Addition reactions continued aldehydes

Carbonyl-addition reactions continue to be the speciality of the French group interested in germylphosphines. Thus the germaphospholan (68) adds to aldehydes to give diastereomeric products (69).62 Steric factors are believed to control the mode... 

Disagreement over whether the result of this addition reaction between aldehyde and bisulfite should be written as structure A or structure B continued for many decades ... 

If the luciferase sample solution contains a flavin-reductase, luciferase activity can be measured by the addition of FMN and NADH, instead of FMNH2. In this case, the turnover of luciferase takes place repeatedly using the FMNH2 that is enzymatically generated thus, the luminescence reaction continues until aldehyde or NADH is exhausted. A crude luciferase extracted from luminous bacteria usually contains a flavin-reductase. 

In the course of the continuing study [9a,b] on the enantioselective addition of dialkylzincs to aldehydes by using chiral amino alcohols such as diphenyl(l-methyl-2-pyrrolidinyl)methanol (45) (DPMPM) [48] A. A -dibutylnorephedrine 46 (DBNE) [49], and 2-pyrrolidinyl-l-phenyl-1-propanol (47) [50] as chiral catalysts, Soai et al. reacted pyridine-3-carbaldehyde (48) with dialkylzincs using (lS,2/ )-DBNE 46, which gave the corresponding chiral pyridyl alkanols 49 with 74-86% ee (Scheme 9.24) [51]. The reaction with aldehyde 48 proceeded more rapidly (1 h) than that with benzaldehyde (16 h), which indicates that the product (zinc alkoxide of pyridyl alkanol) also catalyzes the reaction to produce itself. This observation led them to search for an asymmetric autocatalysis by using chiral pyridyl alkanol. 

The mixed Tishchenko reaction involves the reaction of the aldol prodnct 113 from one aldehyde with another aldehyde having no a-hydrogens to yield an ester The products were proposed to be formed through an aldol step (equation 33), followed by addition of another aldehyde (equation 34) and an intramolecular hydride transfer (equation 35). However, several aspects of this mechanism need to be clarified. As part of the continuing mechanistic studies carried out by Streitwieser and coworkers on reactions of alkali enolates ", it was found that the aldol-Tishchenko reaction between certain lithium eno-lates and benzaldehyde proceeded cleanly in thf at room temperature". Reaction of the lithium enolate of isobutyrophenone (Liibp) with 1 equiv of benzaldehyde in thf at — 65 °C affords a convenient route to the normal aldol product 113 (R = R" = Ph, R = Me). At room temperature, however, the only product observed after acid workup was the diol-monoester 116, apparently derived from the corresponding lithium ester alcoholate (115, R = R" = Ph, R = Me), which was quantitatively transformed into 116 after quenching. As found in other systems", only the anti diol-monoester diastereomer was formed. 

In Chapter 21 we continue the study of carbonyl compounds with a detailed look at aldehydes and ketones. We will first learn about the nomenclature, physical properties, and spectroscopic absorptions that characterize aldehydes and ketones. The remainder of Chapter 21 is devoted to nucleophilic addition reactions. Although we have already learned two examples of this reaction in Chapter 20, nucleophilic addition to aldehydes and ketones is a general reaction that occurs with many nucleophiles, forming a wide variety of products. 

The equilibrium in this reaction favors starting material in Problem 1.14.b, the equilibrium constant for this reaction was calculated to be approximately 10 . Nonetheless, the reaction continues to a stable product because the subsequent step has a much more favorable equilibrium constant. In this next step, the carbonyl group of the aldehyde undergoes nucleophilic addition by the enolate anion to give 3-8 ... 

New auxiliaries and reaction methods are now available for the stereoselective synthesis of all members of the stereochemical family of propionate aldol additions. These also include improvements on previously reported methods that by insightful modification of the original reaction conditions have led to considerable expansion of the versatility of the process. In addition to novel auxiliary-based systems, there continue to be unexpected observations in diastereoselective aldol addition reactions involving chiral aldehyde/achiral enolate, achiral aldehyde/chir-al enolate, and chiral aldehyde/chiral enolate reaction partners. These stereochemical surpri.ses underscore the underlying complexity of the reaction process and how much we have yet to understand. 

Several examples of aldol addition and condensation are given in Scheme 7.3. Entries 1 and 2 are typical aldol reactions of aldehydes, with and without dehydration. The reaction in Entry 1 was done with 15% KOH in aqueous solution at room temperature. The condensation reaction in Entry 2 was carried out at 80°-90°C with 1M NaOH. Entries 3 and 4 show addition and condensation reactions of acetone. Entry 3 features a clever way of overcoming the unfavorable equilibrium of the addition step. The basic catalyst is contained in a separate compartment of a Soxhlet extractor. Acetone is repeatedly passed over the basic catalyst by distillation and the condensate returns to the flask. Since there is no catalyst present in the flask, the adduct remains stable. The concentration of the addition product builds up as the more volatile acetone distills preferentially. The acid-catalyzed condensation in Entry 4 is carried out similarly. The acetone is continuously passed over the acidic resin, and the reaction is driven forward by the stability of the conjugated condensation product. In Entry 5, the final product is a (3-chloroketone, presumably formed by addition of HCl to a dehydrated intermediate. 

Higher aldehydes react with phenol in the same maimer but significantly more slowly than formaldehyde. The reaction is generally performed nnder strong acidic conditions to minimize aldol formation and in a water-free system by continuous aldehyde addition to the phenol melt. 

New protocols for the catalytic asymmetric monoallylation of aldehydes using the title reagent continue to be developed. For example, it has been shown (eq 10) that a range of aromatic and aliphatic aldehydes engage, in the presence of 5 mol % [(/ )-BlNOL]-Ti [OCH(CF3)2]2, in an enantioselective addition reaction with trimethyl 2-[(tributylstannyl)methyl]-2-propenyl -silane to give the expected addition products in >90% ee and 54—94% chemical yield. ... 

An efficient biocatalytic reaction [173] was developed to synthesize (2 )-hexenal at large scale, based on the conversion of 13-HPOT by means of sugar beet HPL extracted from leaves or expressed by recombinant E. coli strains. With the adaptation of fed-batch substrate addition and continuous extraction of volatiles, 3.46 and 1.37 mM of C6-aldehydes were produced with the native HPL at, respectively, 2 and 1001 scale. Furthermore, higher molar productivity of green leaf volatiles was reached with recombinant HPL (5.5 mM at 2-1 scale), while no other side-products from the LOX pathway were formed. 

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