Nitrones alkynylation

In particular, the reactions of electrophilically activated benzonitrile A-oxides with 3-methylenephthalimidines with formation of 2-isoxazolines and oximes and the cycloaddition between alkynyl metal(O) Fischer carbenes and nitrones leading to 4-isoxazolines have been investigated by density functional theory methods <06JOC9319 06JOC6178>. 

Alkynyllead triacetates.1 Pb(OAc)4 reacts with a 1-alkynyltrimethyltin to form trimethyltin acetate and an unstable 1-alkynyllead triacetate (a), which can effect alkynylation of (i-dicarbonyl compounds and nitronates. In general yields are highest with R = QH, and lowest with R = H. 

A study of the regioselectivity of the 1,3-dipolar cycloaddition of aliphatic nitrile oxides with cinnamic acid esters has been published. AMI MO studies on the gas-phase 1,3-dipolar cycloaddition of 1,2,4-triazepine and formonitrile oxide show that the mechanism leading to the most stable adduct is concerted. An ab initio study of the regiochemistry of 1,3-dipolar cycloadditions of diazomethane and formonitrile oxide with ethene, propene, and methyl vinyl ether has been presented. The 1,3-dipolar cycloaddition of mesitonitrile oxide with 4,7-phenanthroline yields both mono-and bis-adducts. Alkynyl(phenyl)iodonium triflates undergo 2 - - 3-cycloaddition with ethyl diazoacetate, Ai-f-butyl-a-phenyl nitrone and f-butyl nitrile oxide to produce substituted pyrroles, dihydroisoxazoles, and isoxazoles respectively." 2/3-Vinyl-franwoctahydro-l,3-benzoxazine (43) undergoes 1,3-dipolar cycloaddition with nitrile oxides with high diastereoselectivity (90% de) (Scheme IS)." " ... 

A kinetic study of the 1,3-dipolar cycloadditions of alkynyl Fischer carbene complexes with nitrones showed tirst-order kinetics for both nitrones and the alkynyl carbene complexes. The 1,3-dipolar cycloaddition of chiral non-racemic Fischer... 

Further examples of the endocychc nitrone route to spirocychc adducts are the total syntheses of (—)-histrionicotoxin (230) by Holmes and of cyhndricines by Weinreb. Histrionicotoxin is one of many spiropiperidine alkaloids isolated from the poison-arrow frog Dendrobates histrionicus and has been the subject of many attempted total syntheses by a nitrone cycloaddition strategy that failed to provide the desired regioisomer, possibly through unfavorable steric interactions (265-268). Unlike these reports, Holmes and co-workers (101) found that the intermolecular reaction of nitrone (231), prepared by the 1,3-APT of the corresponding alkynyl-hydroxylamine carrying Oppolzer s chiral sultam auxiliary, afforded the styrene... 

As another approach, Carreira and coworkers reported the alkynylation of a nitrone using a terminal alkyne and catalytic amounts of Zn(OTf)2 and amine135. In the presence of a chiral ligand, the reaction proceeds enantioselectively to give hydroxyamine with . 

The intramolecular nitrone-alkene cycloaddition reaction of monocyclic 2-azetidinone-tethered alkenyl(alkynyl) aldehydes 211, 214, and 216 with Ar-aIkylhydroxylamincs has been developed as an efficient route to prepare carbacepham derivatives 212, 215, and 217, respectively (Scheme 40). Bridged cycloadducts 212 were further transformed into l-amino-3-hydroxy carbacephams 213 by treatment with Zn in aqueous acetic acid at 75 °C. The aziridine carbaldehyde 217 may arise from thermal sigmatropic rearrangement. However, formation of compound 215 should be explained as the result of a formal reverse-Cope elimination reaction of the intermediate ct-hydroxy-hydroxylamine C1999TL5391, 2000TL1647, 2005EJ01680>. 

The formation of bicyclic nitrones of the 2-azetidinone A-oxide type, 32 and (33), has been achieved in a two-step route, through condensation of the corresponding 2-azetidinone tethered-alkenyl(alkynyl)aldehyde with hydroxylamine followed by phenylselenyl bromide treatment <02JOC7004>. 

Alkynyl Fischer carbene complexes 64 (R = H) in the presence of a nitrone undergo a cascade cycloaddition/cyclopropanation process to afford 4-isoxazolines such as 65 in good yields. Under the same conditions, substituted complexes 64 (R = Me, Ph) gave naphthalenes 66 through a cycloaddition/metathesis process <07OL4143>. 

Besides processes (1) and (2), the reader should be aware that nucleophilic attacks on alkynes are treated in other chapters of this book, dealing with rearrangements, cyclizations, polyacetylenes, cyclic acetylenes and perhaps others. A number of publications overlap with ours in different ways and at different levels -. They treat individual alkynes or families " , e.g. acetylene, diacetylenes , acetylene dicarboxylic esters haloacetylenes , alkynyl ethers and thioethers > ynamines , fluoro-alkynes ethynyl ketpnes , nitroalkynes , etc. synthetic targets, e.g. pyrazoles , if-l,2,3-triazoles , isothiazoles , indolizines S etc. reagents, e.g. nitrones , lithium aluminium hydride , heterocyclic A -oxides - , azomethine ylids - , tertiary phosphorus compounds , miscellaneous dipolar nucleophiles - , etc. The reader will appreciate that all of these constitute alternate entries into our subject. 

Alkynylzinc reagents. The direct alkynylation of aldehydes is subject to asymmetric induction in the presence of a chiral base such as (-l-)-Af-methylephedrine. Addition to the C=N bond of A-tosylimines and nitrones by this procedure is also successful. ... 

A new chiral sulfinamide monophosphine hgand was used in an asymmetric gold(l)-catalyzed formal [4 + 3] cycloaddition reaction between a l-(l-alkynyl)cyclopropyl ketone and a nitrone to give cycloadduct 91 in 94% yield and 89% ee (14AGE4350). 

The CDC between A-f-butyl nitrones and terminal alkynes to form alkynylated nitrones in good to excellent yields, catalysed by zinc trifiate, was achieved using 3,3, 5,5 -tetra-tertbutyldipheno-quinone and O2 as oxidants. The alkynylated nitrones were transformed to regioisomerically pure 3,5-disubstituted isoxazoles. Experimental and DFT computational studies of Pd(OAc)2/pyridine-catalysed intramolecular aerobic oxidative amination of alkenes supported a stepwise mechanism that involved (i) the formation of a Pd(ll)-amidate-alkene chelate with release of 1 equiv. of pyridine and AcOH from the catalyst centre, (ii) insertion of alkene into a Pd—N bond. 

Alternatively, Barluenga and coworkers have described the construction of related polycyclic systems 96 and 97 incorporating a cyclopropane, based on various cascade processes involving alkynyl Fischer carbene complexes of type 95 and nitrones or dihydrofurane, as illustrated in Scheme 5.34. 

Influenced by the ZnMe2-assisted addition of terminal aJkynes to nitrones developed by Chavant et al. [119,120], Micouin et al. performed the same type of reaction using AlMes and obtained several propargylic hydroxylamines [121], For a stereoselective variant, Desvergnes, Py, et al. prepared the carbohydrate-derived nitrone 74, but only achieved high diastereoselectivities in the additirm of phenylacetylene (Scheme 14b) [122]. Moreover, the preformed alkynyl alane had to be used because in situ formation from AlMes and the aUcyne predominantly led to methyl addition. From the reaction of stereoisomeric nitrones of the type 74, it was concluded that the diastereoselectivity solely depended on the configuration at C-3. 

In 2011, Struder and Murarka evaluated the GDC reaction between allqmes and nitrones. A catalytic system based on zinc triflate, diquinone and molecular oxygen as the terminal oxidant afforded the desired alkynylated nitrones in good-to-excellent yields (Scheme 9.22). On the other hand, Jung and co-workers reported the oxidative coupling of terminal acetylene with... 

The reactions of Fischer alkynyl carbene complexes 2 with nitrones 21 regioselectivity give dihydroisoxazole carbene complexes 22 in excellent yields (Scheme 5.6) [13]. The electron-withdrawing property of the metal-carbene complexes 20 is confirmed by the density functional theory calculations on the [3+2] cycloaddition [14], The dihydroisoxazole carbene complexes 22 are readily... 

SCHEME 5.6 [3+2] Cycloaddition of Fischer alkynyl carbene complexes 20 with nitrones 21. 

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