Dimerization dissolving metal

Reduction of Ketones and Enones. Although the method has been supplanted for synthetic purposes by hydride donors, the reduction of ketones to alcohols in ammonia or alcohols provides mechanistic insight into dissolving-metal reductions. The outcome of the reaction of ketones with metal reductants is determined by the fate of the initial ketyl radical formed by a single-electron transfer. The radical intermediate, depending on its structure and the reaction medium, may be protonated, disproportionate, or dimerize.209 In hydroxylic solvents such as liquid ammonia or in the presence of an alcohol, the protonation process dominates over dimerization. Net reduction can also occur by a disproportionation process. As is discussed in Section 5.6.3, dimerization can become the dominant process under conditions in which protonation does not occur rapidly. 

One-electron reduction of pyrylium salts, with dissolving metals or electrochemically, gives dimers (e.g. 382) via pyranyl radicals (80AHC(27)46). 

Winterfeldt and Erning achieved the one-step conversion of 176 into the indolizidine 177 by a dissolving-metal reduction in the presence of diethyl oxalate.236 Treatment of the piperidine analog with sodium ethoxide and diethyl oxalate gave 10% of the dimer 178. 

The reductions of two steroidal ketones, androstan-l7-one (63) and androst-5-en-16-one (64) under various conditions have been studied in some detail. In the case of 17-ketone (63) the -ol (65) is the stable epimer and for the 16-ol (66), the a-isomer is more stable. Dissolving metal reductions of both ketones in the presence of proton donors gave the more stable alcohol as the major product however, reduction of 17-keto steroid (63) is considerably more stereoselective as noted in Table 2. Although pina-cols are not usually obtained in dissolving metal reductions carried out in the presence of proton donors, ketone (63) gave from 6 to 34% of dimeric products under these conditions (Li, 6% Na, 34% K, 13%). 5... 

The reduction of imines to amines (equation 21) by dissolving metals is usually carried out using active metals in a protic solvent, typically Na-alcohol, Zn-NaOH and A1 or Mg in alcohols. - ""- Although the mechanism of these reductions has not been investigated in detail it is almost certainly analogous to that of the reduction of ketones (Section 1.4.2). It has been established that radical anions are intermediates in these reductions and in the absence of a proton donor reductive dimerization is the principal reaction path. ... 

In conclusion, nitriles may be reduced electrochemically or with dissolving metal to produce amines. Nonetheless, such reactions must be used with caution. In addition to competitive decyanation, aldehyde or 2,4,6-trialkyIhexahydro-l,3,5-triazine formation and reductive dimerization are waiting to overwhelm the unwary. 

Because of the intermediacy of radical anions and/or hydroxyallyl free radicals in dissolving metal reductions of enones, dimerization may compete with simple reduction. Scheme 7 shows the three types of dimers that may be produced. 

In reductive acylation and dimerization, the cathode is often superior to dissolving metal or radical anions reductants. So a, j6-unsaturated ketones or esters can be acylated in high yield to 1,4-dicarbonyl compounds at the mercury cathode [39], but the corresponding reaction with sodium in tetrahydrofuran (THE) fails [40]. On the other hand, reductive acylation of double bonds becomes possible in high yield, when vitamin Bj2 is used as mediator [41]. Here cobalt-alkyl complexes play a decisive role as intermediates. 

Radical Anions. Radical anions are common intermediates in organic reactions they are easily prepared from compounds with low-enough LUMOs by the addition of an electron (from a dissolving metal or from a cathode, or the solvated electron itself). Those derived from carbonyl groups (421) dimerize at carbon 339 those derived from a,/ -unsaturated carbonyl compounds (422) dimerize at the /1-position,340 and pyridines dimerize predominantly at the 4-position.341 In each case, the odd electron has been fed into the orbital which was the LUMO of the starting material the site of coupling therefore should, and does, correlate with the site at which nucleophiles attack the neutral compounds. 

On a related front, the reactions of carbonyl compounds with metaliated derivatives of 2-methylthia-zoline furnish adducts (85). Although the initial nucleophilic addition occurs smoothly with a wide variety of aldehydes and ketones, the intermediate P-hydroxythiazolines (85) suffer thermal reversion upon attempted purification by distillation. Moreover, attempted cleavage of the corresponding P-hydroxythia-zolidines, which are readily produced from (85) upon dissolving metal reduction (Al-Hg), leads to the formation of p-hydroxy aldehydes only in simple systems numerous complications arising from dimerization, dehydration and retroaldol processes of the products usually intervene. Consequently it is necessary to protect the initial 1,2-adducts (85 = H) as the corresponding 0-methoxymethyl ether... 

Two mechanistic pathways will be discussed for the dissolving metal reduction of enones30. In both cases the first step is the reversible transfer of an electron from the metal to a vacant orbital of the substrate, yielding a radical anion. This can be protonated to the neutral radical which can dimerize or accept another electron and a proton, Alternatively, a second electron can be transferred reversibly to the radical anion, giving the dianion capable of accepting two protons. The sequence and timing of these steps depends on the substrate, the reduction potential of the reaction medium and the nature of the proton source, as well as on various other factors. In general, the thermodynamically more stable product is formed predominantly, as illustrated in the reduction of cxocyclic enone 134. The rrmw-substituted cyclohexane, with both substituents in an equatorial position, is formed preferentially if the reaction is carried out in the presence of /erf-butyl alcohol as proton source. 

The electrochemical properties of many functional groups have been described in reviews by Steckhan, Degner (industrial uses of electrochemistry), Kariv-Miller,543 and Feoktistov. The synthetic applications of anodic electrochemistry has also been reviewed. There are interesting differences between dissolving metal reductions (secs. 4.9.B-G) and electrochemical reactions. Cyclohexanone, for example, can be reduced to cyclohexanol (sec. 4.9.B) or converted to the 1,2-diol (556) via pinacol coupling by controlling the reduction potential, the nature of the electrode and the reaction medium. 46 Presumably, the more concentrated conditions favor formation of cyclohexanol via reduction of the carbanion. More dilute solutions appear to favor the radical with reductive dimerization to 556. More important to this process, however, is the difference in reduction potential (-2.95 vs. -2.700 V) and the transfer of two Faradays per mole in the former reaction and four Faradays per mole in the latter. 

Sorption reactions, which introduce potentially reactive ligands to a metal at the mineral surface, or modify a preexisting ligand, are important to the dissolution rate (Westall 1988). The adsorption reactions, however, are very rapid whereas dissolution is slow. The discrepancy in reaction time suggests that the adsorbates indirectly influence but do not control dissolution rates. To understand the influence of solution composition on dissolution rates, it is useful to examine the simplest possible analog for mineral dissolution dissociation of a dissolved metal dimer. 

The first example of homogeneous transition metal catalysis in an ionic liquid was the platinum-catalyzed hydroformylation of ethene in tetraethylammonium trichlorostannate (mp. 78 °C), described by Parshall in 1972 (Scheme 5.2-1, a)) [1]. In 1987, Knifton reported the ruthenium- and cobalt-catalyzed hydroformylation of internal and terminal alkenes in molten [Bu4P]Br, a salt that falls under the now accepted definition for an ionic liquid (see Scheme 5.2-1, b)) [2]. The first applications of room-temperature ionic liquids in homogeneous transition metal catalysis were described in 1990 by Chauvin et al. and by Wilkes et ak. Wilkes et al. used weekly acidic chloroaluminate melts and studied ethylene polymerization in them with Ziegler-Natta catalysts (Scheme 5.2-1, c)) [3]. Chauvin s group dissolved nickel catalysts in weakly acidic chloroaluminate melts and investigated the resulting ionic catalyst solutions for the dimerization of propene (Scheme 5.2-1, d)) [4]. 

Coordination polymerization of ethylene by late transition metals is a rather slow process especially when the catalyst is dissolved in water. In a study of the interaction of CH2=CH2 and [Ru(H20)6](tos)2 (tos = tosylate), both [Ru(CH2=CH2)(H20)5](tos)2 and [Ru(CH2=CH2)2(H20)4](tos)2 were isolated by evaporation of the aqueous phase which had been previously pressurized with 60 bar ethylene at room temperature for 6 and 18 hours, respectively. Longer reaction times (72 h) led to the formation of butenes with no further oligomerization. This aqueous catalytic dimerization was not selective, the product mixture contained Z-2-butene, E-2-butene and 1-butene in a 112.2122 ratio [3]. 

The easiest way to 10 goes via the synthesis of KDNM (see Section n.C). Acidification of an aqueous solution of KDNM, which should be buffered with H3PO4 (pH = 6.5), followed by low-temperature extraction with diethyl ether, gives the monomeric emerald-green nitrosolic acid 10 dissolved in the ether phase. Slow removal of the solvent yields the yellowish dimeric form of 10. The acid (10) is only poorly characterized. It is known to slowly decompose into HCN and HNO2 in basic solution (decomposition of the anion DNM), while the free acid (10) rapidly decomposes to give fuhninic acid, HCNO and hyponitrous acid, HON=NOH. It should be noted that both the free acid and its metal DNM salts are highly explosive. 

To a suspension of the cyclopalladated compound (12.95 g, 47 mmol) in acetone (300 mL) is added an excess of LiCl (6.77 g, 150 mmol). This mixture is heated with vigorous stirring until the precipitate has dissolved. It is likely that with an excess of LiCl the salt Li[PdC6H4CH2N(CH3)2Cl2] is formed, which is stable only in acetone in the absence of water. Addition of water to this solution affords immediately the chloro-bridged dimer. The yellow solution is then quickly filtered over a short column of Celite (3 cm) to retain the finely divided metallic palladium and the column washed with 50 mL of acetone. The solution thus obtained is poured into a beaker containing 400 mL of water affording a yellow precipitate. The more quickly this operation is done the better the yield of the reaction the overall time of this purification should not... 

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