Mitsunobu Reagents Research Articles

Teaching old dogs (Fmoc-amine, azodicarboxylate, and phosphine) new tricks (triazolinones)

Abstract Exposure of Fmoc-amines to an excess of standard Mitsunobu reagents, azodicarboxylate and triphenylphosphine, at ambient temperature yielded triazolinone derivatives in high yield and purity. This transformation appeared to be general and the traditional Mitsunobu reaction can be carried out independently of triazolinone formation because the latter requires a high excess of reagents.

Azodicarbonyl dimorpholide (ADDM): an effective, versatile, and water-soluble Mitsunobu reagent

Abstract One of the caveats of the Mitsunobu reaction is the often difficult and laborious purification of the reaction mixture. Herein, we show that azodicarbonyl dimorpholide (ADDM) is an effective and versatile Mitsunobu reagent, which, along with its reduced form ADDM-H2, may be removed from the reaction mixture by a simple aqueous extraction. Furthermore, we demonstrate that the isolated ADDM-H2 may be re-oxidized with silver(I) oxide to regenerate ADDM. Finally, a chromatography-free Mitsunobu reaction is presented.

Back Cover: Recyclable Mitsunobu Reagents: Catalytic Mitsunobu Reactions with an Iron Catalyst and Atmospheric Oxygen (Angew. Chem. Int. Ed. 17/2013)

Back Cover: Recyclable Mitsunobu Reagents: Catalytic Mitsunobu Reactions with an Iron Catalyst and Atmospheric Oxygen (Angew. Chem. Int. Ed. 17/2013)

An Efficient Synthesis of Enantiomerically Pure trans-N1,N2-dimethylcyclohexane-1,2-diamine

A new pathway is described to produce a highly optically pure isomer of trans-N1,N2-dimethylcyclohexane-1,2-diamine through four simple steps. Reaction of cyclohexene oxide with aqueous methylamine, followed by cyclisation with Mitsunobu reagent and ring-opening reactions gave rac-trans- N1,N2-dimethylcyclohexane-1,2-diamine, and the enantiomers were obtained via a kinetic resolution using tartaric acid.

Recyclable Mitsunobu Reagents: Catalytic Mitsunobu Reactions with an Iron Catalyst and Atmospheric Oxygen

Aerobes Recycling: Eine katalytische Menge eines Hydrazinreagens genügt, um Mitsunobu-Reaktionen in Gegenwart von Triphenylphosphan, einem Eisen-Katalysator und Luft zu vermitteln. Die aktive Form des Katalysators, eine Azo-Spezies, kann einfach durch Eisen-katalysierte aerobe Oxidation erzeugt werden. MS=Molekularsieb, Pc=Phthalocyanin.

Recyclable Mitsunobu Reagents: Catalytic Mitsunobu Reactions with an Iron Catalyst and Atmospheric Oxygen

Aerobic recycling: A catalytic amount of a hydrazine reagent is sufficient to promote Mitsunobu reactions in the presence of triphenylphosphine, an iron catalyst, and air. The active form of the catalyst, an azo species, can be readily generated by iron-catalyzed aerobic oxidation. MS = molecular sieves, Pc = phthalocyanine.

Rapid and efficient synthesis of [11C]ureas via the incorporation of [11C]CO2 into aliphatic and aromatic amines

A rapid urea radiolabelling methodology has been developed. [(11)C]CO2 was activated by 1,8-diazabicycloundec-7-ene (DBU) in the presence of aliphatic and aromatic amines and reacted with Mitsunobu reagents to produce asymmetric (11)C radiolabelled ureas in high radiochemical yields.

Formation of an Unusual Four-Membered Nitrogen Ring (Tetrazetidine) Radical Cation

Treatment of triphenylphosphine (Ph(3)P) with an excess of diisopropyl azodicarboxylate at 0-25 °C resulted in the formation of a symmetrical tetraalkyl tetrazetidinetetracarboxylate radical cation, containing the elusive cyclic N(4) ring system. Electron paramagnetic resonance (EPR) spectroscopy revealed a 9-line spectrum, with hyperfine coupling constants indicative of four almost magnetically equivalent nitrogen atoms. The radical species was surprisingly long-lived, and could still be observed several hours after generation and standing at 25 °C. Expansion of the central resonance revealed further splitting into a pentet (hyperfine coupling to the four methine protons). Three mechanistically plausible structures containing the tetrazetidine substructure were proposed based on the 9-line EPR spectrum. Following DFT calculations, the predicted hyperfine coupling constants were used to simulate the EPR spectra for the three candidate structures. The combined calculations and simulations were consistent with a radical cation species, but not a radical anion or radical-carbenoid structure. The lowest energy conformation of the N(4) ring was slightly puckered, with the alkyl carboxylate groups all trans and the four carbonyl groups aligned in a pinwheel arrangement around the ring. Analogous results were obtained with the original Mitsunobu reagents, Ph(3)P and diethyl azodicarboxylate, but not with Ph(3)P and di-tert-butyl azodicarboxylate. A mechanism is proposed based on a radical version of the Rauhut-Currier or Morita-Baylis-Hillman reactions.

ChemInform Abstract: Application of Mitsunobu Reagents to Redox Isomerization of CF3‐Containing Propargylic Alcohols to (E)‐α,β‐Enones.

Isomerization of CF(3)-containing secondary propargylic alcohols proceeds with excellent E selectivity by treatment with Mitsunobu reagents, tris(p-methoxyphenyl)phosphine (TMPP), and 1,1'-(azodicarbonyl)dipiperidine (ADDP) in the presence of phenol.

Application of Mitsunobu Reagents to Redox Isomerization of CF3-Containing Propargylic Alcohols to (E)-α,β-Enones

Isomerization of CF(3)-containing secondary propargylic alcohols proceeds with excellent E selectivity by treatment with Mitsunobu reagents, tris(p-methoxyphenyl)phosphine (TMPP), and 1,1'-(azodicarbonyl)dipiperidine (ADDP) in the presence of phenol.

Regioselective N-alkylation of (2-chloroquinolin-3-yl) methanol with N-heterocyclic compounds using the Mitsunobu reagent

AbstractThe Mitsunobu reaction is a well-established fundamental reaction and has been widely applied in organic synthesis. In this paper, under Mitsunobu conditions dehydration proceeds between (2-chloroquinolin-3-yl)methanol and nitrogen heterocyclic compounds such as quinazolinone, pyrimidone, 2-oxoquinoline in dry THF in the presence of triethylamine, triphenylphosphane and diethyl azodicarboxylate to give the corresponding products. As part of our recent research, we attempted to couple two N-heterocyclic compounds under Mitsunobu reaction conditions to provide efficient building blocks for natural product synthesis.

ChemInform Abstract: A Facile One-Pot Cyanation of Primary and Secondary Alcohols. Application of Some New Mitsunobu Reagents.

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ChemInform Abstract: From Methyl D-Glucopyranoside to Methyl D-Allopyranoside via the Mitsunobu Reaction.

Methyl β-d-glucopyranoside reacted with a 4-molar excess of the Mitsunobu reagents (triphenylphosphine–diethyl azodicarboxylate–benzoic acid) under Weinges et al. [Carbohydr. Res., 164 (1987) 453–458] conditions to furnish four differently benzoylated methyl β-d-allopyranosides in a very good overall yield. The same reaction applied to methyl α-d-glucopyranoside yielded allosides in a low yield and nine other sugar products. These results give an insight into the course of the Mitsunobu esterification–inversion reaction.

Parallel Synthesis of Ureas and Carbamates from Amines and CO2 under Mild Conditions

A mild and efficient library synthesis technique has been developed for the synthesis of ureas and carbamates from carbamic acids derived from the DBU-catalyzed reaction of amines and gaseous carbon dioxide. Carbamic acids derived from primary amines reacted with Mitsunobu reagents to generate isocyanates in situ which were condensed with primary and secondary amines to afford the desired ureas. Similarly, carbamic acids from secondary amines reacted with alcohols activated with Mitsunobu reagents to form carbamates.

Synthetic access to optically active isoflavans by using allylic substitution

A general approach to the ( S)- and ( R)-isoflavans was invented, and efficiency of the method was demonstrated by the synthesis of ( S)-equol (( S)- 3), ( R)-sativan (( R)- 4), and ( R)-vestitol (( R)- 5). The key step is the allylic substitution of ( S)- 6a (Ar 1=2,4-(MeO) 2C 6H 3) and ( R)- 6b (Ar 1=2,4-(BnO) 2C 6H 3) with copper reagents derived from CuBr·Me 2S and Ar 2-MgBr ( 7a, Ar 2=4-MeOC 6H 4; 7b, 2,4-(MeO) 2C 6H 3; 7c, 2-MOMO-4-MeOC 6H 3), furnishing anti S N2′ products ( R)- 8a and ( S)- 8b, c with 93–97% chirality transfer in 60–75% yields. The olefinic part of the products was oxidatively cleaved and the Me and Bn groups on the Ar 1 moieties was then removed. Finally, phenol bromide 9a and phenol alcohols 9b, c underwent cyclization with K 2CO 3 and the Mitsunobu reagent to afford ( S)- 3 and ( R)- 4 and - 5, respectively.

An efficient, one-pot synthesis of trithiocarbonates from the corresponding thiols using the Mitsunobu reagent

A novel Mitsunobu-based protocol has been developed for the synthesis of a variety of symmetrical and unsymmetrical trithiocarbonates from primary, secondary and tertiary thiols using carbon disulfide, in good to excellent yields. This protocol is mild and efficient compared to other reported methods.

Second-Generation Tags for Fluorous Chemistry Exemplified with a New Fluorous Mitsunobu Reagent

A new fluorous DEAD reagent bearing two perfluoro-tert-butyloxy groups with propylene spacers shows excellent promise for use in fluorous Mitsunobu reactions. Pure target products were obtained in good yields after removing fluorous byproducts by FSPE. The new reagent serves as a prototype for a greener second generation of fluorous reagents bearing tags that are not expected to degrade in the environment to compounds that are highly persistent or that bioaccumulate in higher organisms.

The Facile Preparation of Primary and Secondary Amines via an Improved Fukuyama—Mitsunobu Procedure. Application to the Synthesis of a Lung‐Targeted Gene Delivery Agent.

AbstractFor Abstract see ChemInform Abstract in Full Text.

Reactivity of Mitsunobu Reagent Toward Carbonyl Compounds.

AbstractFor Abstract see ChemInform Abstract in Full Text.

Reactivity of Mitsunobu Reagent toward Carbonyl Compounds

ADVERTISEMENT RETURN TO ISSUEPREVAdditions & Corr...Additions & CorrectionsORIGINAL ARTICLEThis notice is a correctionReactivity of Mitsunobu Reagent toward Carbonyl CompoundsRyan D. Otte, Tomoyo Sakata, Ilia A. Guzei, and Daesung LeeCite this: Org. Lett. 2005, 7, 7, 1435Publication Date (Web):February 26, 2005Publication History Published online26 February 2005Published inissue 1 March 2005https://doi.org/10.1021/ol0503586Copyright © 2005 American Chemical SocietyRIGHTS & PERMISSIONSArticle Views539Altmetric-Citations1LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InReddit PDF (4 KB) Get e-AlertsSUBJECTS:Carbonyls,Reactivity,Reagents Get e-Alerts