Ozonolyses of Enantiopure 4‐Alkoxy‐3,6‐dihydro‐2<i>H</i>‐1,2‐oxazines:An Expedient Route to Functionalized α‐Amino‐β‐hydroxy Esters

Helms, Matthias; Reißig, Hans‐Ulrich

doi:10.1002/ejoc.200400734

Cited by 9 publications

(4 citation statements)

References 18 publications

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“…The preparation of spiroketals employs lithiated alkoxyallene as unsaturated acyl anion synthon a . The equivalency of lithiated alkoxyallenes to formyl anion synthon d or homoenolate e has been demonstrated earlier. ,, To our great delight, we also detected less obvious novel synthons, which guided us in unexpected directions (Figure ). The oxidative ring opening of dihydrofurans as described in Scheme demonstrates that lithiated alkoxyallenes are equivalent to the unusual malondialdehyde anion f .…”

Section: Discussionsupporting

confidence: 72%

“…The equivalency of lithiated alkoxyallenes to formyl anion synthon d or homoenolate e has been demonstrated earlier. 40,59,60 To our great delight, we also detected less obvious novel synthons, which guided us in unexpected directions (Figure 3). The oxidative ring opening of dihydrofurans as described in Scheme 4 demonstrates that lithiated alkoxyallenes are equivalent to the unusual malondialdehyde anion f. By mere serendipity, we discovered tripolar synthons such as g, h, and i (Figure 3), which are introduced into functionalized heterocycles via alkoxyallene chemistry.…”

Section: Discussionmentioning

confidence: 90%

“…The addition of lithiated alkoxyallenes to nitrones as electrophiles delivered exceptionally useful products: 1,2-oxazines! , This novel [3 + 3] cyclization allowed for the preparation of precursors to a multitude of biologically active target compounds, from amino alcohols to α-amino-β-hydroxy esters, neuramic acid derivatives, polyhydroxylated pyrrolidines, and azetidines. Moreover, carbohydrate and peptide mimetics could be accessed via novel skeletal rearrangements of 1,2-oxazines leading to bicyclic compounds as key intermediates.…”

Section: Amino Polyols Novel Carbohydrate Mimetics and More From 12-o...mentioning

confidence: 99%

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Sugars, Alkaloids, and Heteroaromatics: Exploring Heterocyclic Chemistry with Alkoxyallenes

2008

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As master craftsmen, modern synthetic chemists are challenged to achieve remarkable feats of efficiency and elegance toward molecular targets. The nature of this pursuit necessitates the collection of synthetic repertoires that are tried and true. With methodologies and pathways increasingly scrutinized, the adept chemist must seek out propitious tools to incorporate into the arsenal. With this in mind, this Account highlights the versatility of alkoxyallenes as precursors to valuable heterocyclic building blocks for such efforts as natural product synthesis. Accessed by the etherification of either propargyl alcohols or propargylic halides, alkoxyallenes are obtained after base-catalyzed isomerizations of the propargylic ethers. A host of umpolung synthons are available through this scheme after metalation, generating C(3) nucleophiles synthetically equivalent to vital anionic and zwitterionic synthons. Reactions with a diverse set of heteroatomic electrophiles yield carbohydrates, spiroketals, alkaloids, and heteroaromatics via [3 + 2] or [3 + 3] cyclizations. By employing lithiated alkoxyallenes into transformation routes, the natural product chemist can utilize this methodology as a viable resource in stereoselective synthesis. A survey of our own utilization of alkoxyallenes along synthetic pathways toward natural product targets reveals their suitability for generating advantageous precursors. A set of four stereoisomeric 2,6-dideoxyhexoses were stereoselectively obtained after an initial lithiated alkoxyallene and lactaldehyde cyclization, followed by the oxidative ring opening of the dihydrofurans. Through the addition of a lithiated alkoxyallene to a functionalized benzaldehyde, an essential spiroketal diastereomer was rapidly achieved in a few steps. We greatly benefitted from alkoxyallenes in the construction of complex nitrogen-containing synthetic targets, whether pyrrolidine alkaloids, substituted imidazole derivatives, or functionalized pyridines. A pinnacle example of their utility came from the coupling of alkoxyallenes to nitrones affording 1,2-oxazines, which served as a gateway to an array of novel polyfunctionalized compounds such as aminopolyols, hydroxylated pyrrolidines, or carbohydrate mimetics. Alkoxyallenes have proven themselves to be powerful C(3) building blocks toward complex molecular targets, revealing novel pathways to a variety of desirable highly functionalized heterocycles. In our view, the full extent of their synthetic utility has yet to be truly realized.

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Section: Discussionsupporting

confidence: 72%

Section: Discussionmentioning

confidence: 90%

Section: Amino Polyols Novel Carbohydrate Mimetics and More From 12-o...mentioning

confidence: 99%

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Sugars, Alkaloids, and Heteroaromatics: Exploring Heterocyclic Chemistry with Alkoxyallenes

2008

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“…In order to protect the isopropylidene group more sensitive to the electrophilic reagents diene 44 was converted into epoxide 45, whose ozonolysis with the subsequent treatment of the peroxide with the mixture Et 3 N-Ac 2 O led to the key epoxyester 46 in a high yield [16] (Scheme 5). The ozonolysis of 1,2-oxazine 47 in methanol followed by the treatment of peroxide ozonolysis products with Et 3 N-Ac 2 O in CH 2 Cl 2 in situ led to the formation of α-aminoester 48 [17] (Scheme 6).…”

Section: Transformations Of Peroxide Products Of Olefins Ozonolysismentioning

confidence: 99%