Epoxides regioselective opening

Displacement of the 3-hydroxyl group of 74 was carried out with Et2NSF3 (DAST) (DAST - diethylaminosulfur trifluoride) in dichloromethane. The expected fluorinated product 75 on treatment with aqueous perchloric acid led to regioselective epoxide ring opening to give 76, which on treatment with hydrazine hydrate at 100 °C for 18 h yielded 3,4-dihydroxy-8-oxo-octahydropyridazino[l,6-r/][l,2,4]triazine-l-carboxylic acid phenylamide 77 (Scheme 3) <1997T9357>. 

Similarly, the synthesis of (+)-T-7 (129) was achieved in a five-step sequence from [2R-(2R)]-22l in 32% overall yield (Scheme 8). The regioselective opening of the epoxide of [2R-(2R)]-223 with lithium dibutylcuprate afforded alcohol [2R-(2R)]-227 that was transformed in a three-step sequence into (+)-T-7 (129) in 51% yield. In an analogous way (+)-T-8 (126) was obtained from [2R-(2S)] 223 in four steps and 35% yield. 

Direct epoxidation of compound 20 with Bu OOH in the presence of VO(acac)2 [10], proceeded chemoselectively to give the epoxide 21 which was regioselectively opened with UAIH4 to afford the 1,2-diol 22 (76%). X-ray diffraction analysis of this compound confirmed the assigned stereochemistry for intermediates 20-22. 

The preparation of the requisite y-keto-p-toluenesulfonate rac-35 as homo-Favorskii precursor commenced with commercially available 2,5-dihy-droanisole (36) that was protected and epoxidized to acetal rac-31 (Scheme 11). Regioselective opening of the epoxide with p-chlorophenylse-lenide followed by sequential oxidation to the selenoxide and thermal elimination generated an allylic alcohol that was protected to give pivaloate rac-38. 

Highly regioselective opening of epoxides and aziridines with sodium azide and Oxone in aqueous acetonitrile in very high yield was reported (equation 52). ... 

Regioselective opening of the epoxides 29 was realized with various nucleophiles (CN, N3", OH"). Instead of a two-step process, direct conversion of chlo-rohydrin (S) -28a yielding cyanohydrin 30 was accomplished in 51% yield (Scheme 2.2.7.16) [45]. 

An epoxide is opened regioselectively to give the most stable carbocation. 

Two classes of structures containing azido- and aziridino-hydroxyl-(3-lactam (I and II, respectively, Fig. 21) have been prepared by means of a stereo- and regioselective epoxide ring opening reaction [296],... 

Advantageous use of homochiral cyclohexadiene-cis-l,2-diol, available by means of biocatalytic oxidation of chlorobenzene with toluene dioxygenase, has enabled the synthesis of all four enantiomerically pure C18-sphingosines (Nugent, 1998), which are known inhibitors of protein kinase C and important in cellular response mediation for tumor promoters and growth factors. The four requisite diastere-omers of azido alcohol precursors were accessed by regioselective opening of epoxides with either azide or halide ions. 

Rough guidelines for the prediction of regioselectivity in epoxide ring openings are summarized in Scheme 4.60. Under neutral or basic reaction conditions alkyl-or aryl-substituted epoxides react with most nucleophiles at the less substituted carbon atom [248-253]. Under acidic reaction conditions, however, product mixtures or preferential attack at the most substituted carbon atom can be observed. Acids can usually be used to enhance the reactivity of epoxides and to promote substitution at the site of an epoxide which forms a carbocation more readily. 

The regioselectivity of epoxide ring opening by amines can occasionally be modified by using a lithium amide instead of the amine. In the example sketched in... 

Scheme4.74. Reagent-controlled regioselectivity of epoxide ring opening with amines [332],...

C—C Bond formation with allylmagnesium chloride. J. Org. Chem. 1997, 62, 9342—9344. Overman, L. E. Renhowe, P. A. Regioselective opening of terminal epoxides with 3-(trialkyl-silvljallvl organometallic reagents. J. Org. Chem. 1994, 59, 4138-4142. 

To circumvent elimination reactions, fluorides have been introduced by nucleophilic ring opening of epoxides.15 The regioselective opening of aldosyl epoxides proceeds ira r-diaxially.16 Epoxides can also be opened with chloride, bromide and iodide ions. The chemistry of epoxides is discussed in detail in Section 3.6. 

The products 125 and 126 are formed with complete regioselectivity, suggesting involvement of an epoxide ring-opened intermediate. Product ratios vary systematically, depending on the steric properties of the epoxides. As the size of the epoxide substituents increases, the amount of the five-membered ring compounds 126 in the reaction mixture decreases appreciably125. 

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