THIOL ESTERS preparation

Another example of this methodology has appeared recently from Masamune and coworkers in connection with a total synthesis of bryostatin (equation 67). The salient point here is the demonstrated utility of the thiol ester, prepared directly through stereoselective boron enolate aldol condensation. Notice Aat no further activation or removal of a chiral auxiliary is necessary for this transformation, unlike other related aldol methodology. 

Thiol esters. Thiol esters can be prepared by reaction of a carboxylic acid (aliphatic or aromatic) with this chloridate and triethylamine in THF to form a rather unstable intermediate (a), which reacts with the T1(I) salts of alkane-thiols to form thiol esters (equation I). Note that hydroxy acids react selectively to form thiol esters. Selected examples of thiol esters prepared in this way are formulated with the yields shown in parentheses. 

These neutral conditions can be used to prepare thiol esters of acid- or base-sensitive compounds including penicillins. ... 

Thiol esters, which are more reactive to nucleophiles than are the corresponding oxygen esters, have been prepared to activate carboxyl groups for both lactoniza-tion and peptide bond formation. For lactonization S-f-butyl and S-2-pyridyP esters are widely used. Some methods used to prepare thiol esters are shown below. The S-r-butyl ester is included in Reactivity Chart 6. 

Thiol acids and thiol esters can be prepared in this manner, which is analogous to 10-8 and 10-24. Anhydrides and aryl esters (RCOOAr) are also used as substrates, but the reagents in these cases are usually SH and SR. Thiol esters can... 

Several variations and extensions of this HHT method have recently been reported. The mildness of this reaction was exemplified through the synthesis of glyphosate thiol ester derivatives 35. The requisite thioglycinate HHT 34 was prepared in high yield by a novel, methylene-transfer reaction between r-butyl azomethine and the ethyl thioglycinate... 

How to Use the Book to Locate Examples of the Preparation of Difunctional Compounds. The difunctional index on p. xi gives the section and page corresponding to each difunctional product. Thus Section 327 (Alcohol, Thiol-Ester) contains examples of the preparation of hydroxyesters Section 323 (Alcohol, Thiol-Alcohol, Thiol) contains examples of the preparation of diols. 

Preparation Of Thiol Acids, Thiol Esters And Amides By Reactions Of Carbonyl Sulfides With Grignard Reagents," Katritzky. A.R. Moutou, J.-L. Yang, Z. Org. Prep. Proceed. Int., 1995, 27, 361... 

Additional acceleration of acylation can be obtained by inclusion of cupric salts, which coordinate at the pyridine nitrogen. This modification is useful for the preparation of highly hindered esters.122 Pyridine-2-thiol esters can be prepared by reaction of the carboxylic acid with 2,2 -dipyridyl disulfide and triphenylphosphine123 or directly from the acid and 2-pyridyl thiochloroformate.124... 

The addition of Grignard reagents to aldehydes, ketones, and esters is the basis for the synthesis of a wide variety of alcohols, and several examples are given in Scheme 7.3. Primary alcohols can be made from formaldehyde (Entry 1) or, with addition of two carbons, from ethylene oxide (Entry 2). Secondary alcohols are obtained from aldehydes (Entries 3 to 6) or formate esters (Entry 7). Tertiary alcohols can be made from esters (Entries 8 and 9) or ketones (Entry 10). Lactones give diols (Entry 11). Aldehydes can be prepared from trialkyl orthoformate esters (Entries 12 and 13). Ketones can be made from nitriles (Entries 14 and 15), pyridine-2-thiol esters (Entry 16), N-methoxy-A-methyl carboxamides (Entries 17 and 18), or anhydrides (Entry 19). Carboxylic acids are available by reaction with C02 (Entries 20 to 22). Amines can be prepared from imines (Entry 23). Two-step procedures that involve formation and dehydration of alcohols provide routes to certain alkenes (Entries 24 and 25). 

Barrett and coworkers have explored hetero-substituted nitroalkenes in organic synthesis. The Michael addition of nucleophiles to 1-alkoxynitroalkenes or 1-phenylthionitroalkenes followed by oxidative Nef reaction (Section 6.1) using ozone gives a-substituted esters or thiol esters, respectively.41 As an alternative to nucleophilic addition to l-(phenylthio)-nitroalkenes, Jackson and coworkers have used the reaction of nucleophiles with the corresponding epoxides (Scheme 4.4).42 Because the requisite nitroalkenes are readily prepared by the Henry reaction (Chapter 3) of aldehydes with phenylthionitromethane, this process provides a convenient tool for the conversion of aldehydes into ot-substituted esters or thiol esters. 

The mixed carbonic anhydride procedure8-7 has been useful in the preparation of amide linkages and thiol esters. Mixed carbonic anhydrides have successfully acylated, under very mild conditions, the carb-anions derived from diethyl ethylmalonate and diethylcadmium.8 The latter gives as a product the corresponding ketone. Mixed anhydrides derived from acetic and acetylsalicylic acids give results similar to those described here.8... 

Because anti/syn ratios in the product can be correlated to the E(0)/Z(0) ratio of the involved boron enolate mixture,10b initial experiments were aimed at the preparation of highly E(0)-enriched boron enolate. The E(0)/Z(0) ratio increases with the bulk of the alkanethiol moiety, whereas the formation of Z(O) enolates prevails with (S )-aryl thioates. (E/Z = 7 93 for benzenethiol and 5 95 for 2-naphthalene thiol esters). E(O) reagent can be formed almost exclusively by reaction of (5)-3,3-diethyl-3-pentyl propanethioate 64 with the chiral boron triflate. High reactivity toward aldehydes can be retained in spite of the apparent steric demand (Scheme 3-22).43... 

Following the same procedure, phosphoric thiol esters are prepared by the treatment of trialkylphosphites with thiols in the presence of TeCl4 and lutidine. ... 

DESULFURIZATION WITH RANEY NICKEL Preparation of Aldehydes from Thiol Esters [1101]... 

This method is an alternative to 0-37 as a way to prepare thiol esters. 

Carboxylic esters have been reduced to aldehydes with DIBALH at -70°C, with di-aminoaluminum hydrides,1224 with LiAlH E NH,1226 and with NaAlH4 at -65 to -45°C, and (for phenolic esters) with LiAlH(0-/-Bu)3 at (fC.1227 Aldehydes have also been prepared by reducing ethyl thiol esters RCOSEt with Et3SiH and a Pd-C catalyst.1228... 

Carboxylic acids can also be attached to solid supports as amides, imides, and thiol esters. Illustrative examples of the saponification of such linkers are listed in Table 3.5. Thiol esters are more sensitive towards nucleophilic attack than the corresponding esters, and can be readily saponified. Resin-bound thiol esters have, however, mainly been used for the preparation of amides by nucleophilic cleavage with amines (see Section 3.3.3). 

Hydroxamic acids and hydrazides can also be prepared by nucleophilic cleavage of resin-bound esters, activated amides, or thiol esters [359] with hydroxylamine and... 

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