Electron-poor aldehyde

Trifluoromethylation can be achieved with the use of imidazolylidene carbene 1 [159], Song and co-workers found this transformation is tolerant of both electron-rich and electron-poor aldehydes (Table 26). Even enolizable aldehydes undergo trifluoromethylation in 81% yield (entry 3). Selective reaction occurs with an aldehyde in the presence of a ketone in the substrate (entry 5). The use of activated ketones as acceptors leads to tertiary alcohols in good yields (entries 7 and 8). 

The effect of the electronic properties of the substituted benzaldehydes (la-c) on the allylation reaction is another interesting issue. Whilst the majority of catalysts shown in Figures 7.1 and 7.2 generally exhibit rather minor variation of the ee-value (typically with less than 20% difference between the electron-rich and electron-poor aldehydes), METHOX (22) appears to be a particularly tolerant catalyst, exhibiting practically the same enantioselectivity (93-96% ee Table 7.2, entries 1-3) and reaction rate across the range of substrates [28b, 29]. By contrast, QUINOX (24) stands on the opposite side of the spectrum, showing the most dramatic differences between the electron-poor and electron-rich substrate aldehyde (12-96% ee entries 4-6) [30]. 

In a typical reaction, a solution of alkyne in THF is cooled to —20°C for 5 min. An equimolar amount of the dialkylzinc is added in toluene (ratio of THF toluene = 1 3). After 15 min, 10 mol % of the ligand is added, followed by the aldehyde. HPLC analysis shows complete reaction usually within 18 h. Both electron-rich and electron-poor aldehydes have been used along with aromatic and aliphatic alkynes. Yields are normally 70-90% with ee being 65-85%. Once again the optimal ligand structure may involve variation of the amine substitution pattern. 

A novel and interesting route to 2-aryl-4-oxo-benzo[c/][l,3]oxazines (392) is furnished by the thermal reaction of o-azidobenzoic acid with benzaldehydes (Scheme 151). The reaction is thought to proceed via a novel type of cycloadduct (391) rather than via a nitrene, as the temperature required ca. 110 °C) is significantly below that at which the azide decomposes (145 C). Yields are good, the reaction works with electron-rich and electron-poor aldehydes, and ort o-azidobenzamides react similarly, giving quinazoline derivatives (see p. 256)."° ... 

Peters and co-workers developed a tertiary amine-catalyzed enantioselective [4+2] cycloaddition of a,p-unsaturated acid chlorides 76a-e and electron-poor aldehyde chloral (77) to provide 5-lactones 79a-e, Scheme 3.27 [42], Vinylketene, which was formed in situ by dehydrohalogenation of a,p-unsaturated acid chloride... 

Isotetronic acids were readily assembled through an organocatalyzed domino aldol-lactonization reaction starting from a-keto carboxylic acids and aldehydes [5]. As chiral organocatalyst, the proline-derived benzimidazol pyrrolidine 8 was employed, which proved superior to proUne itself Electron-poor aldehydes were both more reactive and selective. Thus, as a typical example, pyruvate was converted into isotetronic acid 10 in 77% yield and 83% ee upon treatment with para-nitrobenzyldehyde (9) and 10mol% 8 (Scheme 8.3). 

Alumina sulfuric acid (ASA) was found to be an effective catalyst for the solvent-free one pot Beckmann rearrangement of several alkyl and aryl aldehydes and ketones 1. It has been reported that the electron rich aldehydes and ketones require shorter reaction times than the electron poor aldehydes. Cyclic ketones require longer reaction time than the aryl ketones ascribable to the steric factors. ... 

Scheme 18.19 Electron-poor aldehydes as oxidant for Al-catalysed Oppenauer reaction.

The hypothesis of the A -thiazolium-2-ylide intermediate (10) as a key intermediate is consistent with the fact that electrophilic aldehydes can promote the addition of 2-TST (1) to electrophilic ketones, in particular to a.a -dialkoxy ketones. The effect of several aldehydes on the rate of the reaction of 2-TST (1) with two different ketones (13 and 14), at different temperatures and at different concentrations of the ketones and aldehydes, was studied. It was found that electron-poor aldehydes, particularly 2-fluorobenzaldehyde, enhance the rate of addition of 2-TST (1) to those studied ketones (eqs 21 and 22). 

Inspection of the results listed in Table 1 reveals that electron poor aldehydes are better substrates than their electron rich counterparts. For example, while 3-methoxybenzaldehyde (entry 4) requires over 48 horns to react, 4-cyanobenzaldehyde reaction (entry 5) is con5)lete in 15 minutes. Pyridyl aldehydes (entries 1 and 7) are excellent substrates for this reaction. 

The corresponding cts-cyclopropane 68 gave 2,4-tfans-, 2,5-c -tetrahydrofuran 70 regardless of whether electron-rich or electron-poor aldehydes were used (Scheme 20) [20], Yang et al, believes that the cyclization of 68 proceeds in a stepwise manner with all substituents occupying pse t(o-equatorial positions as indicated by 71. 

A nucleophilic amine 171 could then intercept the sulfene, giving nucleophilic zwitterion 174 that undergoes a formal [2+2] cycloaddition with electron-poor aldehydes 175, giving enantioenriched 3-sultones 170 (Figure 3.12). 

The 2,5-disubstiututed tetrahydrofiirans were obtained in a high degree of diastereoselective control, where the cis-isomers were predominately formed. The reaction proceeded well with both electron-rich and electron-poor aldehydes however, 2-pyridinecarboxaldehyde was unreactive due to the potential coordination of tin triflate with the nitrogen of pyridine. 

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