Burgess reagent, and

A constant interest in the development of new rapid methodologies for the preparation of oxazole hbraries is motivated by their presence in numerous biologically active natural products. Janda and coworkers were hrst to show that oxazoles can be obtained by microwave-assisted treatment of polymer-bound a-acylamino-/f-ketoesters with Burgess reagent [68]. Hydroxybutyl-functionalized /anda/el resin was used for this investigation, with key steps being monitored by on-bead FT-IR. First, a resin-bound acetoacetate was pre-... 

Fig. 13 Synthesis of oxazoles on JandaJel. Reagents and conditions a toluene, alkyl acetoacetate (R0(C0)CH2C0R R =t-Bu), reflux, 6h or alkyl acetoacetate (R = Me, Et), toluene, LiC104, reflux, 6h fc dodecylbenzenesulfonyl azide, EtsN, toluene, rt, 16 h c benzamide, Rh2(oct)4, toluene, 65 °C, Ih rf Burgess reagent, pyridine, chlorobenzene, MW 100 °C, 15 min (or 80 °C, 4 h with conventional heating) e AICI3, piperidine, CH2CI2, rt, 16 h...

A direct conversion of the oxazoline (44) to the thiazoline (45) can be achieved by the thiolysis of the oxazoline (44) with H2S in methanol in the presence of triethylamine followed by cyclodehydration with Burgess reagent. This method is essentially free from racemisation and has been used in the transformation of peptide substrates <95TL6395>. 

In the context of preparing potential inhibitors of histone deacetylase, Vasudevan and a team from Abbott have described the cyclization of 1,2-diacylhydrazides to 1,3,4-oxadiazoles with Burgess reagent under microwave conditions (150 °C, 15 min) (Scheme 6.224 a) [232], A different approach was chosen by Natero and coworkers, who prepared 2-chloromethyl-l,3,4-oxadiazoles by treatment of acyl hydrazides with 1-chloro-2,2,2-trimethoxyethane (Scheme 6.224b) [401]. Here, the reagent was used as solvent and the mixture was heated by microwave irradiation at 160 °C for 5 min. 

In the preparation of novel 1,3,4-oxadiazoles 56 from 1,2-diacylhydrazines 55, Brain and coworkers [29] used a highly efficient cydodehydration assisted by use of micro-waves, in THF as solvent, using polymer-supported Burgess reagent (Scheme 8.21). 

Microwave irradiation coupled with polyethylene glycol)-supported Burgess reagent reduced the reaction time to 2-4 min and led to improved yields. Use of harsh reagents, e. g. SOCl2, POCl3, and polyphosphoric acid, for the cydodehydration were avoided. 

Rearrangement under anhydrous conditions serves as an entry to cyclobutenes. The two most commonly employed reagents are TsOH (Eq. 41) and the Burgess reagent [CH302CNS02N(C2H5)3] (Eq. 42), both in refluxing benzene 74). Hydrolysis... 

Next, the TMS enol ether of 53c underwent oxidation with MCPBA to trimethylsilyloxy ketone 57. in 86% yield (86% conversion). Addition of methylmagnesium bromide in methylene chloride proceeded in almost quantitative yield (95%) to give tertiary alcohol 58. Dehydration with Burgess reagent [19] and acidic workup provided the allylic alcohol 59a in 63% yield, which was converted... 

Tab. 5.4 Cyclodehydration of hydroxyamides and thioamides with polymeric Burgess reagent 26.

Burgess reagent has also been used to effect cyclodehydration of p-hydroxy amides to oxazolines. Representative examples are shown in Table The advantage of this reagent is that the cyclodehydration is performed under essentially neutral and mild conditions, typically in THF at room temperamre or reflux. 

Because of the mild and essentially neutral reaction conditions, Burgess reagent was applied for the construction of the oxazoline intermediates 60 required by Pattendon and co-workers " " for their syntheses of thiangazole 61 and lissoclin-... 

Similarly, Wipf and co-workers " also utilized Burgess reagent in the synthesis of lissoclinamide 7 68. To construct 65 with the required alto-threonine residue, Wipf and co-workers first prepared tripeptide 64 from natural threonine. Inversion... 

A polymer-bound Burgess reagent has also been developed. Aside from the mUd, neutral cyclization conditions, this reagent also offers the advantage of a clean reaction with little epimerization and an easy work-up. Examples are listed in Table 8.9. 

In their synthesis of the macrocyclic hexapeptide bistratamide D, Meyers and co-workers prepared the tran -oxazoline 70 from the corresponding cw-oxazo-line 69 through several steps, the last of which was cyclization to the oxazoline using Burgess reagent. The net outcome is inversion of the stereocenter at the 5-position of the oxazoline (Scheme 8.25). 

Another possible method for the selective introduction of thioamide bonds into cyclic peptides is the use of oxazoles. 513-515 The oxazoles, which can be generated in serine- or threonine-containing peptides by the use of the Burgess reagent [(methoxycarbonyl-sulfamoyl)triethylammonium hydroxide inner salt) or under Mitsunobu conditions (see Section 6.8.5.2.2.2), are thionylated with hydrogen sulfide and triethylamine. A disadvantage of this method is that it is limited to serine- and/or threonine-containing peptides. 

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