Chiral compounds Aldehydes

In the presence of metal catalysts such as rhodium compounds, aldehydes can add directly to alkenes to form ketones. The reaction of co-alkenyl aldehydes with rhodium catalyst leads to cyclic ketones, with high enantioselectivity if chiral ligands are employed. Aldehydes also add to vinyl esters in the presence of hyponitrites and thioglycolates. ° ... 

In reactions of chiral aldehydes, TiIV compounds work well as both activators and chelation control agents, a- or A-oxygcnated chiral aldehydes react with allylsilanes to afford chiral homoallylic alcohols with high selectivity (Scheme 22).85 These chiral alcohols are useful synthetic units for the synthesis of highly functionalized chiral compounds. Cyclic chiral 0,0- and A/O-acetals react with allylsilanes in the same way.86,87 Allenylsilanes have also been reported as allylation agents. 

Enzyme reductions of carbonyl groups have important applications in the synthesis of chiral compounds (as described in Chapter 10). Dehydrogenases are enzymes that catalyse, for example, the reduction of carbonyl groups they require co-factors as their co-substrates. Dehydrogenase-catalysed transformations on a practical scale can be performed with purified enzymes or with whole cells, which avoid the use of added expensive co-factors. Bakers yeast is the whole cell system most often used for the reduction of aldehydes and ketones. Biocatalytic activity can also be used to reduce carbon carbon double bonds. Since the enzymes for this reduction are not commercially available, the majority of these experiments were performed with bakers yeast1 41. 

Nowadays, this chemistry includes a wide range of applications. The organozinc compounds employed in the enantioselective addition include dialkylzincs, dialkenylzincs, dialkynylzincs, diarylzincs and the related unsymmetrical diorganozincs. Electrophiles have been expanded to aldehydes, ketones and imines. Asymmetric amplification has been observed in the enantioselective addition of organozincs. Recently, asymmetric autocatalysis, i.e. automultiplication of chiral compounds, has been created in organozinc addition to aldehydes. 

Enantiomerically pure amino adds owe their great importance among chiral compounds to the fact that not only are they among the most versatile building blocks with a rich and vast history of transformation to other products such as peptides, amino alcohols, amino aldehydes, and many others, but that most natural L-amino acids are important components of infusion solutions, health food, and animal feed preparations. For this reason, several processes exist on a large scale that are described in the following sections. 

Enamine catalysis often delivers valuable chiral compounds such as alcohols, amines, aldehydes, and ketones. Many of these are normally not accessible using established reactions based on transition metal catalysts or on preformed enolates or enamines, illustrating the complimentary nature of organocatalysis and metallocatalysis. 

Resolution of aldehydes, The reagent was introduced by Leonard and Boyer for resolution of carbonyl compounds. It is particularly useful for resolution of chiral aromatic aldehydes (2) complexed with tricarbonylchromium. 

The bulk of oxidations with tert-butyl hydroperoxide consists of epoxidations of alkenes in the presence of transition metals [147, 215, 216, 217, 218]. In this way, a,p-unsaturated aldehydes [219] and ketones [220] are selectively oxidized to epoxides without the involvement of the carbonyl function. Other applications of tert-butyl hydroperoxide such as the oxidation of lactams to imides [225], of tertiary amines to amine oxides [226, 227], of phosphites to phosphates [228], and of sulfides to sulfoxides [224] are rare. In the presence of a chiral compound, enantioselective epoxidations of alcohols are successfully accomplished with moderate to high enantiomeric excesses [221, 222, 223]. 

One of the earliest syntheses of a chiral compound from a carbohydrate was reported by Wolfrom, Lemieux and Olin, who described the preparation of optically active L-alanine from D-glucosamine [17]. This transformation was devised to establish the strucmre of alanine from the known D-glucosamine. Only a few functional group manipulations were needed in this synthesis, such as elaboration of the aldehyde group into the methyl group of alanine through the corresponding dithioacetal. Excision of three carbon atoms was also required (Scheme 11.1). 

Here, the name aldol refers to a /3-hydroxycarbonyl compound which is derived from the nucleophilic additions between enol (or enolate) 13 and ketone (or aldehyde) 14 (O Scheme 5). Sugars, as the chiral polyhydroxy aldehyde or ketone compounds, are natural substrates for these reactions. 

Relatively strong bases are used for the deprotonation of phosphonate reagents, and the phosphonate-stabilized carbanions formed are more basic than the corresponding phosphorane reagents. Such conditions may be incompatible with base-sensitive aldehydes and ketones, causing epimerization of chiral compounds or... 

Because the aldehyde group is an extremely versatile functionality, AH constitutes a useful entree into chiral biologically active compounds such as the nonsteroidal antiinflammatory drug (S)-naproxen (32), commonly called Aleve. Section 9-7-1 highlighted a racemic hydrofomylation that was a key step in the synthesis of ibu-profen. naproxen is quite similar to ibuprofen in structure, but the toxic nature of racemic Naproxen in the body demands that it be synthesized and administered as the much less toxic (S)-enantiomer. Scheme 12.14 shows a possible route to 32, first involving AH of the vinyl naphthalene in the presence of BINAPHOS (34, Fig. 12-6) to create the chiral branched aldehyde and then subsequent oxidative conversion of the aldehyde to the carboxylic acid.83 AH of vinylnaphthalene (33)... 

The reductive cleavage of the amide residue of many chiral auxiliaries is recommended for recovery of chiral compounds and auxiliary regeneration [S.3]. Evans s acyloxazolidinones 3.184 have been transformed into aldehydes by DIBAH or Red-Al at low temperature [CW2, EB5, MSS], but in the case of R =SPh, some epimetization occurs (Figure 3.70). DIBAH has also been proposed to transform N-acylthiazolidintliiones 3.185 [NKl] into the coiresponding aldehydes (Figure... 

Russian workers have reported the preparation of an unusual 11,12,14,15-tetradehydro-(5S, 6R)-dimethylmethanoleukotriene A4 analog 68. The compound was prepared in seven steps from the chiral keto aldehyde synthon, caronic aldehyde 69 (Scheme 5.25). 

The aldehydes used in the reaction can be varied over a wide range chiral compounds such as sugar aldehydes have been employed to some extent. The use of ketones is limited due to their lower reactivity. 

Some commonly used resolving agents are summarized in Table 1 [15-48]. The formation of non-covalent diastereomeric salts is driven by ionic interactions. Therefore, suitable functional groups (acidic or basic) are required to be present in both counterparts. This makes impossible a direct application of the diastereomeric crystallization technique to several classes of chiral compounds such as alcohols, aldehydes, ketones, diols, thiols, dithiols, and phenols. This is a critical disadvantage of this technique. The compounds of the above-mentioned groups may be transformed to their more polar derivatives and resolved as such. However, this requires an additional reaction step, and reagents, and the recovery of the starting material after the resolution may not always be easy. 

The compound 2-lithiothiazole like 2-(trimethylsilyl)thiazole (2-TST) has been used as a formyl anion equivalent used by Dondoni in the scheme below to prepare a chiral compound by a process called aminohomolgation of Gamer aldehyde. Propose stmctures for products A, B, C, and D below. ... 

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