Dipolar cycloadditions with nitrones

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. 

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. 

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 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). 

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

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

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]. 

SCHEME 16.25 Stereoselectivity of dipolar cycloaddition with nitronate 101. 

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