Nucleophilic Opening of Epoxides

Nucleophilic Opening of Epoxides.— Participation by acetamido- and A-acetyl-ureido-groups in acid-catalysed epoxide-opening accounts for the products (68) and (71) formed from trans-compounds (66) and (69) epoxide rings in the cis-compounds (67) and (70) open normally at C-5 to give the same two diaxial 

Both isomeric 2,3-epoxides in the 5a-cholestane, 4,4-dimethyl-5a-cholestane, and 4,4-dimethyl-5a-oestrane series afford normal diaxial fluorohydrins with 

Komeno, H. Itani, H. Iwakura, and K. Nabeyama, Chem. andPharm. Bull. (Japan), 1970, 18, 1145. 

Levisalles and M. Rudler-Chauvin, Bull. Soc. chim. France, 1970, 664. 

Acid-catalysed ring-opening of 20a,21-epoxypregnanes (72) gave both the 20o,21- (73) artd 20, 21-diols (74), by non-selective attack of water. Base-catalysed hydrolysis, in contrast, gave only the 20a,21-diol, by nucleophilic attack of OH at C-21. The 20o,21-diol also resulted from epoxide opening by either dimethyl 

Through the same three-step sequence the analogous ris-diepoxide 10 [33] gave the related lactone 11, identical to 9 except that the two B-ring substituents have switched positions. All steps for both sequences proceeded in excellent yield. 

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Scheme 16 Synthesis of ( )-phoracantholide based on nucleophilic opening of epoxides by ketone enolates...

Aziridines may be prepared by the intramolecular nucleophilic opening of epoxides by amines and their derivatives (84CAR(130)103,92T5639,92TL487,92TL5351) (Scheme 15). 

Ti(IV) isopropoxide is an effective reagent for promoting regioselective attack by nucleophiles at the 3-position of 2,3-epoxy alcohols [69], 2,3-epoxy acids [70], and 2,3-epoxy amides [70]. It has been proposed that this process involves coordination to the metal center in the bidentate manner shown for a 2,3-epoxy alcohol in structure 44. Such Ti-assisted nucleophilic opening of epoxides is thought to play a role in the in situ reactions leading to 41 and 43. 

Alumina-catalyzed ckavage of epoxides (6,16-17 8,10-12). The nucleophilic opening of epoxides by alcohols can also be promoted by alumina used in catalytic amounts. The reaction then requires higher temperatures and longer reaction periods, but is economical for large-scale preparation. The reaction of cydohexene oxide with allyl alcohol (equation I) can be carried out on 0.3 moles of the oxide with only 3 g. of W-200-N alumina as purchased. The yield is the same as that obtained with large quantities of alumina doped with 4 weight % of the alcohol. 

Other examples of the nucleophilic opening of epoxide rings are presented in Sections 12.6 and 20.14. 

The Payne rearrangement of epoxy-alcohols is a special case of an intramolecular nucleophilic opening of epoxides and is of particular synthetic utility when it is applied to epoxides from the Sharpless procedure. ... 

Epoxy olefins 67a-b can be converted to cycloalkanols 69a b respectively on treatment with cobalt(I) dimethylglyoxime using a sunlamp. These reactions proceed via the cyclization of the intermediate j8-hydroxycobaloximes 68a-b, which are produced by a nucleophilic opening of epoxides with cobalt(I) (Scheme 26) [27, 28]. 

Complete details of nucleophilic opening of epoxides (6, 16-17) catalyzed by commercially available alumina (W-200-N) have been published. Some generalizations can be drawn from the extensive investigations. The reactivity of symmetrical cycloalkenc oxides decreases in the order of ring size 6 > 8 > 12 and reactivity of the nucleophiles decreases in the order ROH HOAc > RNHj. One great advantage of this method is that usually only one product is formed. 

In this section, we discuss a few early examples from our laboratory, where water proved to be the optimal medium in a variety of processes. Nucleophilic opening of three-membered rings such as epoxides, aziridines, and episulfides are excellent click reactions because competing elimination processes are stereo electronically disfavored. As a result, high yields of ring-opened products are obtained. We have used the nucleophilic opening of epoxides... 

As in these last examples, the descriptions of diastereoselective epoxidations were accompanied already by details on their subsequent use in ring fission reactions, we shall now switch to the various options of controlled regioselective and diastereoselective epoxide transformations. The nucleophilic opening of epoxides shows a strong dependence on substrate structure, nature of the nucleophile, and the catalyst involved, similarly to nucleophilic substitutions. Lastly, one has to consider the solvent and other details of the reaction conditions including the transition state conformation. 

A series of cyclohexenyl nucleoside analogues such as 130, which can be regarded as a carbovir analogue with an extra methylene group inserted, have been described, as have nucleoside phosphonates of type 131 and the compounds 132 and 133 (B = Gua, Ade, Ura), where the base units were added to the cyclohexyl ring by nucleophilic opening of epoxides. ... 

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