Transition Metal-catalyzed Acylation

In the presence of a catalytic amount of palladium complex 162a, acylation of al- 

Acylsilanes are available for intramolecular acylation of alkynes under catalysis 

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The insertion of unsaturated molecules into metal-carbon bonds is a critically important step in many transition-metal catalyzed organic transformations. The difference in insertion propensity of carbon-carbon and carbon-nitrogen multiple bonds can be attributed to the coordination characteristics of the respective molecules. The difficulty in achieving a to it isomerization may be the reason for the paucity of imine insertions. The synthesis of amides by the insertion of imines into palladium(II)-acyl bonds is the first direct observation of the insertion of imines into bonds between transition metals and carbon (see Scheme 7). The alternating copolymerization of imines with carbon monoxide (in which the insertion of the imine into palladium-acyl bonds would be the key step in the chain growth sequence), if successful, should constitute a new procedure for the synthesis of polypeptides (see Scheme 7).348... 

N-Acyl-a-amino acids are important compounds in both chemistry and biology. They are easily obtained in a transition metal-catalyzed, three-component domino reaction of an aldehyde, an amide, and CO. Whereas cobalt was mainly used for this process, Beller and coworkers [159] have recently shown that palladium has a... 

Recently, two new P- and C-chiral monodentate phosphines 13 were reported. The ligands were applied in a number of transition metal-catalyzed reactions, though ee-values in the rhodium-catalyzed hydrogenation of N-acyl dehydrophenylalanine were only moderate [37]. 

Many such activated acyl derivatives have been developed, and the field has been reviewed [7-9]. The most commonly used irreversible acyl donors are various types of vinyl esters. During the acylation of the enzyme, vinyl alcohols are liberated, which rapidly tautomerize to non-nucleophilic carbonyl compounds (Scheme 4.5). The acyl-enzyme then reacts with the racemic nucleophile (e.g., an alcohol or amine). Many vinyl esters and isopropenyl acetate are commercially available, and others can be made from vinyl and isopropenyl acetate by Lewis acid- or palladium-catalyzed reactions with acids [10-12] or from transition metal-catalyzed additions to acetylenes [13-15]. If ethoxyacetylene is used in such reactions, R1 in the resulting acyl donor will be OEt (Scheme 4.5), and hence the end product from the acyl donor leaving group will be the innocuous ethyl acetate [16]. Other frequently used acylation agents that act as more or less irreversible acyl donors are the easily prepared 2,2,2-trifluoro- and 2,2,2-trichloro-ethyl esters [17-23]. Less frequently used are oxime esters and cyanomethyl ester [7]. S-ethyl thioesters such as the thiooctanoate has also been used, and here the ethanethiol formed is allowed to evaporate to displace the equilibrium [24, 25]. Some anhydrides can also serve as irreversible acyl donors. 

Transition-metal catalyzed transfer of acylcarbenes to nitriles leads to 1,3-oxazoles via nitrile ylide intermediates123. The corresponding nitrile ylide chemistry derived from acyl(silyl)carbenes still awaits a closer look, but it has been shown that the rhodium-catalyzed decomposition of 198 in the presence of methyl cyanoformate and benzaldehyde provides 1,3-oxazole 221 (equation 71) exclusively120. This implies that the carbene moiety has been transferred only to the nitrile but not to the aldehyde. 

The hydroacylation of olefins with aldehydes is one of the most promising transformations using a transition metal-catalyzed C-H bond activation process [1-4]. It is, furthermore, a potentially environmentally-friendly reaction because the resulting ketones are made from the whole atoms of reactants (aldehydes and olefins), i.e. it is atom-economic [5]. A key intermediate in hydroacylation is a acyl metal hydride generated from the oxidative addition of a transition metal into the C-H bond of the aldehyde. This intermediate can undergo the hydrometalation ofthe olefin followed by reductive elimination to give a ketone or the undesired decarbonyla-tion, driven by the stability of a metal carbonyl complex as outlined in Scheme 1. 

The method of combined enzyme- and transition metal-catalyzed reactions widely applied to the DKR of secondary alcohols has also been applied to the DKR of a-hydroxy acid esters rac-1. The principle is based on the enantioselective acylation catalyzed by Pseudomonas species lipase (PS-C from Amano Ltd) using p-Cl-phenyl acetate as an acyl donor in cyclohexane combined with in situ racemization of the non-acylated enantiomer catalyzed by ruthenium compounds [7]. Under these conditions, various a-hydroxy esters of type 1 were deracemized in moderate to good yields and high enantioselectivity (Scheme 13.2). 

Intramolecular transition metal-catalyzed hydro acylation reactions have opened up a new area of synthesizing cyclic ketones. This reaction can also be extended to intermolecular addition reactions. Miller et al. found the first example of an intermolecular hydroacylation of an aldehyde with an olefin giving ketones, when they were studying the mechanism of the rhodium-catalyzed intramolecular cyclization of 4-pentenal using ethylene-saturated chloroform as the solvent (Eqs.46,50) [112]. 

Photochemical decomposition of diazo(trimethylsilyl)methane (1) in the presence of alkenes has not been thoroughly investigated (see Houben-Weyl Vol. E19b, p 1415). The available experimental data [trimethylsilylcyclopropane (17% yield) and la,2a,3j8-2,3-dimethyl-l-trimethylsilylcyclopropane (23% yield)] indicate that cyclopropanation occurs only in low yield with ethene and ( )-but-2-ene. In both cases the formal carbene dimer is the main product. In reactions with other alkenes, such as 2,3-dimethylbut-2-ene, tetrafluoroethene or hexafluoro-propene, no cyclopropanes could be detected.The transition-metal-catalyzed decomposition of diazo(trimethylsilyl)methane (1) has been applied to the synthesis of many different silicon-substituted cyclopropanes (see Table 3 and Houben-Weyl Vol.E19b, p 1415) 3.20a,b,2i.25 ( iQp. per(I) chloride has been most commonly used for carbene transfer to ethyl-substituted alkenes, cycloalkenes, styrene, and related arylalkenes. For the cyclopropanation of acyl-substituted alkenes, palladium(II) chloride is the catalyst of choice, while palladium(II) acetate was less efficient, and copper(I) chloride, copper(II) sulfate and rhodium(II) acetate dimer were totally unproductive. The cyclopropanation of ( )-but-2-ene represents a unique... 

Consequently, pyridine has a reduced susceptibility to electrophilic substitution compared to benzene, while being more susceptible to nucleophilic attack. One unique aspect of pyridine is the protonation, alkylation, and acylation of its nitrogen atom. The resultant salts are still aromatic, however, and they are much more polarized. Details for reactivity of pyridine derivatives, in particular, reactions on the pyridine nitrogen and the Zincke reaction, as well as C-metallated pyridines, halogen pyridines, and their uses in the transition metal-catalyzed C-C and C-N cross-coupling reactions in drug synthesis, will be discussed in Section 10.2. 

Transition metal-catalyzed reductive acylation, coupHng, amination, and cycHzation reactions of oximes and their derivatives 13CJ066. Transition-metal-catalyzed synthesis of aromatic ketones via direct C—H bond activation 12S677. 

I 7 7 Mechanistic Aspects of Transition Metal-Catalyzed Direct Acylation Reactions O O... 

Functionalization of Azaferrocene Catalysts. Chiral azaferrocenes are highly useful in enantioselective acylation as nucleophilic catalysts, and in transition metal-catalyzed asymmetric reactions as chiral ligands. Enantioselective lithiation of an azaferrocene moiety followed by functionalization with (TMS0)2 resulted in a lateral hydroxyl-substituted product with excellent optical purity, but in poor yield (eq 7). The low yield was attributed to the poor reactivity of (TMSO)2 toward the labile azaferrocene substrate. 

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