Enynes/dienynes,

Nickel-mediated intramolecular cyclizations of enynes, dienynes, bis-dienes and diynes leading to heterocycles 92SL539. 

In this account, an overview of the methods employed for the synthesis of conjugated dienes and polyenes is presented. Dienes and polyenes with isolated double bonds are excluded, as they are accessed through methods usually employed for alkene synthesis. Oligomerizations and polymerization reactions leading to polyenes are also not covered. Synthesis of 1,2-dienes, i.e. allenes, is excluded from the purview as there is a volume in the present series devoted to this functional group. Synthesis of heterodienes, conjugated enol ethers, [n]-annulenes and related compounds are also not covered here. However, enynes, dienynes and enediynes syntheses have been included in a few cases in view of their emerging importance. 

Cyclization of enynes, dienynes, and diynes with aryl isocyanides. This combination of reagents (1 2) generates a Ni(0) catalyst (1) which is easier to handle than the air-sensitive bis(l,5-cyclooctadiene)nickel(0), Ni(COD)2. Reaction of 1,6-cnyncs (2) with an aryl isocyanidc in the presence of this Ni(0) catalyst combined with Bu3P (2 cquiv.) results in bicyclic iminocyclopentenes (3) which can be hydrolyzed to the corresponding ketone (4). The overall reaction is an alternative to the Pauson-Khand reaction. 

Nickel (0)-Mediated Intramolecular Cyclizations of Enynes, Dienynes, h/r-Dienes, and Diynes"... 

Treatment of conjugated enyne systems, H C-C=C-CeC-CH-OR, with a suitable base in principle may give rise to 1,6-elimination of HOR with primary formation of the system C=C-C=C=C=C, which subsequently may undergo isomerization to a dienyne. ... 

Guanacastepene A (444) is a novel tricyclic diterpene with fused five-, seven-, and six-membered rings. The possibility of constructing polycyclic compounds via tandem RCM of dienynes was used in Hanna s synthesis of a highly functionalized tricyclic system 443 related to 444. Under the conditions outlined in Scheme 87, trienyne 440 provided the desired tricycle 442 in a single step, as a result of sequential enyne RCM followed by RCM of intermediate 441. Compound 442 was then further functionalized to 443 [182]. 

One productive facet of Pd-catalyzed domino reactions is the cycloisomerization of enynes and allenes, as shown by Trost and coworkers [19]. Thus, transformation of the dienyne 6/1-10 using Pd(OAc)2 led to 6/1-13 in 72% yield, in which the last step is a Diels-Alder reaction of the intermediate 6/1-12 (Scheme 6/1.2). 

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. 

In turn, the propensity of 1 to respond to steric hindrance can be used to control the site of initiation of an RCM reaction in a polyene substrate (Scheme 9) [20]. Thus, dienyne 25 reacts with the catalyst regioselectively at the least substituted site the evolving ruthenium carbene 26 undergoes a subsequent enyne metathesis leading to a new carbene 27, which is finally trapped by the disubsti-tuted olefin to afford the bicyclo[4.4.0]decadiene product 28. By simply reversing the substitution pattern of the double bonds, the complementary bicyclo [5.3.0] compound 32 is formed exclusively, because the cyclization cascade is then triggered at the other end of the substrate. Note that in both examples tri-substituted olefins are obtained by means of a ruthenium based metathesis catalyst [20] ... 

Group-selective enyne metathesis of dienyne 127f having a large substituent on the alkyne proceeds in the presence of aUcene 130 to give small ring compound 131... 

Metal-catalyzed [4 + 2 + 2] cyclotrimerizations of either heteroatom-containing enyne 62 with 1,3-butadiene (Eq. 17) [42] or heteroatom-containing dienyne 64 with an alkyne (Eq. 18) [43] are effected by cationic rhodium complexes generated in situ from a chlo-rorhodium complex modified with silver salts. These processes afford eight-membered ring products 63 and 65, respectively. In both processes, the nature and amount of the silver salt profoundly affect the outcomes. 

Heptadien-l-yne is less volatile and presumably more stable than l,3-hexadien-5-yne. Distilladve separation at atmospheric pressure from El O should therefore be possible without involving the risk of polymerization or decomposition. This allows the preparation of the tosylate and its conversion into the dienyne in the same pot, using EtjO as solvent. Other enynes with a b.p. >100 C/760 mmHg can be prepared in a similar way. 

Further research on this subject was recently reported, in relation to the use of dienynes as substrates for intramolecular cycloaddition. While thermal intramolecular [4+2] cycloadditions of enynes with alkenes only took place at high temperatures, the gold(I) catalyzed transformations provided bi- or tri-cyclic ring systems under mild conditions [152]. 

Certain substituted, 1,6-enynes and related dienynes undergo palladium-catalyzed cycliza-tion to give polycyclic structures containing a three-membered ring via cascade carbopal-ladation (equation 156)343 34S. Transformation of 66 into 67 is representative346. 

Up to this point Pd, Pt and Ru-catalysed enyne metatheses have been explained without involvement of metal-carbenes. However, carbenoid species seem to play a key role in these metatheses (or cycloarrangements) based on the following polycyclization involving cyclopropanation. Polycyclic ring systems are constructed by the cycloisomerization of dienynes catalysed by Ru, Pt, Rh, Ir and Re complexes... 

P Volume 1,1991,283 pp. 109.50/ 69.50 ISBN 1-55938-180-9 CONTENTS Introduction to the Series An Editor s Foreword, Albert Padwa. Preface, Brian Halton. Strain in Organic Chemistry A Perspective, Brian Halton. Gem-Dihalocyclopropanes in Chemical Synthesis, Martin G. Banwell and Monica E. Re-um. 1-Halo- and 1, 2-Dihalocyclopropenes Useful Synthetic Intermediates, Mark S. Baird. Cyciization and Cycloaddition Reactions of Cyclopropenes, Albert Padwa and Glen E. Fryx-ell. New Synthetic Pathways From Cyclobutanones, Edward Lee-Ruff. Cyclic Alkynes, Enynes and Dienynes A Synthetic Challenge, Herbert Meier. Index. 

Stable zirconium, platinum, molybdenum, and tungsten complexes of cyclooctyne, a zirconium complex of cydoocta-5-enyne, and a bimetallic molybdenum complex of cyclocta-3,7-dienyne have been discussed in earlier reviews.28 More recently, two stable zirconocene complexes of cycloocta-trienyne (275 and 276) have been prepared101 by /3-hydride elimination from 274 in the presence of PMe2R [Eq. (45)]. 

Our group has used a combined metathesis-PKR for the synthesis of tricyclic compounds in one step. The process starts from pure cobalt complexed dienynes 52. The cobalt cluster acts first as a protecting group to avoid undesired enyne metathesis processes. The methodology allows the formation of tricyclic [6.5.5] (53) and [7.5.5] (54) structures including, in some examples, oxygen or nitrogen. Tricycles 53 are obtained in a total stereoselective manner, while compounds 54 are formed as mixtures of two diastereomers (Scheme 17) [110]. 

A catalytic tandem cyclopropanation-ring-closing metathesis of dienyne 80 led to derivative 81 in good yield (Scheme 30 <2004JA9524>). For internal alkynes, carbene-mediated ring-closing enyne metathesis was observed. Less favorable alkyne binding leads to preferential reactions of the metal carbene with the 1-alkene moiety. 

Suitable a, tw-enynes can be cyclized when allowed to react with catalytic quantities of [RhCl(PPh3)3]. Alken-2-ynes do not react and the yield is greatly diminished in the case of alk-2-enyne substrates. However, substitution of the alkene bond does not appear to inhibit the dicyclization of dienynes or the cyclization of alkynenones. The dienyne s reaction, shown in equation (21), is catalyzed more effectively by rhodium(I) complexes containing tertiary phosphite ligands. Under similar conditions, trienes can also be cyclized. The cyclopropyl ring can serve as an alkene bond precursor in cyclizations (equation 22). ... 

Irradiation of the dienyne (185) results in hydrogen abstraction from solvent affording the triene (186). In contrast the irradiation of enyne (187) results in bond fission and isomerization yielding the cyclohexene derivative... 

Another intriguing cascade, of an intramolecular Heck type followed by an intermolecular Stille coupling, produces the dienyne 80 starting from the enyne 78 and the stannane 79 (Scheme 3-24) [175]. The reversed sequence of a Stille-type followed by a... 

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