Stereoselective cycloaddition of nitrile oxides to 4-vinyl-oxazolines and -oxazolidines

Boyd, Ewan; Paton, R. M.

doi:10.1016/s0040-4039(00)93409-9

Cited by 15 publications

(8 citation statements)

References 13 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Cycloaddition reactions were performed on selected electron-rich or electron-poor dipolarophiles using diethyl ether as solvent. As expected, the cycloaddition with monosubstituted dipolarophiles showed high regioselectivity, giving only the 5-substituted derivatives 5 and 6 where the oxygen atom is bound to the more hindered terminus of the dipolarophilic site [4]. The relative yields, which are not optimized are in the range of 30-57%.…”

supporting

confidence: 59%

Synthesis of 3‐imidazolylazole derivatives from a new nitrile oxide

Foti¹,

Grassi²,

Risitano³

et al. 2001

Journal of Heterocyclic Chem

View full text Add to dashboard Cite

The synthesis of a series of 3-Imidazolylazole derivatives using cycloaddition reactions of a useful new nitrile oxide is described.J. Heterocyclic Chem., 38, 539 (2001).Imidazole chemistry continues to be an intense investigative area since a large number of natural and synthetic compounds are associated with this class of heterocycle. For example, many naturally occurring imidazoles have remarkable biological activity, and a large number of synthesised compounds are widely used as antibacterial drugs and in cancer therapy [2].The idea of employing an isoxazole or an oxazole substrate, which are widely used by pharmaceutical and agricultural industries, combined with an imidazole ring to obtain more complex heterocycle compounds, led us to design and synthesise the N-methyl-2-imidazolyl nitrile oxide 4. The new nitrile oxide allowed us to prepare, via a 1,3 dipolar cycloaddition with selected substrates, 3-imidazolyl, 5-membered N,O-heterocycles.The 1,3-dipole was synthesised starting from the aldehyde 1 [3] using a three-step procedure (70% overall yield): oxime 2 formation followed by chlorination to 3 and subsequent in situ generation of 4 by dehydrohalogenation with triethylamine.Cycloaddition reactions were performed on selected electron-rich or electron-poor dipolarophiles using diethyl ether as solvent. As expected, the cycloaddition with monosubstituted dipolarophiles showed high regioselectivity, giving only the 5-substituted derivatives 5 and 6 where the oxygen atom is bound to the more hindered terminus of the dipolarophilic site [4]. The relative yields, which are not optimized are in the range of 30-57%.Attempted cycloaddition of the nitrile oxide with nonconjugated nitriles such as acetonitrile and phenylacetonitrile was unsuccessful. However, reaction with benzonitrile in the presence of the appropriate catalyst [5] afforded oxadiazolyl-imidazole 7 in moderate yield.Attempts to oxidise the isoxazoline rings to the isoxazole derivatives, using literature methods employing MnO 2 and NiO 2 [6], were unsuccessful and the required products were not isolated. EXPERIMENTALMelting points were determined with Reichert-Kofler hot stage apparatus and are uncorrected. IR spectra were obtained on Nicolet FT-IR Impact 400D spectrometer, mass spectra were acquired using a Finnigan Mat 90 spectrometer and the microanalyses for C, H, and N on a Carlo Erba 1102. 1 H NMR spectra were recorded on a Bruker ARX 300 spectrometer, in the solvent indicated. Chemical shifts (δ) are relative to TMS, which was used as an internal reference. Column chromatography was performed on Merck silica gel 70-270 mesh. All solvents and reagents were obtained from commercial sources and purified before use if necessary. Preparation of 2-Imidazolyloxime (2).A solution of 20.85 g of NH 2 OH . HCl in 30 ml of water and 60 ml of a 20% NaOH were added to 5.5 g, 0.05 mol of N-methyl-2-formylimidazole in 150 ml of ethanol. The mixture was heated to boiling for a few minutes, and subsequently the alcohol was evaporated under reduced pressure. T...

show abstract

supporting

confidence: 59%

Synthesis of 3‐imidazolylazole derivatives from a new nitrile oxide

Foti¹,

Grassi²,

Risitano³

et al. 2001

Journal of Heterocyclic Chem

View full text Add to dashboard Cite

show abstract

“…The current method of choice would seem to be the procedure of Ohfune 2a which involves a thermal sulfoxide elimination from a methionine derivative giving the Boc-protected amino alcohol in 52% yield and in 5 steps from the amino acid. 3 We 4 and others 5,6 have shown that the Garner aldehyde 2 can be methylenated without epimerisation. Herein we describe a high yielding synthesis of 1 which incorporates a facile preparation of Garner aldehyde 2 , a widely used chiral building block in natural product synthesis and stereochemical studies.…”

mentioning

confidence: 90%

A Simplified Route to the (R)-Garner Aldehyde and (S)-Vinyl Glycinol

Campbell¹,

Raynham²,

Taylor³

1998

Synthesis

View full text Add to dashboard Cite

show abstract

“…The -facial selectivity observed for the reaction of nitrile oxides with the dipolarophiles can be rationalised for the adduct 15 by adapting the 'inside alkoxy group hypothesis' proposed by Houk et al 3 for the cycloaddition of chiral allyl ethers. The preferred formation of the adduct from an alkyne is consistent 15,16 with product formation via the transition state which locates the oxygen substituent in the 'inside' position, the hydrogen 'outside' and the CH 2 O moiety anti (Fig. 1).…”

mentioning

confidence: 55%

“…The preferred formation 15,16 of the adducts can be explained by the fact that the dipolarophile reacts by its preferred conformation with the rac-dipole (Fig. 1).…”

mentioning

confidence: 99%