Regioselective acylating agents

The most interesting point in this reaction is its regioselectivity. Theoretically, the acylating agent (the palladinm-acyl intermediate) conld react either with the NH or the OH group of the hydroxylamine derivative. The regioselectivity of the reaction appears to be strongly influenced by the nature of both the substrate and solvent. 

Regioselective Acylation of Drug Intermediate for an Antileukaemic Agent... 

Another example of regioselective acylation was required for a ribavirin antiviral agent (44) used in combination with a-2-[3-interferon to treat hepatitis C (Scheme... 

Scheme 7.18 Regioselective acylation to synthesize the alanine ester of ribavirin, an antiviral agent.

A part from vinyl acetate, vinyl benzoate was used as acylating agent in the Mucor miehei lipase (MML) and Candida antarctica lipase (CAL)-catalysed benzoylation of 1,2-diols in organic solvents 87.87 The reaction proceeded with high regioselectivity and moderate enantioselectivity. 

Unsymmetric diamines can sometimes be acylated selectively at one amino group only, if one of the amino groups is sterically or electronically deactivated. If the difference in reactivity is only small, acylating agents of low reactivity will usually be required. Some polyamino heteroarenes can be monoacylated or monoalkylated with astonishingly high regioselectivity (Scheme 7.13), which is, however, difficult to predict. 

Aminophenols can be selectively esterified by deprotonation of the hydroxyl group followed by treatment with an acylating reagent of low reactivity (Scheme 7.17). Treatment with a strong acylating agent under acidic conditions will also result in clean esterification. In the presence of weak bases the regioselectivity of the acyla-... 

Regioselective reactions in systems which contain multiple functional groups are an area ideally suited for biocatalysis. Linhardt and co-workers at the University of Iowa s Division of Medicinal and Natural Products Chemistry recently published the synthesis of a series of 1 -O-acyl sucrose derivatives [31], Using Chiro-CLEC -BL (the CLC of subtilisin) and vinyl esters of the acylating agent in pyridine as solvent, the authors prepared l -O-lauryl sucrose, l -O-myristyl sucrose, and l -O-stearyl sucrose in 80-90% yield (Fig. 9). Their method represents a green alternative to the tin chemistry previously used [32],... 

The levulinoyl esters are prepared from the free hydroxyl group by treatment of levulinic acid with DCC [255,256] or l-[3-(dimethylamino)propyl]-3-ethylcarbodiimide hydrochloride (EDAC) [257] in the presence of DMAP (O Scheme 38). Additionally, 3 - and 5 -0-levulinyl protected derivatives of 2 -deoxy nucleosides have been prepared by regioselective enzymatic acylation using a variety of lipases and acetonoxime levulinate as acylating agent [258]. In contrast to other ester substituents, the 0-levulinoyl group is far less prone to migration [259]. 

Acylation at a methyl group in an unsymmetrical ketone, e.g. 15 usually occurs regioselectively even with traditional methods (ester as acylating agent, corresponding alkoxide as base). We shall return to this subject in chapter 10 with other specific enol equivalents, but you can see already that virtually any 1,3-diketone can be made by one of these methods. 

In contrast to castanospermine, 1-deoxynojirimicine 160 contains a primary hydroxy group as well as a much more nucleophilic amino function. If a small excess of trifluoroethyl butanoate is employed, subtilisin converts this alkaloid preferably into the 6-monoester 161 (Fig. 18-22)1266). However, with 6 equiv. of the acylating agent, the 2,6-diester 162 is formed in 77% yield. This diester 162 may be subsequently deacylated regioselectively at the 6-position by means of several different enzymes. 

The silyl group in allylsilanes exerts a strong influence on the regioselectivity of reactions with a variety of electrophiles, and acylating agents in particular. 

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