Regioselectivity three-membered ring formation

Stereoselectivity and Regioselectivity of Three-Membered Ring Formation from S Ylides... 

As for the regioselectivity of the nitrone cycloaddition to MCP and its alkyl or aryl derivatives, a tendency of the three-membered ring to end up at the 4-position of the final isoxazolidine ring clearly emerges from the experimental findings. This result is particularly noteworthy if compared to regiospecific formation of the 5,5-disubstituted isoxazolidines in the reactions of nitrones, not... 

If a radical is joined to a double bond by a chain of three or more carbons, intramolecular addition generates a ring. The regioselectivity of such additions is governed more by stereoelectronic factors than by substituents on the double bond. Thus, five-membered ring formation byway of a l°-cyclized radical dominates the products, as shown in Scheme 2.47. 

Good nucleophiles, such as ammonia and amines, open the highly strained epoxide ring by an S vj2 mechanism and show a regioselectivity for attack of the nucleophile at the less hindered carbon of the three-membered ring. The reaction favors the stereoselective formation of the trans product ... 

Studies on a number of substituted 1, 5-dienes support the thought it has been shown that formation of a three membered ring is regioselective and occurs preferentially across the more substituted allyl moiety. 

The formation of three membered ring is regioselectively favourable and occur preferentially across the more substituted allyl moiety. Hence, 1, 5-diene gives [A) as major product on rearrangement. 

The (phosphino)(silyl)carbene 2a has been shown to exhibit this diagnostic reactivity. Under rather drastic conditions (300°C, 10 2 mm Hg), 2a has been converted into the azaphospholidine 37, in high yield, as a mixture of four diastereomers, which result from the presence of three asymmetric centers.4 The high regioselectivity of the carbene insertion (no formation of a four-membered ring was detected) is intriguing, especially since the same regioselectivity is observed upon thermolysis of bis(diisopropyl-amino)phosphinodiazomethane li.4 Yet, in contrast, four-membered heterocycles were obtained with other phosphinocarbenes (Sections V,C,1 and 3). 

The direct a-alkylation of monoketones normally employs reaction of an alkyl halide or sulfonate with the enolate anion produced using a strong base. This method can be satisfactorily used with symmetrical ketones, which are to be dialkylated with a dihalide, and with intramolecular cyclization reactions, where the formation of five- and six-membered rings is often favored over the formation of three-, four-, seven-, and eight-membered rings (M. Mous-seron, 1937 W.S. Johnson, 1963). Regioselective alkylation of dianions according to Hauser s rule (see p. 9f.) is usually also a satisfactory procedure (F.W. Sum, 1979). 

Reaction of the 2,3-butadienylamine 417 with aryl iodides affords three- and five-membered rings. The regioselectivity depends on reaction conditions. Particularly solvents play an important role. Dioxane is a solvent of choice for the aziridine formation. The chiral aziridine 418 as a main product and 419 as the minor product were obtained from 2,3-butadenylamine 417 without racemization in dioxane. The five-membered ring 420 was not obtained in this case [160]. 

The argument is closely analogous to that used to explain the regioselectivity of formation of bromoacetoxy compounds (Table 9.2) formed in the addition of bromine to alkenes in acetic acid. Similarly, addition of bromine to alkenes in water produces bromohydrins. Although they are more difficult to synthesize, iodohydrins and fluorohydrins are also known. For a review of the synthesis and reactions of halohydrins, see Rosowsky, A. in Weissberger, A., Ed. Heterocyclic Compounds with Three- and Four-Membered Rings, Part One Wiley-Intersdence New York, 1964 p.l. 

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