Lemieux-Johnson reaction

Cleavage of the enamide by the Johnson-Lemieux reaction." The allyl group was the only successfully cleaved group among the many that were examined. 

The next stage of the synthesis called for conversion of the terminal olefin to an aldehyde. This was accomplished using a Johnson-Lemieux oxidation. The resulting ketoaldehyde was then converted to fr-ketal 15. Basic hydrolysis of the formamide provided 16 and hydrolysis of the acetals afforded a mixture of diastereometic enaminoketones 17. An acid-promoted intramolecular Mannich reaction gave 2. Presumably epimerization of the ketone allowed both diastereomers of 17 to follow the path to 2. Reduction of ketone 2 with sodium borohydride provided an alcohol, which underwent formal dehydration upon treatment with thionyl chloride and pyridine, to give porantherine (1) as a racemic mixture. 

This cyclization reaction has been used in the synthesis of a number of A -substituted 5-hy-droxy-2-pyrrolidinones by Lemieux Johnson oxidation of the corresponding amides of the ( )- or (i5)-4-octene-l,8-dioic acids according to the procedure described. 

A great number of transformations has been performed on narceine imide (116) by Czech researchers. Oxidation with potassium permanganate in acetone or with nitric acid caused the cleavage of the alkaloid, giving rise to hemipinic imide (127). A similar result was noted by Rdnsch (129,130) during Lemieux-Johnson oxidation of ene lactam 152 (129,130) in this reaction the basic component (156) was isolated as well. The use of hydrogen peroxide in acetone converted 116 to (Z)-narceine imide N-oxide, which under the action of acetic anhydride underwent N-dealkylation (135). 

Step 1 (3-keto phosphonates often are used for olefmation of ketones (Horner-Wadsworth-Emmons modification of the Wittig reaction). Steps 2 + 3 The cuprate-mediated 1,4-addition and subsequent Lemieux-Johnson oxidation of a vinyl group are excellent procedures for the introduction of the p-formyl group. 

A formal total synthesis of ( )-morphine has been achieved by adopting the above synthetic route (Scheme 18). The tetrahydropyridine 91, prepared from the reaction of A/ -methyl-4-piperidone with 2,3-dimethoxy-phenyllithium, followed by dehydration, was converted to the bicyclic en-amine 92 by treatment with the ylic dibromide. Kinetic protonation of 92 with perchloric acid gave the trans-fused immonium salt, which upon dissolution in methanol equilibrated to the thermodynamically prefered cis isomer 93. Treatment of 93 with diazomethane brought about the formation of the aziridinium salt 94, which was readily transformed into the a-amino aldehyde 95 by its oxidation with dimethyl sulfoxide. It is also worth noting that the Komblum oxidation of aziridinium salts leads to the construction of a-amino aldehydes efficiently. Lewis-acid-catalyzed cyclization of 95 afforded the morphinan carbinol 96 in 80% yield. Successive mesylation and reduction of the mesylate derived from 96 with LiBEtjH afforded morphinan (97) in excellent yield. In this instance, direct conversion of 93 to 97 by treatment with diazomethane gave approximately 1 % of the desired product. Lemieux-Johnson oxidation of 97 under acidic conditions furnished the ketone 98, which was previously transformed into ( )-morphine by Gates. In order to confirm the structure of 98, its conversion to the known... 

Lemieux-Johnson oxidation, 812-813 Lepidine, 702, 1026 Lethargic reactions, 939-940 Leuchs anhydrides, 1014 DL-Leucine, 633 L-Leucine, 839, 1124 amino peptidase, 1204 ethyl ester, 88... 

Oxidative Cleavage of Alkenes. An alternative to the oxidative cleavage of alkenes using ozone or the Lemieux-Johnson protocol has been reported recently. Under the action of catalytic osmium tetroxide, with oxone as a reoxidant, a variety of substituted alkenes were cleaved efficiently to furnish carbonyl compounds (eq 37). Any of the aldehydes that are produced via this sequence are immediately oxidized in situ to give the corresponding acid clearly this does not happen for any ketones so produced. Even electron deficient alkenes such as o , -unsaturated carbonyl compounds could be conveniently oxidized, although the products then underwent a decarboxylation reaction to produce the corresponding diacid. 

This reaction was first reported by Lemieux and Johnson in 1956. It is a conversion of an olefin into two individual aldehydes by means of an oxidative cleavage of a carbon-carbon double bond with osmium tetraoxide-sodium periodate. Therefore, it is known as the Lemieux-Johnson oxidative cleavage, Lemieux-Johnson reaction, or simply Lemieux-Johnson oxidation." In addition, the combination of osmium tetraoxide and sodium periodate is referred to as Lemieux-Johnson reagent. It should be pointed out that a lactol may be obtained directly from the oxidation of the olefin with a hydroxyl group near the oleflnic bond." ... 

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