Radical Cation-Mediated Annulation. Stereoselective Construction of Bicyclo[5.3.0]decan-3-ones by Aerobic Oxidation of Cyclopropylamines

Lee, Hee Bong; Sung, Moo Je; Blackstock, Silas C.; Kun, Jin

doi:10.1021/ja017043f

Cited by 68 publications

(31 citation statements)

References 27 publications

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“…9 In this system, CAN and bromide are soluble in the aqueous phase, whereas the cyclopropyl alcohol is only soluble in the organic phase leading to selective oxidation of the bromide ion. This solvent milieu provided isolated yields of β-bromo products in the range of 71-92% (entries 4,8,12,16).…”

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confidence: 99%

An Efficient and General Approach to β-Functionalized Ketones

et al. 2007

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The oxidation of selected anions (N 3 − , SCN − , I − and Br − ) by ceric ammonium nitrate (CAN) in the presence of substituted cyclopropyl alcohols provides a novel approach to β-functionalized ketones.The protocol has a number of advantages including short reaction times, ease of reagent handling and mild, neutral reaction conditions. Overall, this method provides an alternative pathway to important starting materials and intermediates in organic synthesis.Ketones substituted in the β position are important starting materials in organic chemistry. Among this group, β-haloketones are extremely useful intermediates in organic synthesis and act as precursors to enones, annulated compounds, heterocyclic derivatives, and dicarbonyl products. 1 In spite of their importance as precursors to a large range of important intermediates, 2 only a few of methods have been developed to synthesize β-substituted ketones. 3 The synthesis of β-substituted ketones by 1,4-addition of HX (X = Cl, Br, I) or trimethylsilyl iodide to the corresponding enone are sometimes experimentally inconvenient since the use of reactive or moisture sensitive reagents are required. 3b, 3d More recent approaches to β-substituted ketones, while useful, provide access to a limited range of compounds. 4,5 As a consequence, the development of new synthetic methods offering a general approach for the introduction of diverse functionality to the beta position of a carbonyl group still constitutes a challenge in organic chemistry.Cerium(IV) ammonium nitrate (CAN) has found wide applications in carbon-heteroatom bond forming reactions in organic synthesis. 6 The reported carbon-heteroatom bond formations mediated with CAN include C-Br, C-I, C-S, C-N, and C-Se bonds. These reactions usually involve the generation of heteroatom-centered radicals from the oxidation of anions and addition of the heteroatom radicals to alkenes or alkynes.Based on this precedent, we reasoned that Ce(IV) oxidation of an anion in the presence of a cyclopropyl alcohol would provide a route to β-substituted ketones as shown in Scheme 1. Since cyclopropyl units are readily accessible via the Kulinkovich reaction, 7 the ring opening of cyclopropanols and the carbon-heteroatom bond formation mediated with CAN could provide a novel, efficient, and general approach to a variety of β-substituted ketones.The synthesis of substituted cyclopropyl alcohols 1-4 shown in Table 1 were carried out using the Kulinkovich reaction and provided good isolated yields in the range of 63-82%. In an initial experiment, sodium azide was chosen as the first anion to react with a cyclopropyl alcohol since oxidation of this anion with CAN has been previously reported. 8 Reaction of 1 with NaN 3 in the presence of 2 equivalents of CAN in methanol produced a moderate yield (50%) of the 3-azido-1-phenyl propanone along with dimer and nitrated products as side products.rof2@lehigh.edu. NIH Public Access NIH-PA Author ManuscriptNIH-PA Author Manuscript NIH-PA Author ManuscriptSince solvent is known to play...

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An Efficient and General Approach to β-Functionalized Ketones

et al. 2007

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“…[6] We anticipated that electrochemical methods such as cyclic voltammetry and preparative electrolyses would be tools of choice to gain better insight in this reaction and could lead to the design of a more general and environmentally friendly experimental procedure. [7] For the purpose of this study, aminocyclopropanes 1 a-e, 2 a,b, 3, and 4 were prepared by using intra-or intermolecular Kulinkovich-de Meijere reactions, [8] following a modification Scheme 1. Autocatalytic aerobic oxidation of aminocyclopropanes to aamino endoperoxides.…”

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Electrochemical Aerobic Oxidation of Aminocyclopropanes to Endoperoxides

2007

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“…One-electron reduction could then form the stable (ferrous) MIC complex shown in Figure 7. Precedent for this suggestion can be found in a review by Lindeke [58] which suggested that a structure analogous to 21 (i.e., R = PhCH 2 -, R' = Ph, but with H replacing EnzFe) could undergo decomposition to form benzaldehyde, water and α-nitrosotoluene (PhCH 2 NO) as a precursor to benzaldoxime (2). Further precedent comes from work of Sang et al who showed that alkylhydroperoxy radicals (ROO•) add to the spin-trap reagent C-phenyl-N-tert-butyl nitrone (PBN) to form unstable adducts resembling structure 21…”

Section: Discussionmentioning

confidence: 99%

“…This mechanism is supported by direct observations of ring-opened products in chemical model systems [2][3][4][5], and in the oxidation of cyclopropylanilines by peroxidases [6][7][8]. While the formation of cinnamaldehyde as a metabolite of an N-(2-phenylcyclopropyl)amine has been reported, direct evidence for the formation of ring-opened metabolites of a simple N-cyclopropylamine has not been demonstrated for a P450 system.…”

Section: Introductionmentioning

confidence: 94%

Cyclopropylamine inactivation of cytochromes P450: Role of metabolic intermediate complexes

Cerny

Hanzlik

2005

Archives of Biochemistry and Biophysics

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, "Cyclopropylamine inactivation of cytochromes P450. Role of metabolic intermediate complexes." Arch. Biochem. Biophys. 436, 265-275 (2005). Keywords:Cytochrome P450, flavin-containing monooxygenase, metabolic intermediate complex, mechanismbased inactivation, suicide substrate Abstract:The inactivation of cytochrome P450 enzymes by cyclopropylamines has been attributed to a mechanism involving initial one-electron oxidation at nitrogen followed by scission of the cyclopropane ring leading to covalent modification of the enzyme. Herein we report that in liver microsomes Ncyclopropylbenzylamine (1) and related compounds inactivate P450 to a large extent via formation of metabolic intermediate complexes (MICs) in which a nitroso metabolite coordinates tightly to the heme iron, thereby preventing turnover. MIC formation from 1 does not occur in reconstituted P450 systems with CYP2B1/2, 2C11 or 2E1, or in microsomes exposed to gentle heating to inactivate the flavincontaining monooxygenase (FMO). In contrast, N-hydroxy-N-cyclopropylbenzylamine (3) and Nbenzylhydroxylamine (4) generate MICs much faster than 1 in both reconstituted and microsomal systems. MIC formation from nitrone 5 (PhCH=N(O)cPr) is somewhat faster than from 1, but very much faster than the hydrolysis of 5 to a primary hydroxylamine. Thus the major overall route from 1 to a P450 MIC complex would appear to involve FMO oxidation to 3, further oxidation by P450 and/or FMO to nitrone 5' (C2H4C=N(O)CH2Ph), hydrolysis to 4, and P450 oxidation to α-nitrosotoluene as the precursor to oxime 2 and the major MIC from 1.

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Radical Cation-Mediated Annulation. Stereoselective Construction of Bicyclo[5.3.0]decan-3-ones by Aerobic Oxidation of Cyclopropylamines

Cited by 68 publications

References 27 publications

An Efficient and General Approach to β-Functionalized Ketones

An Efficient and General Approach to β-Functionalized Ketones

Electrochemical Aerobic Oxidation of Aminocyclopropanes to Endoperoxides

Cyclopropylamine inactivation of cytochromes P450: Role of metabolic intermediate complexes

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