A practical technique for laboratory Birch reductions (Chemistry of opium alkaloids, Part VI)

Beyerman, H. C.; Leeuwen, F. F. Van; Lie, T. S.; Maat, L.; Olieman, C.

doi:10.1002/recl.19760951006

Cited by 16 publications

(2 citation statements)

References 8 publications

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“…The desired para−ortho coupling is complicated by three other possible couplings (ortho−ortho, ortho−para, para−para). However, some bioanalogous syntheses involving Grewe-type cyclization catalyzed by acid − or palladium , have led to several successful syntheses.…”

Section: Divergent Synthetic Plan For Opium Alkaloids and Galanthamin...mentioning

confidence: 99%

Divergent Enantioselective Synthesis of (−)-Galanthamine and (−)-Morphine

2005

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An efficient divergent synthetic strategy for the synthesis of the opiate and amaryllidaceae alkaloids emerges by employing a Pd-catalyzed asymmetric allylic alkylation (AAA) to set the stereochemistry. Three generations of syntheses of galanthamine are discussed in detail with particular focus on the scope of the palladium-catalyzed AAA reactions and intramolecular Heck reactions. The pivotal tricyclic intermediate is available in six steps from 2-bromovanillin and the monoester of methyl 6-hydroxycyclohexene-1-carboxylate. This intermediate requires only two steps to convert to (-)-galanthamine. Using a Heck vinylation, we found that the fourth ring of codeine/morphine could be formed. The final ring formation involves a novel visible light-promoted hydroamination. Thus, six steps are required to convert the pivotal tricyclic intermediate into codeine, which has been demethylated in high yield to morphine.

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Section: Divergent Synthetic Plan For Opium Alkaloids and Galanthamin...mentioning

confidence: 99%

Divergent Enantioselective Synthesis of (−)-Galanthamine and (−)-Morphine

2005

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“…Birch reduction of 5 in liq. NH, with Li, and t-BuOH as a proton donor [9], gave the hexahydroisoquinoline 6, converted with ethyl formate into the N-formyl compound 7 with an electron-withdrawing group on the amine N-atom, reducing its basic properties [lo] and making 7 an ideal compound to study Grewe cyclization. Treatment of 6 with HCI [ 1 11 afforded directly the octahydroisoquinolin-6-one 8, isolated…”

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confidence: 99%

Note on Attempts to Prepare Ring‐B Homomorphinan‐6‐ones by Grewe Cyclization from Octahydro‐1‐phenethylisoquinolines

Dumont

Pfander

Brossi

1985

Helvetica Chimica Acta

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Grrive cyclization of the N-formyl-protected octahydroisoquinolin-6-one 1 prepared by conventional chemistry did not afford the expected homomorphinanone. The exclusive reaction product obtained in good yield was the a&unsaturated N-formyloctahydroisoquinolin-h-one 2, further converted by acid hydrolysis into the crystalline octahydroisoquinolin-6-one 8.Grewe cyclization of 1-benzyl-octahydroisoquinolines in strong acid is a well established route to morphinans [l-31 and a key reaction in the total synthesis of opium alkaloids by Rice [4] [5]. We now report that similar treatment of l-phenethyloctahydroisoquinolines failed to give ring closure to ring-B homorphinan-6-ones related to the alkaloid androcymbine [6]. The novel N-protected octahydro-1 -phenethylisoquinoline 1 with a a,y-unsaturated keto group, in principle ideally suited for Grewe cyclization, was prepared by conventional chemistry, and afforded by treatment with 80% H2S0, [7] or triflic acid ( = trifluoromethanesulfonic acid) [4] [5] a$-unsaturated isoquinolinone 2 instead of a tetracyclic ketone2). Removal of the aromatic proton from C(6') required for cyclization is obviously disfavored in the 1 -phenethyl series of octahydroisoquinolines where the aromatic ring is further removed from the double bond than in the 1-benzyl series, disfavored over abstraction of a proton from C(5) resulting in the formation of the a$-unsaturated ketone 2.The synthesis of the required isoquinolines 1 and 7 was accomplished by conventional methods as follows: Amide 3, prepared by heating 3-methoxyphenethylamine and 3-(3-methoxypheny1)propionic acid [XI afforded, with POC1, in MeCN, the 3,4-dihydroisoquinoline 4, and by selective 0-demethylation in refluxing 48% HBr [7] the phenolic compound 5 . Birch reduction of 5 in liq. NH, with Li, and t-BuOH as a proton donor [9], gave the hexahydroisoquinoline 6, converted with ethyl formate into the N-formyl compound 7 with an electron-withdrawing group on the amine N-atom, reducing its basic properties [lo] and making 7 an ideal compound to study Grewe cyclization. Treatment of 6 with HCI [ 1 11 afforded directly the octahydroisoquinolin-6-one 8, isolatedPostdoctoral Fellow at the Section on Medicinal Chemistry, NIADDK, NIH, Bethesda. The chemical reactions reported here were accomplished with racemic materials, and structures shown, therefore, represent racemates.

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TheBirch Reduction of Aromatic Compounds

Rabideau

Marcinow²

1992

Organic Reactions

134

138

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The reduction of aromatic compounds by alkali metals in liquid ammonia represents an important method for the preparation of partially unsaturated six‐membered rings. The reaction was discovered by Wooster and Godfrey, but the major development resulted from the efforts of A. J. Birch, and the reaction has since come to bear his name. Although a variety of metals can be used, the most common are sodium and lithium, and, to a lesser extent, potassium. Cosolvents such as ether or tetrahydrofuran (THF) are often used to improve solubility, and weak acids such as alcohols may be employed during the reaction as proton sources. The latter are necessary for the reduction of benzene and its unactivated derivatives. Improvement in experimental procedures by Wilds and Nelson, the application to polynuclear compounds by Hückel and later by Harvey, and the development of methods for the alkylation of the anions generated in this process (i.e., reductive alkylation) have made this reaction an important approach to the synthesis of a wide variety of organic compounds.

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A practical technique for laboratory Birch reductions (Chemistry of opium alkaloids, Part VI)

Cited by 16 publications

References 8 publications

Divergent Enantioselective Synthesis of (−)-Galanthamine and (−)-Morphine

Divergent Enantioselective Synthesis of (−)-Galanthamine and (−)-Morphine

Note on Attempts to Prepare Ring‐B Homomorphinan‐6‐ones by Grewe Cyclization from Octahydro‐1‐phenethylisoquinolines

TheBirch Reduction of Aromatic Compounds

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