Frances Heaney

X=Y-ZH systems as potential 1,3-dipoles. Part 31. Generation of nitrones from oximes. Background and scope of the tandem 1,2-prototropy-intramolecular cycloaddition sequence.

Abstract 1,2-Prototropy in aryl and aliphatic oximes generates a small equilibrium concentration of the corresponding NH nitrone. Examples of a tandem 1,2-prototropy-intramolecular cydoaddition sequence involving aryl and aliphatic oximes are described and steric and electronic factors that favour or disfavour such a sequence are discussed. Deuterium labelling studies with an aliphatic oxime rule out the involvement of an enehydroxylamine in the prototropic generation of the NH nitrone.

Fast, copper-free click chemistry: a convenient solid-phase approach to oligonucleotide conjugation

Solid-phase oligonucleotide conjugation by nitrile oxide-alkyne click cycloaddition chemistry has been successfully demonstrated; the reaction, compatible with all nucleobases, requires no metal catalyst and proceeds under physiological conditions.

X=Y-ZH systems as potential 1,3-dipoles. Part 34. generation of nitrones from oximes. Tandem michael addition-1,3-dipolar cycloaddition reactions. class 2 processes utilising bifunctional michael acceptor-dipolarophile components. ☆ ☆☆

Aldoximes and ketoximes react with a range of bifunctional Michael acceptor-dipolarophile substrates comprising functionalised 1,3-, 1,4- and 1,5-dienes via a tandem process involving an N-alkenyl nitrone intermediate. The 1,3-dienes react regio- and stereo-specifically to give 1-aza-7-oxabicyclo[2.2.1]heptanes whilst sterically unencumbered aryl aldoximes and 1,4-dienes give 1-aza-2-oxabicyclo[3.2.1]octane derivatives. Ketoximes and 1.4-dienesgive mixtures of 1-aza-2-oxa- and 1-aza-8-oxa-bicyclo[3.2.1]octanes. 1,5-Dienes and ketoximes react regio-and stereo-specifically to give 1-aza-8-oxabicyclo[3.2.1]octane derivatives whilst benzaldoxime gives a 1:1 mixture of epimeric 1-aza-8-oxabicyclo[3.2.1]octanes together with traces of two epimeric 1-aza-2-oxabicyclo[3.2.1]octanes. The regio- and stereo-chemical outcome of the tandem process is controlled by the length and nature of the linking chain in the bifunctional substrate and the steric interactions between substituents on the oxime and dipolarophile in the transition state. A crystal structure of one of the 1-aza-7-oxabicyclo[2.2.1]heptanes is reported.

X=Y-ZH systems as potential 1,3-dipoles. Part 33. Generation of nitrones from oximes. Tandem Michael addition-1,3-dipolar cycloaddition reactions. Class 2 processes in which the dipolarophile is located within the oxime.

Abstract C-3, -4, -5, and -6-Alkenyl oximes react with electronegative olefins at the nitrogen atom via a Michael addition or ene-type process to generate the corresponding C-alkenyl nitrones which undergo an intramolecular cycloaddition. The cycloaddition can occur by one of two modes leading to either bridged- or fused-isoxazolidines. The latter is preferred in most cases except that of the C-(3-alkenyl) nitrone which gives exclusively the bridged-ring product and the C-(4-alkenyl)nitrones derived from N-allylpyrrole-2-carboxyaldehyde oxime which gives both bridged- and fused-ring isoxazolidines.

α-Keto amides as precursors to heterocycles—generation and cycloaddition reactions of piperazin-5-one nitrones

alpha-Keto amides 10a,b, formed from reaction of pyruvic or benzoylformic acid with allyl amine are found to present as single rotameric forms whilst their tertiary amido analogues 10c, d present as two rotamers in solution at rt. The hydroxyimino derivatives 8 share the conformational characteristics of their parents. The geometrical make-up of the new alpha-amidooximes is seen to depend on the structure of the starting acid and on the degree of substitution of the amido group. The oxime 8a derived from pyruvic acid and allyl amine is formed solely as the (E)-isomer whilst its tertiary amido analogue 8c is formed as both (E)- and (Z)-isomers. Oximes derived from benzoylformic acid have the opposite selectivity with both geometrical isomers forming from the secondary amide 8b and only the (Z)-isomer from the tertiary amide 8d. With the exception of 8b all oximes were configurationally stable with (Z)-isomers reacting to form isoxazolopyrrolidinones 11--compounds with a relatively rare bicyclic nucleus and (E)-isomers cyclising to piperazin-5-one nitrones 1--ketopiperazine N-oxides have to date only appeared once in the literature. New nitrones were trapped with phenyl vinyl sulfone, dimethyl acetylenedicarboxylate and methyl propiolate yielding isoxazolidine and isoxazoline fused piperazinones 13, 15, 21 and 22. Cycloadducts from dimethyl acetylenedicarboxylate and 8a, b are thermally labile and their rearrangement provides a novel route to pyrrolopiperazinones 16. The structure of a representative isoxazolopyrrolidinone, 11c, and a 2,3-dihydroisoxazoline fused piperazinone, 21b, are unambiguously solved following x-ray structural analysis.

Orthogonal modification of polymer chain-ends via sequential nitrile oxide–alkyne and azide–alkyne Huisgen cycloadditions

The α- and ω-chain-ends of well-defined polystyrene chains were functionalized using consecutive Huisgen cycloadditions. Firstly, an α-alkyne, ω-azido heterotelechelic polystyrene precursor was synthesized in three steps: (i) atom transfer radical polymerization in the presence of (1,1,1-trimethylsilyl)-2-propynyl 2-bromo-2-isobutyrate, (ii) deprotection of the alkyne function of the initiator and (iii) nucleophilic substitution of the bromine chain-end of the polymer with sodium azide. Afterwards, the chain-ends of the polymer were modified by successive nitrile oxide–alkyne cycloaddition (NOAC) and copper-catalyzed azide–alkyne cycloaddition (CuAAC). 2 Model building blocks were tested for NOAC, while 4 building blocks were studied for CuAAC. In all cases, the orthogonal combination of NOAC and CuAAC allowed the preparation of tailored heterotelechelic polymers.

X=Y-ZH systems as potential 1,3-dipoles. Part 32 generation of nitrones from oximes. Tandem Michael addition-1,3-dipolar cycloaddition reactions. Background and class 1 processes.☆☆☆

Abstract Intermolecular Michael addition of aldoximes and ketoximes to electronegative olefins generates nitrones. The keto nitrones can be trapped in regiospecific intermolecular cycloaddition reactions giving single cycloadducts in good yield. Chemospecific 1:1:1 cycloadducts are obtained from ketoximes, monosubstituted electronegative olefins (Michael acceptor) and N-methylmaleimide (dipolarophile), whilst the chemoselectivity of the corresponding reactions with aldoximes is dependent on the oxime stereochemistry. Z-Aldoximes show high chemospecificity whilst E-aldoximes are much less chemoselective.

Pyrimidine annelated heterocycles—synthesis and cycloaddition of the first pyrimido[1,4]diazepine N-oxides

5-Formyl- and 5-acetyl-4-(alkenylamino)pyrimidines 5 have been prepared as precursors to novel pyrimido[1,4]diazepine N-oxides 3. In addition to cyclisation to the targeted dipoles the substrates 5 have also been observed to form imidazopyrimidines 12 and 39via an intramolecular Michael addition; additionally 5b has been observed to form the pyrimidoazepinone 42. Aldonitrone 3a cycloadded readily to olefinic dipolarophiles; ketodipole 3b did not share this reactivity. Both dipoles reacted with acetylenic dipolarophiles but the ensuing cycloadducts 37 were unstable; facile ring contraction of their isoxazolopyrimidodiazepine skeletons to the pteridine nucleus is noted. The structure of 37c has been determined by X-ray crystallography.

Regio- and stereo-specific class 2 tandem Michael addition−cycloaddition reactions of oximes

Abstract Oximes react regio- and stereo-specifically with 1,3-, 1,4- and 1,5-dienes bearing electronegative substituents via a tandem Michael addition-1,3-dipolar cycloaddition process to give bridged ring cycloadducts in good yield.

A catalytic dehydrogenation route to azomethine imines.

Catalytic dehydrogenation of appropriate N,N,N/- trisubstituted hydrazines with 10 mol% palladium black, ruthenium black, or Wilkinsons catalyst, in hot DMF in the presence of Nmethylmaleimide occurs with high regioselectivity and leads to cycloadducts of the intermediate azomethine imines in moderate to good yield.