Thioesters 2-pyridyl

The reaction of imines with 2-pyridyl thioesters in the presence of aluminium tribromide or ethylaluminium dichloride afforded /ra r-3,4-disubstituted azetidin-2-ones < 1996T2583>. Similar stereoselective addition of silylketene thioacetals to imines is known in the presence of Lewis acids <1996T2573>. An indium-mediated reaction of ethyl bromoacetate with imines yielded 3-unsubstituted azetidin-2-ones in reasonable yields (Equation 195) <2000J(P1)2179>. 

In the presence of a catalytic amount of the chiral titanium reagent (8) prepared from titanium tetraisopropoxide and the (/ )-1,4-diol, kinetic resolution of 5 -(2-pyridyl) thioesters of a-aryl carboxylic acids is achieved with high relative rate of both the enantiomers to give the (f )-isopropyl esters with high optical purity (eq 17). ... 

Carboxylic esters, especially lactones, are conveniently obtained via the pyridyl thioesters (18). Some examples are given in Scheme 1. The 2-pyridyl thiol ester method can be further improved if silver ions (AgC104) are used as activators. Corey and Brunelle have also introduced other heterocyclic disulfides, and (19) was found to be superior to other reagents tested for the formation of lactones from w-hydroxyalkanoic acids. 

One example of lactonization promoted by Ag was reported. Addition of 1 eq. of silver perchlorate to the 2-pyridyl thioester of 15-hydroxypentadecanoic acid in benzene gave a mixture of the monomeric, dimeric, and trimeric lactones in 44% yield within 30 min. at 20°. 

The oxidation-reduction method, developed initially by Mukaiyama et al. [133] and related to the previously described organophosphorus methods, has permitted a variety of important solid-phase applications. The mechanism of the activation is complex and involves the oxidation of the triaryl/ alkyl-phosphine to the oxide as well as reduction of the disulfide to the mercapto derivative. However, different active species, such as 81 (Fig. 11), the 2-pyridyl thioester, or even the symmetrical anhydride, have been postulated to form. For the intermediate 81, the peptide bond formation may proceed through a (cyclic transition state. The method has been used for conventional stepwise synthesis [134], acylation of the first protected amino acid to a hydroxymethyl resin, and to achieve segment condensation on a solid support in the opposite direction (N C) [135,136]. Lastly, it has been used for efficient grafting of a polyethylene glycol (molecular weight 2000) derivative to an aminomethyl resin to prepare PEG-PS resins [137]. 

Alternatively, /7-methoxyphenylimine 579 has been used in a one-pot synthesis of )S-lac-tams [183]. Reaction of 579 with the titanium enolate of a pyridyl thioester 580 produces the )5-lactam nucleus. If R=H, a 65 35 mixture of 581 and 582 is obtained in 54% yield, but if R=CH3 the diastereomeric ratio increases to 98 2 (80% yield). If 581 (R=H) is the desired product, an analogous reaction with the corresponding O-TBS-protected imine gives 581 with a stereoselectivity >98 2. 

Aliphatic nitriles react slowly with phenols and phenyl ethers in the presence of trifluoromethanesulphonic acid to give ketones after hydrolysis, in a variation of the Houben-Hoesch reaction. The crystalline complex of copper(i) triflate and benzene induces the acylation of aromatic substrates with selenol esters, affording a transition-metal mediated version of the Friedel-Crafts reaction. Aromatic carboxylic acids can be converted into symmetrical diaryl ketones in good yield by treatment of their 5-(2-pyridyl)thioesters with bis-(l,5-cyclo-octadiene)nickel [equation (15)]. In contrast to other methods for preparing symmetrical aromatic ketones, this method allows their preparation from a single starting material. 

Alternatives to the established double activation method for the lactonization of >-hydroxy-acids via 2-pyridyl thioesters are use of the more reactive 4-(2-amino-6-methyl)pyrimidyl analogues " or mixtures of 2-chloro-6-methyl-l,3-diphenylpyridinium tetrafluoroborate, 2,6-dimethylpyridine, and benzyl-triethylammonium chloride in refluxing 1,2-dichloroethane. ... 

The 2-pyridyl and related 2-imidazolyl disulfides have found special use in the closure of large lactone rings.118 This type of structure is encountered in a number of antibiotics which, because of the presence of numerous other sensitive functional groups, require mild conditions for cyclization. It has been suggested that the pyridyl and imidazoyl thioesters function by a mechanism in which the heterocyclic nitrogen acts as... 

Recognition of the value of active esters for peptide bond formation emerged from work with vinyl esters ly cyanomethyl esters 5-phenyl thioesters 9,P1 piperidino esters 10, 3-pyridyl esters 4-nitrophenyl esters 12 2,4,6-trichlorophenyl esters,and phthalimido esters 17.t l Many activating moieties have surfaced over the years but only a limited number have survived the test of time and are in use today. These include 4-nitrophenyl 12,M 2,4,5-trichlorophenyl pentachlorophenyl pentafluorophenyl succininoido... 

Under strongly basic conditions, o-bromoacetophenones and carbon disulphide react to give a high yield of a benzothiopyranone. 2-Bromo-3-pyridyl ketones react with thioesters to produce a fused thiopyranone ring. 

Cosstick and co-workers have reported an improved procedure for the synthesis of phosphorothiolate-containing DNA using Arbuzov chemistry in which the nucleoside disulfides are generated in situ from the corresponding thioesters. Several nucleoside disulfides have been prepared and in particular the regioselectivity of reaction of these with a phosphite has been examined. The disulfide (59) allows the preparation of the desired diribonucleoside phosphoro-thiolate (60) but the reaction is accompanied by some (2-10%) formation of the pyridyl phosphorothiolate. 

Corey and Nicolaou used the S-pyridyl ester [19], which was generated by Mukaiyama thioester formation using 2,2 -dipyridyl disulfide and PPhj [20], as an activated precursor for lactonization. In 1976, they first accomphshed the total synthesis of some macrolide molecules including recifeioUde (15), as shown in Scheme 5.1 [21]. 

FUNCTIONAL GROUP proposed that the pyridyl and imidazoyl thioesters function by a mechanism in BY L LEOT which the heterocyclic nitrogen also acts as a base, deprotonating the alcohol group. 

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