Diazoaldehyde Chemistry. Part 4vilsmeier‐haack formylation of diazo compounds: A re‐investigation

Abstract

Diazomethyl ketones (2-diazoethanones) were reacted with the Vilsmeier reagent ((chloromethylidene)dimethylammonium chloride) to yield a-diazo-p-oxoaldehydes and chloromethyl ketones. 2',4-Dimethoxy-udiazoacetophenone gave 2-chloro-1-(2,4-dimethoxyphenyl)-3-(dimethylamino)prop-2-en-l-one ( 5 ) in addition to the expected products. Phenyldiazomethanes gave the corresponding benzyl chlorides but not the (pheny1)diazoacetaldehydes even at temperatures as low as -60". The diazo-transfer reactions of phenylacetaldehydes and 2-azido-1 -ethylpyridjn-l -ium tetrafluomborate also did not yield the expected(pheny1)diazoacetaldehydes.Introduction. -a-Diazo-p-oxoaldehydes (1) are valuable synthetic tools with their interesting chemical behavior. In the first part of this series, we reported a fairly general synthetic method for these compounds using a novel diazo-transfer reaction (Scheme 1) [2]. On the other hand, the first report on their synthesis came from Stojanovic and Arnold almost thirty years ago (Scheme 2) [3], seven years after Bosshard and Zollinger had shown in this journal that the Vilsmeier reactions are due to the intermediate formation of (chloromethy1idene)dimethylammonium chloride from dimethylformamide and thionyl chloride (or sulfuryl chloride) [4]. Although the method was low yielding, it was applied to the syntheses of etyhl a-diazo-cr-formylacetate and 2-diazo-3-oxo-3-phenylpropanol which were the only successful examples. Since it had no alternatives, it has been used so far for the synthesis of those compounds. In his papers, Arnold reported that similar formylations of diazoacetone [ 3 ] , diazoacetaldehyde [5], and phenyldiazomethane [3] had not given any identifiable products. Our method was also not successful in certain cases : p-oxoaldehydes (2) possessing electron-releasing R groups such as 2,4-dimethoxyphenyl, t-Bu, and fury1 have a high tendency to undergo deforinylation during the diazo transfer reaction, thus yielding diazomethyl ketones (3) to a higher extent than

Synthesis of 1-Vinyl 1,2,3-Triazole Derivatives

“…All diazo compounds (1,5) and chloromethylene dimethyliminium chloride (6) were prepared as described in [21,22] All diazo compounds (1,5) and chloromethylene dimethyliminium chloride (6) were prepared as described in [21,22] …”

Metalloradical activation of α-formyldiazoacetates for the catalytic asymmetric radical cyclopropanation of alkenes

“…5e , g , h Considering the demonstrated functional group tolerance of Co( ii )-based metalloradical catalysis (Co( ii )-MRC), 5d , e , j – l we were attracted to the possibility of accessing a new type of α-metalloalkyl radical bearing both α-formyl and α-alkoxycarbonyl functionalities from the metalloradical activation of α-formyldiazoacetates (FDA). 6 Despite the fact that free α-formylalkyl radicals are scarce and prone to H-atom abstraction because of the weak aldehydic C–H bonds, 7 we reasoned that this type of α-metalloalkyl radical might be accessible on the basis of the combined effects of metal stabilization, double H-bonding interaction, and protection by the well-defined cavity of the ligand system ( Scheme 1 : A ). Assuming that the α-formyl-α-alkoxycarbonyl-α-Co( iii )-alkyl radicals ( A ) are capable of undergoing stereoselective radical addition with olefins, followed by the effective 3- exo -tet radical cyclization 8 of the corresponding γ-Co( iii )-alkyl radicals ( B ), we anticipated the potential development of a new catalytic process for the asymmetric synthesis of optically active cyclopropanes bearing both aldehyde and ester functionalities, which would be valuable for stereoselective organic synthesis ( Scheme 1 ).…”

Photoredox/Nickel Dual Catalysis-Enabled Aryl Formylation with 2,2-Dimethoxy-N,N-dimethylethan-1-amine as CO Source

“…The classic industrial production of benzaldehyde involves oxidation of alcohol or chlorination/hydrolysis of toluene, but inevitably releasing a significant amount of waste and causing severe corrosion to equipment . Alternatively, other classical processes such as Vielsmeier–Haack, Gattermann–Koch, and Duff reactions were well-established to introduce the formyl group through electrophilic aromatic substitution on laboratory scale . However, the limited scope with respect to only electron-rich aryl substrates as well as poor regioselectivity obstructed their further applications in some cases.…”