Beckmann rearrangement of adamantanone oxime

Kovacic, Peter; Field, Kurt W.; Wnuk, Thomas A.

doi:10.1021/je60049a036

Cited by 5 publications

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References 3 publications

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“…After conversion of the ketone into the corresponding oxime (91 % yield) by condensation with hydroxylamine, [35] thionyl-chloride-mediated Beckmann rearrangement ensued (54 % yield). [36] The process was completely regioselective, effecting the net insertion of a nitrogen atom at C16 to form 16, as was verified by a significant NOE signal between its lactam NH group and the C20 methylene protons. Functional group manipulation of the cyclopentene substructure within 16 was then initiated by alkene ozonolysis followed by a reductive work up (NaBH 4 ) [11] to afford the corresponding diol.…”

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confidence: 86%

Synthetic Access to the Chlorocyclopentane Cores of the Proposed Original and Revised Structures of Palau′amine

Bultman

Gin

2008

Angew Chem Int Ed

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The pyrrole-imidazole alkaloids constitute a family of more than 100 natural products, [1,2] among which palau'amine (1, Scheme 1) exists as one of the more structurally complex members. This polycyclic guanidine alkaloid, which was isolated from Stylotella aurantium, was found to possess potent cytotoxic, antibiotic, and immunosuppressive activities.[3] Despite the fact that its acute toxicity is relatively low (LD 50 = 13 mg kg À1 in mice), palau'amine exhibited significant cytotoxicity in a variety of cancer cell lines, including P-388 (IC 50 = 0.1 mg mL À1 ) and A-549 (IC 50 = 0.2 mg mL À1 ). Moreover, 1 exhibits remarkable immunosuppressive responses in the mixed lymphocyte assay (IC 50 < 18 ng mL À1 ). Elegant strategies for the synthesis of advanced cyclopentane fragments related to 1 have been reported.[4] These include, inter alia, a tethered Pauson-Khand approach, [5] Diels-Alder chlorination/ring contraction, [6,7] Diels-Alder oxidative ring contraction, [8,9] spirocyclization of alkylidene glycolamidines and alkylidene hydantoins, [10,11] 1,3-dipolar cycloaddition of thiosemicarbazide derivatives and alkene/enamide metathesis, [12,13] Diels-Alder cyclopropane fragmentation, [14] oxidative tandem radical cyclization, [15] and most recently intramolecular guanidine-conjugate addition [16,17] in a total synthesis of the related axinellamine alkaloids. Additionally, synthetic efforts toward the phakellin heterocyclic core of 1 have also been reported. [18][19][20][21][22][23][24][25] The construction of the central chlorinated cyclopentane skeleton within 1, with control over the relative stereochemical configuration of all of its substituents, emerges as a demanding challenge in this synthetic target. This synthetic hurdle is further complicated by the recent discovery highlighting the stereochemical revision of palau'amine [26][27][28][29] based on NMR spectroscopy, molecular calculations, and comparison to related natural products. These data suggest that the endo-disposed C17 chloro group and the C12 cis-fused ring junction in the originally proposed structure 1 a instead exists as its C12,C17 diastereomeric counterpart 1 b, which incorporates a rare trans-fused [3.3.0]-bicyclic skeleton.In focusing on the elaborately substituted cyclopentane scaffold 2 (Scheme 2) of 1 a and 1 b, retrosynthetic disconnection of the C18 À However, direct application of a Diels-Alder transform to 3 is likely to be challenging. Indeed, selectively functionalized cyclopentadienes such as 4 are not trivial to access, and diene isomerization is virtually unavoidable if one of the substituents at C17 is a proton, as in the natural product. However, control over the configuration at C17, along with that of the other substituents on the cyclopentane core, could be established indirectly through the [3,3]-sigmatropic rearrangement of bridged tricyclodecadienes. The classic finding by Woodward and Katz [30] which involves the preparation of the bridged allylic alcohol 6 (Scheme 3), detailed its susceptibility to equilibration th...

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mentioning

confidence: 86%

Synthetic Access to the Chlorocyclopentane Cores of the Proposed Original and Revised Structures of Palau′amine

Bultman

Gin

2008

Angew Chem Int Ed

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“…After conversion of the ketone into the corresponding oxime (91% yield) by condensation with hydroxylamine, [35] thionyl-chloridemediated Beckmann rearrangement ensued (54% yield). [36] The process was completely regioselective, effecting the net insertion of a nitrogen atom at C16 to form 16, as was verified by a significant NOE signal between its lactam NH group and the C20 methylene protons. Functional group manipulation of the cyclopentene substructure within 16 was then initiated by alkene ozonolysis followed by a reductive work up (NaBH 4 ) [11] to afford the corresponding diol.…”

mentioning

confidence: 86%

Synthetic Access to the Chlorocyclopentane Cores of the Proposed Original and Revised Structures of Palau′amine

Bultman

Gin

2008

Angewandte Chemie

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The pyrrole-imidazole alkaloids constitute a family of more than 100 natural products, [1,2] among which palau'amine (1,Scheme 1) exists as one of the more structurally complex members. This polycyclic guanidine alkaloid, which was isolated from Stylotella aurantium, was found to possess potent cytotoxic, antibiotic, and immunosuppressive activities.[3] Despite the fact that its acute toxicity is relatively low (LD 50 = 13 mg kg −1 in mice), palau'amine exhibited significant cytotoxicity in a variety of cancer cell lines, including P-388 (IC 50 = 0.1 μg mL −1 ) and A-549 (IC 50 = 0.2 μg mL −1 ). Moreover, 1 exhibits remarkable immunosuppressive responses in the mixed lymphocyte assay (IC 50 < 18 ngmL −1 ). Elegant strategies for the synthesis of advanced cyclopentane fragments related to 1 have been reported. [16,17] in a total synthesis of the related axinellamine alkaloids. Additionally, synthetic efforts toward the phakellin heterocyclic core of 1 have also been reported. [18][19][20][21][22][23][24][25] The construction of the central chlorinated cyclopentane skeleton within 1, with control over the relative stereochemical configuration of all of its substituents, emerges as a demanding challenge in this synthetic target. This synthetic hurdle is further complicated by the recent discovery highlighting the stereochemical revision of palau'amine [26][27][28][29] based on NMR spectroscopy, molecular calculations, and comparison to related natural products. These data suggest that the endo-disposed C17 chloro group and the C12 cis-fused ring junction in the originally proposed structure 1a instead exists as its C12,C17 diastereomeric counterpart 1b, which incorporates a rare trans-fused [3.3.0]-bicyclic skeleton.In focusing on the elaborately substituted cyclopentane scaffold 2 (Scheme 2) of 1a and 1b, retrosynthetic disconnection of the C18-R 4 and C16-[N] substituents ([N] = nitrogen functional group) would furnish the [2.2.1]-bicyclo substrate 3. The resulting norbornene-like intermediate 3 would possess all of the diverse latent functionalities present in the cyclopentane core, including the C17-chloro substituent. However, direct application of a Diels-Alder

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TheBeckmann Reactions: Rearrangements, Elimination–Additions, Fragmentations, and Rearrangement–Cyclizations

Gawley

1988

Organic Reactions

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The Beckmann rearrangement, the acid‐mediated isomerization of oximes to amides, was discovered by Beckmann in 1886. As one of the oldest and most familiar transformations in organic chemistry, it has been reviewed several times. What has become known as the Beckmann fragmentation was in fact first observed by Wallach in 1889 but was not developed extensively until the 1960s. It has been referred to by several names over the years and has also been reviewed. The rearrangement cyclization is the intramolecular cyclization of a nitrilium ion generated by Beckmann rearrangement from an oxime. Within the context of an aromatic terminator, the process was first reported by Goldschmidt in 1895. Wallach reported the first case of an aliphatic terminator in 1901, although the reported structure was incorrect, and Perkin was apparently the first to observe a heteroatom terminator, but he also reported an incorrect structure. The process has been exploited only quite recently. This chapter is an update of these reactions, last reviewed in this series in 1960. Not covered are transformations that have been labeled Beckmann‐type reactions but are mechanistically unrelated. The most prominent of these is the so‐called photochemical Beckmann rearrangement, first observed by De Mayo in 1963 and discussed in a review several years ago. Worthy of mention, however, is the fact that many oximes that suffer fragmentation under acidic conditions undergo rearrangement when photolyzed. Throughout this chapter, the ( E ) and ( Z ) nomenclature is used to describe oxime geometry.

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Beckmann rearrangement of adamantanone oxime

Abstract: Adamantanone oxime underwent Beckmann rearrangement with thionyl chloride as the promoter to produce 4-azatricyelo[4.3.1 ,l3,8]undecan-5-one in 85% yield. An investigation of reaction variables provided optimum reaction conditions and mechanistic information.

Cited by 5 publications

References 3 publications

Synthetic Access to the Chlorocyclopentane Cores of the Proposed Original and Revised Structures of Palau′amine

Synthetic Access to the Chlorocyclopentane Cores of the Proposed Original and Revised Structures of Palau′amine

Synthetic Access to the Chlorocyclopentane Cores of the Proposed Original and Revised Structures of Palau′amine

TheBeckmann Reactions: Rearrangements, Elimination–Additions, Fragmentations, and Rearrangement–Cyclizations

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