Stereoselectivity 1,3-dipolar cycloaddition

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. 

The highly stereoselective 1,3-dipolar cycloaddition of C-phenyl-iV-glycosylnitrones (336) and (679) to dimethyl maleate D14, with the sugar moiety acting as a chiral auxiliary, has been used in enantioselective syntheses of isoxazolidines (678) and (678 ent) (Scheme 2.292) (118). 

For reviews dealing with stereoselective 1,3-dipolar cycloaddition reactions, see (a) Martin JN, Jones RCF. In The Chemistry of Heterocyclic Compounds Synthetic Applications of 1,3-Dipolar Cycloaddition Chemistry Toward Heterocycles and Natural Products, Padwa A, Pearson WH (Eds.), John Wiley Sons, New-York, Vol. 59, ch. 1, 1-81, 2002 ... 

Recent research deals with stereoselective 1,3-dipolar cycloadditions of nitrones for the syntheses of alkaloids and aza heterocycles asymmetric synthesis of biologically active compounds such as glycosidase inhibitors, sugar mimetics, /3-lactams, and amino acids synthesis of peptido-mimetics and peptides chemistry of spirocyclopropane heterocycles synthesis of organic materials for molecular recognition and photochemical applications. 

Stereoselective 1,3-dipolar cycloaddition of nitrones.1 The cycloaddition of the nitrone 1 with an electron-rich alkene such as ethyl vinyl ether or vinyltrimethyl-silane provides a regioselective route to 3,5-disubstituted isoxazolidines (2) (12, 566), but with low stereoselectivity. 

Fig. 15.41. Orientation-selective and stereoselective 1,3-dipolar cycloaddition of diazomethane. The trans-configured 2-methyl-2-butenoic acid is converted to the trans-configured cycloadduct with a diastereoselectivity of better than 99.997 0.003.

Dihydroisoxazoles can be formed by stereoselective 1,3-dipolar cycloaddition of nitrile oxides, for example, to enantiopure allylic alcohols, and these products can be converted into -amino acids 510 by a characteristic nucleophilic addition to the C=N bond in 509 followed by reductive cleavage of the N—O bond and oxidative cleavage of the diol moiety. The facial selectivity in the nucleophilic addition is dictated by the C(5) substituent (Scheme 109), e.g., <2003JA6846, 2004SL1409, 2005JA5376>. 

Stereoselective 1,3-dipolar cycloaddition of the azomethine imine 283, obtained by reacting acetaldehyde and the dihydropyrazolo[4,3-d]-pyridazin-4-one 282, with the acetylenic derivative 284 resulted in the construction of the second fused pyrazole ring of 285. Condensation of 282 with the dialdoglucopyranose 286 instead of acetaldehyde gave the aldose azomethine imine 287, which added 284 to give the C-nucleoside 288 carrying two carbohydrate moieties (93FA231) (Scheme 87). 

Stereoselective 1,3-dipolar cycloadditions to heterocyclic compounds 00JHC551. 

Alkene-functionalized 1,3-diene complexes undergo regio-and stereoselective 1,3-dipolar cycloaddition reactions with nitrile A-oxides. Related cycloadditions of nitroalkanes in the presence of triethyl amine and phenylisocyanate afford dihydroisoxazoles. This type of cycloaddition was used in a synthesis toward macrolactin A (Scheme 163). 

The first chiral thiourea-catalyzed stereoselective 1,3-dipolar cycloaddition of azomethine ylides with nitroalkenes 210 was reported by Gong, et. al., Scheme 3.68 [85], This reaction afforded highly substituted pyrrolidines 212 with high diastereo-selectivities and moderate enantioselectivities. 

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]. 

The use of stereoselective 1,3-dipolar cycloadditions to heterocyclic compounds in the synthesis of natural products has been reviewed.1,2-, 1,3- and 2,3-dicyanonaphthalenes, e.g. (25), undergo 3 -I- 2-photocycloadditions with alkenes and 1,3-dienes in the presence of Cu(OAc)2 to produce tricyclic adducts, e.g. (26) (Scheme 10). ... 

Developments in the field of stereoselective 1,3-dipolar cycloadditions and their synthetic applications are outlined in Sections 18.2 to 18.4 [22, 23, 28-34]. Subsequently, related [2-i-3]-cycloadditions with 1,3-diradicals and trimethylenemethane equivalents that furnish the corresponding five-membered carbocycles are covered (Section 18.5) [38—41]. The chapter closes with a collection of [2-i-2]-cycloadditions involving ketenes (Section 18.6) [19, 35, 36], photochemical olefin cycloadditions, and Paterno-Biichi reactions (Section 18.7) [36, 37],... 

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