Dehydrative coupling

Novel isosteres 545 of the antiviral agent acyclovir were synthesized in three stages (84JHC697) by dehydrative coupling of 3-amino-6-aminomethyl[ 1,2,4]triazin-5-(4//)-one with 2-(benzoyloxy)ethoxyacetic acid to give the respective amide that cyclized and deprotected to give 545. It showed no activity against herpes simplex virus types I and II in cell culture (Scheme 112). 

We examined several approaches for synthesizing polyanhydrides, including melt polycondensation, dehydrochlorination, and dehydrative coupling. Extensive details of these new polymer synthesis techniques and numerous polymerization conditions for a wide variety of polyanhydrides were previously described (1). 

Leong, K. W., Simonte, V., and Danger, R., Synthesis of polyanhydrides Melt-polycondensation, dehydrochlorination, and dehydrative coupling. Macromolecules, 20. 705-712, 1987. 

These experiments demonstrate that the surface-catalyzed 2 reaction is far more effident than either the or C pathway for the dehydrative coupling of alcohols over the solid add catalysts tested. High selectivity to configurationally inverted chiral ethers ensues, espedally in the case of the HZSM-5 catalyst, in which the minor C or C paths were further suppressed by "bottling" of 3-ethoxypentane by the narrow zeolite chaimels. 

An attractive feature of this dehydrative coupling approach is that it avoids the need for isolation of intermediate glycosyl donors. This can be desirable if a glycosyl donor is not stable to isolation or purification. Moreover, the use of a hemiacetal donor reduces the number of synthetic manipulations of the carbohydrate donor by avoiding hemiacetal derivatization to alternative donor types. In this way, the approach has the potential to streamline time and labor-intensive multiglycosylation sequences. Although there increasingly have been reports of these direct dehydrative... 

One of the most widely used procedures for dehydrative coupling and cyclization reactions is the Mitsunobu reaction in which the components are treated with triphenylphosphine and diethyl azodicarboxylate (DEAD, EtOaC—N=N—COiEt). The overall equation for reaction of an alcohol 67 with an acid 68 to form the ester 69 is as shown and the active species is the zwitterionic... 

In a series of elegant studies, Paquette and coworkers demonstrated the potential of the Claisen rearrangement for the stereocontrolled total synthesis of natural products. Dehydrative coupling of (2)-3-(trimethylsilyl)-2-propen-l-ol with cyclohexanone (51) under Kuwajima s conditions, followed by rearrangement of enol ether (52) in decalin, led in excellent stereoselectivity (>99 1) to aldehyde (53 Scheme 8). Concise construction of the eight-membered core of acetoxycrenulidine was achieved by intramolecular phenylseleno etherification of lactone (54), introduction of the exocyclic vinyl ether double bond by selenoxide elimination and subsequent Claisen rearrangement (Scheme 9, 66% from 54). ... 

Figure 21. Surface binding through the dehydrative coupling of carboxylic acid groups with surface hydroxyl groups to yield ester linkages and water.

Peptide synthesis. In the synthesis of a cyclic hexapeptide, this water-soluble carbodiimide was used for the dehydrative coupling of two tripeptides and also for the cyclization step. 

Dehydrative coupling of hydroxy compounds. Uses of the reagent for coupling two hydroxylic components by elimination of water under mild, neutral conditions have been reviewed. A recent example is the preparation of a symmetrical diacyl peroxide by coupling two moles of an acid with one of hydrogen peroxide. An amount of DCC equivalent to the acid (plus 10% excess) is weighed as a liquid into... 

The most widely used method to synthesize polyanhydrides is melt condensation polymerization, which results in high molecular weight polymers. Other methods include Schotten-Baumann condensation, dehydrative coupling, and ring opening polymerization. 

Another method to synthesize polyanhydrides is by dehydrative coupling of two carboxyl groups. Even though this method produces lower molecular weight products (mostly oligomers) compared with the methods described above, it is a single step polymerization where a dicarboxylie acid monomer can be directly converted into the polymer. Moreover, it can be conducted at low temperatures suitable for monomers that cannot resist harsh reaction conditions. 

A far less developed strategy for glycosidic bond formation is a direct dehydrative coupling procedure in which one begins with a 1-hydroxy carbohydrate (1)... 

When methanesulfonyl chloride was allowed to react with 2,3,4,6-tetra-O-ben-zylglucopyranose and collidine in dichloromethane, the a-glucopyranosyl chloride was isolated regardless of whether the quaternary ammonium bromide was included. Addition of methanol to the reaction mixture resulted in the formation of an anomeric mixtiue of methyl glycosides. Similar results were obtained with toluenesulfonyl chloride, although it was noted that the initial sulfonylation was somewhat slower [8,9]. The use of tosyl chloride in the dehydrative coupling of alcohols with pyranoses was later revisited by Szeja and his coworkers, with the difference that aqueous... 

Pavia and coworkers carried out a careful study of the mechanism of these reactions using F-NMR spectroscopy. They concluded that they were observing simple acid-catalyzed dehydrative couplings in which water was removed from the... 

Goodenough first proposed that carboxylic acids would dehydratively couple with titanol groups to form surface ester linkages (Figure 12.4).42 We have reported spectroscopic evidence for this and for the more commonly observed carboxylate linkage in reactions of Ru(dcb)(bpy)2(PF6)2 and Ru(bpy)2(ina)2(PF6)2, where deb is 4,4 -(C02H)2-bpy and ina is isonicotinic acid, with nanocrystalline Ti02 and colloidal... 

In 1,1 j rearrangements the chairlike transition state is strictly preferred, if the transition state is not too crowded. Thus, Z-configurated ally vinyl ether 2, obtained from (Z)-3-trimethvl-silyl-2-propen-1-ol by dehydrative coupling with 2-single diastereomer (chair/boat > 99 1)519. 

Several approaches were examined for synthesizing polyanhydrides melt polycondensation, dehydrochlorination, and dehydrative coupling. A report of polyanhydride synthesis techniques and polymerization conditions for polyanhydrides appears in Leong et al. (22). 

Amide formation. Dehydrative coupling of an acid and an amine is readily achieved with this readily prepared reagent. No aqueous workup is necessary, and the product is easily separated from the polymer-bound urea by-product by simple filtration, rinse and evaporation. 

Oxepan and other oxygen- or nitrogen-containing saturated heterocycles can be prepared in high yield by the dehydrative coupling of aamino-alcohols, using diethyl azodicarboxylate and triphenylphosphine. The synthetically useful oxepin-2,7-diones (muconic acid anhydrides) can be conveniently prepared by the oxidation of ortho-henzoquinones with w-chloroperoxybenzoic acid. °... 

---