Aromatic acyl donors

A potential liability associated with such reductive hydroacylations resides in the fact that only one acyl residue of the symmetric anhydride is incorporated into the coupling product. For more precious carboxylic acids, selective acyl transfer from mixed anhydrides is possible. Mixed anhydrides derived from pivalic acid are especially convenient, as they may be isolated chromato-graphically in most cases. In practice, mixed anhydrides of this type enable completely branch-selective hydroacylation with selective delivery of the aromatic and a,()-unsalurated acyl donors (Scheme 19). 

Scheldt and co-workers have also illustrated the oxidation of activated alcohols to esters [132], Oxidations of alcohols such as 260 provide the electrophile (acyl donor) for a nucleophilic alcohol 261. Esters 262 are derived from propargylic, allylic, aromatic, and hetero-aromatic substrates (Table 20). The nucleophilic alcohol scope includes MeOH, n-BuOH, f-BuOH, 2,2,2-trichloroethanol, 2-methoxyethanol, and 2-(trimethylsilyl) ethanol. 

This process has many benefits in the context of green chemistry it involves two enzymatic steps, in a one-pot procedure, in water as solvent at ambient temperature. It has one shortcoming, however-penicillin acylase generally works well only with amines containing an aromatic moiety and poor enantioselectivities are often observed with simple aliphatic amines. Hence, for the easy-on/easy-off resolution of aliphatic amines a hybrid form was developed in which a hpase [Candida antarctica hpase B (CALB)] was used for the acylation step and peniciUin acylase for the deacylahon step [22]. The structure of the acyl donor was also optimized to combine a high enanhoselectivity in the first step with facile deacylation in the second step. It was found that pyridyl-3-acetic acid esters gave optimum results (see Scheme 6.8). 

As demonstrated in Scheme 3, the ThDP-bound active aldehyde 6 as an acyl-donor may be added to a second aldehyde cosubstrate (acyl-acceptor) in an acyloin condensation-type reaction. This carboligase reaction was intensively investigated with acetaldehyde as an acyl-donor, which may be either condensed to a further acetaldehyde molecule yielding acetoin [1,26,27,29,63,153,154] or to a wide range of various aliphatic, aromatic and heterocyclic aldehydes [5,14,118,151,154-157,161]. 

Wielechowska et al67 reported the lipase-catalysed transesterification of l-alkylthio-3-aryloxypropan-2-ols 37 having various aromatic substituents using either vinyl or isopropenyl acetate as acyl donors in various organic solvents. The resulting product (S)-38 was obtained with ee up to 91% while the remaining unreacted substrate (R)-37 was recovered with an ee up to 85% depending on the substituents. 

In order to broaden the scope we also examined [30] a combination of lipase-catalyzed acylation with penicillin acylase-catalyzed hydrolysis (deacylation). Good results (high enantioselectivity in the acylation and smooth deacylation) were obtained, with a broad range of both aliphatic amines and amines containing an aromatic moiety, using pyridylacetic acid ester as the acyl donor (Fig. 9.21). 

Catalytic acylation of electron-rich aromatics is achieved with a combination of InCls and silver perchlorate (Scheme 8.114) [157]. Acetic anhydride, acetyl chloride and isopropenyl acetate serve as satisfactory acyl donors. By using an InCl3-impreg-nated Si-MCM-41 catalyst at low concentration, acylation of aromatic compounds (benzene, toluene, p-xylene, mesitylene, anisole, naphthalene, methylnaphfhalene, and methoxynaphfhalene) by acyl chlorides (benzoyl chloride, phenylacetyl chloride, propionyl chloride, or butyryl chloride) can be accomplished rapidly (3 h) at 80 °C in high yield, even in the presence of moisture in the aromatic substrate or solvent (dichloroethane) (Scheme 8.115) [158], In(OTf) j is an efficient catalyst in the sulfonylation of both activated and deactivated aromatic compounds (Scheme 8.116) [159]. 

Transacylation. Silyl esters behave as acyl donors to amines in the presence of the dual-catalyst system and the aromatic anhydride. Silyl ethers instead of the alcohols can be converted to esters under these conditions, and for lactonization, a similar system (AgC104 instead of AgOTf) is effective. 

Lipases were used in organic medium for the resolution of several aliphatic and aromatic cyanohydrins (Scheme 4.8). The study demonstrated the impact of molecular sieves, different acyl donors, temperature and variable organic solvents. High enantioselectivities (E > 200) were obtained using lipase PS-30 in the presence of 4 A molecular sieves, diethyl ether as solvent at 15 °C and vinyl acetate as acyl donor [13]. 

In 2002, a novel aminocyclopentadienyl ruthenium chloride complex was introduced by Park s group involving a new mode of catalytic racemisation which allowed use of the more reactive isopropenyl acetate as an acyl donor and much less lipase. This catalytic system was particularly efficient for the DKR of various aliphatic or aromatic alcohols as shown in Scheme 4.9. Not only simple alcohols, but also functionalised alcohols such as allylic alcohols, alkynyl alcohols, diols, hydroxyl esters and chlorohydrins were successfully transformed into the corresponding chiral acetates. ... 

In 2005, Trauthwein s group reported the synthesis of an easy-to-handle and stable racemisation catalyst for secondary alcohols by an in situ mixture of readily available [Ru(p-cymene)Cl2]2 with chelating aliphatic amines. Optimisation of the reaction revealed that A7,A7,A7 A7 -tetramethyl-l,3-propanedia-mine as the ligand racemised aromatic alcohols completely within five hours. The combination of this catalyst with lipase CAL-B showed a good performance for the DKR of various alcohols in the presence of p-chlorophenyl acetate as the acyl donor, as shown in Scheme 4.14. 

Fu et al. were the first to develop an efficient catalytic system for the KR of primary amines [120], Their method relied on the use of a stoichiometric amount of the O-acylated azlactone 111 as the achiral acyl donor in conjunction with a catalytic amount of a planar chiral DMAP derivative 112. Hence, after optimizing the reaction conditions, they were able to resolve various racemic primary aryl alkyl amines with moderate to good selectivities ranging from s = 11 to 27 independently of the substitution pattern on the aromatic ring or on the alkyl chain (Scheme 41.43). 

The resolution of primary amines with long-chain esters and their corresponding carboxylic acids has been less explored in comparison with the use of EtOAc and alkyl methoxyacetates. However, lauric acid (CJJH23CO2H) has served as an ideal acyl donor for the CAL-B-catalyzed resolution of aliphatic and aromatic amines at 80 °C using heptane as solvent (Figure 9.25) [196]. The use of carboxylic acids led to a marked acceleration of the reaction rates compared to their ethyl ester coxmterparts. 

The reaction is initiated by formation of a donor-acceptor complex 4 from acyl chloride 2, which is thereby activated, and the Lewis acid, e.g. aluminum trichloride. Complex 4 can dissociate into the acylium ion 5 and the aluminum tetrachloride anion 4 as well as 5 can act as an electrophile in a reaction with the aromatic substrate ... 

More than 25 different substituted urea herbicides are currently commercially available [30, 173]. The most important are phenylureas and Cycluron, which has the aromatic nucleus replaced by a saturated hydrocarbon moiety. Benzthiazuron and Methabenzthiazuron are more recent selective herbiddes of the class, with the aromatic moiety replaced by a heterocyclic ring system. With the exception of Fenuron, substituted ureas (i.e., Diuron, Fluometuron, Fig. 10, Table 3) exhibit low water solubilities, which decrease with increasing molecular volume of the compound. The majority of the phenylureas have relatively low vapor pressures and are, therefore, not very volatile. These compounds show electron-donor properties and thus they are able to form charge transfer complexes by interaction with suitable electron acceptor molecules. Hydrolysis, acylation, and alkylation reactions are also possible with these compounds. 

Many other compounds are involved in flavonoid biosynthesis in some species, for example, as donors for methylation or aromatic or aliphatic acylation. For intact plants, these are generally accepted to be available in the cell for the reaction to proceed if the appropriate modification activity is present. 

Some Related Examples. A closely related problem is the rate behavior of aromatic donors in Friedel-Crafts acylation and analogous reactions. Here coordination plays a dual role. The initial Lewis acid which is added is taken up by the best donor species, frequently the substrate. Once this reaction is at equilibrium, additional amounts of Lewis acid can react with the other species present to generate the effective electrophile. The kinetic behavior of such systems was first delineated by Olivier in 1914. He studied the reactions ... 

In Friedel-Crafts acylation of aromatics with acid chlorides and Lewis acid metal halides the reactive electrophile is considered to be formed in the interaction of the reagent and the catalyst. First the highly polarized donor-acceptor complex 1 is formed, which can further give other complexes and ion pairs.24 The various... 

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