Esters leaving group

After the initial demonstration of stoichiometric nucleophilic attack on 7i-allyl ligands, catalytic allylic substitution reactions were pursued. In 1970, groups from Union Carbide [3, 4], Shell Oil [5], and Toray Industries [6] published or patented examples of catalytic allylic substitution. All three groups reported allylic amination with palladium catalysts. The Toray Industries report also demonstrated the exchange of aryl ether and ester leaving groups, and the patent from Shell Oil includes catalysts based on rhodium and platinum. 

Although most of these early reactions were conducted with allylic acetates, reactions of allylic carbonates, trifluoroacetates, and phosphates also occur. Sodium diethylmalonate also reacts with allylic alcohols in the presence of the iridium-triphenylphosphite catalyst. However, the alcohol itself does not act as a leaving group. Instead, transesterification occurs with one equivalent of malonate nucleophile to form a more labile ester leaving group. 

For reviews of triflates. nonaflates. and other fluorinated ester leaving groups, sec Stang I lanack Subramanian Synthesis 1982, 85-126 Howells Me Cown Chem. Rev. 1977, 77, 69-92, pp. 85-87 wCrossland Wells Shiner J. Am. Chem. Soc. 1971, 93, 4217. 

ROTs, etc., includes esters of sulfuric and sulfonic acids in general, for example, ROS02OH. ROSO,OR, ROSO R, etc. R0N02, etc., includes inorganic ester leaving groups, such as ROPO (OH) ROB(OH)2, etc. 

Further insights into the reaction mechanism can be obtained by studying the effects of the silane ester (leaving) group on the hydroxide catalyzed hydrolysis. Akerman has studied the hydroxide anion catalyzed hydrolysis of substituted triethylphenoxysilanes in 48.6% aqueous ethanol [38]. Humffray and Ryan have investigated a similar set of silane esters in 40% aqueous dioxane [36]. 

Scheme 5.1.4. General structures of linear 7 and iso-type 8 substrate mimetics. The site-specific ester leaving groups are emphasized by bold letters. PG, protecting group Ri, R2, individual side-chains R3, site-specific ester leaving group.

Figure 8.10 Stereoselective synthesis of (S,7 ,7 ,S,.R,S)-4,6,8,10,16,18-hexamethyldocosane via reagent-directing o-diphenylphosphanyl benzoate ester leaving groups.

Figure 14.1 Synthesis of 2-[18F]fluoro-2-deoxy-D-glucose (f18F]FDG) using two-step procedure of nucleophilic substitution of [18F]fluoride ion for a triflate ester leaving group followed by base-catalyzed hydrolysis of acetyl protecting groups.

Figure 14.2 Synthesis of 9-(3-[18F]fluoropropyl)-9-desmethyF(+)-(a)-dihydrotetrabenazine (f18F]FP-DTBZ) by a single-step nucleophilic aliphatic substitution of a mesylate ester leaving group.

In attempts to improve the delivery of phosphonoformate, the kinetics and products of hydrolysis of various triesters of phosphonoformic acid (PEA) in MeCN-HjO mixtures at -1 < pH < 14 have been studied. Phosphonoformate triesters are hydrolyzed to give mixtures of phosphites, phosphonoformate esters, and free acids. The rates and product distribution are dependent on pH and ester leaving group abilities. ... 

The evaporative water removal methods discussed above can also be employed to remove volatile reaction products which inactivate biocatalysts, such as methanol or aldehydes and ketones, the latter of which form from the vinyl alcohol activated ester leaving group, as discussed above. 

TABLE 2. Relative rates of nucleophilic displacement of various ester leaving groups... 

B3LYP calculations using the aug-cc-pVTZ and 6-31++G(d) basis sets have been applied in an attempt to find reactivity indicators that would provide leaving group ability of halogen, carboxylate, sulfonate, and phosphinate ester leaving groups in solvolysis reactions. Of the 66 different reactivity indicators tested, none was able... 

Figure 11.2 Nucleophilic attack at an sp carbon bearing a sulfonate ester leaving group.

The synthesis of the TM involves simply mixing the starting materials together with sodium ethoxide in ethanol (note that the alkoxide base is chosen to match the ester leaving group). Recall that an a,P-unsaturated compound such as phenyl vinyl ketone can be prepared via the Mannich reaction. 

More recent examples of ester-amino alcohol couplings involve the use of the organocatalyst BEMP (Scheme 17.17)." This is typically needed in 10 mol% ratio at room temperature for 15 hours. These mild conditions make this process favourable on scale the reaction has a wide substrate scope with aliphatic, aromatic and heteroaromatic systems all being tolerated along with a range of ester leaving groups and amino acids. 

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