Cerium mediated reactions

This approach to C (1) nucleophiles has been recently extended. The Lichten-thaler zinc enolate reacts efficiently with more demanding aldehyde electrophiles to provide C-disaccharides [108,109], and activation of the C(l) bromide 276 can also be carried out using CeCl3/NaI (Scheme 72). The latter method is based on the earlier work of Ftdcuzawa [110] and others [111], although the mechanism of this cerium-mediated reaction has yet to be fully understood. 

The synthesis of diethyl l,l-difluoro-2-oxoalkylphosphonates has been reported by a cerium-mediated reaction between diethyl 1-lithio-1,1-difluoromethylphosphonate and ethyl esters at low temperature in THF. After acidic quench at low temperature, diethyl I, I -difluoro-2-oxoalkyIphosphonates are isolated in good yield.- Addition of diethyl 1-lithio-1,1-difluoromethylphosphonate to di-ferf-butyl oxalate at low temperature in THF affords exclusively the addition product, an unusually stable ferf-butyl hemiketal. When a solution of this material is heated at reflux in ( ,1 f, or chromatographed on silica gel, only a few percent is converted to the hydrate. This conversion is best effected by dissolving the hemiketal in MeCN followed by reaction with aqueous Nal ICO . Subsequent azeotropic dehydration with CgHg affords diethyl l,l-difluoro-2-oxo-2-(fert-butoxycar-bonyl)ethylphosphonate. 5... 

Cerium-mediated reactions are also useful for the synthesis of heterocyclic compounds. 3-Acetylisoxazole derivatives are formed by reaction between alkenes and acetone in presence of CAN (scheme 56) (Itoh et al., 2002 Itoh and Horiuchi, 2004). When acetone is replaced... 

Furopyranopyrandiones have been prepared by the cerium(iv) ammonium nitrate-mediated reaction of 4-hydroxy-277,577-pyrano[4,3- ]pyran-2,5-diones with alkenes (Scheme 14) <2003H(60)939>. 

Johnson, D. C. Widlanski, T. S. Cerium(III) chloride-mediated reactions of sulfonamide dianions./. Org. Chem. 2003, 68, 5300-5309. 

Several interesting approaches to the synthesis of /I-ketophosphonates have recently been described. Typically, standard Arbuzov synthesis of /1-ketophospho-nates is unsatisfactory due to a competing Perkow reaction [51]. However, y,d-unsaturated /1-ketophosphonates are obtained in high yield via Arbuzov reaction of triethyl phosphite with a-iodoenones, readily available from tertiary allenic alcohols [52]. Another successful example of an Arbuzov-based approach involves reaction of bromoacetylated polystyrene with triethyl phosphite, which provided immobilized /J-ketophosphonate in excellent yield [53]. In another approach, the lithio derivative of dimethyl methylphosphonate was reacted with Weinreb amide to obtain the corresponding /J-ketophosphonate [54]. a,a-Diflu-oro-a-ketophosphonates have been synthesized via a cerium-mediated route... 

A useful variation involves the cerium(lll)-mediated reaction of diethyl 1-lithio-1,1-difluoromethylphosphonate with various carboxylic esters. A wide range of substrates, including aliphatic and aromatic compounds, a,p-unsaturated esters, and lactones, can be used to obtain reproducibly high yields of diethyl 2-oxo-1,1-dilluoroalkylphosphonates (57—88%). ... 

Cerium-mediated conjugate addition of diethyl 1-lithio-l,1-difluoromethylphosphonate to 1-phe-nylsulfonyl-3,4-epoxycyclopentene and -cyclohexene proceeds smoothly at low temperature in THF to give the corresponding adduct in 53% and 65% yields, respectively. The possibility of mild reductive removal of the SOiPh moiety makes these reactions attractive. 

Reactions of ammonium hexanitratocerate(IV) with organic substrates other than benzyl alcohol have also been examined, and 1,4-hydroquinone was quantitatively transformed into 1,4-quinone. Anisole and naphthalene can be nitrated. For the cerium-mediated oxidation reactions in ionic liquids, high reaction temperature is beneficial because of the formation of smaller amounts of by-products. 

The rare-earth salts of trifluoromethanesulfonic acid (triflic acid) are popular reagents for lanthanide-mediated organic reactions. Especially scandium(III) triflate, Sc(CF3S03)3, and ytterbium(lll) triflate, Yb(CF3S03)3, are often used as mild Lewis acids for reactions in water (Kobayashi et al., 2002). It is therefore surprising that only very few studies of cerium(IV)-mediated reactions describe the use of cerium(IV) triflate, Ce(CF3 803)4 or Ce(OTf)4, as a reagent. This salt was first reported by Kreh et al. (1987), who prepared a solution of cerium(lV) in aqueous triflic acid by electrochemical oxidation of a cerium(III) triflate solution. They illustrated the use of this reagent for oxidation of alkylaromatic and polycyclic aromatic compounds. Imamoto et al. (1990) prepared cerium(IV) triflate by reaction... 

The maximum rate of electrochemical regeneration of cerium(IV) is obtained with the concentration of cerium(III) at saturation level. When the cerium(III) ion does not interfere with the cerium(IV)-mediated reaction, it is advisable to add more cerium(III) salts to the reaction mixture than the amount that can be oxidized to cerium(IV). The concentration of cerium(IV) that can be reached it limited by the solubility of cerium(IV) in the reaction solvent, and the cerium(IV) solubility is often lower than the cerium(III) solubility. Tzedakis and Savall (1992) showed that the concentration of cerium(III) has no significant influence on the oxidation of 4-methoxytoluene to 4-methoxybenzaldehyde. 

At this stage reference may be made to potential mediators, i.e. substances which undergo reversible oxidation-reduction and reach equilibrium rapidly. If we have a mixture of two ions, say M2+ and M +, which reaches equilibrium slowly with an inert electrode, and a very small quantity of cerium(IV) salt is added, then the reaction ... 

The oxidation of an anthracene suspension in sulfuric acid conducted in the presence of cerium salts can serve as an example of mediated oxidation. In the bulk solution the Ce" ions chemically oxidize anthracene to anthraquinone. The resulting Ce ions are then reoxided at the anode to Ce". Thus, the net result of the electrochemical reaction is the oxidation of anthracene, even though the electrochemical steps themselves involve only cerium ions, not anthracene. Since the cerium ions are regenerated continuously, a small amount will suffice to oxidize large amounts of anthracene. 

Scheme 26. Cross aldol reaction mediated by a cerium enolate complex...

This reaction is conducted on a scale of >200,000 tonnes/annum. More recently, another elegant application of electrochemistry on a multi-thousand-tonne scale has been HydroQuebec s investment in a cerium (IV)-mediated oxidation of naphthalene to naphthaquinone, a process licensed from W.R. Grace.87 HydroQuebec then uses the naphthaquinone in a Diels-Alder reaction with butadiene to produce anthraquinone ... 

Electrophilic aromatic substitution of 5-hydroxy-2,4-dimethoxy-3-methylaniline by reaction with the iron complex salts affords the corresponding aryl-substituted tricarbonyliron-cyclohexadiene complexes. O-Acetylation followed by iron-mediated arylamine cydization with concomitant aromatization provides the substituted carbazole derivatives. Oxidation using cerium(IV) ammonium nitrate (CAN) leads to the carbazole-l,4-quinones. Addition of methyllithium at low temperature occurs preferentially at C-1, representing the more reactive carbonyl group, and thus provides in only five steps carbazomycin G (46 % overall yield) and carbazomycin H (7 % overall yield). 

Mehdi H, Bodor A, Lantos D, Horvath IT, De Vos DE, Binnemans K (2007) Imidazolium ionic liquids as solvents for cerium(IV)-mediated oxidation reactions. J Org Chem 72 517-524... 

The use of lanthanide metal enolates in the aldol reaction has, to date, only been developed to a synthetically useful level in the case of cerium (Scheme S and Table 7). Stereoselectivities are no better than those of lithium enolates, but the cerium enolates of ketones woik well in crossed aldol additions to ketones (Table 7, entries 1-7) and sterically hindered aldehydes (Table 7, entries 9 and 10). Such crossed aldol reactions do not often work well with lithium enolates as enolate equilibration, retroaldolization and steric retardation of addition occur. Imamoto et al. have shown that cerium enolates (44), formed from anhydrous CeCb (1.2 equiv.) and the preformed lithium enolates of ketones in THF at -78 C, undergo such aldol reactions to give the corresponding p-hydroxy ketones (46), usually in high yield. The cerium suppresses the retroaldol reaction by efficient chelation of the aldolate (45). A similar effect is known for zinc halide mediated aldol reactions (Volume 2, (Chapter 1.8). The stereoselectivity of the... 

---