A-heteroatom functionalization

Reactions in chloroaluminate(III) salts and other related binary salts often proceed smoothly to give products. However, it should be noted that these salts are water-sensitive and must be handled under dry conditions. They react with water to give hydrated aluminium(III) ionic species and HCl. When a reactant or product contains a heteroatomic functional group, such as a ketone, a strong ketone/alumini-um(III) chloride adduct is formed. In these cases, this adduct can be difficult to separate from the ionic liquid at the end of a reaction. The isolation of the product often... 

A cyclopentadienylmagnesium bromide containing a heteroatom-functionalized substituent at the cyclopentadienyl group has also been structurally characterized. When l-[2-(dimethylamino)ethyl]-2,3,4,5-tetramethylcyclopentadienylmagnesium bromide is recrystallized from dichloromethane, dimeric [(Mc2N(CH2)2)Me4C5MgBr]2 (206) (Figure 88) is obtained. Its X-ray crystal-structure determination reveals a structure in the solid state... 

The cyclization of a range of a-heteroatom-functionalized radicals has been studied. Botii a-sulfonyl and a-sulfinyl radicals can undergo 5-exo cyclization on to alkenes.40... 

The introduction of a-heteroatom functionalization into an aldehyde or ketone is a very useful class of transformation. Performing it directly and asymmetrically, using organocatalysts, has been reviewed for reactions such as amination, oxygenation, halo- genation, and sulfenylation (44 references).260... 

In this chapter, we will outline the application of organocatalysis for the enantio-selective a-heteroatom functionalization of mainly aldehydes and ketones. Attention will be focused on enantioselective animation-, oxygenation-, fluorination-, chlorination-, bromination-, and sulfenylation reactions catalyzed by chiral amines. The scope, potential and application of these organocatalytic asymmetric reactions will be presented as the optically active products obtained are of significant importance, for example in the life-science industries. 

In the following sections we will describe recent developments and applications in the organocatalytic a-heteroatom functionalization of aldehydes and ketones catalyzed by chiral amines [1]. Notably, the C-H to C-Het transformations associated with amination, oxygenation, halogenation (fluorination, chlorination, bro-mination), and sulfenylation will be outlined (Scheme 2.24). 

Scheme 2.24 Organocatalytic a-heteroatom functionalization of carbonyl compounds.

Scheme 2.25 Mechanism for the catalytic enantioselective a-heteroatom functionalization of aldehydes and ketones catalyzed by secondary chiral amines.

A different mechanism operates in the direct a-heteroatom functionalization of carbonyl compounds when chiral bases such as cinchona alkaloids are used as the catalysts. The mechanism is outlined in Scheme 2.26 for quinine as the chiral catalyst quinine can deprotonate the substrate when the substituents have strong electron-withdrawing groups. This reaction generates a nucleophile in a chiral pocket (see Fig. 2.6), and the electrophile can thus approach only one of the enantiotopic faces. 

Despite the fact that polar entities are catalyst poisons, a variety of acyclic olefins containing a heteroatom functional group can undergo metathesis in the presence of a suitable catalyst, although at a high catalyst level. These include unsaturated esters, ethers, ketones, amines, nitriles, halogens, etc. [14]. In particular metathesis reactions - including ethenolysis - of unsaturated fatty esters and fatty oils are of interest, as they have perspectives for the oleochemical industry [15]. 

Aldol reactions using chiral auxiliaries are popular as the stereochemical outcome is usually highly predictable and, as such, they provide a reliable method for the incorporation of adjacent stereocenters. The oxazolidinone-based imides 36 and (ent)-36 are the most commonly employed, and these lead to syn aldol products with high levels of stereocontrol [20]. The reaction can be extended to include a variety of a-heteroatom functionality as in 37 (Scheme 9-13) [21]. Numerous examples of the use of these auxiliaries in the synthesis of polypropionate natural products have been reported. Many related auxiliaries are also available and the camphor-based sultam 38 is notable [22]. 

One last piece of information is required for synthesis in order to manipulate functional groups. In those cases where a heteroatom functional group interferes with a transformation and cannot be removed, modified, or inserted earlier or later in a synthesis, methods are available to temporarily block it. This method is termed protection and the moiety used to block the reactive fragment is called a protecting group, which will be the focus of Chapter 7. 

Decarboxylation of a-heteroatom-functionalized carboxylic acids occurs smoothly using PhI(OAc)2 and I2 without the requirement for photolysis. When proline derivatives are employed for this reaction, the intermediate A,0-acetal may be treated with nucleophilic agents to give 2-substituted pyrrolidine products (eq 55). 

Lactones are only slowly reduced by NaBHa in alcohol solvents at 25 °C, unless the carbonyl is flanked by an a-heteroatom functionality. Sugar lactones are reduced to the diol when the reduction is carried out in water at neutral pH, or to the lactol when the reaction is performed at lower ( 3) pH. Thiol esters are more reactive and are reduced to primary alcohols with NaBHa in EtOH, without reduction of ester substituents. ... 

Saturated amino acids of all types are discussed, as well as unsaturated, alkyl and aryl substituted, and amino acids that bear a heteroatom functional group. In general, four structural types of alkenyl amino acids are considered. In the first type, the double bond can be conjugated to the carbonyl group and the amine moiety can be attached directly to the double bond. Secondly, the amino group can be attached to the saturated carbon chain. The third and fourth types focus on the double bond, which can be in or out of conjugation with the carboxyl, and the amine group can be attached... 

Propyne allowed to react with methylamine in the presence of Zn(II)-ion-ex-changed Y-Zeolite N-isopropylidenemethylamine. Y 80%. - This is the first synthesis of a heteroatom-functional org. compd. of broad synthetic utility that is not equally or better catalyzed by a non-zeolitic material. F. e. s. R. S. Neale, L. Elek, and R. E. Malz, Jr., J. Catal. 27, 432 (1972). 

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