Copper(II)-Catalyzed [2,3]-Sigmatropic Rearrangement of <i>N</i>-Methyltetrahydropyridinium Ylids

Heath, Peter; Roberts, Edward; Sweeney, Joseph; Wessel, Hans Peter; Workman, James

doi:10.1021/jo034147v

Cited by 31 publications

(8 citation statements)

References 10 publications

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“…We have previously reported methods for the stereoselective synthesis of 3-alkenyl pyrrolidines, compounds a simple oxidation away from the dicarboxylate motif of kainoids and analogues; 9 given the rich synthetic possibilities offered by the vinyl moiety, extrapolation of the orig-inal method by judicious placement of carbon substituents in the ring system (Scheme 1) would enable access to the 4-substituted pyrrolidine core of bioactive pyrrolidines. Moreover, one can envisage a diverse range of analogous compounds would easily be accessed by such a method.…”

Section: Figure 1 Potent Bioactive Pyrrolidine Carboxylatesmentioning

confidence: 99%

Probing the Effect of Allylic Substitution on Cyclic Ammonium Ylid Rearrangements

Sançon¹,

Sweeney²

2010

Synlett

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The [2,3]-sigmatropic rearrangement of tetrahydropyridine-derived ammonium ylids is a valuable method for the preparation of substituted pyrrolidine carboxylates. The presence of an allylic substituent does not intrinsically reduce the yield of rearrangements, and the diastereoselectivity of rearrangement is related to the structure of the diazo reactant. The method represents a very rapid means of accessing complex pyrrolidines, as shown by preparation of a precursor to the core of lactacystin.Substituted pyrrolidine carboxylates are structures of both biological and synthetic significance. In particular, the kainoid 1 and acromeloid 2 families of neurotransmitters have attracted particular attention, 3 due both to their potent biological activity 1,4 and the fundamental synthetic challenges 5 still posed by densely functionalized pyrrolidines. Perhaps pre-eminent amongst this diverse class of bioactive structures, the pyrrolidine carboxylate thioester lactacystin 6 ( Figure 1) has attracted unprecedented interest from medicinal 7 and synthetic chemists 8 alike. Figure 1 Potent bioactive pyrrolidine carboxylatesWe have previously reported methods for the stereoselective synthesis of 3-alkenyl pyrrolidines, compounds a simple oxidation away from the dicarboxylate motif of kainoids and analogues; 9 given the rich synthetic possibilities offered by the vinyl moiety, extrapolation of the original method by judicious placement of carbon substituents in the ring system (Scheme 1) would enable access to the 4-substituted pyrrolidine core of bioactive pyrrolidines. Moreover, one can envisage a diverse range of analogous compounds would easily be accessed by such a method.The key issue in the predicted reaction is the effect of the allylic substituent upon the course of the reaction: in addition to the likely stereoinduction, the additional steric compression of the transition state might deter the overall reaction. Thus we were eager to examine the preparation and reaction of a simple ylid (R 1 = Me) as an indicator to the feasibility of the process. We report here the preliminary data arising from our studies to date.Scheme 1 Access to densely functionalized pyrrolidines by [2,3]-sigmatropic rearrangement of 5-substituted tetrahydropyridinium ylids We envisaged ylids 1 being accessible according to the retrosynthetic rationale outlined in Scheme 2. Thus, a sequence of allylamine ring opening of butadiene monoepoxide, alkene metathesis and copper-catalyzed methylation of the key allylic acetate 2, would give tetrahydropyridine 3, the direct precursor to ylids 1.Thus, butadiene monoepoxide was ring-opened by N-methyl allylamine, giving an inseparable mixture of alcohols dominated by the desired secondary isomer 4 (80:20 ratio,

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Section: Figure 1 Potent Bioactive Pyrrolidine Carboxylatesmentioning

confidence: 99%

Probing the Effect of Allylic Substitution on Cyclic Ammonium Ylid Rearrangements

Sançon¹,

Sweeney²

2010

Synlett

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“…A route for the synthesis of proline derivatives was developed [77] Eq. A route for the synthesis of proline derivatives was developed [77] Eq.…”

Section: Ammonium Ylide Formation-rearragement Reactionmentioning

confidence: 99%

Rhodium(II)-Catalyzed Reaction of Diazocompounds in the Service of Organic Synthesis of Natural and Non-Natural Products

Wee

2006

COS

112

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The rhodium(II)-carbenoid mediated transformation of diazocarbonyl compounds is well recognized as a useful process for the facile formation of carbon-carbon and carbon-heteroatom bonds under mild reaction conditions. In this review, the incorporation of rhodium(II)-carbenoid transformations in the synthetic planning and the eventual application of rhodium(II) carbenoid reactions in the synthesis of natural products, non-natural compounds of medicinal importance, and advanced intermediates are discussed. Focus is placed on the use of intermolecular and intramolecular C-H and X-H insertion, intermolecular and intramolecular cyclopropanation, and tandem ylide (carbonyl, ammonium, oxonium, sulfonium) formation/1,3-dipolar cycloaddition, [2,3]-sigmatropic or Stevens [1,2]-rearrangement reactions as key step(s) in the synthetic routes.

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“…Although many such reactions have been successfully developed, pursuit of asymmetric versions is still a challenging goal. In this respect, the [2,3]-sigmatropic rearrangement of allylic onium salts (Scheme ), − such as ammonium, , sulfonium, oxonium, , selenonium, and iodonium salts, , have been investigated, establishing the rearrangement as a powerful C−C bond-forming reaction. The rearrangement is believed to proceed via a five-membered cyclic transition state, , and the stereochemical outcome is dependent on steric and electronic interactions between the migrating allyl moiety and the anion-stabilizing group (G, Scheme ) in the exo and endo transition states…”

Section: Introductionmentioning

confidence: 99%

Lewis Acid Mediated Asymmetric [2,3]-Sigmatropic Rearrangement of Allylic Amines. Scope and Mechanistic Investigation

Blid¹,

Panknin²,

Tuzina³

et al. 2007

J. Org. Chem.

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The first asymmetric [2,3]-sigmatropic rearrangement of achiral allylic amines has been realized by quaternization of the amines with an enantiomerically pure diazaborolidine and subsequent treatment with Et3N. The resultant homoallylic amines were obtained in good yields and excellent ee's. The observed diastereo- and enantioselectivities were rationalized by invoking a kinetically controlled process, and support for this model was obtained from an NMR spectroscopic investigation of the chiral Lewis acid-substrate complex. The structure of the Lewis acid-product complex was established by X-ray crystallographic analysis and supported the proposed mechanism.

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Copper(II)-Catalyzed [2,3]-Sigmatropic Rearrangement of N-Methyltetrahydropyridinium Ylids

Abstract: A ring-contractive and highly diastereoselective [2,3]-sigmatropic rearrangement occurs when N-methyl-1,2,3,6-tetrahydropyridine is treated with sub-stoichiometric amounts of copper or rhodium salts, in the presence of ethyl diazoacetate, giving ethyl cis-N-methyl-3-ethenyl proline (4).

Cited by 31 publications

References 10 publications

Probing the Effect of Allylic Substitution on Cyclic Ammonium Ylid Rearrangements

Probing the Effect of Allylic Substitution on Cyclic Ammonium Ylid Rearrangements

Rhodium(II)-Catalyzed Reaction of Diazocompounds in the Service of Organic Synthesis of Natural and Non-Natural Products

Lewis Acid Mediated Asymmetric [2,3]-Sigmatropic Rearrangement of Allylic Amines. Scope and Mechanistic Investigation

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