Enynes intramolecular cyclization

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

The early woric with thiyl radicals primarily involved the intramolecular cyclization of alkenes. The reaction appears to be useful since high yields and stereoselective formation of products are observed (equation 7). Under a variety of conditions the diallyl diester (12) produces a 6 1 mixture of stereo-isomeric cyclopentanes (13) and (14) in high yield. ° When enynes are treated with thiyl radicals, low to moderate yields of addition products are observed (equation 8). ... 

Endo-skeletal rearrangements also take place with 1,6-enynes, bnt the proposed mechanism is just a variation of the exo-single-cleavage rearrangement. Formed by endo cyclization, bicyclo[4.1.0]hept-4-ene derivatives arise in some cyclizations of 1,6-enynes by proton loss and protodemetalation ofthe endo cyclopropylcarbene. " That is the case from 1,6-enynes tethered as sulfonamides and in the intramolecular cyclization of 1,6-enol ethers with alkynes (equation 40). ... 

Another important development in the area of catalytic Pauson-Khand type cy-clizations has been the discovery of other transition metal carbonyl complexes which are capable of effecting the catalytic synthesis of cyclopentenones. Two recent reports from Murai and Mitsudo detailed a Ru3(CO)i2-catalyzed enyne cyclocarbonylation, Eqs. (10) and (11) [34,35]. While this protocol allowed for the cyclization of a variety of l,6-enynes,the cyclizations of terminal alkynes as well as 1,7-enynes were problematic. The feasibility of using Cp2Ti(CO)2 as a catalyst for the intramolecular Pauson-Khand type cyclization of a variety of 1,6-and 1,7-enynes (vide infra) has also been demonstrated [36]. Based on the wide array of transition metals that are capable of effecting stoichiometric Pauson-Khand type cyclizations (vide supra), the development of more catalytic systems is to be expected this should greatly facilitate the search for catalytic asymmetric variants. 

Metal-mediated cyclizations have been applied to piperidine synthesis (Scheme 16). Ring closing metathesis catalyzed by Ru catalysts is used to prepare chiral piperidines <97TL677, 97AG(E)3036>. Similarly to the cyclization to 37 is Ti-(II)-mediated intramolecular cyclization of optically active enyne precursors for preparing chiral piperidines <97TL8351>. 

Cycloisomerization of enynes has been employed to construct an array of natural products.f " Although the precise mechanistic details of the reaction have not been elucidated, and may vary from case to case, one potential mechanism is shown in Scheme 28. Generation of an alkyl- or hydridopaUadium complex in the presence of enyne 183 may lead to carbo- or hydridopalladation to give an alkenyl palladium intermediate 184. Intramolecular cyclization (184 185) then follows to form five-, six-, or seven-membered rings followed by /3-hydride elimination to yield 1,4-diene 186 and/or 1,3-diene 187. There are also examples of yne-yne cyclizations in natural product synthesis. ... 

The thermail intramolecular cyclization of aUenyl enyne via a o,x-biradic2il intermediate generated by the bonding between C2 and C7 is generally known as the Myers-Saito cyclization (Scheme 9.37)... 

Complexation of triynes to Pd(0) has been reported to give homoleptic palladium alkyne complexes that show a trigonal-planar arrangement with all of the alkyne carbons and Pd in the same plane. Complex 73 is a macrocyclic complex synthesized by reaction of the triyne with Pd(PPh3)4- Due to coordination to the metal, the alkyne carbons are shifted to the center of the cycle and their substituents deviate from linearity by about 22°. Complex 74 undergoes clean intramolecular cyclization at room temperature upon addition of PPh3 (Equation (24)). No intermediate complexes were detected in the course of this reaction, which is an example of the important cycloisomerization of alkynes and enynes catalyzed, among other transition metal complexes, by Pd(0) derivatives. 

A possible mechanism for the formation of 272, its structural isomer 273, and small quantities of [Os3(CO)9(/x-CO)(/X3-r7 -PhG2G=GPh)] 229 is illustrated in Scheme 25. The first step involves the formation of an alkenyl intermediate, followed by an intramolecular cyclization process that leads to the formation of 272 and 273. An alternative pathway involves the coordination of the second hydride onto the coordinated ligand which results in the expulsion of an enyne and the further reaction of an unsaturated Os3(GO)io fragment with another diyne molecule to give 229. 

The reaction of 1,6-enynes with secondaiy phosphine oxides under appropriate conditions resulted in the formation of phosphinoyl-fluorene derivatives as the end product. The addition of the >P(0)H species to the acetylenic moiety was followed by two intramolecular cyclizations (Scheme 36). ... 

Liang et al. demonstrated a novel CuClj-catalyzed synthesis of 4-carbonyl-quinolines through aerobic oxidative intramolecular cyclization of enynes using O2 as an oxygen source. A Cu(III) and Cu(II) mechanism is involved for this transformation for the C-H bond activation [156] (Scheme 8.86). 

Scheme 8.86 Synthesis of 4-carbonylquinolines through aerobic oxidative intramolecular cyclization of enynes.

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

The intramolecular cyclization of alkene to conjugated enyne by Au(I) catalysis has been observed by Echavarren, the triple bond being activated by the cationic metal (Scheme 7) [17]. The obtained product features an exocychc conjugated diene and the selectivity originated from the intramolecular attack of the olefin to the triple bond. In the process, a molecule of MeOH traps the cationic intermediate. 

The cross-coupling of alkynylzinc halides or fluorinated alkenyizinc halides with fluorinated alkenyl iodides allows the preparation of a range of fluorinated dienes or enynes. "" Functionalized allylic boronic esters are prepared by the cross-coupling of (dialkylboryl) methylzinc iodide with functionalized alkenyl iodides. The intramolecular cyclization of the product provides polycyclic compounds such as 399 (Scheme 1-129). In some cases, reduction reactions or halogen-zinc exchange reactions have been observed. 

Enyne compounds underwent the cyclopropanation reaction in the presence of catalytic amounts of PtCl2. Malacria and coworkers reported that intramolecular cyclization/cyclo-propanation progressed from 1,5-enyne-containing mediumsized rings 365 and 366 to give tiicycUc cyclopropanes 367 and 368, respectively (Scheme 1.174) [246]. 

The intramolecular cyclization of alkynals promoted by Brpnsted acids in tandem with a Nazarov cyclization has been reported to construct hydroazulenone skeletons from enyne acetals (Scheme 167). °... 

Zirconocene or titanocene mediated intramolecular cyclization reactions of enynes followed by CO insertion into their corresponding five-membered metallacycles led to the formation of bicyclic cyclopentenones (Eqs.40,41) [37,38]. Intermolecular coupling of alkynes, alkenes, and CO mediated by zirconocene or titanocene affording cyclopentenone derivatives have also been achieved (Eq. 39) [18, 39, 40]. It is noteworthy that, in order to obtain the desired cyclopentenones from the reaction of zirconacyclopentenes with CO, termination of the reaction mixture with I2 is necessary. Alcohols are normally formed if the reaction mixture is treated with aqueous acid. However, in case of titanacy-clopentenes, quenching with 3 N HCl gave cyclopentenones exclusively [18]. 

Intramolecular cyclizations of enynes using catalytic amounts of octacarbonyldicobalt (3 mol %) succeed in the presence of biphenyl phosphite (10 mol %) under 3 atm of CO, typically in DMFat 120 C. ... 

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