Chemoselective acylation

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). ° ... 

Other authors have described the lipase-catalyzed chemoselective acylation of alcohols in the presence of phenolic moities [14], the protease-catalyzed acylation of the 17-amino moiety of an estradiol derivative [15], the chemoselectivity in the aminolysis reaction of methyl acrylate (amide formation vs the favored Michael addition) catalyzed by Candida antarctica lipase (Novozym 435) [16], and the lipase preference for the O-esterification in the presence of thiol moieties, as, for instance, in 2-mercaptoethanol and dithiotreitol [17]. This last finding was recently exploited for the synthesis of thiol end-functionalized polyesters by enzymatic polymerization of e-caprolactone initiated by 2-mercaptoethanol (Figure 6.2)... 

Finally, a recent example on the biocatalyzed synthesis of new cytotoxic derivatives of the anthracycline doxurobicin (8) deserves to be mentioned. In the presence of Mucorjavanicus lipase or subtilisin Carlsberg ion-paired with Aerosol , the primary C-14 OH was chemoselectively acylated to give the corresponding derivatives, such as the valerate 8a [19]. However, optimization of this enzymatic synthesis did not provide a synthetic approach suitable for the preparative synthesis of gram quantities of Valrubicin (N-trifluoroacetyl doxurobicin-14-valerate, 8b)... 

P. Y. Chung, S. L. Highly chemoselective acylation of substituted aminophenols with... 

To make as much carboxylic acid derivative as possible available to the nucleophile at all stages of the reaction, the nucleophile is added dropwise to the carboxylic acid derivative and not the other way around. In Figure 6.41, the approach to chemoselective acylations of hydride donors and organometallic compounds, which we have just described, is labeled as strategy 2 and compared to two other strategies, which we will discuss in a moment. 

Fig. 6.41. Three strategies for the chemoselective acylation of hydride donors, organometallics and heteroatom-stabilized "carbanions" with carboxylic acid derivatives.

Fig. 6.44. Chemoselective acylation of an organometallic compound C with the Weinreb amide D of Figure 6.21 a general approach to ketones.

Fig. 6.45. Chemoselective acylation of organolithium compounds with lithium-carboxylates (A). In order to generate the substrates the choice is between the deprotonation of the corresponding carboxylic acid and the addition of an organolithium compound to carbon dioxide, i.e. via C,C bond formation.

In Figure 6.41, the reaction of certain heteroatom-stabilized carbanions with carboxylic acid derivatives is presented as strategy 3 of Figure 6.32 for achieving chemoselective acylations. This strategy can be used to convert esters into /i-ketophosphomc acid esters with... 

Fig. 6.47. Top three reactions chemoselective acylations of weakly nucleophilic organometallic compounds with carboxylic acid chlorides.

Bottom reaction (as a reminder) chemoselective acylation of an aromatic compound with an activated carboxylic chloride (Friedel-Crafts acylation, cf. Section 5.2.7). 

Fig. 6.48. Preparation of Horner-Wadsworth-Emmons reagents (synthetic applications Section 11.3) by chemoselective acylation of a phosphonatestabilized "carb-anion" with an ester.

Fig. 6.49. Preparation of methyl ketones by (1) chemoselective acylation of a sulfinyl-stabilized "carbanion," (2) reduction (mechanism analogous to Figure 17.48).

The Weinreb amide syntheses in Figure 6.50 proceeding via the stable tetrahedral intermediates B and F are chemoselective SN reactions at the carboxyl carbon atom of carbon acid derivatives that are based on strategy 1 of the chemistry of carboxylic acid derivatives outlined in Figure 6.41. Strategy 2 of the chemistry of carboxylic acid derivatives in Figure 6.41 also has a counterpart in carbon acid derivatives, as is demonstrated by a chemoselective acylation of an organolithium compound with chloroformic acid methyl ester in this chapter s final example ... 

The SN reaction under consideration is not terminated until water, a dilute acid, or a dilute base is added to the crude reaction mixture. The tetrahedral intermediate B is then protonated to give the compound E. Through an El elimination it liberates the carbonyl compound C (cf. discussion of Figure 6.4). Fortunately, at this point in time no overreaction of this aldehyde with the nucleophile can take place because the nucleophile has been destroyed during the aqueous workup by protonation or hydrolysis. In Figure 6.32 this process for chemoselective acylation of hydride donors, organometallic compounds, and heteroatom-stabilized carbanions has been included as strategy 1. ... 

Fig. 6.36. Chemoselective acylation of organolithium compounds with lithiumcarboxylates.

Fig. 6.37. Top three reactions Chemoselective acylations of weakly nucleophilic...

Naik, S., Bhattacharjya, G., Kavala, V. R., Patel, B. K. Mild and eco-friendly chemoselective acylation of amines in aqueous medium. ARKIVOC (Gainesville, FL, United States) 2004, 55-63. 

Scheme 7.16 Chemoselective acylation of a hydroxy group in the presence of an amine.

A more spectacular case of chemoselective acylation using the right catalyst [29] is shown in Scheme 7.17. Here the catalyst addresses selectively the 4-position of a glycoside, obviating the previously used route with two protecting groups ... 

A similarly tethered phosphonate was used to prepare the exocyclic olefin in Danishefsky s synthesis of calicheamicinone 347 [147]. Chemoselective acylation of the advanced intermediate 348 provided the olefination precursor 349, and subsequent cyclization gave 5-lactone 350, enforcing the desired stereochemistry of the double bond. The additional conjugative stabilization of the exocyclic olefin with the ester also facilitated subsequent transformations of the azide to the methyl carbamate functionality, and further manipulations ultimately led to the first synthesis of calicheamicinone 347 (Scheme 10-117). 

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