Cycloaddition of nitrone

The tricyclic compound (441) is a key compound in the synthesis of enan-tiomerically pure indolizidine (442). It was obtained in an intramolecular 1,3-cycloaddition of nitrone (440), by retro-cycloaddition from isoxazolidine (439) (Scheme 2.215) (708). 

Dipolarophiles D1 and D2. In the study of steric and electronic factors on regioselectivity and stereoselectivity of 1,3-cycloaddition of nitrones to olefins, 1-decene (734) and styrene derivatives (735) have been used. By comparative analyses of the kinetic and thermodynamic parameters in the 1,3-cycloadditions... 

Recently, dipolarophile 1)13 (fumaronitrile) (777) has been used in the synthesis of indolizine lactone (677). Both, intermolecular and intramolecular cycloadditions were studied. Intermolecular 1,3-cycloaddition of nitrone (671) to D13 led to the formation of isoxazolidine (672). Subsequent deprotection and esterification of the obtained alcohol (673) with (674) gave isoxazolidine (675) in 65% yield. Ester (675), when refluxed in xylene for 10 min, after elimination of fumaronitrile by cyclo-reversion, underwent spontaneously intramolecular cycloaddition to give the tricyclic cycloadduct (676) in 84% yield (Scheme 2.291). 

Cycloadditions of nitrones. cw-N-Methyl-3-oxa-2-azabicyclo[3.3.0]octane can be prepared in 417o yield by the reaction of 5-hexenal and freshly prepared N-methylhydroxylamine (equation I). The reaction involves an intramolecular... 

Cycloaddition of a-aryl-A-phenylnitrones to the C16-C17 n-bond in 16-dehydropregnenolone-3P-acetate (545) involves only the minor rotamer (A-form) of the nitrones. It proceeds regio-, stereo- and Jt-facial-selectively to give steroido[16,17-d]isoxazolidines (546) in high yield (Scheme 2.257), (Table 2.24) (760). Similarly the cycloaddition of a,N -diphenylnitrones proceeds with five-membered heterocyclic enones (761). 

Regio- and stereospecific 1,3-cycloaddition of di-tert-butylated acyl nitrone (548), generated in situ from (547), with Z-2-cyclodecanone and subsequent aromatization is the key step in the synthesis of biomimetic pyridomacrolidin... 

Reactivity with Aromatic Nitrones. Rubber bound AO 179 based on 1,3-cycloaddition of aromatic nitrones (180) to C = C double bonds of IR or BR were formed during the vulcanization process [236]. In IR, 50-89% of nitrones was bound-in in the dicumyl peroxide vulcanizate, 39-85% in the tetramethylthiuram disulfide vulcanizate. Pendant stabilizing moieties are attached to the rubber chain by means of the isoxazolidine moiety. Crosslinks are formed with bis-nitrones. It should be mentioned that aromatic nitrones unfavourably influence the scorch time of the both conventional and sulfurless IR or BR compounds. Aminic stabilizer 179a is an effective but discoloring and staining AO. Unhindered... 

Cycloaddition reactions. The aminophosphite Hg-2C derived from octahydro-BINOL is found to promote the [3+3]cycloaddition of nitrones and trimethylenemethane derivatives to furnish 1,2-oxazines. Remarkable ligand effects have been observed in the spiroannulation of oxindoles products possessing opposite configuration at the spirocyclic center arise by changing the naphthyl substituents on the pyrrolidine ring (7A [a-Np] vs. 7B [P-Np])."... 

Some new combinations of chiral ligands with different Lewis acids have been lately evaluated in catalytic asymmetric 1,3-DC reactions of nitrones. When the complex derived from copper(II) triflate and bis(oxazoline) 72 was used as chiral catalyst in the cycloaddition of nitrone 66 and crotonate 68, both endo and exo isomers were obtained with very high enantioselectivities (7 3 dr > 99% ee). In this reaction, the presence of molecular sieves 4 A (MS) was crucial as in their absence the nitrone decomposed and almost no cycloadduct was obtained <04TL9581>. Sibi et al. found that square planar complexes derived from copper triflate and some chiral bisoxazolines favour the COZ-exo approach in the 1,3-DC of nitrone... 

Very recently, a different synthetic approach to fluorinated p-lactams involving catalytic hydrogenolysis of the N-O bond of isoxazohdines appeared in the literature. The method involves the synthesis of isoxazohdines (71) by 1,3-cycloaddition of aromatic nitrones to fluorinated alkenes, followed by N-O bond cleavage by hydrogenolysis using palladium catalyst (Scheme 2.34). ... 

Slereoselection in 1,3-DC reactions of chiral allyl ethers <01EJ01033> and kinetic resolution by means of cycloaddition reaction, including 1,3-DC of nitrones <01EJO2999>, have been reviewed. 

MacKenzie DA, Pezacki JP (2014) Kinetics studies of rapid strain-promoted [3 -1- 2] cycloadditions of nitrones with bicyclo[6.1.0]nonyne. Can J Chem 92(4) 337-340. doi 10.1139/cjc-2013-0577... 

Scheme 1.3 Cycloaddition of diphenyl nitrone with o,p-unsaturated aldehydes.

Scheme 1.5 Cycloaddition of nitrones with 3-(alk-2-enoyl)thiazolidine-2-thiones.

Scheme 1.23 Formal [3 + 3] cycloaddition of nitrones with 2-substituted cyclopropane-1,1-dicarboxylates.

SCHEME 16J5 Intramolecular [3-1-2] cycloaddition of nitronates tethered at C(6) with dipolarophiles. 

A rapid protocol has been developed for the synthesis of number of 4-aza-2, 3 -dideoxynucleosides in high yields by microwave-assisted 1,3-cycloaddition of vinyl nucleobases with nitrones in solvent-free condition (Bortolini et al., 2008). 

Furukawa et al. also applied the above described palladium catalyst to the inverse electron-demand 1,3-dipolar cycloaddition of nitrones with vinyl ethers. However, all products obtained in this manner were racemic [81]. 

We are the first group to succeed with the highly enantioselective 1,3-dipolar cycloadditions of nitronates [75]. Thus, the reaction of 5,6-dihydro-4H-l,2-oxazine N-oxide as a cyclic nitronate to 3-acryloyl-2-oxazilidinone, at -40 °C in dichloro-methane in the presence of MS 4 A and l ,J -DBFOX/Ph-Ni(II) complexes, gave a diastereomeric mixture of perhydroisoxazolo[2,3-fe][l,2]oxazines as the ring-fused isoxazolidines in high yields. The J ,J -DBFOX/Ph aqua complex prepared from... 

This homoenolate methodology has been extended to the use of nitrones 170 as electrophiles [72]. Scheldt and co-workers have shown that enantiomerically enriched y-amino esters 172 can be prepared with excellent levels of stereocontrol from an enal 27 and a nitrone 170 using the NHC derived from triazolium salt 164 (Scheme 12.37). The oxazinone product 171, formally a result of a [3-1-3] cycloaddition, is cleaved to afford the y-amino ester product 172. The reaction shows broad substrate scope, as a range of substituted aryl nitrones containing electron donating and withdrawing substituents are tolerated, while the enal component is tolerant of both alkyl and aryl substituents. 

Scheme 10.7 1,3-Dipolar cycloadditions of nitrones with 1,1-diethoxypropene catalysed by oxazaborolidines derived A-tosyl-L-a-amino acids.

N-donor ligand. The reaction appears to proceed via an acyclic iminoplatinum(II) intermediate that undergoes a subsequent intramolecular cyclization. Some mechanistic aspects of this versatile reaction have been elucidated.225,226 A4-l,2,4-oxadiazolines have been prepared by the [2+3] cycloaddition of various nitrones to coordinated benzonitrile in m-[PtCl2( D M SO)(PhCN)] precursors.227,228 Racemic and chiral [PtCl2(PhMeSO)(PhCN)] complexes have also been used in order to introduce a degree of stereoselectivity into the reaction, resulting in the first enantioselective synthesis of A4-l,2,4-oxadiazolines, which can be liberated from the complexes by the addition of excess ethane-1,2-diamine. 

Asymmetric 1,3-dipolar cycloaddition of cyclic nitrones to crotonic acid derivatives bearing chiral auxiliaries in the presence of zinc iodide gives bicyclic isoxazolidines with high stereoselectivity (Eq. 8.51). The products are good precursors of (3-amino acids such as (+)sedridine.73 Many papers concerning 1,3-dipolar cycloaddition of nitrones to chiral alkenes have been reported, and they are well documented (see Ref. 63). 

Diastereoselective intramolecular cycloaddition of nitrones is useful for constructing nitrogen- containing cyclic structures. The reaction serves as a key step in a number of natural product syntheses.63 Tufarriello and coworkers have used this strategy for preparing cocaine and other alkaloids.74 As a classical example, enantioselective total synthesis of (+)-luciduline is presented in Scheme 8.13, in which a useful feature of the 1,3-dipolar addition of nitrones is nicely illustrated.75... 

Intramolecular cycloadditions of chiral nitrones provide a useful tool for the preparation of bioactive heterocyclic compounds.63 Shing et al. demonstrated that 1,3-dipolar cycloaddition of nitrones derived from 3-0-allyl-hexoses is dependent only on the relative configuration at C-2,3, as shown in Scheme 8.16. Thus 3-0-allyl-D-glucose and -D-altrose (both with threo-configuration at C-2,3) produce oxepanes selectively, whereas 3-O-allyl-D-allose and -D-man-nose (both with erythro-configuration at C-2,3) give tetrahydropyranes selectively.80... 

A series of 3-substituted-2-isoxazoles are prepared by the following simple procedure in situ conversion of nitroalkane to the silyl nitronate is followed by 1,3-dipolar cycloaddition to produce the adduct, which undergoes thermal elimination during distillation to furnish the isoxazole (Eq. 8.74). 5 Isoxazoles are useful synthetic intermediates (discussed in the chapter on nitrile oxides Section 8.2.2). Furthermore, the nucleophilic addition to the C=N bond leads to new heterocyclic systems. For example, the addition of diallyl zinc to 5-aryl-4,5-dihydroi-soxazole occurs with high diastereoselectivity (Eq. 8.75).126 Numerous synthetic applications of 1,3-dipolar cycloaddition of nitronates are summarized in work by Torssell and coworker.63a... 

Asymmetric 1,3-dipolar cycloaddition of nitronates using chiral alkenes has been reported,... 

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