Nonaqueous carbonylation

Most metal carbonyls are synthesized in nonaqueous media. Reactive metals, such as sodium (85), magnesium (105), zinc (106), and aluminum (107,108), are usually used as reducing agents. Solvents that stabilize low oxidation states of metals and act as electron-transfer agents are commonly employed. These include diethyl ether, tetrahydrofiiran, and 2-methoxyethyl ether (diglyme). 

Active carbonyl compounds such as benzaldehyde attack the electron-rich double bond in DTDAFs to give a dipolar adduct, which immediately undergoes dissociation with formation of two molecules of 146 (64BSF2857 67LA155).Tlie existence of by-products such as benzoin led to the synthetic application of thiazolium salts in the acyloin condensation. For example, replacement of the classic cyanide ion by 3-benzyl-4-methyl-5(/3-hydroxyethyl) thiazolium salts allowed the benzoin-type condensation to take place in nonaqueous solvents (76AGE639) (Scheme 57). 

On one-electron rednction, aldehydes and ketones give anion-radicals. It is the carbonyl group that serves as a reservoir for the unpaired electron Ketones yield pinacols exclusively. Thus, acetophenone forms 2,3-diphenylbutan-2,3-diol as a result of electrolysis at the potential of the first one-electron transfer wave (nonaqueous acetonitrile as a solvent with tetraalkylammonium perchlorate as a supporting electrolyte) (van Tilborg and Smit 1977). In contrast, calculations have shown that the spin densities on the carbonyl group and in the para position of the benzene ring are equal (Mendkovich et al. 1991). This means that one should wait for the formation of three types of dimer products head-to-head, tail-to-tail, and head-to-tail (cf. Section 3.2.1). For the anion-radical of acetophenone, all of the three possible dimers are depicted in Scheme 5.21. 

Marcantoni E, Nobili F, Bartoli G, Bosco M, Sambri L (1997) Cerium(III) chloride, a novel reagent for nonaqueous selective conversion of dioxolanes to carbonyl compounds. J Org Chem 62 4183 1184... 

Hajipour and coworkers prepared benzyltriphenylphosphonium peroxymonosulfate (BnPhsPHSOs) in a very high yield (95%) and purity (99%). This new oxidizing reagent was applied successfully in various deprotection reactions such as the conversion of oximes, phenylhydrazones, 2,4-dinitrophenylhydrazones and semicarbazones to the corresponding carbonyl compounds in the presence of bismuth chloride under nonaqueous conditions . Oxidative deprotection of trimethylsilyl ethers, tetrahydropyranyl ethers and ethylene acetals with BnPh3PHS05 under microwave irradiation affords the corresponding carbonyl compounds in very high yields (equation 71). The same reaction also proceeds under nonaqueous conditions ". 

The v(CO)t- slopes for saturated CO adlayers at both single-crystal and polycrystalline Pt-nonaqueous interfaces are noticeably smaller than those for the corresponding solvated Pt carbonyl clusters. These differences are explained as being chiefly due to larger effective... 

The prototypically zero oxidation state complexes of the group are the binary hexacarbonyls M(CO)6. Early studies of the electrochemistry of these 18-electron closed-shell systems in nonaqueous electrolytes has perhaps been seminal in understanding the electron-transfer reactions of more substituted systems and of metal carbonyls in general. 

When two molecules of ester undergo a condensation reaction, the reaction is called a Claisen condensation. Claisen condensation, like the aldol condensation, requires a strong base. However, aqueous NaOH cannot be used in Claisen condensation, because the ester can be hydrolysed by aqueous base. Therefore, most commonly used bases are nonaqueous bases, e.g. sodium ethoxide (NaOEt) in EtOH and sodium methoxide (NaOMe) in MeOH. The product of a Claisen condensation is a P-ketoester. As in the aldol condensation, one molecule of carbonyl compound is converted to an enolate anion when an a-proton is removed by a strong base, e.g. NaOEt. 

The reduction of metal ions in higher oxidation states by CO and H20 has been known for many years. Work on the reduction of Hg2+, Ag+, Ni2+, Cu2 +, and Pd2+ has been summarized recently (4). The reduction of these metal ions does not proceed via a stable intermediate carbonyl. Since a metal carbonyl must be an intermediate in this reaction, however, the coordinated carbonyl must be very susceptible to attack by water, reacting as soon as it is formed. The ability of a metal in a higher oxidation state to activate a coordinated carbonyl to attack by as weak a nucleophile as water was noted previously in the description of the work by James et al., on the reduction of rhodium(III) by carbon monoxide and water (62). Here a stable rhodium(III) carbonyl, Rh(CO)Cl2-, can be observed as the initial product of reaction of RhCl3 3HzO with CO. The Rh(III) is then efficiently reduced to the rhodium(I) anion [RhCl2(CO)2], even in nonaqueous solvents such as dimethylacetamide, where the only water available for reaction is the water of hydration of the starting rhodium chloride. 

Baker s yeast reduction of organic compounds, especially carbonyl compounds, is an extremely useful method of obtaining chiral products255-257. Recently, much effort has been expended to improve the ee obtained in this process. In one very useful example, l-acetoxy-2-alkanones have been reduced enantioselectively into (5 )-l-acetoxy-2-alkanols in 60-90% yields and with 95-99% ee258. The reaction readily occurs in a variety of solvents, both aqueous and nonaqueous. The reduction is fairly selective and so may be brought about in the presence of a-amide, ether, ester and other acid functional groups, in reasonable yields and with excellent ee (equation 65)259 -261. Thus, in the synthesis of the C-13 side chain of taxol, the key step was the reduction of a w-ketoester to the corresponding alcohol in 72% overall yield (equation 66)262. 

Decomposition reactions are another reaction class often employed in nonaque-ous solvents. In these reactions, the starting materials are decomposed to create the final product. The preferred starting materials have ligands that are very good leaving groups, such as carbonates, carbonyls, and acetates. The decomposition is facilitated by several different techniques, such as heat in thermolysis, light in photolysis, and sound in sonolysis. The reaction is the same in almost every case ... 

The mechanism of the Montedison reaction has been studied in some detail, and tentative mechanisms have been offered. The proposed catalytic cycle is shown in Fig. 4.11. The biphasic reaction medium consists of a layer of diphenyl ether and that of aqueous alkali. In the presence of alkali, the precatalyst Co2(CO)8 is converted into 4.7. The sodium salt of 4.7 is soluble in water but can be transported to the organic phase, that is, a diphenyl ether layer by a phase-transfer catalyst. The phase-transfer catalyst is a quaternary ammonium salt (R4N+X ). The quaternary ammonium cation forms an ion pair with [Co(CO)4]. Because of the presence of the R groups, this ion pair, [R4N]+[Co(CO)4], is soluble in the organic medium. In the nonaqueous phase benzyl chloride undergoes nucleophilic attack by 4.7 to give 4.40, which on carbonylation produces 4.41. The latter in turn is attacked by hydroxide ion transported from the aqueous phase, to the organic phase again by the phase-transfer catalyst. The product phenyl acetate and 4.7 are released in the aqueous phase as the sodium or quaternary ammonium salts. 

Cyclic immonium salts such as 205 are reduced in a nonaqueous solvent such as acetonitrile through a radical to a dimer (206).207 The reaction is analogous to pinacol formation from carbonyl compounds. 

The problem of the hydrocyanation of conjugated carbonyl compounds has been reviewed in detail by Nagata and Yoshioka [281. The reactions proceed smootltly and base or acid catalysts are sometime useful with HCN. Cyanides (KCN. NaCN. etc.) arc recommended reagents in some cases, particularly in nonaqueous Solvents (28], and even cyanohydrins (e.g., acetone cyanohydrin) have been used as cyanation reagents. 

For metal carbonyls, redox reactions (see Redox Properties Processes) have been studied in a smaller number of cases, relative to substitution reactions. The simplicity of binary metal carbonyls and the possibility for these compounds to undergo electron transfers make them excellent substrates for studying redox processes in nonaqueous media. Convenient organometallic one-electron oxidants or reductants (number of valence electrons in parenthesis) are " V(CO)e... 

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