From aldol reaction reactions

Difunctional products often come from aldol type reactions. The following example, 2- hydroxymethyl)-2-methylbutanal, needs no further comment (F. Nerdel, 1968). 

The reaction conditions needed for aldol dehydration are often only a bit more vigorous (slightly higher temperature, for instance) than the conditions needed for the aldol formation itself. As a result, conjugated enones are usually obtained directly from aldol reactions without isolating the intermediate jS-hydroxy carbonyl compounds. 

Hydroxy-substituted iron-acyl complexes 1, which are derived from aldol reactions of iron-acyl enolates with carbonyl compounds, are readily converted to the corresponding /i-methoxy or /1-acetoxy complexes 2 on deprotonation and reaction of the resulting alkoxide with iodomethane or acetic anhydride (Tabic 1). Further exposure of these materials to base promotes elimination of methoxide or acetate to provide the a,/ -unsaturated complexes (E)-3 and (Z)-3 (Table 2). 

C-H insertion a to oxygen results in the formation of /3-hydroxyester derivatives that are generally prepared from aldol reactions (Figure 3). For the C-H insertion chemistry to be a viable surrogate of the aldol reaction, the reaction would need to be highly diastereoselective and enantioselective. 

The addition prodnct from aldol reactions frequently dehydrates by heating in acid or in base... 

Considerable efforts have been directed towards the development of a system to maximize enantiomerically pure diastereomers from aldol reactions. The most effective systems... 

The (0)-reagent (91) is formed almost exclusively from S-3-(3-ethyl)pentyl propanethioate (92) and borolanyl triflate (90). Despite its apparent steric demand, (91) still retains a high degree of reactivity towards aldehydes (in Scheme 21 the interaction between R and Me is not exceedingly large). Summarized in Table 6 are the results obtained from aldol reactions of representative aldehydes with (91 Scheme 38). All reactions proceed smoothly at -78 °C and the major products have the 2,3-anti stereochemistry (antiisyn > 30 1). With (2 ,55)-(90) the aldehydes examined provide, in most cases, the (2R) aldol products with more than 98% ee. It is important to note that the external chiral moiety can be recovered as its 2,2-dimethylaminoethanol complex, and that the aldol products are equipped with a versatile thioate functionality for further synthetic transformation. 

Scheme 6.76). Heathcock developed a synthetic strategy wherein the 1,2-stereoselection obtainable from aldol reaction is parlayed by a subsequent Claisen rearrangement into 1,4 and 1,5-stereoselection [118]. Claisen-Johnson, Claisen-Eschenmoser and Claisen-Ireland rearrangements were examined in this study. However the orthoester Claisen-Johnson rearrangement was not the most convenient in this case. The rather harsh reaction conditions often led to dehydration and other byproducts. An example of this rearrangement is given in Scheme 6.76. 

Enones (e.g. H2C = CH-COCH3) derived from aldol condensation reactions can undergo further carbon—carbon bond forming reactions on addition of carbon nucleophiles. When the nucleophile adds at the 4-position (rather than the 2-position) of the enone, this is called the Michael reaction (or 1,4-addition or conjugate addition). 

FIGURE 19.70 The base-catalyzed elimination of water from aldol. The reaction mechanism is ElcB. If no a hydrogen is available for eUmination, then the initial aldol product can he isolated as shown in... 

A) The option to reductively dehalogenate chiral a-halo-/3-hydroxy imides, resulting from aldol reactions with chiral bromoacetates, offers an altemative route to chiral... 

The higjily water-soluble dienophiles 2.4f and2.4g have been synthesised as outlined in Scheme 2.5. Both compounds were prepared from p-(bromomethyl)benzaldehyde (2.8) which was synthesised by reducing p-(bromomethyl)benzonitrile (2.7) with diisobutyl aluminium hydride following a literature procedure2.4f was obtained in two steps by conversion of 2.8 to the corresponding sodium sulfonate (2.9), followed by an aldol reaction with 2-acetylpyridine. In the preparation of 2.4g the sequence of steps had to be reversed Here, the aldol condensation of 2.8 with 2-acetylpyridine was followed by nucleophilic substitution of the bromide of 2.10 by trimethylamine. Attempts to prepare 2.4f from 2.10 by treatment with sodium sulfite failed, due to decomposition of 2.10 under the conditions required for the substitution by sulfite anion. 

Chiral 2-oxazolidones are useful recyclable auxiliaries for carboxylic acids in highly enantioselective aldol type reactions via the boron enolates derived from N-propionyl-2-oxazolidones (D.A. Evans, 1981). Two reagents exhibiting opposite enantioselectivity ate prepared from (S)-valinol and from (lS,2R)-norephedrine by cyclization with COClj or diethyl carbonate and subsequent lithiation and acylation with propionyl chloride at — 78°C. En-olization with dibutylboryl triflate forms the (Z)-enolates (>99% Z) which react with aldehydes at low temperature. The pure (2S,3R) and (2R,3S) acids or methyl esters are isolated in a 70% yield after mild solvolysis. 

A useful catalyst for asymmetric aldol additions is prepared in situ from mono-0> 2,6-diisopropoxybenzoyl)tartaric acid and BH3 -THF complex in propionitrile solution at 0 C. Aldol reactions of ketone enol silyl ethers with aldehydes were promoted by 20 mol % of this catalyst solution. The relative stereochemistry of the major adducts was assigned as Fischer- /ir o, and predominant /i -face attack of enol ethers at the aldehyde carbonyl carbon atom was found with the (/ ,/ ) nantiomer of the tartaric acid catalyst (K. Furuta, 1991). 

Diethyl 3-oxoheptanedioate, for example, is clearly derived from giutaryl and acetic acid synthons (e.g. acetoacetic ester M. Guha, 1973 disconnection 1). Disconnection 2 leads to acrylic and acetoacetic esters as reagents. The dianion of acetoacetic ester could, in prin-ciple,be used as described for acetylacetone (p. 9f.), but the reaction with acrylic ester would inevitably yield by-products from aldol-type side-reactions. 

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