A Crossover Mechanistic Investigation of the Wolff vs. photo-Favorskii Rearrangement of Diazo-p-Hydroxyacetophenone: Methoxy Substituent Effects on p-Hydroxyphenacyl Cage; Exploratory Studies of Hydroxyquinoline-Based Phototriggers

A series of substituted p-hydroxyphenacyl (pHP) and 8-hydroxyquinoline photoremovable protecting groups were designed, synthesized and their photochemistry explored. The light-induced release of phosphates, carboxylates, phenyl ethers and molecular nitrogen (N2) was studied. It was found that photorelease of diethyl phosphate from o-methoxy substituted pHP derivatives were 50% more efficient than the m-methoxy derivatives. In addition, convenient, high yield, one-pot syntheses of several p-HP chromophores were made from their corresponding benzoic acids via the α-diazo-p-hydroxyacetophenones. Photochemical and photophysical studies of the diazo pHP derivatives provided insight into the mechanism of N2 release. Time-resolved IR spectroscopic measurements, sensitization and quenching studies and product analyses support a mechanism for nitrogen release that proceeds via a photochemical Wolff rearrangement pathway. A preliminary study on the photochemistry of 1,5-substituted 8-hydroxyquinolines showed a strong dependence on the leaving group and the presence or absence of oxygen for this heterocyclic pHP analog

2-Diazo-1-(4-hydroxyphenyl)ethanone: A Versatile Photochemical and Synthetic Reagent

α-Diazo arylketones are well-known substrates for Wolff rearrangement to phenylacetic acids through a ketene intermediate by either thermal or photochemical activation. Likewise, α-substituted p-hydroxyphenacyl (pHP) esters are substrates for photo-Favorskii rerrangements to phenylacetic acids by a different pathway that purportedly involves a cyclopropanone intermediate. In this paper, we show that the photolysis of a series of α-diazo-p-hydroxyacetophenones and p-hydroxyphenacyl (pHP) α-esters both generate the identical rearranged phenylacetates as major products. Since α-diazo-p-hydroxyacetophenone (1a, pHP N2) contains all the necessary functionalities for either Wolff or Favorskii rearrangement, we were prompted to probe this intriguing mechanistic dichotomy under conditions favorable to the photo-Favorskii reangement, i.e., photolysis in hydroxylic media. An investigation of the mechanism for conversion of 1a to p-hydroxyphenyl acetic acid (4a) using time-resolved infrared (TRIR) spectroscopy clearly demonstrates the formation of a ketene intermediate that is subsequently trapped by solvent or nucleophiles. The photoreaction of 1a is quenched by oxygen and sensitized by triplet sensitizers and the quantum yields for 1a–c range from 0.19 to a robust 0.25. The lifetime of the triplet, determined by Stern-Volmer quenching, is 15 ns with a rate for appearance of 4a of k = 7,1 × 106 s−1 in aq. acetonitrile (1:1 v:v). These studies establish that the primary rearrangement pathway for 1a involves ketene formation in accordance with the photo-Wolff rearrangement. Furthermore we have also demonstrated the synthetic utility of 1a as an esterification and etherification reagent with a variety of substituted α-diazo-p-hydroxyacetophenones, using them as synthons for efficiently coupling it to acids and phenols to produce pHP protect substrates

Org. semin. abstr.

Issued by: University of Illinois, Department of Chemistry and Chemical Engineering, 1962-1963/semester I-; University of Illinois at Urbana-Champaign, Department of Chemistry, <1982-83-

Design and synthesis of components for optically active metal-organic frameworks (MOFs) and synthetic routes to diverse deuterium labelled α-diazoacetates, α-diazoacetamides, α-diazoketones, and the antibiotic azaserine

Metal-organic frameworks (MOFs) are porous crystalline solids that consist of metal nodes connected to organic linkers that assemble into one-, two- or three-dimensional frameworks. Among other applications they have recently found use in heterogeneous asymmetric catalysis. Since that time the demand for new optically active MOFs has increased and novel chiral non-racemic building blocks for their assembly are required. The first part of this PhD thesis entails the synthesis of a novel linear organic linker equipped with ester functional groups for the future introduction of a chiral centre. In addition, a selection of novel axially chiral (S)-BINOL-derived building blocks bearing 1,2,3-triazole moieties is described. Secondary functional groups can undergo post-synthetic modification resulting in the introduction of a catalytically active site. Within this research project an effective method for purification of commercially available acetylene was developed and a reliable protocol for a [2+2+2] cycloaddition reaction of 1,6-diyne with acetylene was established. The 2,2'-bipyridine moiety was successfully installed in the axially chiral (S)-BINOL-based linker providing a highly effective chelating ligand. α-Diazocarbonyl compounds are useful intermediates for various chemical transformations. Although known since the mid-1800s, they still offer an area for future studies and development of preparative methods as well as applications. With the recently growing need for labelled compounds, they appear to be ideal candidates for the introduction of deuterium. This area of research is presented in the second part of this PhD thesis. The synthesis of an array of α-diazocarbonyl acetic acid esters and α-diazoketones and their utilisation in a hydrogen / deuterium exchange reaction are described. Within this research project a quick, reliable and highly efficient protocol for a base-catalysed hydrogen / deuterium exchange reaction at the α-carbon atom of α-diazocarbonyl compounds was successfully developed furnishing products with moderate to high yields (63% to 90%) and excellent levels of deuterium incorporation (≥96%). This protocol was also successfully utilised in the synthesis of α-deutero-α-diazoacetic acid ester-derived α-amino acids and α-diazoacetamide-derived α- and β-amino acids. The first chemical synthesis of a deuterium-labelled azaserine analogue was accomplished. Additionally, two protocols for the preparation of α-deuterated aromatic aldehydes have been established. The third part of this PhD thesis illustrates briefly the synthesis of (S)-N-triflyl VANOL phosphoramide and its employment as a catalyst in asymmetric aziridination reactions

Asymmetric 1,3-dipolar cycloadditions of acrylamides

This critical review, which is relevant to researchers in synthetic organic chemistry, focuses on asymmetric 1,3-dipolar cycloadditions with acrylamides. The use of chiral acrylamides as dipolarophiles leads to high levels of stereocontrol, due to conformational constraint in the acrylamides. Employment of chiral tertiary acrylamides containing nitrogen heterocycles is particularly effective in controlling the stereoselectivity. Following a general overview of 1,3-dipolar cycloadditions, the main body of the review focuses on asymmetric 1,3-dipolar cycloadditions of acrylamides with nitrile oxides, nitrones, diazoalkanes and azomethine ylides, with particular emphasis on the rationale for the observed stereocontrol (215 references)