Nitrones cycloaddition with

Alkenylboronic esters undergo regio- and stereoselective 1,3-dipolar cycloadditions with nitrones. These reactions lead to boronic ester-substituted isoxazolidines, which can be converted by oxidation with H202 to the corresponding 4-hydroxy derivatives (Eq. 8.48).69 The high selectivity could be the result of a favorable interaction between the boronic ester and the amino group. 

Kibayashi and coworkers have used enantiometrically pure allylic silyl ethers obtained from amino acids in cycloaddition with nitrones (Eq. 8.49).71 Cyclic nitrone reacts with a chiral allyl ether to give selectively the exo and erythro isomer (de 90%). Optically active alkaloids containing a piperidine ring such as (+)-monomorine,71c (+)-coniine,71a and (-)-oncinotine71b have been prepared from the addition product. 

These experimental findings, as well as earlier data on alkylidenecyclopropanes, clearly disclose a peculiar effect of a cyclopropylidene system both on reaction rates and regioselectivity. In fact, the parent MCP as well as its derivatives exhibit a high reactivity in 1,3-dipolar cycloadditions with nitrones. In contrast, the related open chain isobutene and its derivatives are well known to enter 1,3-dipolar cycloadditions sluggishly [51c-d, 70]. For example, there is no chance to obtain a cycloadduct from 256 and an open chain trialkyl or tetraalkylethylene, as was obtained in the reaction of 256 with 270 and 271. 

The symmetric nature of bicyclopropylidene (3) eludes the regioisomeric question in cycloadditions with nitrones (Scheme 45). 

Methyl 2,3-butadienoate can undergo 1,3-dipolar cycloaddition with nitrones leading to the formation of 528, which would undergo homolytic cleavage of the N-O bond followed by radical rearrangement and coupling to afford benzazepinone 531 [239]. 

The reaction is versatile and proceeds with a variety of cyclic and acylic alkenes substituted with alkyl, aryl, vinyl and heteroatom substituents. Allene derivatives also undergo cycloaddition with nitrones ". A variety of cyclic and acyclic aliphatic nitrones bearing aliphatic and aromatic substituents has been tested. The reaction is, however, relatively sensitive to steric constraints and proceeds easily only for mono- and disubstituted alkenes. Steric requirements for a nitrone molecule are similar and, although several reactions with R, R2 are known, good yield has been achieved only with R = H (equation 105). 

The use of chiral vinyl ethers in 1,3-dipolar cycloadditions with nitrones allows for the subsequent removal and recovery of the chiral group. Using the chiral vinyl ether 197 and the cyclic nitrone 77, the cycloaddition proceeded with high diastereoselectivity (Scheme 12.56). The endo/exo-selectivity was not given in this communication by Carmthers et al. (313), but this is of minor importance for the final outcome of this work, since one of the chiral centers was destroyed in the conversion of 198 into the final product 199. The chiral auxiliary can by recovered in this reaction sequence, and 199 was obtained with an optical purity of >95% ee. 

The J0rgensen and Desimoni groups have also carried out bis(oxazoline)-metal complex-catalyzed 1,3-dipolar cycloadditions with nitrones. Cycloaddition of a,(3-unsaturated oxazolidinones such as 69, 80a, and 130 with nitrone 127 in the presence of phe-box ligands 6 and ent-6 provided quantitative yields of cycloadducts. Selectivities of up to 100 0 endo/exo ratio and corresponding endo ee as high as 82% were achieved (Table 9.22, Fig. 9.41a). 

The palladium it-allyl complex formed from y-methylidene-y-valerolactones 150 undergoes efficient [4+3] cycloaddition with nitrones to yield 1,2-oxazepines 151 in good yields and... 

Some chiral versions of 1.3-dipolar cycloadditions with nitrones, utilizing chiral sulfoxides, chiral nitrones, and sulfones substituted with a chiral group, are known. 

With 1,1-disubstituted trifluoromethylated alkenes, such as a-(trifluoromethyl)styrene, cycloaddition with nitrone 1 is regioselective, and a 50 50 mixture of the c/s/trans-isomers is obtained, as observed in Diels-Alder cycloaddition reactions (see Section 2.1.1.6.2.1.1, ).5 When the reaction is performed solvent-free under microwave irradiation, instead of under thermal conditions (boiling toluene), the yield is improved from 65% to 98% and the reaction time decreases from 48 hours to 4 minutes, however, stereoselectivity is not improved.79... 

Besides methyl acrylate and styrene, the reactivity of three other mono-substituted dipolarophiles in the [3 + 2] cycloaddition with nitronate (16b) was investigated. 

The stereochemical limits of this type of domino reaction were also studied [8j. When l-phenyl-2-nitropropene 15b was used, the only product isolated was nitronate (16b). Nitroalkene 15b failed to react as a dipolarophile in the second cycloaddition with nitronate 16b, under even more extreme conditions (15 kbar, 50 °C, 96 h, Scheme 9.17). However, nitronate 16b reacted with y -nitrostyrene (15a) at 15 kbar, RT within 72 h completely regio- and stereoselectively producing the bicyclic nitroso acetal 49. 

Alkenoylation of a camphor-based cyclic acylhydrazide leads to substrate-defined dipolarophiles (for nitrile oxides)." On temporary (in situ) derivatization with 75, enals are activated to undergo enantioselective cycloaddition with nitrones. ... 

Perchlorate Ring expansion of azetidinium salts by 3 atoms 1,3-Dipolar cycloaddition with nitrones... 

Doyle and coworkers [19] presented an elaborate mechanism for their formation of tricychc heterocycles, although stiU in a more or less speculative state. Treating both reactants with an appropriate Rh catalyst transforms a diazo compound into 46. Presumably, the vinylogous double bond now undergoes an electronic activation, which tailors it for a cycloaddition with nitrone 45 furnishing exclusively... 

It was demonstrated that the reaction proceeds without racemisation of the stereogenic phosphorus atom and with total selectivity towards the ( )-alke-nylphosphine oxide. Unexpectedly, it was also possible to dimerise phosphine oxide 109 (with R = Me) with 5% of 112b to obtain the corresponding optically pure ( )-diphosphine oxide in 85% yield. The crystal structure of this compound has been determined by X-ray diffraction and has been used as dipolarophile in 1,3-dipolar cycloadditions with nitrones, yielding several optically pure diphosphine oxides. Similar homometathesis reactions have been investigated in more detail by Grela, Pietrusiewicz, Butenschon and co-workers with other (racemic) substrates such as 109 and different catalysts. Gouverneur and co-workers studied a similar dimerisation of... 

Alkenylboronic esters undergo regio- and stereoselective 1,3-dipolar cycloadditions with nitrones to provide boronic ester substituted isoxazoUdines. These heterocycles present a trans relationship between substituents at die C3-C4 stereocenters and between H4 and H5, which suggests a preferred transition state A. Oxidation of the B-C bond with hydrogen peroxide yielded die corresponding 4-hydroxy derivatives (Scheme 9.45) [98]. For reactions conducted with chiral dioxazaborocines, the enantiomeric purities of the hydroxyisoxazolidines were around 70% ee (Scheme 9.45) [95]. 

Unsaturated lactones, e.g. 2,3-dideoxy-D-g/ycero-l,4-pent-2-enonolactone undergo intermolecular cycloaddition with nitrone 37 to afford products, e.g. 38, by way of exo-transition states. ... 

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