Isopropenyl acetate groups

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... 

A -Dien-3-ol esters e.g., acetates) have greater utility as reaction intermediates than as protecting groups. They are prepared from A" -3-ketones by reaction with the acetic anhydride"" or by exchange with isopropenyl acetate. 

An additional feature of this DKR is the use of isopropenyl acetate, which is readily available, more active than PCPA and easily separable from the DKR mixtures [26]. Although the mechanism of the catalytic racemization is not clear yet, according to our interpretation, it can be deduced that the amino group in 6 seems to play a crucial role in the racemization. 

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. 

Starting with tropone 330, the azido compound 331 was first synthesized, as shown in Scheme 55. Then, compound 331 was chemoselectively reduced to unsaturated amine 332 by Lindlar catalyst, and this material was elaborated to the meso carbamate 333, ready for enzymatic asymmetrization. Treatment of 333 with Amano P-30 lipase in the presence of isopropenyl acetate resulted in formation of the enantiomerically pure (>98% ee) monoacetate 334, the common intermediate to both calystegines 337 and ent-337. Using conventional chemistry, elaboration of the functional groups within tropane 334... 

A-Acylation is, of course, rendered more difficult by the presence of substituents in positions 1 and 9, owing to steric effects. Massie and Kadaba observed that 1-substituted derivatives may be acetylated with acetic anhydride in pyridine, but the use of anhydrous solvents throughout the synthesis and purification is required, since the products are very readily hydrolyzed. 1-Chloro-lO-acetylpheno-thiazine, for example, loses its acyl group even on pouring the reaction mixture into water. Isopropenyl acetate has been recommended by the same authors as an acetylating agent which is able to overcome the steric hindrance in 1-substituted phenothiazines. 

Bromination of androstan-i6-ones is complicated by rearrangements and by dibromination, but appears to favour 17a (pseudo-axial) attack initially. Enolisation of the 16-0x0 group is slow and inefficient compared with a 17-ketone, at least when isopropenyl acetate is used [x i], although the same (A ) double bond is produced. The enol acetate bromi-nates selectively at the lya-position [152]. The alternative enol acetate (A ) is formed in minor amount, and gives the 15 -bromoketone. Both 17a- and i5) -attack correspond to pseudo-axial approach of the reagent as required by stereo-electronic factors. 

The reagent is prepared in about 50% yield by reaction of malonic acid and acetone with either acetic anhydride - or isopropenyl acetate, in each case in the presence of a catalytic amount of sulfuric acid. This acetonide is a strong acid and can be hydrolyzed under very mild conditions . since the methylene group is... 

Progesterone (5) presents an interesting case. Moffett and Weisblat heated progesterone with isopropenyl acetate and p-toluenesulfonic acid monohydrate (TsOH) and obtained (6), in which the A -3-keto group has afforded a A - -dienol acetate... 

The esterases and lipases are members of a still larger group of enzymes that catalyze acyl transfer, either in the direction of solvolysis or by acylation of the substrate. Both types of enzymes are called hydrolases. In water, hydrolysis occurs, but in the presence of alcohols, transesterification can occur. Reactions in the acylation direction are done in the presence of acyl donors. Esters of enols such as vinyl acetate or isopropenyl acetate are often used as sources of the acyl group. These enol esters are more reactive than alkyl esters, and the enol that is displaced on acyl transfer is converted to acetaldehyde or acetone. To avoid side products arising from these carbonyl compounds, one can use 1-ethoxyvinyl esters, which give ethyl acetate as the by-product. ... 

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. ... 

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