5me 452 catalyzed by Wilkinson s catalyst gave 1-exo-methylene-2-cyclohexene 453 via a 6-exo-trig mode in 83% yield (Scheme 2-50). Terminal substitution on the alkene moiety dramatically suppressed the cyclization, and substitution of the terminal alkyne moiety was detrimental to the reaction as well. 

General procedure for the gold-catalyzed cycloisomerization of 1,6-enynes to conjugated diene ... 

Six-membered dienes with an exocyclic double bond can also be obtained by gold-catalyzed cycloisomerization of 1,6-enynes. This transformation is stereospecific i.e., substrates with defined double-bond geometries afforded the products as single stereoisomers (Scheme 4-23). Low temperatures and electron-withdrawing... 

Various other nucleophiles can be employed for the trapping of cyclopropyl gold carbenes formed by cycloisomerization of 1,6-enynes. The intermolecular hydroxycyclization or alkoxycyclization of 1,6-enynes in the presence of water or alcohols is also catalyzed by Pt(II) or Pd(II), but they proceed under milder conditions and more efficiently in the presence of cationic gold(I) catalysts. ... 

The formation of chiral cyclic 1,4-dienes from cycloisomerization of 1,6-enynes and 1,7-enynes has triggered the search for enantioselective catalytic... 

Cycloisomerization of 1,6-enynes in the presence of a dicationic platinum(IV) catalyst has been reported to give five-membered ring systems (Scheme 146) ° ... 

Enantiospecific platinum-catalysed cycloisomerizations of 1,6-enynes give oxabi-cyclo[4.1.0]heptenes and a model for the stereochemical transfer has been proposed (Scheme 148). (g)... 

The cycloisomerization of 1,6-enynes is one of the most widely studied and developed reaction within gold catalysis. In the absence of nucleophiles, a variety of products can be obtained (Scheme 1.14) [8, 159-164]. 

Scheme 1.39 Gold(I)-catalyzed cycloisomerization of 1,6-enynes bearing a caibonyl group at...

In the presence of an aldehyde (or ketone) such as 36, the cycloisomerization of 1,6-enyne 37 evolves toward the formation of 2-oxabicyclo[3.1.0]hexanes 42 (Scheme 5.14) [63]. According to the authors, the 5-exo-dig carbenoid intermediate... 

Finally, enantioselective cycloisomerizations of 1,6-enynes 45 have been reported using an iridium catalyst in the presence of tolBinap as the chiral ligand, leading to the expected aza-bicyclo[4.1.0]heptane derivatives 46 in good yields but moderate (up to 78%) enantioselectivities (Scheme 5.16) [66],... 

Taking advantage of the rich chemistry of transition-metal-catalyzed cycloisomerization of 1,6-enynes, the electron-rich, conformationally blocked cyclohepta-1,3, 5-triene has been envisioned as a 6-% nucleophilic component [59]. Thus, cycloisomerization of l-(pent-4-ynyl)cyclohepta-l,3,5-trienes in the presence of catalytic amounts of platinum(II) chloride led to a formal intramolecular [64-2] cycloaddition in good to excellent yields [60]. These reactions are conducted at room temperature in toluene as the solvent. A heteroatom in the tether between the unsaturated subunits is tolerated, although in these cases other catalytic pathways were also observed. A mechanism involving cationic intermediates resulting from the nucleophilic attack of the triene on the metal-alkyne moiety has been proposed (Scheme 8.38). The occurrence of ionic intermediates was supported with... 

Gallium(III) chloride catalyzes a new type of cycloisomerization of 1,6-enynes having a 1,4-cyclohexadiene subunit to generate 1,3,6-cyclooctatrienes (Scheme 8.39) [61]. The formation of 1,3-diene moiety of the cycloadduct is believed to occur through cycloreversion of cyclobutene or fragmentation of cyclobutylgallium zwitterion intermediate. 

A catalyst system consisting of Pd2(dba)3 and AcOH or PhC02H effectively promotes the Alder-ene-type cycloisomerization of 1,6-enyne 34 to give 1,4-diene 35 (phosphine ligand is sometimes necessary). A cationic Pd(II) hydride species is believed to be generated in these reactions, the anion of which affects catalyst activity and selectivity (eq 22). 

Inducing Asymmetry in -Elimination Pathway Apart from its racemic variants, cycloisomerization of enynes has been successfully employed in asymmetric synthesis. In the first example of an asymmetric cycloisomerization reaction, Trost et al. used a combination of palladium(O) and a chiral acid to catalyze the cycloisomerization of 1,6-enynes resulting in a rather low enantioselectivity of 33% ee for the formation of 1,4-diene (35) (Scheme 7.17(a)) [35]. Modem development of chiral phosphoric acids has allowed the reexamination of this approach. Thus, when palladium(O) and chiral (5)-TRIP were used with enyne 36 a 71% yield of diene 37 was isolated in 88% ee [36]. Under the same eon-cept, Mikami and coworkers found that cationic palladium... 

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