Hydroxylamine ethers synthesis

The aUcoxylamines have a >N—O—C substrucmre and may be considered O-substituted hydroxylamine ethers. The simplest example of these species is MeONH2 with a gas phase enthalpy of formation of —25.1 kJmol which was discussed in a previous section. Consider now the perfluorinated species (CF3)2N0CF2CF20N(CF3)2 and its synthesis shown in equation 9. 

A rational extension of ortho-tolyl benzamide metalation [68], part of the broadly encompassing lateral metalation protocol [69] that can be DoM-connected, is the DreM equivalent, 154 —> 155 (Scheme 41), which provides a general regioselective route to 9-phenanthrols (156, 157, 158) [70] and may be extended to diaryl nitriles, hydroxylamine ethers, and hy-drazones 160, which provide the corresponding 9-amino derivatives 161 of similar generality 162-165 (Scheme 42), as may also be applied in natural product synthesis [71]. Further opportunities for DoM-cross-coupling and reduction/oxidation chemistry (159) have also been demonstrated [70a]. 

Pd/C-cyclohexene in refluxing benzene T selectivity. 1-Alkene oxides undergo C-O t treatment with Pd/C and HCOONH in ethaa Amidoximes [RC(NH2)=NOH], which hydroxylamine, are hydrogenolyzed (H Pd/ Ether synthesis. Hydrogenation of a e affords ether. A hemiacetal is the intermedu... 

Aziridines represent an important class of building block within synthesis. This structural motif is also embedded within a number of biologically significant natural products, and thus robust and efficient methods for their construction represent an important contribution to the synthetic toolkit. Cordova reported an enantiose-lective aziridination of a,P-unsaturated aldehydes catalysed by diarylprolinol ether 30 using protected hydroxylamine 91 as the nitrogen source (Scheme 38) [150]. The reaction was proposed to proceed via iminium ion formation followed by... 

Strategies that lead to the formation of isoxazoles during cleavage from an insoluble support include the oxidative cleavage of /V-(4-alkoxybenzyl)isoxazolidincs with DDQ to yield isoxazolines (Entry 14, Table 15.16), the nucleophilic cleavage of 2-acyl enamines with hydroxylamine (Entry 15, Table 15.16), and the acidolysis of 2-cyano-phenols etherified with an oxime resin (Entry 17, Table 15.16). The required oxime ethers for the latter synthesis were prepared by reaction of the corresponding 2-fluorobenzonitriles with Kaiser oxime resin [203],... 

The Beckmann rearrangement is used in a similar way to produce the lactam 32, an intermediate in the synthesis of swainsonine 33. Stereoselective addition of dichloroketene to the enol ether 30 gave one isomer ( 95 5) of cyclobutanone 31. Beckmann rearrangement with a sulfonated hydroxylamine and dechlorination gave the lactam 32 in 34% yield over five steps7 from a precursor of 30. Note that the m-alkene 30 gives the trans cyclobutanone selectively. 

Enmein was converted to 20-hydroxykaur-6-en-15a-pyranylether (382), which was oxidized with chromium trioxide in pyridine to afford the aldehyde 383. The latter was converted with hydroxylamine to the oxime 384. The nitrone 385 was prepared by treatment of 384 with bromine azide. Photolysis of 385 gave the desired compound 381 in 46% yield. This intermediate possesses several useful functionalities (e.g., carbinolamine ether linkage), which may be of interest for synthesis of C20-diterpenoid alkaloids after minor changes in this scheme. 

Pyridine synthesis.1 Dihydropyrans (1), formed by cycloaddition of aryl en-ones with vinyl ethers (12,561), can serve as protected 1,5-dicarbonyl compounds and react with hydroxylamine (2 equiv.) to form 2,4-disubstituted pyridines (2). 

The reduction can also be achieved by utilizing in situ generated BHj THF (from sodium borohydride and boron trifluoride etherate). The scope of this reaction includes the synthesis of novel 3-chroman-amine derivatives (60 equation 33). This stereoselective reaction proceeds via the hydroxylamine intermediate only c/s-2-aryl-3-amino derivatives are obtained. 

In 1996, Ciufoiini and Roschanger reported a total synthesis of phenanthroindolizidine alkaloids (tylophorine and antofine) from the sterically congested 2-substituted 4,5-diarylpyridine 61, which was prepared by a modified Knoevenagel-Stobbe synthesis [61]. Scheme (6) outlines the steps in their approach. Central to the success of this effort was the ability of a-dicarbonyl enone 58 to combine in a formal [4+2]-cycloaddition with the sterically demanding vinyl ether 56, The resultant pyran 59 was treated with DIBAL and protected with benzyl chloride giving 60, which was then treated with hydroxylamine hydrochloride to give diarylpyridine 61, After a two-step conversion of 61 to 63, a cyano... 

Petrini and co-workers used the bis(methoxymethyl)-protected nitrone 150, also derived frern L-tartrate, as an electrophile rather tfaiui as a 1,3-dipole (Scheme 21, top line) (89). In their key step, reaction with 4-ben loxybutylmagnesium bromide gave the cyclic hydroxylamine 151 in 82% yield (de 90%). Transfer hydrogenation with ammonium formate and a palladium catalyst cleaved both the hydroxylamine and the benzyl ether, affording the aminoalcohol 152. Cyclization via the corresponding primary chloride created the protected indolizidine 153, acidic hydrolysis of t ch completed this short synthesis of ( + )-132 in 16%... 

The readily available 2,3,4,6-fefra-O-benzyl-D-glucopyranose (11) can be used for the synthesis of both nojirimycin (1) and 1-deoxynojirimycin (2) (Schemed).It was treated with EtSH to furnish 12, which was oxidized to the corresponding ketone 13 using TPAP, while the Swern oxidation method failed to produce 13. Treatment of 13 with mercury(ll) salts in the presence of methanol followed by treatment with hydroxylamine hydrochloride in the presence of pyridine afforded the oxime 14 in 73% yield. Treatment of 14 with LiAlH4 in diethyl ether followed by N-protection of the resulting diastereomeric mixture of amines with di-rert-butyl dicarbonate furnished 15 and 16 in 65 and 15% yield, respectively. Pearlman s catalytic hydrogenation of 15 over palladium hydroxide in ethanol followed by treatment of the resulting tetrol with SO2 in water furnished the sulfonic acid 17 in 80% yield. Conversion of 17 into 1 was accomplished by treatment with Dowex 1X2 (OH ) resin. 

The total synthesis of ( )-trichostatin A has been carried out by two routes [67] one uses the y-alkylation of a silyl dienol ether with an acetal which gives the ether in a Mukaiyama reaction. A Wittig olefination followed by DDQ oxidation gives a ketoester which reacts with hydroxylamine to give trichostatin A in 22% overall yield (Scheme 20). 

Method 6 (best yield) CPB 19,46(1971), JCS 121,1638(1922) To prepare diethylacetone dicarboxylate (1) proceed as in method 3 for cocaine synthesis, substituting 720 ml ethanol for methanol. To 197 g (I), add rapidly with stirring and cooling 208 g PClj, keeping temperature below 50°. When HCl evolution stops, pour into water and add ice as necessary to cool. Extract the red oil with ether and dry, evaporate in vacuum. Boil residue 2 /2 hours with 20% HCl, evaporate the water and dissolve the residue in ether. Dry and evaporate in vacuum to get 100 g 3-CI-giutaconate (II). 100 g (II), 300 g ethanol, 50 ml sulfuric acid and reflux while passing in ethanol vapor until 1.5 L collects. Add water, extract with ether, wash with aqueous Na carbonate and dry, evaporate in vacuum to get 113 g diethyl-3-CI-glutaconate (III). Mix 28 g NaOH, 140 ml water, 10.4 g hydroxylamine.HCl, 280 ml ethanol and cool to -35° in acetone-dry ice bath. Stir and add 30.3 g (111) in 50 ml ethanol over two minutes stir one hour (can let stand twelve hours). Neutralize with... 

Benzofurans and Other Annelated Furans.-A new synthesis of benzofurans (73) is by the reaction of the phosphonium salt (72) with acid chlorides RCOCl in the presence of triethylamine. The benzofuran (74) results from the condensation of hexafluorobenzene with acetylacetone. Three instances of the formation of benzofurans from O-aryl-hydroxylamines, i.e. the oxygen analogue of the Fischer indole synthesis, have been reported O-phenylhydroxylamine hydrochloride and benzenesulphonylacetone give a 2 1 mixture of compounds (73 R = CH2S02Ph) and (75), the oxime ether (76) is converted into the aldehyde (77 ... 

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