Ketones, 2,3-epoxy ring opening

Ceriumflll) chloride heptahydrate. 14,75-77,15,72-73,16,67-68 18,87 20,75 a-Chloro enones. a,p-Epoxy ketones undergo ring opening and dehydration, but changing the solvent system from aq MeOH to MeCN stops the dehydration step. The behavior of 2,3-epoxycyclopentanone differs from that of the cyclohexanone homologue in that the product dehydrates much more readily. 

Photoreactions of epoxy ketones have been extensively investigated, and these studies demonstrated that several types of photochemical processes are open to these compounds. " Thus, it was often difficult to control the regioselectivity of the epoxy ring-opening because the reactivity depends on the substitution and the nature of their excited states. 

Whereas the acid-catalyzed ring opening of 4,5-epoxy-3-ketones in the a-and -series normally gives rise to the type of products discussed above, in some circumstances 4, 5jS-epoxy-3-ketones give abnormal, rearranged products. These products are 2a-hydroxy-A" -3-ketones (or esters thereof) (166). 

A decisive solvent effect is also observed with other a,/ -epoxy ketones. Specifically, 3jS-hydroxy-16a,17a-epoxypregn-5-en-20-one and its acetate do not react with thiocyanic acid in ether or chloroform. However, the corresponding thiocyanatohydrins are formed by heating an acetic acid solution of the epoxide and potassium thiocyanate. As expected, the ring opening reaction is subject to steric hindrance. For example, 3j6-acetoxy-14f ,15f5-epoxy-5) -card-20(22)-enoIide is inert to thiocyanic acid in chloroform, whereas the 14a,15a-epoxide reacts readily under these conditions.Reactions of 14a,15a-epoxides in the cardenolide series yields isothiocyanatohydrins, e.g., (135), in addition to the normal thiocyanatohydrin, e.g., (134). 

Additionally, 1,2-dihydroxyethylene dipeptide analogues without the C-terminal carboxylic acid have been used to obtain aspartyl proteases inhibitors.[641 These efforts include stereoselective alkylation of imines, one-pot reductive amination of epoxy ketones, ring opening of epoxides with sodium azide, diastereoselective dihydroxylation of allylic amines, and enzymatic resolution and stereocontrolled intramolecular amidation. 

The method is a modification of one used by Barton and McCombie.8 Reduction of ketones.9 Ketones can be reduced to alcohols by Bu3SnH in the presence of either AIBN or a Lewis acid, but this reaction is limited to unhindered ketones. However, even sterically hindered ketones, such as f-butyl methyl ketone, can be reduced under high pressure (10 kbar) in the absence of a catalyst. This method is particularly useful in the case of cyclopropyl and a,p-epoxy ketones, which are reduced to the corresponding alcohols. Reduction of these ketones with Bu3SnH under radical conditions results in ring-opened products. 

When dienones such as 55 are subjected to the epoxidation conditions the electron-poorer C=C double bond is selectively epoxidized. The other C=C bond can be functionalized further, for example, it can be dihydroxylated, as shown in the synthesis of the lactone 56 (Scheme 10.11) [82]. Stannyl epoxides such as 57 (Scheme 10.11, see also Table 10.8, R1 = n-Bu3Sn) can be coupled with several electrophiles [72], reduction of chalcone epoxide 58 and ring opening with alkyl aluminum compounds provides access to, e.g., the diol 59 and to phenylpropionic acids (for example 60). Tertiary epoxy alcohols such as 61 can be obtained with excellent diastereoselectivity by addition of Grignard reagents to epoxy ketones [88, 89]. 

Hasegawa and colleagues recently reported the reductive ring opening of epoxy ketones 114 to 3-hydroxy ketones 116 catalyzed by 1 mol% of 110 (Fig. 29). Dihydrobenzimidazole 115 served as a reducing agent acting similarly to 112 [182]. 

Fig. 29 Photoredox-catalyzed ring opening reactions of epoxy ketones...

OL-Hydroxy aldehydes. A new method for one-carbon homologation of ketones to a-hydroxy aldehydes involves Darzens condensation with chloromethyl phenyl sulfone to give an ex,p-epoxy sulfone followed by ring opening by hydroxide ion. The anhydrous potassium hydroxide obtained by controlled addition of water to potassium /-butoxide (8,... 

The ring-opening reaction is not limited to conventional nucleophiles. Ceric ammonium nitrate in the presence of excess nitrate ion converts oxiranes to / -nitrato alcohols <1995T909>. The reaction is believed to proceed via a one-electron transfer to form an oxiranium radical cation that is subsequently captured by a nitrate ion. Nitric oxide adds to 2,3-epoxy phenyl ketones <2004TL1565>. 

For epoxy-protected ketones, highly regioselective ring opening leading to 3-keto alcohols was attained (equation 10). In the reduction of a diepoxide, 1,4-diol derivatives were predominantly obtained (equation 11). ... 

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