Selective reaction acylation

Acyl halides react with organometallic reagents without catalysts, but sometimes the Pd-catalyzed reactions give higher yields and selectivity than the Lincatalyzed reactions. Acyl halides react with Pd(0) to form the acylpalladium complexes 846, which undergo facile transmetallation. 

Interesting results have been obtained in intramolecular acylation reactions involving pyrrole and thiophene derivatives. A muscone synthesis involves selective intramolecular acylation at a vacant a-position (Scheme 18) (80JOC1906). In attempts to prepare 5,5-fused systems via intramolecular acylation reactions on to a jS-position of a thiophene or a pyrrole, in some cases ipso substitution occurs with the result that rearranged products are formed (Scheme 19) (82TH30200). 

This enolate can then react with a plethora of electrophiles, setting a new stereocenter by a diastereoface-selective reaction. The simplest electrophile to trap enolate 71 is H" ", which can, for example, originate from methanol [89] or diphenyl acetaldehyde (as a readily enolizable aldehyde) [90] leading to the acy-lated catalyst species (Fig. 38). The free catalyst is regenerated by acyl-group transfer to methanol(ate) or the aldehyde-derived enolate, producing methyl or enolesters 72/73 in good yields and enantioselectivities. 

Acyl azides show selectivity for acylation at secondary (rather than primary) hydroxyl groups in nucleosides. Thus, on reaction with an excess of N-(benzyIoxycarbonyl)glycyIglycyl azide in 1,4-dioxane-water at 8° and pH 9, adenosine gave the 2 (3 )-0-(aminoacyl) and 2, 3 -di-0-(aminoacyl) derivatives.183 Furthermore, adenosine and uridine were converted into a variety of 2 (3 )-esters of aromatic amino acids by reaction with the appropriate acyl azide.184... 

Syn stereoselectivity in reduction of acylic chiral ketoxime ethers of type 91 (equation 63) can be obtained using bulky tetramethylammonium triacetoxyborohydride that produces FeUdn-type products with high selectivity . Reaction of a-tolylsulfinylketoximes 92 (equation 64) with L-Selectride also results in syn products 93. 

In a kinetic study of the acylation of toluene, with p-xylene and the corresponding perdeutero compounds with aroyl triflates, correlation was found between the primary kinetic isotope effect and the ortho para ratio.35 Different conformations of the bent cr complexes36 for the two isomers resulted in a much higher rate of deprotonation and rearomatization for the para isomer. By appropriately selecting reaction conditions and thereby affecting the ratio of the two conformations, unusually high amounts of ortho products may be obtained.37,38... 

However, the reactivity of phenolic hydroxy groups can be modified by a fused heterocyclic ring. Thus, hydroxy groups peri to a carbonyl group, e.g. (600), are hydrogen bonded they do not react with diazomethane, and are difficult to acylate. This allows selective reactions in polyhydroxychromones. 

The 1,6-anhydride bond is rather stable toward bases, permitting not only highly selective reactions of free hydroxyl groups, such as acylation, sulfonylation, and alkylation by conventional methods, but also by selective nucleophilic attack of the oxirane ring. On the other hand, the 1,6-anhydride bond is cleaved in acid solutions (concurrently with the... 

The selectivity of acylations or alkylations of polyamines can also be modulated by protonation [78] or by conversion to cyclic aminals [71, 79, 80]. The latter strategy has, for instance, been used successfully for the preparation of monofunctionalized 1,4,7-triazacyclononanes (Scheme 10.18). In this reaction the first alkylation leads to the formation of an amidinium salt, which is more difficult to alkylate than a tertiary amine. Thus, the use of only one equivalent of alkylating agent leads to a clean monoalkylation. 

In a series of elegant studies, Miller and colleagues demonstrated that small peptides containing modified histidine residues (re-methyl-histidine) were effective catalysts for enantioselective acylation and phosphorylation reactions [12, 13]. As peptides in this family are able to transfer stereochemical information, these catalysts were also tested to carry out site- and regio-selective reactions, which take place against kinetic expectations. The screening of a small library (36 members)... 

Alcohol protection. Primary and secondary hydroxyl groups are esterified by 1 in the presence of pyridine (71-92% yield). The usual selectivity for acylation of primary versus secondary hydroxyl functions obtains. The resulting 2-di-bromomethylbenzoates 2 are deprotected under neutral conditions by silver perchlorate mediated hydrolysis to 2-formylbenzoate esters 3 (2,6-lutidine or 2,4,6-collidine is added to maintain a virtually neutral reaction medium). Addition of morpholine then leads to rapid dcacylation with release of the alcohol in high yield... 

Asymmetric Alkylation. 4-Pseudoephedrine ([IS, 2S]-(+)) is a commodity chemical employed in over-the-counter medications with annual worldwide production in excess of 300 metric tons. The enantiomer, /-pseudoephedrine, is also readily available in bulk and is inexpensive. Pseudoephedrine has been shown to be highly effective as a chiral auxiliary in asymmetric alkylation reactions. Treatment of either enantiomer of pseudoephedrine with carboxylic acid chlorides and anhydrides leads to efficient and selective iV-acylation to form the corresponding tertiary amide derivatives (Table 1). Typically, the only by-product in the acylation reactions is a small amount (<5%) of the A,0-diacylated product, which is easily removed by crystallization or flash column chromatography. Because intramolecular 0- -N acyl transfer within pseudoephedrine 3-amino esters occurs rapidly, and because the A-acyl form is strongly favored under neutral or basic conditions, products arising from (mono)acylation on oxygen rather than nitrogen are not observed. 

Acyl or acid chlorides are used frequently in amide formation as activated forms of the corresponding carboxylic acid. A wide selection of acyl chlorides is available commercially. Otherwise, they can be prepared readily from the corresponding carboxylic acid in the presence of reagents such as thionyl chloride (9), oxalyl chloride 5 (10), phosphorus trichloride (11), and phosphorus pentachloride (12). Reactions that use oxalyl chloride or thionyl chloride are promoted by the addition of a catalytic amount of DMF (13) (see Fig. 3). 

Homing and Muchowski have recently presented a modification of the general procedures described above. In an attempt to replace selectively the acyl halogen in 48 with azide ion, these authors examined the reactions of dimethylformamide-acyl halide complexes (49) with nucleophiles (equation 35). The site of attack of a nucleophile on the ambident cation (49) is markedly influenced by the nature of the solvent and the temperature. Control reactions with aniline as the nucleophile enabled the optimum conditions for attack at the acyl carbon atom to be elucidated. With azide ion under these conditions, acyl azides were obtained in 60-100% yield (based on... 

---