Aldol reaction indirect

In the text below organocatalytic asymmetric aldol reactions are classified into indirect aldol reactions and direct aldol reactions . Indirect aldol reactions are syntheses which require a modified ketone as a starting material (Scheme 6.9, pathway 1). For example, enolates which are prepared in a previous step starting from the ketone are often used. Syntheses which allow the direct use of a ketone, in a non-activated form, as a nucleophile are defined as direct aldol reaction (Scheme 6.9, pathway 2). 

Enantioselective nitro-aldol reaction (see Section 3.3) or Michael reaction (see Section 4.4) followed by radical denitration is useful as an alternative indirect method of enantioselective 1,2- or 1,4-addition of alkyl anions (see Eq. 7.7087 and Eq. 7.7188). 

The next task was to form the C2-C3 aldol bond stereoselectively. However, asymmetric coupling of acetate derivatives to aldehydes is often accompanied by poor / -induction [89]. Moreover, the C3-C4 bond is particularly sensitive to retro-aldol reaction, especially under basic conditions. In the natural products, this was observed to be the main decomposition reaction. The first total syntheses of epothilones circumvented this problem by constructing this part of the molecule in an indirect manner, e.g., by using reduced forms at Cl or C5. We decided to employ our chromium-Reformatsky methodology, which avoids these problems and allows the direct use of reagents in the correct oxidation state. The non-basic reaction conditions, the intermediacy of a chromium(III) aldolate that is resistant to retro-aldol reaction, and the potential of a direct asymmetric carboxymethyl ( acetate ) transfer favor the use of this method [90]. 

Indirect" aldol reaction with modified ketone... 

Several organic molecules have been found to catalyze this process efficiently. As described in Section 6.2.1.1, the syntheses can be performed as indirect or direct aldol reactions. Thus, as nucleophiles, ketones were applied directly or enolates can be used as starting materials. 

Because of their tendency to undergo aldol reactions, various conditions have been investigated to develop methods for the sulfenylation of aldehydes. Indirect methods involving metallation of the corresponding imines (10 Scheme 11 ) offer a preferred alternative to the low temperature direct sulfenylation described above, but better methods are still required. One possibility may Ite to exploit the rapid room temperature enolization of aldehydes observed on treatment with potassium hydride in THF. ... 

The products of the phospho-aldol reaction, a-functionalised phosphonate esters such as a-hydroxy- and a-aminophosphonates, find widespread application directly or indirectly as precursors to enzyme inhibitors (such as the enzymes renin [6], thrombin [7],EPSP synthase [8], HIV protease [9] and various classes of PTK and PTPs [10]) and phosphate analogues [11], antibiotics [ 12], antiviral agents [ 13], and in nucleotide technology [ 14]. Within each application stereochemistry of the phosphonate is crucial to eliciting the required properties [15]. 

The Mannich reaction represents a useful extension of aldol-type approaches for the stereoselective formation of C-C bonds with concomitant introduction of O- and N-functionality. In this reaction two carbraiyl compounds and an amine react to form p-amino-carbonyl compounds. Besides indirect variants using preformed enolates the use of unmodified nucleophiles (direct variant) has attracted considerable interest (92). Therefore, it is not surprising that the first example of a direct organocatalytic Mannich reaction was published only shortly (93) after the first proline-catalyzed aldol reaction (28). p-Anisidine (102) is commonly used for... 

Small-molecule-Catalyzed Asymmetric Aldol Reactions with Preformed Enol Ethers The methodologies of intermolecular direct asymmetric aldol reactions still tend to give mediocre results when enolizable carbonyl compounds are used. Even if current indirect small-molecule-catalyzed aldol reactions all require preactivation... 

At this point, one can see the impact of the chiral Lewis acid catalysis in the indirect small-molecule-catalyzed asymmetric aldol reactions. More examples together with exhaustive discussions about the stereochemical... 

When performing a Mannich reaction in its initial three-component design, the selectivity is sometimes difficult to obtain due to the competition with the side processes, primarily the auto-aldol condensation [52, 80], A common solution for this problem is the pre-formation of an imine or the enolate, or both and thus the sequential (indirect) performance of the reaction (Scheme 35) [52],... 

The -Cannizzaro reaction often occurs indirectly when aldehydes containing a-hydrogen atoms are treated with alkali. The first products usually are those formed by aldol condensation, and these may undergo Cannizzaro reactions of either the normal or crossed variety. 

Phenyl-substituted oxiranes may be reduced in DMF akin to benzyl ethers by direct and indirect methods the regioselectivity is slightly higher in the indirect reduction [76]. Benzoyloxiranes can be reduced in MeCN to aldoles addition of acetic acid prevents a retroaldol reaction catalyzed by the EGB [77]. The ring opening is analogous to the reduction of 2-alkoxyacetophenone to acetophenone. 

A series of carbonates (47-49) - derived from earbonate formation of the corresponding MBH adduct (for 47 and 49) or indirect synthesis from 3-methylbutanal and 3-(dimethylamino)-A, A-dimethylpropanamide following a sequence of transformations that includes aldol reaetion, carbonate formation and p-elimination of N-oxide (for 48) - have been used in palladium(0)-cata-lyzed stereoselective carbonylation reactions to give alkylidenesuccinate and anaolgues in moderate to good yields (Scheme 3.13). While the carbonates 47... 

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