Acetylation chemoselective

AC2O, BF3 Et20, THE, 0°. These conditions give good chemoselectivity for the most nucleophilic hydroxyl group. Alcohols are acetylated in the presence of phenols. 

Four years later, Nelson and Stoddart designed di- and tetra-valent lactosylated dendrons according to a convergent pathway and under mild and chemoselective conditions (Scheme 46).320 The strategy was based on the photochemical addition of hepta-0-acetyl-l-thio-/j-lactose (448) onto bisallyl trisaccharide 449 to form divalent adduct 450. Two nearly quantitative deprotection steps consisting in standard... 

The initially formed titanium enolate 80 adds, in a diastereoselective fashion, to the electrophilic center of the activated oxime. The generated adduct 81 cyclizes chemoselectively to afford the desired /f-azetine, which is converted, with retention of configuration, to the corresponding /3-amino carbonyl compounds 82 via 3V-acetylation followed by hydrolysis. 

Acid- and base-sensitive lipidated peptides can be selectively deprotected by enzymatic hydrolysis of choline esters.[13al Choline esters of simple peptides, but also of sensitive peptide conjugates like phos-phorylated and glycosylated peptides,1141 nucleopep-tides1151 and lipidated peptides,113,1631 can be cleaved with acetyl choline esterase (AChE) and butyryl choline esterase (BChE) under virtually neutral conditions with complete chemoselectivity. Acid-labile farnesyl groups and base-sensitive thioesters are not attacked. 

While a variety of techniques are available for the monoprotection of symmetrical diols, there are few methods that allow for the chemoselective functionalization of the more hindered hydroxyl in an unsymmetrical 1,3-diol.5 The acid-catalyzed reaction of an unsymmetrically substituted cyclic formal with acetyl chloride described here invariably proceeds via preferential rupture of the less congested C(2)-0 bond to give a product having an acetate at the less congested site... 

The total synthesis of the carbazomycins emphasizes the utility of the iron-mediated synthesis for the construction of highly substituted carbazole derivatives. The reaction of the complex salts 6a and 6b with the arylamine 20 leads to the iron complexes 21, which prior to oxidative cyclization have to be protected by chemoselective 0-acetylation to 22 (Scheme 13). Oxidation with very active manganese dioxide followed by ester cleavage provides carbazomycin B 23a [93] and carbazomycin C 23b [94]. The regioselectivity of the cyclization of complex 22b to a 6-methoxycarbazole is rationalized by previous results from deuterium labeling studies [87] and the regiodirecting effect of the 2-methoxy substituent of the intermediate tricarbonyliron-coordinated cyclo-hexadienylium ion [79c, 79d]. Starting from the appropriate arylamine, the same sequence of reactions has been applied to the total synthesis of carbazomycin E (carbazomycinal) [95]. 

Several methods were described for the selective de-S-acetylation of 0-acetyl protected 1-thioglycoses. Sodium methoxide in methanol at low temperature (below -20 °C) was known to afford mainly the de-S-acetylated compound [16] or exclusively this compound when the reaction was quenched at low temperature by adding H-l- resin [17]. Demercuration of tetra-O-acetyl-l-phenylmercury(II)-thio- -D-glucopyranose (12) (Scheme 4) obtained by treatment of (8e) with phenylmercury(II)acetate afforded a convenient synthesis of tetra-0-acetyl-l-thio-/3-D-glucose (8a) [18]. This sequence applied to the a-anomer (10a) (Scheme 3) led to the expected de-S-acetylated compound (10b) [19]. Chemoselective deprotection of thioacetate at the anomeric position of peracetylated 1-thioglycoses was also achieved in good yield by action of cysteamine in acetonitrile or hydrazinium acetate in DMF [20,11]. 

The 2(3/T)-oxazolone homopolymer 217 and the 2(37f)-oxazolone copolymer 219 with a carbon-carbon bond backbone structure are readily obtained by heating a 3-acyl-2(3/7)-oxazolone alone or with styrene, respectively, at 70 °C in the presence of BPO with the exclusion of air." " ° The A -acetyl polymers serve as regioselective and chemoselective acylating reagents for amines and alcohols (Fig. 5.53). ° ... 

When artemisinin 9a was treated with 2-lithiothiazole followed by in situ O-acetylation, the thiazole carbonyl adduct 161 was formed chemoselectively in good yield (Scheme 22) the same reaction with PhLi produced a mixture of uncharacterized products. When this acetyl adduct 161 was exposed to TMSOTf, the corresponding elimination product 162 was formed, which was converted in three steps without purification of intermediates into aldehyde 163. This was reacted with high chemoselectivity in reactions with organometallics ( -BuLi, PhMgBr) and with phosphonium ylides in a Wittig procedure <1999T3625>. 

AcOH, followed by hydrolysis, gives the (/ )- , 3-dienecarboxylic acid 152. Then the acetoxylactone 153 can be prepared by the Pd-catalysed intramolecular trans-1,4-functionalization of the 1,3-cyclohexadiene 152. On the other hand, the acetate 155 is obtained by the Pd-catalysed chemoselective displacement of the allylic carbonate moiety in 154 with malonate under neutral conditions. The (5)-1,3-dienecarboxy 1ic acid 156 is obtained by Pd-catalysed 1,4-elimination of 155. The Pd-catalysed 1,4-functionalization of the 1,3-cyclohexadiene 156 and acetylation, afford 157, which is an enantiomer of 153 [101]. 

CPL spectroscopy may also be used to signal the nature of the ternary anion adduct. In the series of phospho-anion complexes of [Eu.la]3+, Figure 5, complexes of HP042 and glucose-6-phosphate give identical CPL spectra - consistent with their very similar NMR spectral profile. Adducts with phospho-tyrosine, N-acetyl phospho-Tyr and a short peptide (phosphorylated at the Pyr residue) are also near-identical, consistent with chemoselective binding of the Tyr-OP phospho-anion. 

Kumar, P. Pandey, R. K. Bodas, M. S. Don-gare, M. K. Yttria-zircona based Lewis add an efficient and chemoselective catalyst for acetylation reactions. Synlett 2001, 206-209. 

But with just one equivalent of acetic anhydride in the presence of a base (pyridine) only the NH2 group is acylated, and paracetamol is the product. This is chemoselectivity, and it is to be expected that the NH2 group is more nucleophilic than the OH group. It is even possible to hydrolyse the doubly acetylated product to paracetamol with aqueous sodium hydroxide. The ester is more reactive than the amide and hydrolyses much more easily (Chapter 12). 

The relative reactivity of the alcohol and amine in the example just given could be overturned by conducting a reaction under thermodynamic control. In kinetically controlled reactions, the idea that you can conduct chemoselective reactions on the more reactive of a pair of functional groups— carbonyl-based ones, for example—is straightforward. But what if you want to react the less reactive of the pair There are two commonly used solutions. The first is illustrated by a compound needed by chemists at Cambridge to study an epoxidation reaction. They were able to make the following diol, but wanted to acetylate only the more hindered secondary hydroxyl group. 

An illustrative example of a change in chemoselectivity is the inversion of substrate specificity of the serine protease Subtilisin Carlsberg in the transesterification reaction of ethyl esters of A-acetyl-L-serine and A-acetyl-L-phenylalanine with 1-propanol, measured in twenty anhydrous organic solvents. The enzyme-catalysed reaction with the serine substrate is strongly favoured in dichloromethane, while the reaction with the phenylalanine substrate is preferred in t-butylamine, with a 68-fold change in substrate specificity [313]. 

The chemoselective reduction of a series of 2-oximo-l-tetralones (99-103 equation 22) to the corresponding aminotetralones has been carried out using Zn-HOAc-Ac20 in 55- 5% yield. The amino group is acetylated under these conditions and the 2-acetamidotetralone is the product which is isolated. ... 

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