Synthesis of enantiomerically pure <i>N</i>-(2,3-dihydroxypropyl)arylamides via oxidative esterification

Raghunadh, Akula; More, Satish S.; Chaitanya, T. Krishna; Kumar, Yadla Sateesh; Meruva, Suresh Babu; Rao, Lu; Kumar, U. K. Syam

doi:10.3762/bjoc.9.250

Cited by 6 publications

(1 citation statement)

References 40 publications

(20 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The ring phthalimide is considered as a stable here aromatic cyclic structure with variable pharmacological interest (Raghunadh et al, 2013[ 31 ]). The effective mechanism of published derivatives is still unclear and needs more research for SAR interpretation (Ahmed et al, 2016[ 2 ]).…”

Section: Study Rationale and Designmentioning

confidence: 99%

Discovery of novel phthalimide analogs: synthesis, antimicrobial and antitubercular screening with molecular docking studies

Rateb

Ahmed

et al. 2016

EXCLI Journal; 15:Doc781; ISSN 1611-2156

View full text Add to dashboard Cite

Section: Study Rationale and Designmentioning

confidence: 99%

Discovery of novel phthalimide analogs: synthesis, antimicrobial and antitubercular screening with molecular docking studies

Rateb

Ahmed

et al. 2016

EXCLI Journal; 15:Doc781; ISSN 1611-2156

View full text Add to dashboard Cite

Radical [1,3] Rearrangements of Breslow Intermediates

Alwarsh

Qian

et al. 2015

Angewandte Chemie

View full text Add to dashboard Cite

Breslow intermediates that bear radical stabilizing N-substituents including benzyl, cinnamyl, and diarylmethyl undergo facile homolytic C-N bond scission under mild conditions to give products of formal [1,3]-rearrangement rather than benzoin condensation. EPR experiments and computational analysis support a radical mechanism. Implications for thiamine based enzymes are discussed. Keywords N-heterocyclic carbene; Breslow intermediate; radical; rearrangement; thiamineThiamine diphosphate (TDP) is an essential cofactor for all living things. It is involved in several critical metabolic processes, including the tricarboxylic acid cycle, the pentose phosphate pathway, and amino acid catabolism. 1,2 In 1958, Ronald Breslow postulated that key intermediates in thiamine catalyzed enzymatic pathways included an N-heterocyclic carbene (1) and an enaminol, e.g. 2 (Scheme 1). 3 In pyruvate decarboxylation, for example, addition of the TDP carbene to pyruvate is followed by extrusion of CO 2 to provide unstable enaminol 2. This and related heterocyclic enaminols have collectively been called "Breslow intermediates." 4 Only recently have such compounds been rigorously characterized, 5,6 and new chemistry continues to be revealed. 7 We recently reported that Breslow intermediates such as 2a derived from N-allyl benzothiazolium bromide and aromatic aldehydes could be captured in a unique Claisen rearrangement to provide 2-butenyl benzothiazoles (Scheme 2, R=H). 8,9 In the course of examining the scope of the reaction, we were surprised to find that N-cinnamyl substituted salt 3b provided principally [1,3]-rearrangement product 4b upon reaction with benzaldehyde, accompanied by only ca. 5% of the nominal [3,3]-product. The [1,3]-rearrangement product clearly implied a stepwise process in competition with the concerted rearrangement.Correspondence to: Matthias C. McIntosh, mcintosh@uark.edu. Supporting information for this article is given via a link at the end of the document. HHS Public Access Author Manuscript Author ManuscriptAuthor Manuscript Author ManuscriptReaction of N-benzyl and N-diphenylmethyl benzothiazolium salts under the same conditions also yielded [1,3]-rearrangement products, albeit in diminished yield in the case of benzyl salt 3c (Scheme 3). The structures were confirmed by X-ray crystallography.Many NHC catalyzed reactions of aldehydes are presumed to proceed via a Breslow intermediate, 10 so these observations are relevant to NHC catalysis and catalyst design. Since benzothiazolium salts are only occasionally employed as NHC catalysts, 11 we exposed thiazolium and triazolium salts to the reaction conditions (Scheme 4). Reaction of thiazolium salt 3e with benzaldehyde gave high yield of [1,3]-rearrangement product 4e, as well as a few percent of ketone 5e. Treatment of symmetrically substituted 1,2,4-triazole 3f provided rearrangement product 4f in low yield as the only isolable product, although interestingly as a single regioisomer resulting from migration of the N-4 substituent. No significant ...

show abstract