Stereoselective nitrile oxide cycloadditions to chiral allyl ethers and alcohols. The inside alkoxy effect

Houk, K. N.; Moses, S. R.; Wu, Yong; Rondan, Nelson G.; Jäger, Volker; Schohe, R.; Fronczek, Frank R.

doi:10.1021/ja00325a040

Cited by 287 publications

(98 citation statements)

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“…The isolated yields are reasonable (in the case of 5d, material loss from evaporation contributes to a lower yield) and the gas chromatography (GC) purities are quite acceptable by present standards, especially considering that deliberate stoichiometry mistakes generated large amounts of by-products. Interestingly, the anti/syn ratio obtained in 5e is virtually identical to the ratio obtained in nitrile oxide cycloadditions with normal (nonfluorous) trialkylsilyl ethers (16).…”

supporting

confidence: 67%

Fluorous Synthesis: A Fluorous-Phase Strategy for Improving Separation Efficiency in Organic Synthesis

Studer

Hadida

Ferritto

et al. 1997

Science

495

187

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Recovery and purification difficulties can limit the yield and utility of otherwise successful organic synthesis strategies. A "fluorous synthesis" approach is outlined in which organic molecules are rendered soluble in fluorocarbon solvents by attachment of a suitable fluorocarbon group. Fluorocarbon solvents are usually immiscible in organic solutions, and fluorous molecules partition out of an organic phase and into a fluorous phase in a standard liquid-liquid extraction. Simple yet substantive separations of organic reaction mixtures are achieved without resorting to chromatography. Because fluorous synthesis combines in many respects the favorable purification features of solid-phase synthesis with the favorable reaction, identification, and analysis features of traditional organic synthesis, it should prove valuable in the automated synthesis of libraries of individual pure organic compounds.

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supporting

confidence: 67%

Fluorous Synthesis: A Fluorous-Phase Strategy for Improving Separation Efficiency in Organic Synthesis

Studer

Hadida

Ferritto

et al. 1997

Science

495

187

View full text Add to dashboard Cite

show abstract

“…4,64 Therefore, considering the three staggered rotamers, for each regioisomer it is possible to find six structures for the transition state, three for each face. The stereoselectivity in the cycloadditions of nitrile oxides with chiral allylic ethers 65,66 and homoallylic alcohols 59 is explained by Houk and co-workers. While groups with α-alkoxy substituents prefer to guide the alkoxy groups in the inside position (the "inside alkoxy effect"), 4,66 hydroxyl groups have a preference for the outside position, in order to enable hydrogen bonding with the incoming nitrile oxide oxygen.…”

Section: Stereoselectivities Of Transition Structuresmentioning

confidence: 95%

“…The stereoselectivity in the cycloadditions of nitrile oxides with chiral allylic ethers 65,66 and homoallylic alcohols 59 is explained by Houk and co-workers. While groups with α-alkoxy substituents prefer to guide the alkoxy groups in the inside position (the "inside alkoxy effect"), 4,66 hydroxyl groups have a preference for the outside position, in order to enable hydrogen bonding with the incoming nitrile oxide oxygen. However, in both cases, large alkyl groups prefer the anti position, 59,66,67 but steric interactions from Z-alkenes have been found to alter the conformational preference of electronegative substituents.…”

Section: Stereoselectivities Of Transition Structuresmentioning

confidence: 95%

“…While groups with α-alkoxy substituents prefer to guide the alkoxy groups in the inside position (the "inside alkoxy effect"), 4,66 hydroxyl groups have a preference for the outside position, in order to enable hydrogen bonding with the incoming nitrile oxide oxygen. However, in both cases, large alkyl groups prefer the anti position, 59,66,67 but steric interactions from Z-alkenes have been found to alter the conformational preference of electronegative substituents. 61 Considering these effects, seven transition structures were calculated for the first cycloaddition (TS1) ( Figure S1).…”

Section: Stereoselectivities Of Transition Structuresmentioning

confidence: 99%

“…27, No. 7, 2016 Secondary interactions between orbitals As well as the preference of alkoxy groups for the inside position, 66 the preference for the anti position in the gas phase and the out position when including solvent effects could be explained in terms of the secondary interactions between orbitals. In this way, the charge and natural population analysis of atoms could provide a good estimate of how nucleophilic or electrophilic it is.…”

Section: 76mentioning

confidence: 99%

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The 1,3-Dipolar Cycloaddition of Nitrile Oxide to Vinylacetic Acid: Computational Study of Transition States Selectivity, Solvent Effects, and Bicyclo Formation

Toldo¹,

Merlo²,

Gonçalves³

2016

Journal of the Brazilian Chemical Society

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The 1,3-dipolar cycloaddition reaction is a powerful tool for the cycloaddition of nitrile oxides to olefins, and this reaction is of considerable interest to obtain isoxazolines. Density functional theory (DFT) was used to study the 1,3-dipolar cycloaddition reaction mechanism that initially occurs between benzonitrile oxide and vinylacetic acid to yield a bicyclo, from successive cycloadditions. PBE1PBE, B3LYP and CAM-B3LYP functionals were used together with 6-311+G(2d,p) basis set. CCSD(T)/6-311+G(2d,p) calculations were done to compare the DFT energy barriers. The solvent effects were included using polarizable continuum model (PCM), with three different solvents. In the first cycloaddition, only the 3,5-regioisomer is expected. In the gas phase, the β face attack, that originates the trans-bicyclo, is slightly favored, but the cis-bicyclo is considerably more stable. However, the α face attack was favored with solvent effects. The PBE1PBE functional gives the closest activation energies and reaction energies to CCSD(T). The inclusion of solvent effects changes the preferential rotamer in each cycloaddition.

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Diastereo- and Enantioselective Synthesis ofN-Protected 2-Amino 1,4-Diols by an Oxa Michael Addition/1,3-Dipolar Cycloaddition Protocol

Enders¹,

Haertwig²,

Runsink³

1998

Eur. J. Org. Chem.

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An enantioselective synthesis of N‐protected amino diols has been accomplished by employing a diastereoselective inter‐ and intramolecular 1,3‐dipolar cycloaddition reaction of optically active nitrile oxides as a key step. The nitro alkane starting materials were obtained by diastereoselective oxa Michael addition of (1R,2S)‐(–)‐N‐formylnorephedrine (1) to aliphatic (E)‐nitro alkenes 2, 6a, b (de = 96 – ≥ 98%). Subsequent diastereo‐ and regioselective cycloaddition reactions to highly substituted 4,5‐isoxazolines 5a–e, 8a, b (52‐81%) and reductive ring opening led – after cleavage of the auxiliary – to amino diols 13, 14 in good overall yields (27‐40%, over five steps) and with excellent diastereomeric and enantiomeric excesses (de,ee ≥ 96%).

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Stereoselective nitrile oxide cycloadditions to chiral allyl ethers and alcohols. The inside alkoxy effect

Cited by 287 publications

References 0 publications

Fluorous Synthesis: A Fluorous-Phase Strategy for Improving Separation Efficiency in Organic Synthesis

Fluorous Synthesis: A Fluorous-Phase Strategy for Improving Separation Efficiency in Organic Synthesis

The 1,3-Dipolar Cycloaddition of Nitrile Oxide to Vinylacetic Acid: Computational Study of Transition States Selectivity, Solvent Effects, and Bicyclo Formation

Diastereo- and Enantioselective Synthesis ofN-Protected 2-Amino 1,4-Diols by an Oxa Michael Addition/1,3-Dipolar Cycloaddition Protocol

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