2,3-epoxycyclohexanones

FRAGMENTATION OF a,(J-EPOXYKETONES TO ACETYLENIC ALDEHYDES AND KETONES PREPARATION OF 2,3-EPOXYCYCLOHEXANONE AND ITS FRAGMENTATION TO 5-HEXYNAL... 

B. 5-Hexynal. To a solution of 5.60 g. (0.050 mole) of 2,3-epoxycyclohexanone in 120 ml. of benzene in a 500-ml. round-bottomed flask is added 10.82 g. (0.051 mole) of trans-1 -amino-2,3 diphenylaziri-dine.2 Initially, after brief swirling at room temperature, the reaction mixture is a colorless, homogeneous solution however it rapidly turns yellow and cloudy due to separation of water. After 2 hours the benzene and water are removed as an azeotrope under reduced pressure on a rotary evaporator with the bath maintained at approximately 30°. The resulting crude mixture of diastereomeric hydrazones weighs 15.4 g. (Note 7) and is subjected directly to the fragmentation reaction (Note 8). 

Gas chromatographic analysis at 120° on a 2.2-m. column packed with 10% diethylene glycol succinate showed the forerun fraction to contain approximately 50% product. The other fraction is pure 2,3-epoxycyclohexanone. 

The N-aminoaziridine version7 of the a,/3-epoxyketone->alkynone fragmentation is a possible alternative in situations where the simple tosylhydrazone version6-9 fails. The tosylhydrazone method often gives good yields at low reaction temperatures, but it tends to be unsuccessful with the epoxides of enones that are not cyclic or are not fully substituted at the /5-carbon atom. For example, it has been reported9 that 2,3-epoxycyclohexanone docs not produce 5-hexynal by the tosylhydrazone route. The A-aminoaziridine method can also be recommended for the preparation of acetylenic aldehydes as well as ketones. 

Recently (82), pure 3,5-dimethylcyclohexenone epoxide was obtained by Toda using a complexation method with optically active 1,6-di(o-chlorophenyl)-l,6-diphenylhexa-2,4-diyne-l,6-diol. The method was not applicable to unsubstituted 2,3-epoxycyclohexanone (82). 

Ss2 reaction with a,fi-epoxy ketones.6 The enolate 1 of 2,3-epoxycyclohexanone reacts with methyllithium to give, after acidic work-up, 2-methy -2-cyclohexenone (3), the product of SN2 addition. Reaction of 1 with lithium dimethyl cuprate on the other hand results in 6-methyl-2-cyclohexcnonc (2), the product of Sv2 addition. 

Stereoselective reduction. 2,3-Epoxycyclohexanones can be reduced predominately to the trans-epoxy alcohol by sodium borohydride if catalytic amounts of CeClj are present.1... 

A nonclassical substrate for the Heck reaction is 2,3-epoxycyclohexanone. The reactivity of this molecule under Heck coupling conditions is most likely attributed to its in situ isomerization to 1,2-cyclohexanedione. The 1,2-diketone subsequently reacts with aryl bromides as an olefin via the enol tautomer. Thus, within 5 to 30 min of directed microwave heating of the aqueous PEG mixture, up to 13 different C3-arylations were conducted using less than 0.05 mol % palladium acetate and no phosphine ligand (Scheme 12) [51]. 

The molecular helices and propellers discussed above contain no center of chirality, and the P and M nomenclature is thus the only way of describing their absolute configuration. This nomenclature, however, is also applicable to some series of chiral compounds which display several centers of chirality. As will be discussed in Section 6, the presence in a molecule of two or more centers of chirality usually implies the existence of several stereoisomers, but steric reasons may reduce down to two the possible number of stereoisomeric forms. Thus, 2,3-epoxycyclohexanone contains two asymmetric carbon atoms, but for steric reasons only two stereoisomers, namely the (2S 3S)-(—)- and the (2/ 3/J)-( + )-enantiomer, exist the former is depicted in diagram XL [49]. 

Synthesis of Optically Active Epoxides. Alkaloids and alkaloid salts have been successfully used as catalysts for the asymmetric synthesis of epoxides. The use of chiral catalysts such as quinine or quinium benzylchloride (QUIBEC) have allowed access to optically active epoxides through a variety of reaction conditions, including oxidation using Hydrogen Peroxide (eq 5), Darzens condensations (eq 6), epoxidation of ketones by Sodium Hypochlorite (eq 7), halohydrin ring closure (eq 8), and cyanide addition to a-halo ketones (eq 9). Although the relative stereochemistry of most of the products has not been determined, enan-tiomerically enriched materials have been isolated. A more recent example has been published in which optically active 2,3-epoxycyclohexanone has been synthesized by oxidation with t-Butyl Hydroperoxide in the presence of QUIBEC and the absolute stereochemistry of the product established (eq 10). ... 

Marino [68] showed that the silyl enol ethers of substituted 2,3-epoxycyclohexanones react with (PhCuCN)MgBr and (C2H3CuCN)MgBr to give, respectively, the Sn2 and Sn2 products [Eq. (56)]. 

Eelix, D., Wintner, C., Eschenmoser, A. Eragmentation of a,P-epoxyketones to acetylenic aldehydes and ketones preparation of 2,3-epoxycyclohexanone and its fragmentation to 5-hexynal. Org. Synth. 1976, 55, 52-56. 

These workers note, however, that 2,3-epoxycyclohexanone does not yield the corresponding l-hexyne-6-ol, which indicates that the presence of a /3-hydrogen atom alters the reaction. 

The enol ethers of substituted 2,3-epoxycyclohexanones, e.g. (192), react with organocuprates, e.g. MeCu(CN)Li, in a regio- and stereo-specific manner to yield (in most cases) the l,4-rra s-adducts (193) (95%). ... 

Oxidations. Alcohols are oxidized in dichloroethane with catalytic amounts of a dichromate salt using sodium percarbonate as a recycling agent and PTC. - Epoxidations of enones by sodium perborate or NaOCP under PTC conditions give high yields. However, with NaOCl and hexaethylguanidinium chloride, cyclohexenones give 6,6-dichloro-2,3-epoxycyclohexanones. 

Epoxycyclohexanone of 20% ee was first prepared in 1980 by an enantioselecti-ve epoxidation of 2-cyclohexenone. However, enantiomerically pure 3-methyl- (34),... 

Epoxycyclohexanone has been prepared in 30% yield by epoxi-dation of 2-cyclohexen-l-one with alkaline hydrogen peroxide, using a procedure described for isophorone oxide (4,4,6-trimethyl-7-oxabicyclo[4.1.0]heptan-2-one). A better yield (66%) was obtained using hydroperoxide (1,1-dimet.hydethylhydroperoxide) and... 

Fragmentation of a, -epoxyketones (5, 328). The use of this reaction for the synthesis of 5-hexynal from 2,3-epoxycyclohexanone has been published. Further examples and a mechanistic discussion have been recorded. ... 

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