General Methodology for the Preparation of 2,5-Disubstituted-1,3-oxazoles

Williams, David R.; Fu, Liangfeng

doi:10.1021/ol902833p

Cited by 68 publications

(28 citation statements)

References 30 publications

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“…Owing to the important applications of oxazole derivatives, various synthetic methodologies for these compounds have been reported. Generally, the procedures for the synthesis of oxazoles include the cyclodehydration of acyclic precursors [12][13][14][15][16], the oxidation of oxazolines [17][18][19] and the coupling of the prefunctionalized oxazoles with organometallic reagents [20][21][22]. In light of these applications, the development of milder and more general procedure to access oxazoles is still desirable.…”

Section: Introductionmentioning

confidence: 99%

Metal-free synthesis of polysubstituted oxazoles via a decarboxylative cyclization from primary α-amino acids

Guo

Zha

et al. 2013

sustain chem process

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Background: The ubiquitous oxazoles have attracted more and more attention in both industrial and academic fields for decades. This interest arises from the fact that a variety of natural and synthetic compounds which contain the oxazole substructure exhibit significant biological activities and antiviral properties. Although various synthetic methodologies for synthesis of oxazols have been reported, the development of milder and more general procedure to access oxazoles is still desirable. Results: In this manuscript, a novel method for synthesis of polysubstituted oxazoles was developed from metalfree decarboxylative cyclization of easily available primary α-amino acids with 2-bromoacetophenones. Conclusions:The method was simple, and this reaction could be carried out smoothly under mild and metal-free conditions. By virtue of this method, various polysubstituted oxazoles were obtained from the primary α-amino acids with moderate yields.

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Section: Introductionmentioning

confidence: 99%

Metal-free synthesis of polysubstituted oxazoles via a decarboxylative cyclization from primary α-amino acids

Guo

Zha

et al. 2013

sustain chem process

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“…Indeed, diversely substituted bromooxazoles were reported as multipurpose building blocks for various transformations, including:• palladium-catalyzed Negishi reactions, [31,32] Suzuki-Miyaura, [31][32][33][34][35][36][37][38][39][40][41][42] Stille, [31][32][33][34][35] and including sp 3 -sp 2 cross-coupling, [36] Heck reaction with alkenes and alkynes; [37] Buchwald-Hartwig amination, [38] alkoxylation [38] and aminocarbonylation. The method was optimized, and its scope was extended to all three isomeric parents, as well as various alkyl-and aryl-substituted bromooxazoles.…”

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confidence: 99%

Widely Exploited, Yet Unreported: Regiocontrolled Synthesis and the Suzuki–Miyaura Reactions of Bromooxazole Building Blocks

et al. 2019

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An approach to synthesis of 2‐, 4‐, and 5‐bromooxazoles is described. The method was optimized, and its scope was extended to all three isomeric parents, as well as various alkyl‐ and aryl‐substituted bromooxazoles. It was found that direct regiocontrolled lithiation followed by reaction with electrophilic bromine source was common for all substrates and led exclusively to the target substituted 2‐, 4‐ and 5‐bromooxazoles on multigram scale. The utility of the multipurpose building blocks obtained in this work was demonstrated in the Suzuki–Miyaura cross‐coupling reaction under parallel synthesis conditions.

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“…Subsequent reactions for displacement of the 2-(phenylsulfonyl) group have established a general route to 2,5-disubstituted-1,3-oxazoles 11. Prior literature reveals relatively little information regarding useful methods for C-4 and C-5 halogenation of oxazoles 12.…”

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confidence: 99%

“…Prior literature reveals relatively little information regarding useful methods for C-4 and C-5 halogenation of oxazoles 12. However, the well-behaved carbanion from 7 (Scheme 3, R = SO 2 Ph, X = Li) facilitates convenient halogenation and stannylation reactions yielding 9 and 10 , respectively 11. Furthermore, we have shown that 5-bromo-2-(phenylthio)-1,3-oxazole ( 8 ) undergoes a facile base-induced isomerization, characterized as a halogen dance rearrangement to provide access to the 4-bromo-1,3-oxazole 11 (85%) 13.…”

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confidence: 99%

Efficient Suzuki and Stille Reactions for Regioselective Strategies of Incorporation of the 1,3-Oxazole Heterocycle: Mild Desulfonylation for the Synthesis of C-4 and C-5 Monosubstituted Oxazoles

Williams¹,

Fu²

2010

Synlett

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Suzuki and Stille cross-coupling reactions are surveyed for site-selective C-4 and C-5 elaboration of 2-(phenylsulfonyl)-1,3-oxazole derivatives. Conditions for mild reductive desulfonylations provide for direct incorporation of the intact oxazole heterocycle through bonding at C-4 and C-5. Keywords cross-coupling reactions; arylation; alkenylation; reductive desulfonylationOxazoles represent an important class of five-membered heterocycles. 1 In recent years, this heterocyclic system has frequently been identified as a significant structural feature, embedded within the architecture of complex natural products. 2 Several interesting antibiotics prominently display 1,3-oxazoles as a result of cyclodehydration of serine or threonine residues in the course of biosynthesis. 3 Not surprisingly, a number of cyclodehydration strategies, beginning with acyclic amides, have been developed to provide for the de novo preparation of substituted 1,3-oxazoles. 4 These pathways for oxazole synthesis have limitations, which are often based on the reactivity and the availability of the starting amide precursors. As a result, there is a need for generally applicable techniques, which permit regioselective incorporation of the intact oxazole heterocycle. Our studies have documented a synthetic design utilizing 2-(phenylsulfonyl)-1,3-oxazole (1) for site specific arylations, alkenylations, and alkylations of the heterocyclic ring leading to the production of 2,4-and 2,5-disubstituted oxazoles 2 as well as 4-and 5-monosubstituted-1,3-oxazoles 3 (Scheme 1).Several laboratories have described examples of cross-coupling processes of arylation and alkenylation at C-2 of the oxazole nucleus, 5 and Stille reactions of 2-phenyl-1,3-oxazole have led to C-4 and C-5 arylation reactions. 6 Recently, Stambuli and coworkers have described the selective C-5 deprotonation of 2-methylthio-1,3-oxazole with tert-butyllithium affording access to 2,5-disubstituted oxazoles. 7 These efforts have advanced the previous studies of Shafer and Molinski, 8 as well as a previous report by Marino and Nguyen disclosing the regioselective allylation of 2-(n-butylthio)-1,3-oxazole. 9Fax +1(812)8558300; williamd@indiana.edu. Supporting Information for this article is available online at http://www.thieme-connect.com/ejournals/toc/synlett. NIH Public Access Author ManuscriptSynlett. Author manuscript; available in PMC 2011 July 1. Published in final edited form as:Synlett. In 1997, we reported the site-selective (C-4) deprotonation of 1-[2′-(trimethylsilyl) ethoxymethyl]-2-(phenylsulfonyl)-imidazole (4), and subsequent reactions with a variety of electrophiles (Scheme 2). 10 As illustrated with the formation of 6, mild removal of SEM protection and reductive desulfonation with 2% Na(Hg) provided a scheme for imidazole incorporation.Our studies also examined the analogous (C-5) ring metalation of 2-(phenylsulfonyl)-1,3-oxazole and alkylations of this reactive carbanion. Subsequent reactions for displacement of the 2-(phenylsulfonyl) group have established a ...

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General Methodology for the Preparation of 2,5-Disubstituted-1,3-oxazoles

Cited by 68 publications

References 30 publications

Metal-free synthesis of polysubstituted oxazoles via a decarboxylative cyclization from primary α-amino acids

Metal-free synthesis of polysubstituted oxazoles via a decarboxylative cyclization from primary α-amino acids

Widely Exploited, Yet Unreported: Regiocontrolled Synthesis and the Suzuki–Miyaura Reactions of Bromooxazole Building Blocks

Efficient Suzuki and Stille Reactions for Regioselective Strategies of Incorporation of the 1,3-Oxazole Heterocycle: Mild Desulfonylation for the Synthesis of C-4 and C-5 Monosubstituted Oxazoles

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