Absolute rate and philicity studies of methoxyphenylcarbene. An extended range for carbenic ambiphilicity

Moss, Robert A.; Shen, S.; Hadel, L. M.; Kmiecik-Lawrynowicz, Grazyna; Wlostowska, J.; Krogh‐Jespersen, Karsten

doi:10.1021/ja00248a034

Cited by 69 publications

(38 citation statements)

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“…These intermediates can undergo insertion to generate the labeled amino acids that we observe [34,36]. For reactions in the frozen state (77 K), we anticipate based on previous characterizations that amino-acid insertion products could be driven by both short-lived, groundstate carbenes and by diazo-mediated carbocations following carbene rearrangement [50].…”

Section: Photolysis Products -Additional Considerationsmentioning

confidence: 78%

“…Such data would be very useful as a normalization control. Some efforts have been made towards understanding the reactivity of various carbenes towards a variety of substrates [33][34][35][36], but the side chain insertion preferences for carbenes have not been explored in sufficient depth [24]. In this study, we characterized the insertion preferences for a set of simple aliphatic diazirine labeling reagents in the solid state, and sought to determine if the nature of the diazirine scaffold has as strong a targeting effect in primary structure as we observed in higher-order structure.…”

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confidence: 98%

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Amino Acid Insertion Frequencies Arising from Photoproducts Generated Using Aliphatic Diazirines

Ziemianowicz

Bomgarden

Etienne

et al. 2017

J. Am. Soc. Mass Spectrom.

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Abstract. Mapping proteins with chemical reagents and mass spectrometry can generate a measure of accessible surface area, which in turn can be used to support the modeling and refinement of protein structures. Photolytically generated carbenes are a promising class of reagent for this purpose. Substituent effects appear to influence surface mapping properties, allowing for a useful measure of design control. However, to use carbene labeling data in a quantitative manner for modeling activities, we require a better understanding of their inherent amino acid reactivity, so that incorporation data can be normalized. The current study presents an analysis of the amino acid insertion frequency of aliphatic carbenes generated by the photolysis of three different diazirines: 3,3'-azibutyl-1-ammonium, 3,3'-azibutan-1-ol, and 4,4'-azipentan-1-oate. Leveraging an improved photolysis system for single-shot labeling of sub-microliter frozen samples, we used EThCD to localize insertion products in a large population of labeled peptides. Counting statistics were drawn from data-dependent LC-MS 2 experiments and used to estimate the frequencies of insertion as a function of amino acid. We observed labeling of all 20 amino acids over a remarkably narrow range of insertion frequencies. However, the nature of the substituent could influence relative insertion frequencies, within a general preference for larger polar amino acids. We confirm a large (6-fold) increase in labeling yield when carbenes were photogenerated in the solid phase (77 K) relative to the liquid phase (293 K), and we suggest that carbene labeling should always be conducted in the frozen state to avoid information loss in surface mapping experiments.

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Section: Photolysis Products -Additional Considerationsmentioning

confidence: 78%

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confidence: 98%

Amino Acid Insertion Frequencies Arising from Photoproducts Generated Using Aliphatic Diazirines

Ziemianowicz

Bomgarden

Etienne

et al. 2017

J. Am. Soc. Mass Spectrom.

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“…Moss and co-workers published a series of papers in the late 1980's describing the unusual ambiphilic reactivity of these aryl alkoxy species when compared to the cyclopropanation and dimerisation transformations expected of traditional carbenes (Scheme 6). [29] Scheme 6. Aryl alkoxy carbenes, generated from diazirines, react with electron deficient alkenes…”

Section: Discussionmentioning

confidence: 99%

Silicon‐Derived Singlet Nucleophilic Carbene Reagents in Organic Synthesis

Priebbenow

2020

Adv Synth Catal

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“…Azines result from the reaction of carbenes with the parent diazirine or diazo compound [79] [84-881 or by (stereoselective) dimerization of diazo compounds with loss of N, [89] [90]. Diazo compounds may be formed even from donor-substituted diazirines [91] [92]. We found no evidence for the formation of an intermediate diazo compound, but cannot exclude the rearrangement of some 1 to the corresponding diazo compound.…”

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confidence: 88%

Glycosylidene Carbenes. Part 13. Synthesis and thermolysis of representative 1‐azi‐glycoses

Vasella

Witzig

Waldraff

et al. 1993

Helvetica Chimica Acta

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Dedicated to Duilio Arigoni on the occasion of his 65th birthday (1.X.93)In the context of the hypothesis postulating a heterolytic cleavage of a C-N bond during thermolysis of alkoxydiazirines (Scheme I ) , we report the preparation of the diazirines4,5,7, and 8, the kinetic parameters for the thermolysis in MeOH of the diazirines 1 and 4-9, and the products of their thermolysis in an aprotic environment. The diazirines 4,5,7, and 8 (Schemes 2-5) were prepared from the known hemiacetals 10,19,34 (prepared from 31 in an improved way), and 42 according to an established method. The oximes 11,20,35, and 43 were obtained from the corresponding hemiacetals as (E/Z)-mixtures; 43 was formed together wlth the cyclic hydroxylamine 44. Oxidation of 11,35, and 43 (N-chlorosuccinimide/l,8-diazabicyclo[5.4.0]undec-7-ene (NCS/DBU) or NaIO,) gave good yields of the (Z)-hydroximolactones 12, 36, and 45, while the oxime 20 led to a mixture of the (E)-and (2)-hydroximolactones 21 and 22, which adopt different conformations. Their configuration was assigned, inter alia, by a comparison with the enol ethers 28 and 29, which were obtained, together with 30, from the reaction of the diazirine 5 with benzaldehyde and PBu,. Treatment of the hydroximolactone 0-sulfonates 13,23,37, and 46 with NH,/MeOH afforded the diaziridines 15,25,38, and 47 in good yields, while the (E)-sulfonate 24 decomposed readily. Oxidation of the diaziridines gave 4, 5, 7, and 8, respectively. Thermolysis of the diazirines 1 and 4-9 in MeOH yielded the anomeric methyl glycosides 50/51,16/17,26/27,52/53,39/40,48/49, and 54/55, respectively. A comparison of the kinetic data of the thermolysis at four different temperatures shows the importance of conformational and electronic factors and is compatible with the hypothesis of a heterolytic cleavage of a C-N bond. An early transition state is evidenced by the absence of torsional strain by an annulated 1,3-dioxane ring. Thermolysis of 1 in MeCN at 23" led mostly to the diastereoisoineric (Z,Z)-, (E,E)-, and (E,Z)-lactone azines 56, 57, and 58 (Scheme 6), which convert to 56 under mild conditions, and to 59 (3%). The benzyloxyglucal59 was obtained in higher yields (IS%), together with 44% of 5658, by thermolysis of solid 1. Similarly, thermolysis at higher temperatures of4 in toluene, THF, or dioxane and of 9 in CH2C12 or THF yielded the (Z,Z)-lactone azines 60 and 61, respectively, the latter being accompanied by the dihydro-oxazole 62.Introduction. -Diazirines [I] are important precursors of carbenes, and the mechanism of their thermolysis attracted considerable attention, which focused on the concertedness of the cleavage of the two C-N bonds and the homo-or heterolytic nature of the bond breaking [2-71. The mechanism and the kinetics of the thermolysis of (a1koxy)alkyldiazirines (see [8] and earlier papers of the series [9-131) have not been studied, but we hypothesized that thermolysis of 1-azisugars, such as 1, i.e. cyclic (alkoxy)alkyldiazirines, is initiated by heterolysis of one of the C( 1)-N bonds, accord-

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Absolute rate and philicity studies of methoxyphenylcarbene. An extended range for carbenic ambiphilicity

Cited by 69 publications

References 0 publications

Amino Acid Insertion Frequencies Arising from Photoproducts Generated Using Aliphatic Diazirines

Amino Acid Insertion Frequencies Arising from Photoproducts Generated Using Aliphatic Diazirines

Silicon‐Derived Singlet Nucleophilic Carbene Reagents in Organic Synthesis

Glycosylidene Carbenes. Part 13. Synthesis and thermolysis of representative 1‐azi‐glycoses

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