Nitrones to olefins

Dipolar cycloadditkm reactions of nitrones to olefins, 46, 1,3-Dipolar cycloadditions with 3-phenylsydnone, 45, 98 Dispiro[5 1 5 l]tetradecane-7,14-dione, photolysis to cyclohexylidene-cyclohexane, 47, 34 preparation from cyclohexanecarbonyl chlonde and triethylamine, 47,34 Displacement of bromine from 1-bromo-2-fluoroheptane to give 2-fluoro-heptyl acetate, 46, 37... 

Intermolecular Reactions Intermolecular 1,3-dipolar cycloaddition reactions of nitrones to olefins seem to be the most studied. They are widely used for the synthesis of different enantiomerically pure compounds, including biologically active ones. For example, two new glycosidase inhibitors have been obtained by the nitrone cycloaddition strategy (Fig. 2.32) (733). 

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... 

I. Intermolecular [3+2]-Addition of Nitronates to Olefins Of all known types of nitronates (see Section 3.2), alkyl- and silyl nitronates as well as cyclic C5-C6 nitronates are involved in [3+ 2]-cycloaddition reactions. Detailed comparative kinetic studies for different types of nitronates have not been reported. However, a few data (162, 336, 337) allow one to deduce some sequences (Chart 3.10). 

Attempts to Catalyze [3 + 2]-Cycloaddition of Nitronates to Olefins In Section 3.2.1.2.2.2, it was noted that [4+ 2]-cycloaddition reactions of nitro-alkenes and alkenes proceed much faster in the presence of LA. At the same time, in the presence of LA, nitronates can rapidly decompose (49) or undergo rearrangements (see Section 3.4.2.5.6 ). Hence, it is not surprising that catalysis of 1,3-dipolar cycloaddition reactions of nitronates with alkenes by LA has attracted little attention until very recent times. An exception is the study by the Japanese... 

Besides, cyclic nitroso acetals have attracted considerable interest because [3+ 2]-cycloaddition of nitronates to olefins provides a simple and efficient procedure for the synthesis of five-membered cyclic nitrosals (see Scheme 3.153). Hence, knowledge of the configurations of these products allows conclusions about the mechanism of this very important process. However, it is impossible to distinguish kinetic and thermodynamic products of [3+ 2]-cycloaddition of nitronates to olefins without studying such a fundamental problem as the stereodynamics of five-membered cyclic nitroso acetals, that is, the ring and nitrogen inversions. 

The procedure described illustrates the use of 1,3-dipolar addition7 of nitrones to olefins for the preparation of isoxazoli-dines The preparations of 2,3,5,5-tetraphenylisoxazolidine and ethyl 2,3-diphenyl-5-methylisoxazolidine-4-carboxylate, as described in Notes 9 and 10, respectively, indicate the versatility of the method. 

Dipolar cycloaddition of nitrones to olefins is also catalyzed by chiral cationic palladium complexes [66]. When nitrone 119 is treated with 3-(( )-2-butenoyl)-l,3-oxazoli-din-2-one (120) under the influence of (5)-BINAP PdCla (10 mol %) and AgBF4 (20 mol %), isoxazolidine 121 is obtained in 61 % yield as a 45 55 mixture of endo and exo forms. The endo isomer is obtained in 91 % ee (Sch. 32). The chemical yield and endo selectivity are improved by employing (5 )-p-Tol-BINAP as chiral ligand. 

A very significant contribution to the development of isoxazole chemistry came in the period 1930-1946 from Quilico s studies on synthetic approaches to the ring system from nitrile oxides and unsaturated compounds <19300172, 1950NAT226>. However, the study of isoxazolidines began very much more recently being related to the availability of this nucleus and then to the discoveries of cycloadditions of nitrones to olefins <1960TL9> and intramolecular cyclizations of unsaturated nitrones <1959JA6334>. 

The 1,3-dipolar cycloaddition of nitrones to olefins gives 1,2-oxazolidines. Because nitrones can undergo (Z)/( )-isomerization, diastereomers are formed, especially if the reaction is performed at elevated temperature (Scheme 10.16). In addition, 1,3-dipolar cycloadditions of nitrones to olefins may proceed via endo- or exo-transition states [41]. 

Isoxazolidines, Isoxazolines, Oxazolines, and Oxazines isoxazoiidines, easily obtained by cycloaddition of nitrones to olefins, are reduced to 1,3-amino alcohols by reaction with LAH in ether media. The synthesis of racemic sedridine from 3.256 is illustrative [TA2] (Figure 3.100). 

According to the concerted reaction pathway, in most cases the dipolarophile stereochemistry (( )/(Z)-configuration) is preserved during the cycloaddition. For cycloaddition reactions of nitrones to olefins both e/5 /-discrimination as well as endolexo selectivity have to be discussed." ... 

Dipolar cycloaddition of nitrones to olefins gave excellent yield of the product in much shorter time (Scheme-9) compared to the usual reaction conditions. 

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