Acetoxy group

Figure C2.4.13. Thiol-tenninated hexasaccharide, where acetoxy groups can be replaced by hydroxyl groups, botlr before and following adsorjDtion [221],...

Allylic acetoxy groups can be substituted by amines in the presence of Pd(0) catalysts. At substituted cyclohexene derivatives the diastereoselectivity depends largely on the structure of the palladium catalyst. Polymer-bound palladium often leads to amination at the same face as the aoetoxy leaving group with regioselective attack at the sterically less hindered site of the intermediate ri -allyl complex (B.M. Trost, 1978). 

Unsymmetrically substituted dipyrromethanes are obtained from n-unsubstitued pyrroles and fl(-(bromomethyl)pyiToIes in hot acetic acid within a few minutes. These reaction conditions are relatively mild and the o-unsubstituted pyrrole may even bear an electron withdrawing carboxylic ester function. It is still sufficiently nucleophilic to substitute bromine or acetoxy groups on an a-pyrrolic methyl group. Hetero atoms in this position are extremely reactive leaving groups since the a-pyrrolylmethenium( = azafulvenium ) cation formed as an intermediate is highly resonance-stabilized. 

It is possible to prepare 1-acetoxy-4-chloro-2-alkenes from conjugated dienes with high selectivity. In the presence of stoichiometric amounts of LiOAc and LiCl, l-acetoxy-4-chloro-2-hutene (358) is obtained from butadiene[307], and cw-l-acetoxy-4-chloro-2-cyclohexene (360) is obtained from 1.3-cyclohexa-diene with 99% selectivity[308]. Neither the 1.4-dichloride nor 1.4-diacetate is formed. Good stereocontrol is also observed with acyclic diene.s[309]. The chloride and acetoxy groups have different reactivities. The Pd-catalyzed selective displacement of the chloride in 358 with diethylamine gives 359 without attacking allylic acetate, and the chloride in 360 is displaced with malonate with retention of the stereochemistry to give 361, while the uncatalyzed reaction affords the inversion product 362. 

Vinyl acetate reacts with the alkenyl triflate 65 at the /3-carbon to give the 1-acetoxy-1,3-diene 66[68]. However, the reaction of vinyl acetate with 5-iodo-pyrimidine affords 5-vinylpyrimidine with elimination of the acetoxy group[69]. Also stilbene (67) was obtained by the reaction of an excess of vinyl acetate with iodobenzene when interlamellar montmorillonite ethylsilyl-diphenylphosphine (L) palladium chloride was used as an active catalyst[70]. Commonly used PdCl2(Ph3P)2 does not give stilbene. 

The rather unreactive chlorine of vinyl chloride can be displaced with nucleophiles by the catalytic action of PdCb. The conversion of vinyl chloride to vinyl acetate (797) has been studied extensively from an industrial standpoint[665 671]. DMF is a good solvent. 1,2-Diacetoxyethylene (798) is obtained from dichloroethylene[672]. The exchange reaction suffers steric hindrance. The alkenyl chloride 799 is displaced with an acetoxy group whereas 800 and 801 cannot be displaccd[673,674]. Similarly, exchange reactions of vinyl chloride with alcohols and amines have been carried out[668]. 

In some instances, the resist polymer can be prepared in a single step by direct polymerization of the protected monomer(s) (37,88), entirely avoiding the intermediate PHOST. HOST-containing resist polymers have also been prepared by free-radical copolymerization of a latent HOST and a stable, acid-labile monomer, eg, the copolymerization of acetoxystyrene with tert-huty acrylate, followed by selective removal of the acetoxy group (89) (Fig. 30). 

Nitrogen nucleophiles used to diplace the 3 -acetoxy group include substituted pyridines, quinolines, pyrimidines, triazoles, pyrazoles, azide, and even aniline and methylaniline if the pH is controlled at 7.5. Sulfur nucleophiles include aLkylthiols, thiosulfate, thio and dithio acids, carbamates and carbonates, thioureas, thioamides, and most importandy, from a biological viewpoint, heterocycHc thiols. The yields of the displacement reactions vary widely. Two general approaches for improving 3 -acetoxy displacement have been reported. One approach involves initial, or in situ conversion of the acetoxy moiety to a more facile leaving group. The other approach utilizes Lewis or Brmnsted acid activation (87). 

Conversion to a more facile, sulfur-derived, leaving group can be achieved by treatment with sodium thiosulfate or salts of thio and dithio acids (75,87). Under anhydrous conditions, boron tribromide converts the 3 -acetoxy group to a bromide whereas trimethyl silyl iodide gives good yields of the 3 -iodide (87,171,172). These 3 -halides are much more reactive, even when the carboxyl group is esterified, and can be displaced readily by cyano and by oxygen nucleophiles (127). 

Attempted displacement of the acetoxy group with Grignard reagents gives very poor yields of 4-alkylazetidin-2-ones however, treatment of the 4-sulfonylazetidin-2-ones (92)... 

Compounds in which conformational, rather than configurational, equilibria are influenced by the anomeric effect are depicted in entries 4—6. Single-crystal X-ray dilfiaction studies have unambiguously established that all the chlorine atoms of trans, cis, ira j-2,3,5,6-tetrachloro-l,4-dioxane occupy axial sites in the crystal. Each chlorine in die molecule is bonded to an anomeric carbon and is subject to the anomeric effect. Equally striking is the observation that all the substituents of the tri-0-acetyl-/ -D-xylopyranosyl chloride shown in entry 5 are in the axial orientation in solution. Here, no special crystal packing forces can be invoked to rationalize the preferred conformation. The anomeric effect of a single chlorine is sufficient to drive the equilibrium in favor of the conformation that puts the three acetoxy groups in axial positions. 

Sometimes reduction of a ketone by NaBH4 is accompanied by hydrolysis of an ester elsewhere in the molecule. Norymberski found that a 20-keto-21-acetoxy compound with NaBH4 in methanol at 0° for 1 hour gives the 20/ ,21-diol. 50 % aqueous dimethylformamide has been used as the solvent in an attempt to prevent acetate hydrolysis, but sometimes under these conditions the 21-acetoxy group migrates to the 20-position. The rearrangement is favored by addition of the 20-acetate as seeds or by addition of... 

A 21-acetoxy group stabilizes a 20-ketal with respect to a A -3-ketal, so that the latter group is cleaved selectively [(38) (39)]. 

A 17a-hydroxyl group reduces the reactivity of the 20-ketone but direct ketalization with ethylene glycol is not impeded, Ketalization can also be effected in the presence of 17a- and/or 21-hydroxy substituents. Thus the 3,20-biscycloethyleneketal (88) is obtained from (87) in high yield by the direct procedure, or better by distillation under vacuum without a diluent. A bromine atom at C-17 and a 21-acetoxy group even in the absence of a 17a-hydroxyl group strongly hinder ketalization at C-20. ... 

An acetoxy group at C-21 inhibits reaction of the 20-ketone with semi-carbazide hydrochloride,but in buffered medium 20-semicarbazones can be prepared in high yield even from 17-hydroxy-21-acetoxy compounds. ... 

In the case of the 3a-acetoxy-5a,6a-epoxide (33), the electronic and conformational factors are opposed to each other. Thus, the energy of the system is lowered when the axial 3a-acetoxy group is permitted to become... 

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