Low-valent metal salts

The reductive couphng of imines can follow different pathways, depending on the nature of the one-electron reducing agent (cathode, metal, low-valent metal salt), the presence of a protic or electrophihc reagent, and the experimental conditions (Scheme 2). Starting from the imine 7, the one-electron reduction is facihtated by the preliminary formation of the iminiiim ion 8 by protonation or reaction with an electrophile, e.g., trimethylsilyl (TMS) chloride. Alternatively, the radical anion 9 is first formed by direct reduction of the imine 7, followed by protonation or reaction with the electrophile, so giving the same intermediate a-amino radical 10. The 1,2-diamine 11 can be formed from the radical 10 by dimerization (and subsequent removal of the electrophile) or addition to the iminium ion 8, followed by one-electron reduction of the so formed aminyl radical. In certain cases/conditions the radical 9 can be further reduced to the carbanion 12, which then attacks the... 

Reductions by Electrochemically Generated Low-Valent Metal Salts and Base Metals... 

In a general sense, the Reformatsky reaction can be taken as subsuming all enolate formations by oxidative addition of a metal or a low-valent metal salt into a carbon-halogen bond activated by a vicinal carbonyl group, followed by reaction of the enolates thus formed with an appropriate electrophile (Scheme 14.1).1-3 The insertion of metallic zinc into a-haloesters is the historically first and still most widely used form of this process,4 to which this chapter is confined. It is the mode of enolate formation that distinguishes the Reformatsky reaction from other fields of metal enolate chemistry. 

Scheme 14.1 The Reformatsky reaction X = halogen, E =+ electrophile, M = Zn (this chapter) or another metal or low-valent metal salt.

Low-valent metal salts have been used to bring about reductive cleavage of oximes. Corey and Rich-man used chromium(II) acetate to convert O-acetyl ketoximes into imines, which were hydrolyzed to ketones. " Aqueous titanium(III) chloride and vanadium(II) salts also reduce oximes again, the imines are usually hydrolyzed in situ, but some hindered imines, such as compound (37), are isolable." A method of preventing hydrolysis is to carry out the reduction in anhydrous conditions in the presence of an acylating agent. The products of such reactions, when applied to oximes of enolizable ketones, are en-amides. For example, these ketoximes are converted into A/-formylenamines when heated in acetonitrile with anhydrous titanium(III) acetate and acetic formic anhydride cyclohexanone oxime gives the en-amide (38 97% Scheme 22)." This type of reduction has been used by Barton and coworkers to prepare enamides from steroidal oximes. They reported that the reaction could be performed by acetic... 

REDUCTION WITH METALS OR LOW-VALENT METAL SALTS... 

Sodium borohydride, a representative borohydride reagent, behaves as an effective source of nucleophilic hydride in an aprotic polar solvent, such as DMSO, sulfolane, HMPA, DMF or diglyme, and is used for the reduction of alkyl halides. As shown in Table 3, primary and secondary iodides, bromides and chlorides are converted to hydrocarbons at temperatures between 25 and 100 C using sodium borohydride. Vicinal dihalides, such as 1,2-dibromooctane, are smoothly converted to the corresponding saturated hydrocarbons, in contrast to the reductions using LiAlH4 or low-valent metal salts, which predominantly afford alkenes. 

Low-valent metal salts, such as chromium(II) acetate and samarium iodide, have been reported to be useful. With chromium(II) acetate, a steroid epoxy ketone is efficiently converted to a p-hy-droxy ketone (equation 26). 

For pyrophoric materials, oxidation of the compound by oxygen or moisture in air proceeds so rapidly that ignition occurs. Many finely divided metals are pyrophoric, and their degree of reactivity depends on particle size, as well as factors such as the presence of moisture and the thermodynamics of metal oxide or metal nitride formation. Many other reducing agents, such as metal hydrides, alloys of reactive metals, low-valent metal salts, and iron sulfides, are also pyrophoric. 

Some low valent metal salts are good reagents for the reduction of azides through a SET mechanism. CtCh in acidic aqueous solutions was initially used. However, samarium diiodide turns out to be a more convenient reagent under neutral conditions in organic solvents. Simultaneous reduction-ring expansion of some azidoketones allows to prepare maaolactams (Scheme 8.39). ... 

Metal-induced reductive dimerization of carbonyl compounds is a useful synthetic method for the formation of vicinally functionalized carbon-carbon bonds. For stoichiometric reductive dimerizations, low-valent metals such as aluminum amalgam, titanium, vanadium, zinc, and samarium have been employed. Alternatively, ternary systems consisting of catalytic amounts of a metal salt or metal complex, a chlorosilane, and a stoichiometric co-reductant provide a catalytic method for the formation of pinacols based on reversible redox couples.2 The homocoupling of aldehydes is effected by vanadium or titanium catalysts in the presence of Me3SiCl and Zn or A1 to give the 1,2-diol derivatives high selectivity for the /-isomer is observed in the case of secondary aliphatic or aromatic aldehydes. 

Ru, Os, and Ir carbene complexes have been prepared from reactions of anionic or low-valent metal complexes with some organic salts or neutral compounds with highly ionic bonds. Oxidative addition of halothiazole and -oxazole species to IrCl(CO)(PMe2Ph)2 affords Ir(III) complexes which on protonation yield cationic carbenes (69), e.g.,... 

Transition metal salts and transition metal complexes allow for smooth and highly-yield reductions of alkyl halides in the presence of protic solvents. A review of the use of low-valent metal species has covered the reduction of halides8. 

Oxidative addition of C2 - H bonds of imidazolium salts to low valent metals was first observed by Nolan and coworkers in 2001, who proposed a NHC - Pd - H intermediate in the catalytic cycle of the dehalogenation of aryl halides with Pd(dba)2 in the presence of imidazolium salts [154]. More direct evidence of this process was described by Crabtree and coworkers two years later [155]. The reaction between a pyridine-imidazolium salt and Pd2(dba)3 afforded the preparation of bis-NHC - Pd(II) complexes by C2 - H oxidative addition (Scheme 40). The presumed Pd - H intermediates were not detected. The authors proposed a mechanism via two successive C - H oxidative additions followed by reductive elimination of H2 [ 155]. 

Unfortunately, many of these complexes do not react with hydrogen and therefore caimot act as hydrogenation catalysts. The complexes that did react with hydrogen were usually low oxidation state complexes. The tertiary phosphine ligands also stabilized these low oxidation states and could often be used as the reducing agents in their formation from higher-valent metal salts. 

A variety of other electron transfer reagents have been employed in reactions which appear to be mechanistically similar to the more common metal-NH3 or metal-alcohol systems. These include K-graphite, Zn-KOH-DMSO and both Li and AP amalgams. The amalgams from Zn, Mg, Ni, Cu, Sn and Pb have been found not to be effective in the reduction of cyclohexanone in aqueous THF. Also, several low-valent metal cations have been employed in the reduction of carbonyl compounds to alcohols. Among these reagents are low-valence salts of Ti, " Ce and Sm. ... 

A number of low-valent metal ions have been shown to reduce a-halocarbonyl compounds. The most commonly used species for this purpose have been chromium(II) and low-valent titanium " salts, although vanadium(II), samarium(II), iron(II) and tin(II) salts have also been used. 7 222 chloro, bromo and iodo ketones can all be reduced by chromium(II) and titanium(III) salts. Selective reductions are possible axial halides are reduced in preference to equatorial, and a,a-dihalo ketones can be selectively reduced to the corresponding monohalides (equation 10). 7 The use of samarium(II) iodide has recently been advocated for such a-cleavages.72 a-Halo esters and ketones are reduced instantaneously at -78 °C in excellent yields. a-Acetoxy esters are stable to this reagent. 

As we said earlier, we do not know the structure and of course the mechanism of the formation of complex reducing agents. However, we formulated the hypothesis that at some step of their synthesis, the role of NaH—RONa is to give electrons to metallic salts leading to low-valent metal species which evolve towards metallic hydrides. 

Our present hypothesis is that without additional ligand, NaH-f.AmONa reacts with metallic salts to give some hydride reducing species. On the contrary, in the presence of additional ligand, the reaction takes another way and leads to low valent metallic species with poor reducing properties. 

We have previously reported that N-acyliminium salts can undergo rapid oxidative addition to low valent metals to generate metal-chelated amides (11). Similarly, the addition of the catalyst (5 mol% Pd2(dba)3 CHCI3 and 10% bipyridine) to this solution of 6 (Step B, Scheme 1) results in the rapid conversion of the palladium source into a new complex (7). This same conplex 7 can be prepared and isolated upon the stoichiometric reaction of 6, 0.5 equiv. Pd2(dba)3 CHCI3 and... 

In the case of alkyl complexes of other transition metals, the reverse course of Scheme 8.18 may not possess enough driving force to cause the nucleophilic substitution to be completed. Some unique device to stabilize a rather unstable low valent metal moiety could allow such substitution. A related nucleophilic attack may have probably been involved in Pd-catalyzed oxidation of alkenes by the use of auxiliary oxidants such as Pb(IV) and Cu(II) salts (e.g. Scheme 8.19)... 

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