Lanthanide triflates reactivity

The indium-mediated allylation of trifluoroacetaldehyde hydrate (R = H) or trifluoroacetaldehyde ethyl hemiacetal (R = Et) with an allyl bromide in water yielded a-trifluoromethylated alcohols (Eq. 8.56).135 Lanthanide triflate-promoted indium-mediated allylation of aminoaldehyde in aqueous media generated (i-airiinoalcohols stereoselectively.136 Indium-mediated intramolecular carbocyclization in aqueous media generated fused a-methylene-y-butyrolactones (Eq. 8.57).137 Forsythe and co-workers applied the indium-mediated allylation in the synthesis of an advanced intermediate for azaspiracids (Eq. 8.58).138 Other potentially reactive functionalities such as azide, enone, and ketone did not compete with aldehyde for the reaction with the in situ-generated organo-indium intermediate. 

Thus, a new type of Lewis acid, lanthanide triflates, is quite effective for the catalytic activation of imines, and has achieved imino Diels-Alder reactions of imines with dienes or alkenes. The unique reactivities of imines which work as both dienophiles and azadienes under certain conditions were also revealed. Three-component coupling reactions between aldehydes, amines, and dienes or alkenes were successfully carried out by using Ln(OTf)3 as catalysts to afford pyridine and quinoline derivatives in high yields. The triflates were stable and kept their activity even in the presence of water and amines. According to these reactions, many substituted pyridines and quinolines can be prepared directly from aldehydes, amines, and dienes or alkenes. A stepwise reaction mechanism in these reactions was suggested from the experimental results. 

The iminium ion electrophile can be synthesised separately, as a crystalline solid known as Eschenmoser s salt (Me2N =CH2 1 ) and with this reactive electrophile the reaction is nonnally carried out in a non-polar solvent. Examples which illustrate the variation in iminium ion structure which can be tolerated, include the reaction of indole with pyrimidine, with benzylidene derivatives of arylamines catalysed by lanthanide triflates, and the mineral acid-catalysed dimerisation of indole. In the first example protonated pyrimidine is the electrophile, in the last indole is attacked by protonated indole as shown below. 

Conjugate addition reactions, including the Robinson annulation, which make use of reactive Michael acceptors such as methyl vinyl ketone, can suffer from low yields of the desired adduct. The basic conditions required for enolate formation can cause polymerization of the vinyl ketone. Further difficulties arise from the fact that the Michael adduct 42 and the original cyclohexanone have similar acidities and reactivities, such that competitive reaction of the product with the vinyl ketone can ensue. These problems can be minimized by the use of acidic conditions. Sulfuric acid is known to promote the conjugate addition and intramolecular aldol reaction of 2-methylcyclohexanone and methyl vinyl ketone in 55% yield. Alternatively, a silyl enol ether can be prepared from the ketone and treated with methyl vinyl ketone in the presence of a Lewis acid such as a lanthanide triflate" or boron tri fluoride etherate (BF3 OEt2) and a proton source to effect the conjugate addition (followed by base-promoted aldol closure). 

Lewis acid-catalyzed reactions are of great interest due to their increased reactivity and selectivity under mild reaction conditions. A wide variety of reactions using Lewis acids have been developed, and they have been applied to the synthesis of natural and unnatural compounds. Traditionally, Lewis acids such as AICI3, BF3, TiCU, and SnCLt, have been employed in these reactions however, more than stoichiometric amounts of the Lewis acids are needed in many cases. Moreover, these Lewis acids are moisture sensitive and are easily decomposed or deactivated in the presence of even a small amount of water. Furthermore, these Lewis acids cannot be recovered and reused after the reactions are completed. In 1991, the first water-compatible Lewis acids, lanthanide triflates [Ln(OTf)3], was reported. ... 

Lewis acid catalysis is one of the most useful methods in modern organic synthesis. However, many of the common Lewis acids are highly water-labile and have been used in organic synthesis under strictly anhydrous conditions. Contrary to this, it was found that lanthanide triflates catalyzed aldol reactions of formaldehyde (Scheme 3.6). Formaldehyde is one of the most highly reactive Cl electrophiles. In this reaction, not gaseous formaldehyde but a commercially available aqueous solution was used as the formaldehyde source. This invaluable find introduced the concept of Lewis acid catalysis in aqueous media to many chemists. Later, it was also reported that other aldol reactions, with a variety of aldehydes and silyl enol ethers, as well as allylation reactions, proceeded smoothly in aqueous media to afford the desired compounds in high yields. ... 

The reaction is believed to proceed via a mechanism analogous to hydroamina-tion and hydrophosphination. There is experimental evidence for a rate-determining insertion step (Fig. 23). The high oxophilicity of the lanthanide ion results in a high barrier for the olefin insertion and therefore, diminished reactivity of alkenyl alcohols. Rare-earth metal triflates are also capable to catalyze cyclization of alkenyl alcohols in ionic liquids [193], although the mechanism is unlikely to be similar to the o-bond metathesis mechanism discussed above. 

The A, stretching frequencies were found to increase steadily in magnitude across the lanthanide period for the [Ln(H20)x(NC>3)](0Tf)2 salts starting at 1450 cm-1 for lanthanum (r3+ = 1.172 A, Z/r = 2.56) and ending at a value of 1497 cm1 for lutetium (r3+ = 1.00, Z/r = 3.00) (Table 4). This structural data correlates extremely well with the observed reactivity of the respective lanthanide(m) triflates for nitration and can be taken as strong evidence for the proposed mode of action. 

Lanthanide halides, nitrates and triflates are not only common reagents in organic synthesis (Fig. 1) but also represent, in dehydrated form, key precursor compounds for the more reactive organometallics (Scheme 2). As a rule, in compounds of strong monobasic acids or even superacids, cation solvation competes with anion complexation, which is revealed by fully or partially separated anions and solvated cations in their solid state structures. The tendency to form outer sphere complexation in coordinating solvents [47] is used as a criterion of the reactivity of inorganic salt precursors in organometallic transformations. 

Finally, sugar 1,2-cyclic sulfites have been investigated as glycosyl donors. Preliminary studies exploited these compounds for the introduction of reactive nucleophiles, such as azide or benzoate, on the anomeric position [156]. EflFective P-O-glycosylations with sugar cyclic sulfites were then reported, under catalysis of lanthanide(III) triflates. However, the reactions required high temperatures (from 80 to 100 °C), limiting their application only to simple alcohols [157]. 

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