Reductive dimerization cyclization

Zinc-mediated reductive dimerization cyclization of 1,1-dicyano-alkenes occurs to give functionalized cyclopentenes in good yields under saturated aqueous NH4CI-THF solution at room temperature. The trans isomers are the major products (Eq. 10.38).89... 

Lund and co workers [51] reported interesting stereochemical results in the reductive dimerization-cyclization of benzylidenemalononitrile, but the reaction pathway was not stereochemically clarified. Recently, it has been clearly demonstrated by some workers [51-54] that the reductive cyclodimerization of activated olefins in aprotic media affords the 1,2-disubstituted cyclobutanes as shown in Eq. (4). 

Properties and Reactions of Ylidenemalononitriles, F. Freeman (1980). Dicyanomethylene compounds, their molecular structure and spectral properties, toxicity and analyses are reviewed. Various reactions like hydrolysis, oxidation and reduction, dimerizations, cyclizations, photochemistry and thermolysis are discussed. The review, which contains 380 references, also deals with unsaturated compounds, oxygen, nitrogen, phosphorous and sulfur compounds. 

Palladium-catalyzed cyclic carboxylation of dienes can be utilized for the synthesis of lactones.2 Polymer-supported Pd catalyst could also be used for this reaction (Scheme 42).61 The reaction is initiated by dimerization of two molecules of diene to give a bis-7r-allylpalladium intermediate such as 123. The incorporation of C02 takes place at the internal position of an allyl unit to afford the 7r-allylpalladium carboxylate 124 which, after reductive elimination/ cyclization, yields the (5-lactone 121 (Scheme 43). 

Pyrroles can also be obtained from aminocrotonates by oxidation. The transformation is actually a dimerization resulting from a two-electron oxidation of the enamine (Scheme 12) (83T793). 1,4-Addition of nitrometh-ane to the vinilogous ester of A A in presence of l,8-diazabicyclo[5.4.0]un-dec-7-ene (DBU) gave a 1 1 diastereomeric mixture of adducts which, upon reduction, spontaneously cyclized into a mixture of pyrrolidinones, formed in a ratio of 8 2 (Scheme 13) (93TL7529). 

The McMurry reaction (the reductive dimerization of carbonyl compounds giving olefins after treatment with the low-valent titanium reagents TiCla/Mg and TiCla/Zn in THF at 40°C) (CR891513) is a key step in the synthesis of photochromic cyclopentene derivatives. Later, it has been shown that TiCU, which is easier to handle than TiCls, can be used. The cyclization products are formed in 50-60% yields (98S1092,03EJO155). The advantages of this method are that the reactions can be scaled and inexpensive starting materials can be used. 

An interesting transformation which involves dimerization and cyclization was discovered when the y-enone 81 was reductively converted to 82. The mechanism of this dimerization-cyclization is yet to be elucidated. It involves two molecules of reactant, reduction and some aldol type condensation. The process is catalyzed by DMP+ and proceeds with high stereoselectivity yielding a single isomer. 

Dimerization-cyclization of 81 was significant in DMF with 0.1 M (C4H9)4NBF4 at —2.9 V(SCE). However, under these conditions some simple alcohol 83 was also formed and the composition of the electrolysis product was 75% 82 and 20% 83. DMP+ catalyzed this reduction and upon addition of 0.005 M (DMP)BF4 81 could be reduced at —2.70 V(SCE). The DMP+ mediated reduction yielded only 82 (80% isolated pure product). 

Since the introduction of the titanocene chloride dimer 67a to radical chemistry, much attention has been paid to render these reactions catalytic. This field was reviewed especially thoroughly for epoxides as substrates [123, 124, 142-145] so only catalyzed reactions using non-epoxide precursors and a few very recent examples of titanium-catalyzed epoxide-based cyclization reactions, which illustrate the principle, will be discussed here. A very useful feature of these reactions is that their rate constants were determined very recently [146], The reductive catalytic radical generation using 67a is not limited to epoxides. Oxetanes can also act as suitable precursors as demonstrated by pinacol couplings and reductive dimerizations [147]. Moreover, 5 mol% of 67a can serve as a catalyst for the 1,4-reduction of a, p-un saturated carbonyl compounds to ketones using zinc in the presence of triethylamine hydrochloride to regenerate the catalyst [148]. 

Zhou and Hirao showed that a low-valent catalyst generated from CP2VCI2 or VC12 and zinc in the presence of chlorotrimethylsilane is active in tandem reductive dimerization/Thorpe-Ziegler-type cyclizations of arylidenemalononitriles 96 (Fig. 29) [188]. The low-valent catalyst transfers an electron to 96 and the thus generated radical anion 96A adds to another molecule of 96. The resulting distonic... 

PET cyclizations of donors-substituted phenylgloxylates have been intensively studied by the groups of Neckers and Hasegawa. For the thioether derivatives 1 the efficiency of the cyclization depended on the linker chain length (Sch. 5) [18]. With increasing carbon tether (>7 = 2-10) the yield dropped steadily and secondary reductive dimerizations or Norrish Type II processes became competitive. Consequently, the Cn-linked substrate solely underwent dimerization and cleavage [18b]. 

Electrochemical reduction of aryl halides in the presence of olefins (94), (equation 54) leads to the formation of arylated products (95). Electroreduction of several aralkyl halides at potentials ranging from -1.24 V to -1.54 V (see) gives products which involve dimerization, cyclization, and reduction to the arylalkanes. Carbanions and/or free radicals were again postulated as intermediates79. Aryl radicals generated from the electrochemical reduction of aryl halides have been added to carbon-carbon double bonds80,81. Electrochemical reduction of aryl halides in the presence of olefins leads to the formation of arylated products78. Preparative scale electrolyses were carried out in solvents such as acetonitrile, DMF and DMSO at constant potential or in liquid ammonia at constant current. The reaction is proposed to involve an S l mechanism. 

Symmetrical 3,5-dialkyl-l,2,4-trithiolanes (178) can be synthesized in reasonable yield by chlorination of dialkyl disulfides (175) to a-chiloroalkyl sulfenyl chlorides (176), which are then reacted with potassium iodide to give di-a-chloroalkyl disulfides (177). Subsequent cyclization with sodium sulfide gave (178) (72T3489). When (176) was treated with one molar equivalent of sodium sulfide, the reductive dimerization and cyclization was effected in one step (78HCA1404). Treatment of perfluoropropene with sodium hydrogen sulfide in THF resulted in the formation of 3,5-bis(2,2,2-trifluoroethyl)-l,2,4-trithiolane (179) (72IZV2517). 

Reductive dimerization of enones to form a new carbon-carbon bond at the p-position, known as hydrodimerization or electrohydrodimerization, has considerable synthetic utility.For example, high yields of cyclic products are achieved when cyclization is kinetically favorable, leading to three- to six-membered rings from the corresponding unsaturated diesters (Scheme 19). ... 

Dicarboxylic esters in the presence of Na in ether or in benzene (carcinogen) cyclize to furnish not (3-keto esters but instead a-hydroxy ketones (acyloins). This acyloin condensation involves reductive dimerization of a ketyl radical anion (see Chapter 9). ... 

Reductive dimerization. Alkenes, which are geminally substituted with two activators, undergo dimerization at the (3-position. Cyclization follows. 

Biphenanthridine (138) has been prepared by reductive dimerization of phenanthridine by alkali metals, and its structure confirmed by an independent synthesis via a double Pictet-Gams cyclization of an oxamide, as shown in Scheme 46 (62JOC4171). It has also been prepared by thermolysis... 

Dimerization of alkylallene 160 proceeded regioseleetively at each C-2 carbon, and the cross-conjugated triene 161 was obtained in high yield using P(< -Tol)3 as a ligand and p-nitrophenol as an additive [53]. In the presenee of formic acid, reductive dimerization at C-2 carbons occurred to give the conjugated dienes 164 and 165. The dimerization is explained by the formation of the palladacycle 163, formed by oxidative cyclization, as an intermediate [54]. 

An alternative procedure for the cyclization is oxidative/reductive dimerization of dienes on low-valent metal centers. It is followed by the cleavage of the formed metal-carbon bonds to release the product and the catalytically active metal species that again joins the catalytic cycle. There are several possible reaction pathways to achieve this process and they depend on the nature of the transition metal. 

Pd-cataly2ed reactions of butadiene are different from those catalyzed by other transition metal complexes. Unlike Ni(0) catalysts, neither the well known cyclodimerization nor cyclotrimerization to form COD or CDT[1,2] takes place with Pd(0) catalysts. Pd(0) complexes catalyze two important reactions of conjugated dienes[3,4]. The first type is linear dimerization. The most characteristic and useful reaction of butadiene catalyzed by Pd(0) is dimerization with incorporation of nucleophiles. The bis-rr-allylpalladium complex 3 is believed to be an intermediate of 1,3,7-octatriene (7j and telomers 5 and 6[5,6]. The complex 3 is the resonance form of 2,5-divinylpalladacyclopentane (1) and pallada-3,7-cyclononadiene (2) formed by the oxidative cyclization of butadiene. The second reaction characteristic of Pd is the co-cyclization of butadiene with C = 0 bonds of aldehydes[7-9] and CO jlO] and C = N bonds of Schiff bases[ll] and isocyanate[12] to form the six-membered heterocyclic compounds 9 with two vinyl groups. The cyclization is explained by the insertion of these unsaturated bonds into the complex 1 to generate 8 and its reductive elimination to give 9. 

This procedure is representative of a new general method for the preparation of noncyclic acyloins by thiazol ium-catalyzed dimerization of aldehydes in the presence of weak bases (Table I). The advantages of this method over the classical reductive coupling of esters or the modern variation in which the intermediate enediolate is trapped by silylation, are the simplicity of the procedure, the inexpensive materials used, and the purity of the products obtained. For volatile aldehydes such as acetaldehyde and propionaldehyde the reaction Is conducted without solvent in a small, heated autoclave. With the exception of furoin the preparation of benzoins from aromatic aldehydes is best carried out with a different thiazolium catalyst bearing an N-methyl or N-ethyl substituent, instead of the N-benzyl group. Benzoins have usually been prepared by cyanide-catalyzed condensation of aromatic and heterocyclic aldehydes.Unsymnetrical acyloins may be obtained by thiazol1um-catalyzed cross-condensation of two different aldehydes. -1 The thiazolium ion-catalyzed cyclization of 1,5-dialdehydes to cyclic acyloins has been reported. 

Many anodic oxidations involve an ECE pathway. For example, the neurotransmitter epinephrine can be oxidized to its quinone, which proceeds via cyclization to leukoadrenochrome. The latter can rapidly undergo electron transfer to form adrenochrome (5). The electrochemical oxidation of aniline is another classical example of an ECE pathway (6). The cation radical thus formed rapidly undergoes a dimerization reaction to yield an easily oxidized p-aminodiphenylamine product. Another example (of industrial relevance) is the reductive coupling of activated olefins to yield a radical anion, which reacts with the parent olefin to give a reducible dimer (7). If the chemical step is very fast (in comparison to the electron-transfer process), the system will behave as an EE mechanism (of two successive charge-transfer steps). Table 2-1 summarizes common electrochemical mechanisms involving coupled chemical reactions. Powerful cyclic voltammetric computational simulators, exploring the behavior of virtually any user-specific mechanism, have... 

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