Isopropenyl acetate, acylation

Isocrotonic acid, 53, 123 (+)-ISOPINOCAMPHEOL, 52, 59 Isopropenyl acetate, acylation of, 52, 1... 

Acetylsucrose [63648-81-7] has been prepared in 40% yield by direct acetylation of sucrose using acetic anhydride in pyridine at 40° C (36). The 6-ester has subsequently been obtained in greater than 90% yield, by way of 4,6-cycHc orthoacetate. Other selective methods for the 6-acylated derivatives include the use of alkyl tin reagents such as dibutyl tin oxide (37) and of dibutyl stannolane derivatives (38). Selective acetylation of sucrose by an enzymic process has also been described. Treatment of sucrose with isopropenyl acetate in pyridine in the presence of Lipase P Amano gave, after chromatography, 6-0-acetylsucrose (33%) and 4/6-di-O-acetylsucrose (8%). The latter compound has been obtained in 47% yield by the prolonged treatment (39). 

Enol esters are another useful family of acylating agents. The acetate of the enol form of acetone, isopropenyl acetate, is the most commonly used member of this group of... 

In 1992, Oda et al. reported a one-pot synthesis of optically active cyanohydrin acetates from aldehydes, which were converted to the corresponding racemic cyanohydrins through transhydrocyanation with acetone cyanohydrin, catalyzed by a a strongly basic anion-exchange resin [46]. The racemic cyanohydrins were acetylated by a lipase from P. cepacia (Amano) with isopropenyl acetate as the acyl donor. The reversible nature of the base-catalyzed transhydrocyanation enabled continuous racemization of the unreacted cyanohydrins, thereby effecting a total conversion (Figure 4.21). 

Hence, enol esters such as isopropenyl acetate are good acylating agents for alcohols. Isopropenyl acetate can also be used to convert other ketones to the corresponding enol acetates in an exchange reaction ... 

With a less reactive olefin such as isopropenyl acetate, diazoketone 86 gives only a low yield of cyclopropane 90 a-acyl enol ether 92, resulting from an intramolecular rearrangement of the ketocarbenoid, becomes the favored reaction product. If 91... 

In the presence of an active acyl donor such as isopropenyl acetate, a reductive acetylation of a ketone can be performed in the presence of MPVO catalysts... 

In conjunction with the establishment of the cyanohydrin DCL, the DCR process was subsequently addressed. Thus, selected lipases and a suitable acyl donor [isopropenyl acetate (34)] were applied to the system (Scheme 6.7). This selective enzymatic resolution of the DCL provided cyanoacetate product (35) as the major product at the reaction conditions used, thus demonstrating the efficiency of the concept. 

The diacylation of isopropenyl acetate with anhydrides of dicarboxylic acids is applicable for the synthesis of several other cyclic jS-triketones in moderate yield. - It has been used for the synthesis of 2-acetylcyclohexane-l,3-dione (40% yield), 2-acetyl-4-methylcyclopentane-l,3-dione (10% yield), 2-acetyl-4,4-dimethylcyclopentane-l,3-dione (10% yield), 2-acetyl-5,5-dimethylcyclohexane-l,3-dione (10% yield), 2-acetylcyclo-heptane-l,3-dione (12% yield) and 2-acetylindane-l,3-dione (26% yield). Maleic anhydrides under more drastic conditions give acetylcyclopent-4-ene-l,3-diones in yields from 5% to 12%. The corresponding acylation of the enol acetate of 2-butanone with succinic anhydride has been used to prepare 2-methylcyclopentane-l,3-dione, an important intermediate in steroid synthesis. - ... 

Irreversible Transesterification. A new preparation of chiral glycerol acetonide (2,2-dimethyl-l,3-dioxolane-4-methanol) involving an enantioselective hydrolysis of 2-0-benzylycerol diacetate to the (R)-monoacetate catalyzed by a lipoprotein lipase (47) has recently been developed. In an effort to prepare the (S)-enantiomer, we have used the aforementioned irreversible transesterification reaction using isopropenyl acetate as an acylating reagent, which upon reaction gives acetone as a... 

DKR of secondary alcohol is achieved by coupling enzyme-catalyzed resolution with metal-catalyzed racemization. For efficient DKR, these catalyhc reactions must be compatible with each other. In the case of DKR of secondary alcohol with the lipase-ruthenium combinahon, the use of a proper acyl donor (required for enzymatic reaction) is parhcularly crucial because metal catalyst can react with the acyl donor or its deacylated form. Popular vinyl acetate is incompatible with all the ruthenium complexes, while isopropenyl acetate can be used with most monomeric ruthenium complexes. p-Chlorophenyl acetate (PCPA) is the best acyl donor for use with dimeric ruthenium complex 1. On the other hand, reaction temperature is another crucial factor. Many enzymes lose their activities at elevated temperatures. Thus, the racemizahon catalyst should show good catalytic efficiency at room temperature to be combined with these enzymes. One representative example is subtilisin. This enzyme rapidly loses catalytic activities at elevated temperatures and gradually even at ambient temperature. It therefore is compatible with the racemization catalysts 6-9, showing good activities at ambient temperature. In case the racemization catalyst requires an elevated temperature, CALB is the best counterpart. 

Significantly improved DKR was reported by Backvall et al. who used diruthenium complex 1 together with CALB [8]. This work demonstrated for the first time the superiority of PCPA as the acyl donor over popular acyl donors such as vinyl and isopropenyl acetate. The DKR of 1-phenylethanol by this procedure afforded optically pure (R)-l-phenylethyl acetate in a high yield (Scheme 1.9) [8b]. 

An interesting innovation involves the use of isopropenyl acetate or acetic anhydride to accomplish irreversible acyl transfer63, as exemplified in the resolution of 1-phenylethanol (12) and the amino diol derivative 3- cr/ butyl-5-(2-hydroxyethyl)-2-oxazolidinone (14) ( ) ... 

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. 

Kinetic resolution of some more complex arylalkylcarbinols have also been achieved by acylation with isopropenyl acetate catalyzed by CALB (Scheme 4.21)... 

Below -ester products 85-92 via CALB-catalyzed acylation of rac-alcohols, isopropenyl acetate, room temp, until 50% conversion. Then Mitsunobu reaction ( DIAD, TPP, CH3COOH, ether 0 -> 20 °C, 24 h) ... 

The application of enzymatic acylation for the resolution of racemic alcohols in organic solvent has shown to be an effective method to rapidly synthesize chiral alcohols. The racemic alcohols are treated with the lipase and acylating agent one enantiomer remains unconverted whereas the second enantiomer is esterified and easily separated by distillation (Scheme 7.2). Vinyl acetate or isopropenyl acetate are typical acylating agents, as the generated vinyl alcohol tautomerizes rapidly... 

Primary alcohols have been successfully used as substrates for lipases. Monterde et. Al60 reported the resolution of the chiral auxiliary 2-methoxy-2-phenylethanol 1 via Candida antarctica lipase B (CAL-B)-catalyzed acylation using either vinyl acetate (R=H) or isopropenyl acetate (R= CH3) as acyl donor (cf. fig. 8) and the alkoxycarbonylation using diallyl carbonate as the alkoxycarbonylation agent in THF at 30 °C (cf. fig. 9). 

Figure 8 Lipase-catalyzed enantioselective acylation of 2-methoxy-2-phenylethanol (rac-1) using either vinyl acetate or isopropenyl acetate as acyl donor.

Numerous examples can be found in literature and only a few selected examples are included in this survey. Schurig et al reported a series of reports about the utility of isopropenyl acetate as an innocuous acyl donor in the lipase-catalyzed transesterification of secondary alcohols. The non-reacting alcohol enantiomers were obtained in > 99%... 

Figure 14 Lipase-catalyzed transesterification of secondary alcohols using isopropenyl acetate as acyl donor in...

Figure 15 Gas chromatographic chiral separation of (left) racemic l-(4-methoxy-phenyl)ethanol 22 and its corresponding acetate 22a (reference) and (right) lipase-catalyzed transesterification of l-(4-methoxy-phenyl)ethanol 22 (4 hrs) using isopropenyl acetate as acyl donor in toluene as organic solvent ees= 99.9 eep= 87 conv. =53.4, E=141.

In order to reduce the time needed to perform a complete kinetic resolution Lindner et al53 reported the use of the allylic alcohol 30 in enantiomerically enriched form rather than a racemic mixture in kinetic resolution. Thus, the kinetic resolution of 30 was performed starting from the enantiomerically enriched alcohol (R) or (S)-30 (45%) ee obtained by the ruthenium-catalyzed asymmetric reduction of 32 with the aim to reach 100 % ee in a consecutive approach. Several lipases were screened in resolving the enantiomerically enriched 30 either in the enantioselective transesterification of (<5)-30 (45% ee) using isopropenyl acetate as an acyl donor in toluene in non-aqueous medium or in the enantioselective hydrolysis of the corresponding acetate (R)-31, (45% ee) using a phosphate buffer (pH = 6) in aqueous medium. An E value of 300 was observed and the reaction was terminated after 3 h yielding (<5)-30 > 99% ee and the ester (R)-31 was recovered with 86% ee determined by capillary GC after 50 % conversion. 

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. 

A set of -methylene-/ -hydroxy esters 42 were resolved via enzymatic enantioselective transesterification with Pseudomonas sp. lipase (PCL), free and immobilized one using either vinyl or isopropenyl acetate as acyl donors under different conditions. The corresponding (R)-(+)-acetates (R)-43 and the unreacted (S)-(-)-substrates (S)-42 were obtained with an ee up to >99%.70... 

Ghanem, A. Schurig, V. Lipase-catalyzed transesterification of secondary alcohols using isopropenyl acetate as acyl donor in organic solvents. Monateshefte fur chemie, 2003, 134, 1151-1157. 

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