2-Pyridinethiol esters

Pyridinethiolate esters, which are easily prepared from acyl chlorides, also react with Grignard reagents to give ketones (see Entry 6 in Scheme 7.3).92 /V-Mclhoxy-/V-mclhylamides are also converted to ketones by Grignard reagents (see Entries 17 and 18). 

Corey s double activation procedure (Method 2) does not use an external reagent to activate the functional group, but effects cyclization by heating a solution of the 2-pyridinethiol ester of a hydroxy acid for a prolonged period. Several pieces of evidence point to the intermediacy of 2 in this lactonization.10 If one accepts this intermediate, it follows that a hydroxy(2-pyridinethiolJ ester, heavily substituted near the reaction centers (i.e., near the hydroxyl and acyl groups), would encounter a high... 

Method 2. Corey s double activation method for lactone formation is patterned after Mukaiyama s procedure for peptide formation and involves refluxing a solution of the 2-pyridinethiol ester of a hydroxy acid in a high-boiling solvent for a prolonged period of time.6... 

In 1974, Corey and Nicolaou [14] found that hydroxy acid 11 can be efficiently activated by 2,2 -dipyridyl disulfide (DPDS). As shown in Scheme 5, in the presence of triphenylphosphine, 11 reacts with DPDS yielding 2-pyridinethiol ester 12. The proton transfer from hydroxyl group to carbonyl in 2-pyridinethiol ester 12 is facilitated by the basic nitrogen of the pyridine nucleus and a dipolar intermediate 13 is formed. Then a facile, electrostatically driven cyclization occurs. 

The 2-pyridinethiol ester 12 can also be prepared from hydroxy acid and... 

Mixed cuprates. Corey et aV allowed the mixed cuprate 2 to react with the 2-pyridinethiol ester 3 to produce the a,jS-unsaturated ketone 4, a key intermediate in the synthesis of erythronolide A (5) ... 

Esterification of cephalosporanic acids Usual esterification methods of these acids lead to mixtures of and A -esters. This undesired isomerization is prevented by conversion of the acid into the 3-nitro-2-pyridinethiol ester (2) by reaction with 1 and triphenylphosphine. This stable intermediate (obtainable in about 90% yield) reacts with various alcohols to form the desired esters in 60-80% yield (equation I). 

Pyridinethiol esters. In combination with triethylamine 1 converts acids into 2-pyridinethioi esters in over 95% yieid. The method is superior to the usual eariier route invoiving treatment of an acid with 2,2 -dipyridyl disulfide and tri-phenylphosphine (5, 286 6, 246). ... 

Lactonization of ta-hydroxy esters to macrolides. Gerlach and co-workers have reported that silver salts can catalyze the cyclization of v-hydroxy-2-pyridinethiol esters to macrolides (6, 246 7, 142). Nimitz and Wollenberg have found that silver perchlorate has an even more pronounced and consistent effect on the cyclization of (u-hydroxy thiolesters of 2-amino-4-mercapto-6-methylpyrimidine, Optimal yields are obtained with use of 1.1 equiv. of the silver salt. In addition, high dilution is not necessary. In the example cited, the yield of the lactone in the absence of the catalyst is 41%. 

The modified Corey-Nicoiaou macroiactonization was applied for the construction of the BCD ring system of brevetoxin A by K.C. Nicolaou and co-workers. The dihydroxy dicarboxylic acid substrate was subjected to a one-pot bis-lactonization. After the formation of the bis-2-pyridinethiol ester, the lactonization was conducted at low substrate concentration (0.013 M) in toluene at reflux temperature. 

Corey et al. [36] developed an efficient and mild lactonization method using 2-pyridinethiol ester. Slow addition of 2-pyridinethiol esters, prepared from to-hydroxy acids by reaction with 2,2 -dipyridyl disulfide and Ph3p or 2-fhiopyridyl chloroformate and EljN, to refluxing xylene under dilution conditions yielded... 

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