Activation of aldehyde

Practical experience enables us to emphasize the simplicity and the efficiency of the activation of aldehydes by their conversion into N- -haloalkyl)heteroarylium halides upon treatment with an azine and a thionyl halide. Preparation of these salts requires a minimum of precautions, and a wide variety of solvents can be used. Special glassware and/or the use of an inert gas is not necessary. Tire salts can be reacted under numerous experimental conditions and, in most cases, it is unnecessary to isolate them. Tire flexibility of the method represents an interesting feature for the study of the reactivity of A-(l-haloalkyl)heteroarylium halides and deserves further investigations in this held. Many elegant compromises can be found in a judicious choice of the precursors and of the experimental conditions, and it is possible to design readily a salt suitable for each individual purpose. 

C8—Ge—C18 137.7° (3)] (Figure 24). The distortion of the internal O—Ge—C angles leads to an enhanced Lewis acidity, which was illustrated by the promotion of pericyclic reactions involving activation of aldehyde carbonyl groups. 

Carreira and Kruger reported facile transmetallation of silicon enolates to other soft metal enolates including Gu derivatives.499 They reasoned that the use of soft metal fluoride complexes enabled silyl metal transmetallation with catalytic use of a soft metal source. The concept is illustrated in Scheme 103. Normal Lewis acid-catalyzed reactions of silicon enolates with aldehydes proceed via activation of aldehydes by carbonyl oxygen coordination to Lewis acids, as shown in the upper equation of Scheme 103. A key step for catalytic turnover is the desilyation of 233 by the... 

Aldehyde dehydrogenase (activity of-) Aldehydes ENZ. POST-CR PRE-CD with 174... 

For these and similar reactions recently a variety of Lewis acidic aluminium, rare earth metals, and titanium alkoxides have been applied. Alkoxides have the additional advantage that they can be made as enantiomers using asymmetric alcohols which opens the possibility of asymmetric catalysis. Examples of asymmetric alcohols are bis-naphtols, menthol, tartaric acid derivatives [28], Other reactions comprise activation of aldehydes towards a large number of nucleophiles, addition of nucleophiles to enones, ketones, etc. 

A chiral dinuclear Ti(IV) oxide 20 has been successfully designed by Maruoka and coworkers and can be used for the strong activation of aldehydes, thereby allowing a new catalytic enantioselective allylation of aldehydes with allyltributyltin (Scheme 12.18). ° The chiral catalyst 20 can be readily prepared either by treatment of bis(triisopropoxy)titanium oxide [(/-Pr0)3Ti-0-Ti(0/-Pr)3] with (S)-BINOL or by the reaction of ((5)-binaphthoxy)isopropoxytitanium chloride with silver(I) oxide. The reaction of 3-phenylpropanal with allyltributyltin (1.1 equiv) under the influence of 20 (10 mol%) gives l-phenyl-5-hexen-3-ol... 

Because a comprehensive discussion of the transition state of hydrogen-bond catalysis will be presented by Berkessel in Chapter 3, the hydrogen bond catalyzed hetero Diels-Alder reaction of butadiene with carbonyl compounds will be discussed briefly here. Huang and Rawal reported that the hetero Diels-Alder reaction of aminodiene with aldehyde exhibited significant solvent effects (Scheme 2.7) [15]. The reaction in CHCfi was accelerated 30 times in comparison with that in THF, while that in i-PrOH was accelerated 630 times. They proposed that the Diels-Alder reaction was promoted by the hydrogen-bond activation of aldehyde. This finding resulted in the development of TADDOL catalyst [3]. 

Obe, G. Beek, B. (1979) Mutagenic activity of aldehydes. Drug Alcohol Depend., 4, 91-94 Obe, G. Ristow, H. (1977) Acetaldehyde, but not ethanol, induces sister chromatid exchanges... 

A marked difference in hepatic activity of aldehyde oxidase between rats and monkeys was found to be responsible for the reported marked species difference in the metabolism of Zaleplon in vivo. In the postmito-chondrial fractions, S-9s, from liver homogenates of these animals, zaleplon was transformed in the presence of NADPH into the side chain oxidation product, N-desethyl-zaleplon, and the aromatic ring oxidation product, 5-oxo-zaleplon. In the rat S-9, N-desethyl-zaleplon and 5-oxo-zaleplon were a major and a very minor metabolites, respectively. 

Esposti, S., Dondi, D., Fagnoni, M., and Albini, A. (2007) Acylation of electrophilic olefins through decatungstate-photocatalyzed activation of aldehydes. Angewandte Chemie, International Edition, 46, 2531-2534. 

Pandey et al. recently developed two useful photo systems for one-electron reductive chemistry and applied them to the activation of aldehyde... 

The allylic activation of 1,3-dienes by Ru(COD)(COT) makes possible their hydroacylation to form /5,y-unsaturated ketones via C-H activation of aldehydes at the same metal center [117], and their selective coupling with acrylic compounds [18] (Eq. 87). 

Indium trichloride catalytically promotes the alkynylation of aldehydes in which InCl3 plays two roles transme-tallation with tin compounds and activation of aldehydes as a Lewis acid (Equation (65)).219... 

The authors apphed this new concept to chemoselective functionalization of carbonyls rather than acetals [194], which is usually quite difficult to achieve because of the high reactivity of the acetal counterparts with Lewis acids. Reaction of a mixture of 1 equiv. each of acetophenone and its dimethyl acetal with ketene silyl acetal 191 under the influence of bidentate aluminum Lewis acid 188 in CH2CI2 at -78 °C for 3 h afforded aldol products 195 exclusively (88 % yield). It is worth noting that employment of dibutyltin bis(triflate) (DBTT) (10 mol%) as catalyst [195], which is quite useful for activation of aldehyde carbonyls rather than acetals, gave unsatisfactory results, producing the y3-methoxy ester preferentially (Sch. 147). 

The Mukaiyama aldol reaction of carbonyl substrates with silyl enol ethers is the most widely accepted of Lewis acid-promoted reactions. Many Lewis acids for the reaction have been developed and used enantioselectively and diastereoselectively. In 1980, catalytic amounts of la were found by Noyori et al. to effect aldol-type condensation between acetals and a variety of silyl enol ethers with high stereoselectivity [2c,20]. Unfortunately, la has poor Lewis acidity for activation of aldehydes in Mukaiyama s original aldol reaction [21]. Hanaoka et al. showed the scope and limitation of 11-cat-alyzed Mukaiyama aldol reaction, by varying the alkyl groups on the silicon atom of silyl enol ethers [22]. Several efforts have been since been made to increase the reactivity and/or the Lewis acidity of silicon. One way to enhance the catalyst activity is to use an additional Lewis acid. 

The use of Ln(OTf)3 in the activation of aldehydes other than formaldehyde was also investigated [18], Several examples of the present aldol reaction of silyl enol ethers with aldehydes are listed in Table 14-1. In every case, the aldol adducts were obtained in high yields in the presence of a catalytic amount of Yb(OTf)3, Gd(OTf)3, or Lu(OTf)3 in aqueous media. Diastereoselectivities were generally good to moderate. One feature in the present reaction is that water-soluble aldehydes, for instance, acetaldehyde, acrolein, and chloroacetaldehyde, can be reacted with silyl enol ethers to afford the corresponding cross aldol adducts in high yields (entries 5-7). Some of these aldehydes are commercially supplied as water solutions and are appropriate for direct use. Phenylglyoxal monohydrate also worked well (entry 8). It is known that water often interferes with the aldol reactions of aldehydes with metal enolates and that, in the cases where such water... 

The origin of the highly enantioselective catalysis by 55 is the simultaneous activation of aldehydes and TMSCN by the Lewis acid (Al) and the Lewis base (the oxygen atom of the phosphine oxide), respectively. The enantioselectivity of the reaction may be explained by the working model depicted in Fig. 1, with the... 

Thomas has reported elegant studies of transmetalations in the course of allylation reactions with aldehydes. As illustrated in Scheme 5.2.47, chiral, non-racemic 207 undergoes transmetalation with SnCU to provide stabilization of the trichlorostannyl species 208 by vicinal coordination with the benzyl ether. Activation of aldehyde and addition proceeds via the closed, chair-like transition state 209. The features of the four-membered metallocycle 209 account for the exclusive formation of the Z-homoallylic alcohol and the observed 1,5-xyn-diastereoselection in 210. Similar results are obtained with ethers that have coordinating capabilities (PMB and MOM). 

The use of InCls for Lewis acid activation of aldehyde substrates leads to rapid transmetalation of the allylic stannane, followed by carbonyl addition reactions of an allyl indium reagent. Premixing of InCb and the allylic stannane in the absence of aldehyde often produces precipitation and poor results. On the other hand, allyl indium reagents have been independently prepared by several procedures, including reductive metalations. Several important reviews describe the methods of preparation and the reactivity of allyl indium compounds. This discussion will be limited to key factors regarding the transmetalation of allylic stannanes in the presence of aldehydes. Stereochemical events leading to the production of anti adducts as major products are illustrated in Scheme 5.2.55. 

Cu(OTf)2 is a stable Lewis acid in aqueous media and can be used for activation of aldehydes [76]. The f ji(()Tf)2-catalyzed reaction of aromatic aldehydes with acetophenone TMS enolate gives the corresponding adducts in good to high yields. The same reaction of aliphatic aldehydes results in moderate yields. 

The use of Ln(OTf)3 in the activation of aldehydes other than formaldehyde was also investigated [18]. The model reaction of 1-trimethylsiloxycyclohexene (2) with benzaldehyde under the influence of a catalytic amount of Yb(OTf)3 (10 mol%) was examined. The reaction proceeded smoothly in H20-THF (1 4), but the yields were low when water or THF was used alone. Among several Ln(OTf)3 screened, neodymium triflate (Nd(OTf)3), gadolinium triflate (Gd(OTf)3), Yb(OTf)3, and lutetium triflate (Lu(OTf)3) were quite effective, while the yield of the desired aldol adduct was lower in the presence of lanthanum triflate (La(OTf)3), praseodymium triflate (Pr(OTf)3) or thulium triflate (Tm(OTf)3) (Table 2). 

Similar studies with f/-ans-4-hydroxy-2-none-nal (HNE, a cytotoxic byproduct of biological membrane lipid peroxidation), indicate that it is also metabolically activated by CYP2B1 and -2B4 to a reactive species that binds irreversibly to their prosthetic heme"". Unlike the mechanism-based inactivation by aromatic aldehydes, strucmral analyses of the corresponding heme adduct (MW 770) revealed that the reaction proceeds without deformylation and involves an acyl carbon radical that partitions between addition to the heme and formation of the carboxylic acid"". Together these findings suggest that the P450-mediated metabolic activation of aldehydes is a versatile process wherein the enzyme may be inactivated via mechanistically diverse heme modifications. 

Table 5.1 C—H bond activation of aldehydes using Nai2[Cp Ir(PMe3)(Me)(CH2=CH2) CGa4(23)6] (5.41) (reproduced from reference " ).

An interesting example of enamine activation of aldehydes by the L,L-prolylprolinol 9/3-fluoro benzoic acid system, has been illustrated by Gong and coworkers, in a tandem Michael/acetalisation process starting from 2-(2-nitrovinyl)phenols (Scheme 7.17). ... 

Following this, Chen and co-workers [43,44] successfully reported an aza-HAD (Scheme 6.16). They applied the J0rgensen-Hayashi catalyst 46 for catalytic HOMO activation of aldehydes 66 that readily underwent DA with enimine 73 to give optically active piperidine derivatives 74. The adducts 74 were obtained in moderate... 

Very recently, the same group successfully extended this methodology also to a-branched aldehydes [128], Cinchona based primary amine LX (Scheme 8.27) for activation of aldehydes and (-)-CSA as chiral acid for carbocation formation efficiently catalyzed alkylation reaction, giving best results in solvent system CH3CN/H2O. 

ThefoUowingdominoreactiondevelopedbyj0rgensenandco-workers [44a] involves enamine activation of aldehydes by diphenylprolinol silyl ether promoting an enantioselective Michael addition onto quinones, followed by an intramolecular hemiacetaliza-tion (Scheme 16.22). The resulting dihydrobenzofiirans were obtained with high yields... 

A new organocatalytic Michael/a-amination sequence based on double enamine activation of aldehydes produces a-hydrazino-aldehydes bearing a quaternary stereocentre in high yield and ee ... 

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