Tertiary from carboxylic esters

Scheme 2 presents the most apphed cleavage strategies for esters of type A (carboxyhc and sulfur esters) with an aUcyl or an aryl substrate directly bound to the ester linkage. The bandwidth of products obtainable from carboxylic esters includes esters 14, acids 13, primary and tertiary alcohols... 

Generally, nitrosamides I undergo irreversible thermal rearrangements (at temperatures ranging from ambient to ca.lOO ) to diazo esters III which themselves decompose even faster under these conditions to give the carboxylic esters or acids and the olefins derived from the R group (1,2). The stability of nitrosamides and the final products from III are very much dependent on the nature of the R group (primary, secondary, tertiary... 

However, an analysis of C—OR bond distances in more than 2000 ethers and carboxylic esters (all with sp carbon) shows that this distance increases with increasing electron withdrawal in the R group and as the C changes from primary to secondary to tertiary.61 For these compounds, mean bond lengths of the various types ranged from 1.418 to 1.475 A. 

Carboxylic esters are produced by the addition of carboxylic acids to olefins, a reaction that is usually acid-catalyzed (by proton or Lewis acids182) and similar in mechanism to 5-4. Since Markovnikov s rule is followed, hard-to-get esters of tertiary alcohols can be prepared from olefins of the form R2C=CHR.183 When a carboxylic acid that contains a double bond in the chain is treated with a strong acid, the addition occurs internally and the product is a y- and/or a 8-lactone, regardless of the original position of the double bond in the chain, since strong acids catalyze double bond shifts (2-2).184 The double bond always migrates to a position favorable for the reaction, whether this has to be toward or away from the carboxyl group. Carboxylic esters have also been prepared by the acyloxymercuration-demercuration of olefins (similar to the procedures mentioned in 5-2 and 5-4).185... 

The wide range of standard procedures that are available for the formation of carboxylic esters of primary and secondary alcohols in the presence of suitable acid catalysts is discussed in detail in Section 5.12.3, p. 695. Also included is the mild method for methyl ester formation from the carboxylic acid and diazomethane, and a method appropriate for sterically hindered esters involving the acid, a secondary or tertiary alkyl halide, and the non-nucleophilic base DBU (Expt 5.151). An example of the formation of a t-butyl ester is noted in Expt 6.165. 

The reaction depicted was run in THF at 0 C, other solvents having been found to be inferior. The S-(2-pyridyl) thioates may be prepared through reaction of the corresponding acid chloride and 2-pyridine-thiol in the presence of a tertiary amine. They are also available directly from carboxylic acids by reaction with 2,2 -dipyridyl disulfide (Aldrithiol-2) and triphenylphosphine. In the case illustrated above, protection of the ketone would seem unnecessary if Grignard addition was selective for the thiol ester however, the starting material, 5-(2-pyridyl) y-oxopentanethioate, is not stable to the lactonization shown in equation (18). 

Gancet, C Preparation of Esters of Carboxylic Acids Directly From Carboxylic Acids and Alcohols Using a Catalyst System Comprising a Sulfonic Acid and a Polymer-Bound Tertiary Amine. European Patent 1,167,337, Jan 2, 2002. 

A study similar to that of the carboxylic esters was done for carboxylic amides by Chakrabarti and Dunitz [28]. A general conclusion for the amides from primary, secondary and tertiary C(a) amines is that the C(a)-CGff) bond of an alkyl substituent avoids the synperiplanar arrangement to the C(0)-N bond. For the (er(-alkyl substituents one of the C - C bonds is therefore always in an antiperiplanar position... 

Mixed anhydrides can be obtained by those of the above methods in which acid chlorides are used. Further, formation of anhydrides from carboxylic acids and acetic anhydride involves mixed anhydrides as intermediates, and in some cases these can be isolated, e.g., the mixed formic acetic anhydride.977 This anhydride can replace the unstable formic anhydride itself, for only the reactive formyl group is transferred in its reactions this fact has been utilized in the preparation of numerous formic esters, which in turn can be transformed into esters of tertiary alcohols that are otherwise difficult of access (see page 376). 

Boric acid is a mild dehydrating agent suitable for removal of water from some primary, secondary, or tertiary alcohols. Since the acid and the alcohol form first a trimeric metaboric ester, which then regenerates the boric acid when it decomposes to the olefin,36 the reaction is somewhat similar to pyrolysis of carboxylic esters but the boric acid dehydration occurs at appreciably lower temperatures (250-300°). Olefins are readily obtained by heating approximately molar equivalents of boric acid and 1-octanol, 1-heptanol, 1-hexanol, (—)-menthol, cyclohexanol, or 5cyclohexane-methanol, and cyclobutanemethanol.38... 

Esterification. Activated esters derived from carboxylic acids with the title reagent react with alcohols (including tertiary alcohols) to give esters. 

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