Switching Pathways: Room‐Temperature Neutral Solvolysis and Substitution of Amides

Hutchby, Marc; Houlden, Chris E.; Haddow, Mairi F.; Tyler, Simon N. G.; Lloyd‐Jones, Guy C.; Booker‐Milburn, Kevin I.

doi:10.1002/ange.201107117

Cited by 37 publications

(30 citation statements)

References 33 publications

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“…[74,75] The maximum possible value for a fully perpendicular amide bond amounts to AEt + c N = 1508. Compared to this value, the total distortion in our most non- planar DKP trans-1 amountst oo nly 31.28,a nd our resultst hus show that even as mall additive amide distortion of one fifth of the maximum value suffices in normal-sizedl actams to trigger interesting and unusualr eactivity.T he here-reported additive distortion values are similart ot hose found in sterically hindered amides VIII reported by Lloyd-Jones and Booker-Milburn [24] and in N-acylazetidines studied by Ohwada [76] and Szostak. [77]…”

Section: Discussionsupporting

confidence: 87%

“…Scattered examplesd ocument CÀN s bond-cleavager eactions in twisted amides of types V and VI under reductive, oxidative, anda lkylative conditions, as reported by the Aube [18,19] and Szostak [20,21] groups.T he pK a of the aCÀHb ondt ot he carbonyl group is dramatically lowered, and as ar esult of amide nitrogenp yramidalization in VII,i ts use in aldol additions is enabled. [22,23] Similar effects were observed by Lloyd-Jones and Booker-Milburn in sterically hindereda mides such as VIII, [24] which undergo rapid proton switch via at wisted conformer because of their enhanced aCÀHa cidity.…”

Section: Introductionmentioning

confidence: 99%

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Unique Stereoselective Homolytic C−O Bond Activation in Diketopiperazine‐Derived Alkoxyamines by Adjacent Amide Pyramidalization

Amatov

Jangra

Pohl

et al. 2018

Chemistry A European J

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Simple monocyclic diketopiperazine (DKP)-derived alkoxyamines exhibit unprecedented activation of a remote C-O bond for homolysis by amide distortion. The combination of strain-release-driven amide planarization and the persistent radical effect (PRE) enables a unique, irreversible, and quantitative trans→cis isomerization under much milder conditions than typically observed for such homolysis-limited reactions. This isomerization is shown to be general and independent of the steric and electronic nature of both the amino acid side chains and the substituents at the DKP nitrogen atoms. Homolysis rate constants are determined, and they significantly differ for both the labile trans diastereomers and the stable cis diastereomers. To reveal the factors influencing this unusual process, structural features of the kinetic trans diastereomers and thermodynamic cis diastereomers are investigated in the solid state and in solution. X-ray crystallographic analysis and computational studies indicate substantial distortion of the amide bond from planarity in the trans-alkoxyamines, and this is believed to be the cause for the facile and quantitative isomerization. Thus, these amino-acid-derived alkoxyamines are the first examples that exhibit a large thermodynamic preference for one diastereomer over the other upon thermal homolysis, and this allows controlled switching of configurations and configurational cycling.

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Section: Discussionsupporting

confidence: 87%

Section: Introductionmentioning

confidence: 99%

Unique Stereoselective Homolytic C−O Bond Activation in Diketopiperazine‐Derived Alkoxyamines by Adjacent Amide Pyramidalization

Amatov

Jangra

Pohl

et al. 2018

Chemistry A European J

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“…While Weinreb amides (entry 1), 19 tmp amides (entry 2), 14 and acylpyrroles (entry 3) 11g provided a trace or none of the desired ketone product, by using the imide derivative 1a (entry 4) 13 the proposed cross-coupling was indeed feasible, providing the ketone product in excellent 98% yield. Furthermore, less distorted systems such as imide 1e (entry 5) 13 resulted in a dramatic decrease in efficiency, consistent with previous studies on amide bond activation.…”

mentioning

confidence: 96%

Sterically Controlled Pd-Catalyzed Chemoselective Ketone Synthesis via N–C Cleavage in Twisted Amides

2015

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Highly chemoselective, palladium(0)-catalyzed, direct cross-coupling between boronic acids and geometrically activated amides is reported. The reaction proceeds via selective activation of the N-C(O) bond, shows excellent functional group tolerance, and delivers the versatile ketone products in high yields. The observed reactivity is consistent with a decrease of nN → π*C═O conjugation resulting from destabilization of the amide ground state. Notably, the method provides direct access to acyl-metal intermediates from sterically distorted, bench-stable amide precursors under mild catalytic conditions.

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“…Methanolysis of sterically twisted amides 19 (category (c) in Figure 2) bearing a TMP (2,2,6,6-tetramethylpyperizine) moiety on amide nitrogen with a 4-nitrophenyl group adjacent to the carbonyl α position was much faster than that of an amide with a 4-methoxyphenyl group. [22] As shown in Scheme 12, amides 19 were converted through a proton switch/amine elimination mechanism to ketene intermediates 20, which further reacted with methanol to afford the corresponding methyl esters. The bulky TMP group provoked pyramidalization of the amide nitrogen so that the nitrogen basicity increased to spontaneously induce the proton switch process.…”

Section: P E R S O N a L A C C O U N T T H E C H E M I C A L R E C O R Dmentioning

confidence: 99%

Catalytic Cleavage of Amide C−N Bond: Scandium, Manganese, and Zinc Catalysts for Esterification of Amides

Mashima

Nishii

Nagae

2019

The Chemical Record

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Amide CÀ N bonds are thermodynamically stable and their fission, such as by hydrolysis and alcoholysis, is considered a long-challenging organic reaction. In general, stoichiometric chemical transformations of amides into the corresponding esters and acids require harsh conditions, such as strong acids/bases at a high reaction temperature. Accordingly, the development of catalytic reactions that cleave not only primary and secondary amides, but also tertiary amides in mild conditions, is in high demand. Herein, we surveyed typical stoichiometric transformations of amides, and highlight our recent achievements in the catalytic esterification of amides using scandium, manganese, and zinc catalysts, together with some recent catalyst systems using late-transition metal reported by other groups. Scheme 1. Chemical transformations of amides to esters and acids. Scheme 2. Amide alcoholysis via N-nitroamides. P e r s o n a l A c c o u n t

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Switching Pathways: Room‐Temperature Neutral Solvolysis and Substitution of Amides

Cited by 37 publications

References 33 publications

Unique Stereoselective Homolytic C−O Bond Activation in Diketopiperazine‐Derived Alkoxyamines by Adjacent Amide Pyramidalization

Unique Stereoselective Homolytic C−O Bond Activation in Diketopiperazine‐Derived Alkoxyamines by Adjacent Amide Pyramidalization

Sterically Controlled Pd-Catalyzed Chemoselective Ketone Synthesis via N–C Cleavage in Twisted Amides

Catalytic Cleavage of Amide C−N Bond: Scandium, Manganese, and Zinc Catalysts for Esterification of Amides

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