- Sulfone–Metal Exchange and Alkylation of Sulfonylnitriles
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The first general sulfone–metal exchange is described. Treating substituted 2-pyridylsulfonylacetonitriles with either BuLi or Bu3MgLi generates metalated nitriles that efficiently intercept a variety of electrophiles to afford quaternary nitriles. The 2-pyridylsulfone is critical for the sulfone–metal exchange because chelation anchors the organometallic proximal to the electrophilic, tetrasubstituted sulfone to override complex-induced deprotonation. Alkylating commercial 2-pyridinesulfonylacetonitrile with mild bases, either K2CO3 or DBU, and subsequent sulfone–metal exchange and alkylation rapidly assembles quaternary nitriles by three alkylations, only one of which requires an organometallic reagent.
- Yang, Xun,Nath, Dinesh,Gau, Michael R.,Steward, Omar W.,Fleming, Fraser F.
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supporting information
p. 7257 - 7260
(2017/06/13)
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- Chemoselective Alkylations with N- and C-Metalated Nitriles
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Metalated nitriles exhibit complementary chemoselectivities in electrophilic alkylations. N-Lithiated or C-magnesiated nitriles can be prepared from the same nitrile precursor and selectively reacted with a 1:1 mixture of methyl cyanoformate and benzyl br
- Yang, Xun,Nath, Dinesh,Fleming, Fraser F.
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supporting information
p. 4906 - 4909
(2015/10/12)
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- Arylthio-metal exchange of α-arylthioalkanenitriles
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The addition of BuLi, Bu3MgLi, Et2ZnBuLi, or Me 2CuLi to α-arylthioalkanenitriles triggers an arylthio-metal exchange. NMR spectroscopic analyses implicate organometallic attack on sulfur forming a three-coordinate sulfidate as the key intermediate. Electrophilic trapping affords tertiary and quaternary nitriles in high yield. The method addresses the challenge of improving the functional group tolerance and preventing polyalkylations.
- Nath, Dinesh,Skilbeck, Melanie C.,Coldham, Iain,Fleming, Fraser F.
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- C11/C9 helices in crystals of αβ hybrid peptides and switching structures between helix types by variation in the α-residue
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Close-packed helices with mixed hydrogen bond directionality are unprecedented in the structural chemistry of α-polypeptides. While NMR studies in solution state provide strong evidence for the occurrence of mixed helices in (ββ)n and (αβ)
- Basuroy, Krishnayan,Karuppiah, Vasantham,Balaram, Padmanabhan
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supporting information
p. 4614 - 4617
(2015/04/14)
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- Sulfinylnitriles: Sulfinyl-metal exchange-alkylation strategies
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Adding organolithiums, Grignard reagents, or zincates to sulfinylnitriles triggers a facile sulfinyl-metal exchange to afford N- or C-metalated nitriles. Sulfinyl-magnesium exchange-alkylations efficiently install quaternary and tertiary centers, even in
- Nath, Dinesh,Fleming, Fraser F.
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p. 2023 - 2029
(2013/03/14)
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- The structural characterization of folded peptides containing the conformationally constrained β-amino acid residue β 2,2Ac6c
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Backbone alkylation has been shown to result in a dramatic reduction in the conformational space that is sterically accessible to α-amino acid residues in peptides. By extension, the presence of geminal dialkyl substituents at backbone atoms also restricts available conformational space for β and γ residues. Five peptides containing the achiral β2,2- disubstituted β-amino acid residue, 1-(aminomethyl)cyclohexanecarboxylic acid (β2,2Ac6c), have been structurally characterized in crystals by X-ray diffraction. The tripeptide Boc-Aib-β 2,2Ac6c-Aib-OMe (1) adopts a novel fold stabilized by two intramolecular H-bonds (C11 and C9) of opposite directionality. The tetrapeptide Boc-[Aib-β2,2Ac 6c]2-OMe (2) and pentapeptide Boc-[Aib-β 2,2Ac6c]2-Aib-OMe (3) form short stretches of a hybrid αβ C11 helix stabilized by two and three intramolecular H-bonds, respectively. The structure of the dipeptide Boc-Aib-β2,2Ac6c-OMe (5) does not reveal any intramolecular H-bond. The aggregation pattern in the crystal provides an example of an extended conformation of the β2,2Ac6c residue, forming a 'polar sheet' like H-bond. The protected derivative Ac-β2,2Ac6c-NHMe (4) adopts a locally folded gauche conformation about the Cβi?£?C α bonds (θ=-55.7°). Of the seven examples of β2,2Ac6c residues reported here, six adopt gauche conformations, a feature which promotes local folding when incorporated into peptides. A comparison between the conformational properties of β2,2Ac6c and β3,3Ac6c residues, in peptides, is presented. Backbone torsional parameters of H-bonded αβ/βα turns are derived from the structures presented in this study and earlier reports. Copyright
- Basuroy, Krishnayan,Karuppiah, Vasantham,Shamala, Narayanaswamy,Balaram, Padmanabhan
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p. 2589 - 2603
(2013/03/13)
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- Nitrile alkylations through sulfinyl-metal exchange
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Triple alkylation: Phenylsulfinyl- and phenylthioacetonitrile can function as trianion equivalents of acetonitrile by sequential alkylation and sulfinyl-metal exchange (see scheme; mCPBA=meta-chloroperoxybenzoic acid). The metalated nitriles alkylate a range of electrophiles to obtain nitriles with quaternary centers. The sulfinyl-metal exchange proceeds under very mild conditions and has a high functional-group tolerance. Copyright
- Nath, Dinesh,Fleming, Fraser F.
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supporting information; experimental part
p. 11790 - 11793
(2012/01/06)
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- KHMDS enhanced SmI2-mediated reformatsky type α-cyanation
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A novel combination of SmI2, KHMDS, and TsCN can be utilized to introduce a cyano group into structurally diverse and highly sensitive 2-alkyl-chroman-4-ones. Subsequent oxidation allows the formed 2-alkyl-3-cyanochromones to be isolated in yields ranging from 49 to 77%. In addition, α-bromoketones and esters were found to undergo equally effective α-cyanation.
- Ankner, Tobias,Friden-Saxin, Maria,Pemberton, Nils,Seifert, Tina,Grotli, Morten,Luthman, Kristina,Hilmersson, Goeran
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supporting information; experimental part
p. 2210 - 2213
(2010/08/04)
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- Synthesis and structure-activity relationship of a novel, achiral series of TNF-α converting enzyme inhibitors
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A novel series of achiral TNF-α converting enzyme (TACE) inhibitors has been discovered. These compounds exhibited activities from 0.35 to 11 nM in a porcine TACE assay and inhibited TNF-α production in an LPS-stimulated whole blood assay with an IC5
- Gilmore, John L.,King, Bryan W.,Harris, Cathy,Maduskuie, Thomas,Mercer, Stephen E.,Liu, Rui-Qin,Covington, Maryanne B.,Qian, Mingxin,Ribadeneria, Maria D.,Vaddi, Krishna,Trzaskos, James M.,Newton, Robert C.,Decicco, Carl P.,Duan, James J.-W.
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p. 2699 - 2704
(2007/10/03)
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- Metalated nitriles: Organolithium, -magnesium? and -copper exchange of α-halonitriles
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(Chemical Equation Presented) α-Halonitriles react with alkyllithium, organomagnesium, and lithium dimethylcuprate reagents generating reactive, metalated nitriles. The rapid halogen-metal exchange with alkyllithium and Grignard reagents allows selective exchange in the presence of reactive carbonyl electrophiles, including aldehydes, providing a high-yielding alkylation protocol. Lithiated and magnesiated nitriles react with propargyl bromide by SN2 displacement whereas organocopper nitriles react by S N2′ displacement, correlating with the formation of a C-metalated nitrile.
- Fleming, Fraser F.,Zhang, Zhiyu,Liu, Wang,Knochel, Paul
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p. 2200 - 2205
(2007/10/03)
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- Metalated Nitriles: Halogen - Metal Exchange with α-Halonitriles
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(Equation presented) α-Halonitriles react with organometallic reagents in a facile halogen-metal exchange. The halogen-metal exchange is extremely fast with Grignard and alkyllithium reagents, generating metalated nitriles in situ with aldehyde, ketone, a
- Fleming, Fraser F.,Zhang, Zhiyu,Knochel, Paul
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p. 501 - 503
(2007/10/03)
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