Staudinger aza-Wittig Reaction Research Articles

Mechanochemical synthesis of β-cyclodextrin urea derivatives under reactive CO2 atmosphere by Staudinger aza-Wittig reaction

Easily synthesize various ureido β-cyclodextrins with minimal environmental impact using a fast and solvent-free mechanochemical process under carbon dioxide reactive atmosphere.

Isoquinoline-Forming Staudinger–aza-Wittig Reaction Enabled by Atroposelective PIII/PIV=O Redox Catalysis

Isoquinoline-Forming Staudinger–aza-Wittig Reaction Enabled by Atroposelective PIII/PIV=O Redox Catalysis

Spotlight on the Winners of the DCO‐SCF 2021 Awards – An Ever Valuable Collaboration with EurJOC

Spotlight on the Winners of the DCO‐SCF 2021 Awards – An Ever Valuable Collaboration with EurJOC

Enantioselective Synthesis of Quaternary Oxindoles: Desymmetrizing Staudinger-Aza-Wittig Reaction Enabled by a Bespoke HypPhos Oxide Catalyst.

This paper describes a catalytic asymmetric Staudinger-aza-Wittig reaction of (o-azidoaryl)malonates, allowing access to chiral quaternary oxindoles through phosphine oxide catalysis. We designed a novel HypPhos oxide catalyst to enable the desymmetrizing Staudinger-aza-Wittig reaction through the PIII/PV═O redox cycle in the presence of a silane reductant and an IrI-based Lewis acid. The reaction occurs under mild conditions, with good functional group tolerance, a wide substrate scope, and excellent enantioselectivity. Density functional theory revealed that the enantioselectivity in the desymmetrizing reaction arose from the cooperative effects of the IrI species and the HypPhos catalyst. The utility of this methodology is demonstrated by the (formal) syntheses of seven alkaloid targets: (-)-gliocladin C, (-)-coerulescine, (-)-horsfiline, (+)-deoxyeseroline, (+)-esermethole, (+)-physostigmine, and (+)-physovenine.

Catalytic Asymmetric Staudinger-aza-Wittig Reaction for the Synthesis of Heterocyclic Amines.

Many natural products and medicinal drugs are heterocyclic amines possessing a chiral quaternary carbon atom in their heterocyclic ring. Herein, we report the first catalytic and asymmetric Staudinger-aza-Wittig reaction for the desymmetrization of ketones. This highly enantioselective transformation proceeds at room temperature to provide high yields-even on multigram scales-of nitrogen heterocycles featuring a chiral quaternary center. The products of this reaction are potential precursors for the synthesis of pharmaceuticals. A commercially available small P-chiral phosphine catalyst, HypPhos, induces the asymmetry and is recycled through in situ reduction of its oxide, mediated by phenylsilane in the presence of a carboxylic acid. The efficiency, selectivity, scalability, mild reaction conditions, and broad substrate scope portend that this process will expedite the syntheses of chiral heterocyclic amines of significance to chemistry, biology, and medicine.

Approach to 5-substituted 6,7,8,9-tetrahydro-5H-pyrido[3,2-c]azepines

An approach to 5-substituted 6,7,8,9-tetrahydro-5H-pyrido[3,2-c]azepines via the cyclization of 1-(2-(3-azidopropyl)pyridin-3-yl)alkanones under Staudinger–aza-Wittig reaction conditions is described. The overall reaction sequence includes eight steps and allows for the preparation of gram quantities of the title products. In some cases, the formation of 5,7,8,9-tetrahydrooxepino[4,3-b]pyridine derivatives was observed.

Synthesis of new saccharide azacrown cryptands

New cryptands including bis-azacrown and saccharidic moieties in their structure were prepared in several steps by applying Staudinger–aza-Wittig reaction (SAW). Syntheses have been started from cheap, easily available commercial compounds such as D-glucose, D-cellobiose and D-lactose subsequently transformed into their derivatives in fairly good yields (60–65%) and suitable to give desired final cryptands by direct SAW coupling reactions.

Capped guanidino-α-cyclodextrin first synthesis based on intramolecular Staudinger-Aza-Wittig (SAW) reaction

An intramolecularly promoted SAW reaction between a phosphinimide and an isocyanate intermediate led to an original bridged trisubstituted ((A,C),E)-α-cyclodextrin. The latter was in a second step converted into a new capped (ACE)-(guanidino)-α-cyclodextrin.

ChemInform Abstract: A New Synthesis of Pyrido[4,3‐d]pyrimidin‐2‐ones.

AbstractTitle compounds [(V) and (VIII)] are synthesized using the Staudinger—aza—Wittig reaction of dihydropyrimidinone derivatives (IV) or (VII), respectively.

One-pot sequential synthesis of isocyanates and urea derivatives via a microwave-assisted Staudinger–aza-Wittig reaction

A fast and efficient protocol for the synthesis of N,N'-disubstituted urea derivatives from alkyl halides and primary or secondary amines has been developed. The synthetic pathway combines nucleophilic substitutions and a Staudinger–aza-Wittig reaction in the presence of polymer-bound diphenylphosphine under 14 bar of CO2 pressure and has been performed in a one-pot two-step process. The protocol has been optimized under microwave irradiation and the scale-up experiment has been conducted under conventional conditions in a Parr reactor. The final compounds were isolated after simple filtration in almost quantitative overall yields which makes this procedure facile and rapid to execute.

A new synthesis of pyrido[4,3-d]pyrimidin-2-ones

Title compounds [(V) and (VIII)] are synthesized using the Staudinger—aza—Wittig reaction of dihydropyrimidinone derivatives (IV) or (VII), respectively.

Flow synthesis of organic azides and the multistep synthesis of imines and amines using a new monolithic triphenylphosphine reagent

Here we describe general flow processes for the synthesis of alkyl and aryl azides, and the development of a new monolithic triphenylphosphine reagent, which provides a convenient format for the use of this versatile reagent in flow. The utility of these new tools was demonstrated by their application to a flow Staudinger aza-Wittig reaction sequence. Finally, a multistep aza-Wittig, reduction and purification flow process was designed, allowing access to amine products in an automated fashion.

Synthesis of 2‐Alkylidenepyrrolidines and Pyrroles by Condensation of 1,3‐Dicarbonyl Dianions with α‐Azidoketones and Subsequent Intramolecular Staudinger—Aza‐Wittig Reaction.

AbstractChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract, please click on HTML or PDF.

De Novo Synthesis of Sugar‐Aza‐Crown Ethers via a Domino Staudinger Aza‐Wittig Reaction.

AbstractChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract, please click on HTML or PDF.

Synthesis of Sugar-Aza-Crown Ethers

A simple and efficient preparation of sugar-aza-crown (SAC) ethers is described. The key step is a domino Staudinger aza-Wittig reaction for cyclodimerization of C-glycosyl azide aldehydes 1. Treatment of 1 with polymer-bound diphenylphosphine in THF gave the cyclic imines 2 in good yields. Reduction of imines 2 led to the desired sugar-aza-crown (SAC) ethers 3 in 65-74% yield.

De Novo Synthesis of Sugar-Aza-Crown Ethers via a Domino Staudinger Aza-Wittig Reaction

A short and highly efficient route to sugar-aza-crown (SAC) ethers has been developed. The key step of the transformation is a one-pot cyclodimerization of C-glycosyl azido aldehydes via a domino Staudinger aza-Wittig reaction. This process allows the preparation of various orthogonally protected SAC ethers, from both alpha- and beta-C-glycosyl azido aldehydes.

Highly Efficient Synthesis of Medium‐Sized Lactams via Intramolecular Staudinger—aza‐Wittig Reaction of ω‐Azido Pentafluorophenyl Ester: Synthesis and Biological Evaluation of LY411575 Analogues.

AbstractFor Abstract see ChemInform Abstract in Full Text.

Highly efficient synthesis of medium-sized lactams via intramolecular Staudinger–aza-Wittig reaction of ω-azido pentafluorophenyl ester: synthesis and biological evaluation of LY411575 analogues

A highly efficient method for the synthesis of medium-sized lactams based on intramolecular Staudinger–aza-Wittig reaction of ω-azido pentafluorophenyl ester has been developed. A variety of 7–10 membered lactams were synthesized in excellent yields. Application of the method to the synthesis of analogues of a potent γ-secretase inhibitor LY411575 and their biological evaluation are also described.

One-step synthesis of non-anomeric sugar isothiocyanates from sugar azides

Tandem Staudinger–aza-Wittig reaction of primary azidodeoxy sugars with triphenylphosphine–carbon disulfide affords the corresponding primary deoxyisothiocyanato sugars in high yield. No products arising from O→N acyl migration or formation of dimeric carbodiimides were observed. Interestingly, a polymer-supported triarylphosphine can advantageously replace triphenylphosphine, thus limiting the purification step to a simple filtration process. The reaction also allows the preparation of 5-deoxy-5-isothiocyanato sugars, a hitherto unknown class of compounds, from the corresponding azide precursors. Secondary sugar azides bearing the azido group at an endocyclic carbon atom afforded much lower isothiocyanation yields under these reaction conditions.