Complex cationic olefin cyclization

Starting from tetrahydrocyclopenta[f)]furan-2-one 342, enyne 343, the substrate for the domino reaction, was prepared in 12 steps and with an overall yield of 45%. Exposure of 343 to the electron-rich gold(I) complex (t-Bu)2P(o-biphenyl)AuCl at room temperature afforded cis-hydrindanone 344 in 78% yield as a single stereoisomer (Scheme 14.54). The postulated mechanism involved Au(I) activation of the alkyne to initiate the cationic olefin cyclization of 346 to give carbocation 347, which then underwent a pinacol rearrangement to the final product 344. An originally attempted Lewis acid-catalyzed domino Prins/pinacol rearrangement of... 

Thus, one equivalent of dimethylaluminium chloride has been shown to result in an ene reaction to give the alcohol (46), compared to the use of two equivalents, which produces complex mixtures by means of cation-olefin cyclizations. ... 

Stereospecific 2,3-epoxidation of squalene, followed by a nonconcerted carbocationic cyclization and a series of carbocationic rearrangements, forms lanosterol [79-65-0] (77) in the first steps dedicated solely toward steroid synthesis (109,110). Several biomimetic, cationic cydizations to form steroids or steroidlike nuclei have been observed in the laboratory (111), and the total synthesis of lanosterol has been accomplished by a carbocation—olefin cyclization route (112). Through a complex series of enzyme-catalyzed reactions, lanosterol is converted to cholesterol (2). Cholesterol is the principal starting material for steroid hormone biosynthesis in animals. The cholesterol biosynthetic pathway is composed of at least 30 enzymatic reactions. Lanosterol and squalene appear to be normal constituents, in trace amounts, in tissues that are actively synthesizing cholesterol. 

It was not fully realized until my breakthrough using superacids (vide infra) that, to suppress the deprotonation of alkyl cations to olefins and the subsequent formation of complex mixtures by reactions of olefins with alkyl cations, such as alkylation, oligomerization, polymerization, and cyclization, acids much stronger than those known and used in the past were needed. 

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... 

Certain unsaturated aldehydes may be converted to cyclic ketones by a related mechanism. The formyl group reacts with Rh(I) complexes to form an acyl-Rh hydride species, which undergoes intramolecular reaction with the olefinic linkage present in the same molecule (117a). Asymmetric induction is observed with a chiral diphosphine ligand (Scheme 53) (117b-d). Enantioselective cyclization of 4-substituted 4-pentanals into 3-substituted cyclopentanones in greater than 99% ee is achieved with a cationic BINAP-Rh complex. 

For the dimerization of 4,4 -dimethoxystilbene, it has been possible to demonstrate spectroelectrochemically [115] and at the rotating ring-disk electrode [116] that the product is formed mainly by radical dimerization of the intermediate radical cations [path B, Eq. (13)]. Fast derivative CV, however, supports for the same olefin a complex ECE pathway [path A, Eq. (13) [117]. Depending on the oxidation potential and the kind of the nucleophiles (acetate, water, or methanol), a tetrahydronaphthalene derivative (Table 6, number 3) [118], a monomer diacetate [118], a tetrahydrofuran [115], or a dimer dimethoxy compound is found. When methanol is replaced by aqueous dichloromethane or by aqueous acetonitrile emulsions as solvent, styrene (Table 6, number 4) [119a] and a-methylstyrene [119b] yield 2,5-diphenyltetrahydrofurans. In some cases cyclization occurs by electrophilic aromatic substitution (analogous to Table 6, number 3). 

Rhodium complexes facilitate the reductive cyclization of diyne species in good yield, although the product olefin geometry depends on the catalysts used. Moderate yields of -dialkylideneclopentane 169 resulted if a mixture of diyne 146 and trialkylsilane was added to Wilkinson s catalyst ClRh[PPh3]3 (Eq. 33) [101]. If, however, the diyne followed by silane were added to the catalyst, a Diels-Alder derived indane 170 was produced (Eq. 34). Cationic Rh complex, (S-BINAP)Rh(cod) BF4, provides good yields of the Z-dialkylidenecyclopentane derivatives, although in this case, terminal alkynes are not tolerated (Eq. 35) [102]. 

The mechanism of hydroformylation by Pt/Sn systems has been investigated with the help of model complexes (Scheme 42). Only platinum SnCla complexes react with H2 to give EtCHO and close the cycle. 4-Pentenal is cyclized to cyclopentanone by cationic rhodium catalyst such as [Rh(dppe)2] in nitromethane or dichloromethane at 20 °C. The initiating step of the process is the oxidative addition of aldehyde-CH to the Rh(I) centre, a reversal of the final step in an olefin hydroformylation sequence. The mechanism was probed by deuteration studies direct evidence for the catalytic intermediates by NMR was unobtainable. The intermediates are involved in the reversible formation of side products, although selectivity to cyclopentanone can be as high as 98%. The essential features of the reaction are outlined in Scheme 43. ... 

Later, the groups of Sakai and of Tanaka and Suemune, respectively, extended the scope of the enantioselective cyclizations by employing desymmetrization of the aldehyde substrates bearing two identical terminal olefin moieties, and the cyclopentanone products with two vicinal stereo-centers, 8 or 9, could be obtained using a catalytic amount of the cationic Rh complex (5 mol%) (Table 8.2). However, if neutral Rh catalysts were employed, a high catalyst loading at 50 mol% was needed (entries 1, 2). Tanaka, Suemune, and co orkers also developed the kinetic resolution of unsymmetrical racemic diene-aldehyde 10 via a Rh-catalyzed asymmetric hydroacylation reaction (Scheme 8.5). The cyclization product could be obtained in >95% ee. ... 

More elaborate functionalizations could be accomplished when the donor or the radical cation underwent more complex reactions. As an example, the above synthesis of alkyltricyanobenzenes could be varied into a ROCAS reaction (Scheme 14.9, right part) [48, 49]. Thus, photolysis of a mixture of TCB as acceptor, 2-methyl-2-phenyl-l,3-dioxolane (13) as donor and an electron-poor olefin formed a 3-aryl substituted 2-pentanone, which cyclized during purification on silica gel to afford isocoumarine 14 in 75% yield [48], This three-component reaction is based... 

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