Aldehyde reaction with nucleophiles

It has long been known that a, / -unsaturated sulfones resemble a, /i-unsaturated ketones and aldehydes in undergoing addition reactions with nucleophilic reagents43. These reactions are initiated by nucleophilic attack at the carbon to the sulfone group ... 

Domino Michael/aldol processes, which are initiated by the addition of a halide to an enone or enal, have found wide attention. They are valuable building blocks, as they can be easily converted into a variety of extended aldols via subsequent SN2 reactions with nucleophiles or a halide/metal exchange. As an example, a-haloalkyl- 3-hy-droxy ketones such as 2-76 have been obtained in very good yields and selectivities by reaction of enones 2-71 with nBu4NX in the presence of an aldehyde 2-74 and TiCl4as described by the group of Shinokubo and Oshima (Scheme 2.16) [24]. 

The presence of electron-withdrawing substituents at C(4) facilitates reactions with nucleophiles, which may well be initiated by attack at C(5). Thus oxazole-4-aldehydes undergo ring-fission on treatment with aqueous alkali to form (acylamino)malondialdehydes (equation 3), and 2-pentyloxazole-4-carboxylic acid yields 2-pentylimidazole, with concomitant decarboxylation, when heated with ammonia at 150 °C. An example of a more complex ring transformation is the formation of 3-aminopyridines (131) by the action of malononitrile on 4-acetyloxazoles under alkaline conditions (equation 4). 

Both aromatic aldehydes and ketones undergo normal carbonyl group reactions with nucleophilic reagents. 

A common electrophile is the aldehyde moiety, which of course can be involved in many reactions with nucleophiles. The key problem is to avoid foUow-up reactions such as multiple additions or oligomerizations, which are likely to occur with many support-bound substrates. Thus, irreversible reactions are employed to achieve the desired product selectivity. In many cases these reactions require strongly basic conditions and involve Grignard reagents, or Zn, li and even In organyls [365]. N-acyliminiun ion chemistry has recently received great attention in SPOC. 

Reactions of a,fi-unsaturated aldehydes ndketones with nucleophiles (Section 18.13) ... 

Solution A characteristic of both ketones and aldehydes is the carbonyl functional group they possess. Thus, to characterize and identify ketones and aldehydes, reactions with the carbonyls are often done. Since oxygen is more electronegative, (electron-attracting) than carbon, the carbonyl carbon becomes susceptible to nucleophilic attack. Hydroxylamine, derived from its hydrochloride salt, can act as a nucleophilic reagent. 

Due to the presence of carbonyl, aldehyde or ketone radicals, sugars are capable of addition reactions with nucleophilic reagents such as phenylhydrazine (C6H5-NH-NH2). The addition of three phenylhydrazine molecules to an aldose (Figure 3.12) leads to the formation of osazone, a crystallized product with specific physicochemical characteristics, especially its melting point. This makes it possible to identify the corresponding sugar. 

A general method for the synthesis of dialdoses and nucleoside 5 -aldehydes has been described, and their asymmetric reaction with nucleophiles discussed. The reversible interconversion of GDP-D-mannose and -L-galactose which is brought about by a Chorella enzyme system was proposed to occur as shown in Scheme 2 following the observation that tritium incorporation from the solvent occurred equally at C-3 and C-5. Epimerizations at positions a to the carbonyl groups can also be photoinduced, and compound (1) has now been isolated in... 

The perhydroxyl anion, HO2 , is quite a powerful nucleophile and, as seen later, will attack substrates such as electron-deficient olefins (e.g. a,P-unsaturated ketones) and aldehydes - reactions with some synthetic utility, and also of value in bleaching and product purification, particularly of natural materials. In addition, HO2 can be used to generate more powerful oxidants by mixing with electron-deficient acyl compounds (giving peracids) or with nitriles (Payne system, see section 9.3.3.3). 

This chapter will revisit the lUPAC nomenclature system for aldehydes, ketones, and carboxylic acids, as well as introduce nomenclature for the four main acid derivatives acid chlorides, anhydrides, esters, and amides. The chapter will show the similarity of a carbonyl and an alkene in that both react with a Br0nsted-Lowry acid or a Lewis acid. The reaction of a carbonyl compound with an acid will generate a resonance stabilized oxocarbenium ion. Ketones and aldehydes react with nucleophiles by what is known as acyl addition to give an alkoxide product, which is converted to an alcohol in a second chemical step. Acid derivatives differ from aldehydes or ketones in that a leaving group is attached to the carbonyl carbon. Acid derivatives react with nucleophiles by what is known as acyl substitution, via a tetrahedral intermediate. 

The explanation used for these two experiments suggests that the reaction of cyanide ion with 9 is reversible with an aldehyde or a ketone, so the yield of cyanohydrin is expected to be poor. The acid-catalyzed reaction, however, leads first to an oxocarbenium ion that easily reacts with cyanide. Therefore, the acid-catalyzed reaction gives a good yield of the cyanohydrin. This difference between direct substitution and acid-catalyzed addition is an important key to understanding and controlling reactions with nucleophiles. Note that when cyanide reacts with the carbonyl unit of 9, a new carbon-carbon bond is formed as the carbonyl 7t-bond is broken. 

The carbonyl unit carbonyl (C=0) is the functional group for aldehydes and ketones as well as esters (see Chapter 5, Section 5.9). All discussions in previous chapters focused on the carbonyl group and acyl addition or acyl substitution reactions with nucleophiles. The carbonyl group is electron withdrawing with respect to the attached carbon atoms in an aldehyde or ketone. Therefore, the carbonyl group will induce a dipole in the adjacent carbon (the a-carbon is 6-), which in turn leads to a dipole between that carbon and its attached hydrogen (the a-proton), as shown in 1. This so-called a-hydrogen or a-proton is 5f. 

Chiral aldehydes 28 with a-stereocenters undergo addition reactions with nucleophiles with predictable stereoselectivity patterns. The Felkin-Anh model proposes that the nucleophile approaches anti to the a-substituent that is either the largest or a heteroatom, and approaches the aldehyde via the... 

The dipolar character of phosphorus ylides is shown by their reactions with nucleophiles (e.g. aldehydes and ketones) or with electrophiles (e.g. proton donors). Ylides Ph3P=CHR (R = alkyl) are readily hydrolysed, even by cold water, so it is usual to carry out reactions involving them under anhydrous conditions. An inert atmosphere (usually nitrogen) is also necessary as oxidation... 

Aldehydes and ketones undergo irreversible nucleophilic addition reactions with nucleophiles that are strong bases. 

Aldehydes and ketones undergo nucleophilic addition-elimination reactions with nucleophiles that have a lone pair on the attacking atom. 

These compounds are sources of the nucleophilic anion RC=C and their reaction with primary alkyl halides provides an effective synthesis of alkynes (Section 9 6) The nucleophilicity of acetylide anions is also evident m their reactions with aldehydes and ketones which are entirely analogous to those of Grignard and organolithium reagents... 

Because etiolate anions are sources of nucleophilic carbon one potential use m organic syn thesis IS their reaction with alkyl halides to give a alkyl denvahves of aldehydes and ketones... 

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