Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 36
Filtrar
Mais filtros










Base de dados
Intervalo de ano de publicação
1.
Artigo em Inglês | MEDLINE | ID: mdl-33444481

RESUMO

We report an electrochemical method for coupling biomass-derived C5/C6 compounds to value-added fuel precursors. Using only 2 % of equivalent charges, 2-methylfuran (2-MF) was oxidized to yield a cation radical, which readily reacted with 3-hexene-2,5-dione, a derivate of 2,5-dimethylfuran, to produce 3-(5-methylfuran-2-yl)hexane-2,5-dione. The product was converted to 4-ethylnonane (a component of biodiesel/jet fuel) in a single step in excellent yield. Importantly, the reaction was not sensitive to oxygen, and a trace amount of water was found to promote the reaction. Detailed mechanistic studies confirmed the proposed reaction pathways. Key to the mechanism is the radical generation that is enabled by electrochemistry. The radical is regenerated at the end of a reaction cycle to ensure chain propagation for an average of ca. 47 times, resulting in an apparent Faradaic efficiency of 4700 %.

2.
J Am Chem Soc ; 141(32): 12493-12497, 2019 08 14.
Artigo em Inglês | MEDLINE | ID: mdl-31357865

RESUMO

A novel strategy for the synthesis of main-chain polymers through radical ring-closing/ring-opening cascade polymerization is reported. Efficient radical cyclopolymerization was achieved through systematic optimization of the electronic properties of 1,6-diene structures. Fusing 1,6-diene with allylic sulfide or allylic sulfone motifs enabled a ring-closing/ring-opening cascade reaction that provides a strong driving force for the ring-opening polymerization of large macrocyclic monomers. The ability of 1,6-diene-fused allylic sulfone to undergo efficient SO2 extrusion generated a propagating alkyl radical capable of reversible deactivation. This strategy provides a general platform for the synthesis of polymers incorporating complex main-chain structures and degradable functionalities.

3.
J Am Chem Soc ; 141(22): 9072-9078, 2019 06 05.
Artigo em Inglês | MEDLINE | ID: mdl-31082254

RESUMO

Two new 1,2-azaborine building blocks that enable the broad diversification of previously not readily accessible C4 and C5 ring positions of the 1,2-azaborine heterocycle are developed. 1,2-Azaborine's distinct electronic structure allowed the resolution of a mixture of C4- and C5-borylated 1,2-azaborines. The connection between the electronic structure of C4 and C5 positions of 1,2-azaborine and their distinct reactivity patterns is revealed by a combination of reactivity studies and kinetic measurements that are supported by DFT calculations. Specifically, we show that oxidation by N-methylmorpholine N-oxide (NMO) is selective for the C4-borylated 1,2-azaborine, and the Ir-catalyzed deborylation is selective for the C5-borylated 1,2-azaborine via kinetically controlled processes. On the other hand, ligand exchange with diethanolamine takes place selectively with the C4-borylated isomer via a thermodynamically controlled process. These results represent the first examples for chemically distinguishing a mixture of two aryl mono-Bpin-substituted isomers.


Assuntos
Compostos de Boro/química , Compostos Heterocíclicos com 1 Anel/química , Compostos de Boro/síntese química , Catálise , Teoria da Densidade Funcional , Compostos Heterocíclicos com 1 Anel/síntese química , Irídio/química , Cinética , Modelos Químicos , Oxirredução , Termodinâmica
4.
J Am Chem Soc ; 140(10): 3663-3673, 2018 03 14.
Artigo em Inglês | MEDLINE | ID: mdl-29442502

RESUMO

A mechanistic investigation of the carbohydrate/DBU cocatalyzed enantioselective diboration of alkenes is presented. These studies provide an understanding of the origin of stereoselectivity and also reveal a strategy for enhancing reactivity and broadening the substrate scope.


Assuntos
Alcenos/química , Compostos de Boro/química , Glicóis/química , Catálise , Cinética , Modelos Moleculares , Estereoisomerismo
5.
J Am Soc Mass Spectrom ; 28(10): 2170-2180, 2017 10.
Artigo em Inglês | MEDLINE | ID: mdl-28699065

RESUMO

Collision-induced dissociation (or tandem mass spectrometry, MS/MS) of a protonated peptide results in a spectrum of fragment ions that is useful for inferring amino acid sequence. This is now commonplace and a foundation of proteomics. The underlying chemical and physical processes are believed to be those familiar from physical organic chemistry and chemical kinetics. However, first-principles predictions remain intractable because of the conflicting necessities for high accuracy (to achieve qualitatively correct kinetics) and computational speed (to compensate for the high cost of reliable calculations on such large molecules). To make progress, shortcuts are needed. Inspired by the popular mobile proton model, we have previously proposed a simplified theoretical model in which the gas-phase fragmentation pattern of protonated peptides reflects the relative stabilities of N-protonated isomers, thus avoiding the need for transition-state information. For singly protonated Ala n (n = 3-11), the resulting predictions were in qualitative agreement with the results from low-energy MS/MS experiments. Here, the comparison is extended to a model tryptic peptide, doubly protonated Ala8Arg. This is of interest because doubly protonated tryptic peptides are the most important in proteomics. In comparison with experimental results, our model seriously overpredicts the degree of backbone fragmentation at N9. We offer an improved model that corrects this deficiency. The principal change is to include Coulombic barriers, which hinder the separation of the product cations from each other. Coulombic barriers may be equally important in MS/MS of all multiply charged peptide ions. Graphical Abstract ᅟ.


Assuntos
Peptídeos/química , Espectrometria de Massas em Tandem/métodos , Arginina/química , Isomerismo , Modelos Químicos , Nitrogênio/química , Conformação Proteica , Prótons
6.
Angew Chem Int Ed Engl ; 56(38): 11485-11489, 2017 09 11.
Artigo em Inglês | MEDLINE | ID: mdl-28718214

RESUMO

We describe an unusual net [2+2] cycloaddition reaction between boron alkylidenes and unactivated alkenes. This reaction provides a new method for the construction of carbocyclic ring systems bearing versatile organoboronic esters. Aside from surveying the scope of this reaction, we provide details about the mechanistic underpinnings of this process, and examine its application to the synthesis of the natural product aphanamal.


Assuntos
Alcenos/química , Alquinos/química , Boro/química , Reação de Cicloadição , Teoria da Densidade Funcional , Estrutura Molecular
7.
Angew Chem Int Ed Engl ; 56(30): 8736-8741, 2017 07 17.
Artigo em Inglês | MEDLINE | ID: mdl-28560721

RESUMO

A broadly applicable, practical, scalable, efficient and highly α- and enantioselective method for addition of a silyl-protected propargyl moiety to trifluoromethyl ketones has been developed. Reactions, promoted by 2.0 mol % of a catalyst that is derived in situ from a readily accessible aminophenol compound at ambient temperature, were complete after only 15 minutes at room temperature. The desired tertiary alcohols were isolated in up to 97 % yield and 98.5:1.5 enantiomeric ratio. Alkyl-, alkenyl-, alkynyl-, aryl- or heteroaryl-substituted trifluoromethyl ketones can be used. Utility is highlighted by application to a transformation that is relevant to enantioselective synthesis of BI 653048, a compound active against rheumatoid arthritis.


Assuntos
Artrite Reumatoide/tratamento farmacológico , Benzamidas/uso terapêutico , Compostos de Boro/química , Cetonas/química , Morfinanos/química , Piridinas/uso terapêutico , Pirróis/uso terapêutico , Benzamidas/síntese química , Benzamidas/química , Catálise , Eletrônica , Estrutura Molecular , Piridinas/síntese química , Piridinas/química , Pirróis/síntese química , Pirróis/química , Estereoisomerismo
8.
Chembiochem ; 18(5): 479-482, 2017 03 02.
Artigo em Inglês | MEDLINE | ID: mdl-28042934

RESUMO

Cyclic peptides have been proposed as privileged scaffolds that might mimic the folding and function of natural proteins. However, simple cyclic peptides typically cannot fold into well-defined structures. Herein, we describe a foldable cyclic peptide scaffold on which functional side chains can be displayed for targeted recognition of biomolecules. The foldable scaffold is based on prolinomycin, a proline-rich analogue of valinomycin. We report synthetic mutants of prolinomycin that retain the metal-assisted folding behavior under physiological conditions. The predictable structure formation of prolinomycin makes it a powerful platform to enable the development of synthetic receptors for biomolecules of interest. We demonstrate the potential of this scaffold by creating prolinomycin mutants that selectively bind anionic vesicles and bacterial cells.


Assuntos
Simulação por Computador , Peptídeos Cíclicos/química , Peptídeos Cíclicos/metabolismo , Valinomicina/análogos & derivados , Sequência de Aminoácidos , Estrutura Molecular , Mutação , Peptídeos Cíclicos/síntese química , Peptídeos Cíclicos/genética , Cloreto de Potássio/química , Dobramento de Proteína , Proteínas/síntese química , Proteínas/genética , Cloreto de Sódio/química , Valinomicina/química
9.
Nat Chem ; 8(8): 768-77, 2016 08.
Artigo em Inglês | MEDLINE | ID: mdl-27442282

RESUMO

Organofluorine compounds are central to modern chemistry, and broadly applicable transformations that generate them efficiently and enantioselectively are in much demand. Here we introduce efficient catalytic methods for the addition of allyl and allenyl organoboron reagents to fluorine-substituted ketones. These reactions are facilitated by readily and inexpensively available catalysts and deliver versatile and otherwise difficult-to-access tertiary homoallylic alcohols in up to 98% yield and >99:1 enantiomeric ratio. Utility is highlighted by a concise enantioselective approach to the synthesis of the antiparasitic drug fluralaner (Bravecto, presently sold as the racemate). Different forms of ammonium-organofluorine interactions play a key role in the control of enantioselectivity. The greater understanding of various non-bonding interactions afforded by these studies should facilitate the future development of transformations that involve fluoroorganic entities.


Assuntos
Boro/química , Flúor/química , Cetonas/química , Álcoois , Alcenos/química , Boro/metabolismo , Catálise , Indicadores e Reagentes , Cetonas/metabolismo , Compostos Orgânicos/química , Eletricidade Estática , Estereoisomerismo
10.
J Am Chem Soc ; 138(8): 2508-11, 2016 Mar 02.
Artigo em Inglês | MEDLINE | ID: mdl-26854364

RESUMO

Catalytic enantioselective diboration of alkenes is accomplished with readily available carbohydrate-derived catalysts. Mechanistic experiments suggest the intermediacy of 1,2-bonded diboronates.


Assuntos
Alcenos/química , Compostos de Boro/química , Glicóis/química , Compostos de Boro/síntese química , Catálise , Estereoisomerismo
11.
J Am Chem Soc ; 137(45): 14232-5, 2015 Nov 18.
Artigo em Inglês | MEDLINE | ID: mdl-26509216

RESUMO

Stereoselective catalysis is described that proceeds with catalyst control but without the need to synthesize preformed chiral catalysts or ligands. Iron-based catalysts were discovered to effect the stereoselective polymerization of lactides starting from a single achiral precursor and the proper choice of an achiral silanol additive. Spectroscopic analysis of the polymer revealed that the stereoselectivity originates from an enantiomorphic site rather than a chain end stereocontrol mechanism. Iron intermediates that are stereogenic at iron are proposed to form in situ as a result of desymmetrization that occurs from a change in the metal coordination number. The proposed mechanism is supported by a combination of spectroscopic measurements, model complexes, kinetic measurements, and DFT calculations.

12.
J Am Chem Soc ; 137(33): 10585-602, 2015 Aug 26.
Artigo em Inglês | MEDLINE | ID: mdl-26263513

RESUMO

Broadly applicable enantioselective C-B and C-Si bond-forming processes catalyzed by an N-heterocyclic carbene (NHC) were recently introduced; these boryl and silyl conjugate addition reactions (BCA and SCA, respectively), which proceed without the need for a transition-metal complex, represent reaction pathways that are distinct from those facilitated by transition-metal-containing species (e.g., Cu, Ni, Pt, Pd, or Rh based). The Lewis-base-catalyzed (NHC) transformations are valuable to chemical synthesis, as they can generate high enantioselectivities and possess unique chemoselectivity profiles. Here, the results of investigations that elucidate the principal features of the NHC-catalyzed BCA and SCA processes are detailed. Spectroscopic evidence is provided illustrating why the presence of excess base and MeOH or H2O is required for efficient and enantioselective boryl and silyl addition reactions. It is demonstrated that the proton sources influence the efficiency and/or enantioselectivity of NHC-catalyzed enantioselective transformations in several ways. The positive, and at times adverse, impact of water (biphasic conditions) on catalytic enantioselective silyl addition reactions is analyzed. It is shown that a proton source can facilitate nonenantioselective background reactions and NHC decomposition, requiring the catalyst to surpass such complications. Stereochemical models are presented that account for the identity of the observed major enantiomers, providing a rationale for the differences in selectivity profiles of BCA and SCA processes.


Assuntos
Boro/química , Compostos Heterocíclicos/química , Cetonas/química , Metano/análogos & derivados , Silanos/química , Catálise , Radicais Livres/química , Hidróxidos/química , Cinética , Metano/química , Metanol/química , Modelos Moleculares , Conformação Molecular , Permeabilidade , Estereoisomerismo , Água/química
13.
J Am Chem Soc ; 136(32): 11304-7, 2014 Aug 13.
Artigo em Inglês | MEDLINE | ID: mdl-25089917

RESUMO

Catalytic enantioselective multicomponent processes involving bis(pinacolato)diboron [B2(pin)2], 1,3-enynes, and aldehydes are disclosed; the resulting compounds contain a primary C-B(pin) bond, as well as alkyne- and hydroxyl-substituted tertiary carbon stereogenic centers. A critical feature is the initial enantioselective Cu-B(pin) addition to an alkyne-substituted terminal alkene. This and other key mechanistic issues have been investigated by DFT calculations. Reactions are promoted by the Cu complex of a commercially available enantiomerically pure bis-phosphine and are complete in 8 h at ambient temperature; products are generated in 66-94% yield (after oxidation or catalytic cross-coupling), 90:10 to >98:2 diastereomeric ratio, and 85:15-99:1 enantiomeric ratio. Aryl-, heteroaryl-, alkenyl-, and alkyl-substituted aldehydes and enynes can be used. Utility is illustrated through catalytic alkylation and arylation of the organoboron products as well as applications to synthesis of fragments of tylonolide and mycinolide IV.

14.
Angew Chem Int Ed Engl ; 53(26): 6795-9, 2014 Jun 23.
Artigo em Inglês | MEDLINE | ID: mdl-24838444

RESUMO

We report the first general synthesis of boron-substituted monobenzofused 1,4-azaborines using ring-closing metathesis of an enamine-containing diene as a key synthetic strategy. As part of our investigations, we discovered that the B-C3 moiety in a 1,4-azaborine can serve uniquely as a η(2)-L-type ligand. This functionality is exemplified by two κ(2)-N-η(2)-BC Pt complexes of a boron-pyridyl-substituted monobenzofused-1,4-azaborine. Single-crystal X-ray diffraction analysis of the Pt complexes shows a strong structural contribution from the iminium resonance form of the monobenzofused-1,4-azaborine ligand. We also demonstrate that a palladium(0) complex supported by a 1,4-azaborine-based phosphine ligand can catalyze hydroboration of 1-buten-3-yne with unique selectivity. In view of the importance of arene-metal π-interactions in catalytic applications, this work should open new opportunities for ligand design involving the 1,4-azaborine motif as an arene substitute.


Assuntos
Compostos Aza/química , Compostos de Boro/síntese química , Complexos de Coordenação/química , Boro/química , Compostos de Boro/química , Complexos de Coordenação/síntese química , Cristalografia por Raios X , Ligantes , Conformação Molecular , Paládio/química
15.
J Am Chem Soc ; 136(10): 3780-3, 2014 Mar 12.
Artigo em Inglês | MEDLINE | ID: mdl-24588835

RESUMO

A practical catalytic method for enantioselective addition of an allene unit to aldimines is disclosed. Transformations are promoted by an in-situ-generated B-based catalyst that is derived from a simple, robust, and readily accessible (in multigram quantities) chiral aminoalcohol. A range of aryl-, heteroaryl-, and alkyl-substituted homoallenylamides can be obtained in 66-91% yield and 84:16 to >99:1 enantiomeric ratio through reactions performed at ambient temperature and in the presence of 0.1-3.0 mol% of the chiral catalyst and a commercially available allenylboron reagent. The catalytic protocol does not require strict anhydrous conditions, can be performed on gram scale, and promotes highly selective addition of an allenyl unit (vs a propargyl group). The utility of the approach is demonstrated through development of succinct approaches to syntheses of anisomycin and epi-cytoxazone.


Assuntos
Alcadienos/química , Amidas/síntese química , Amino Álcoois/química , Boro/química , Alcadienos/síntese química , Amidas/química , Catálise , Estereoisomerismo
16.
J Am Chem Soc ; 136(9): 3362-5, 2014 Mar 05.
Artigo em Inglês | MEDLINE | ID: mdl-24555471

RESUMO

A catalytic method for the efficient and enantioselective addition of a 1-trimethylsilyl-substituted allene moiety to phosphinoylimines is presented. Transformations are promoted by 5.0 mol % of a copper complex of an N-heterocyclic carbene in the presence of a propargylboron reagent that can be readily prepared in multigram quantities. Within 10 min of reaction, products are obtained in up to 91% yield, 98% allene (vs propargyl) selectivity, and 98:2 enantiomeric ratio. An assortment of aldimines serve as suitable substrates. The phosphinoyl and silyl groups can be removed efficiently and orthogonally. The silylallene moiety may be transformed to versatile derivatives that are difficult to access via nonsilylated allenes. The special features and utility of the approach are highlighted through a succinct enantioselective synthesis of marine alkaloid S-(-)-cyclooroidin.


Assuntos
Alcenos/química , Amidas/síntese química , Compostos de Boro/química , Cobre/química , Iminas/química , Metano/análogos & derivados , Pirróis/síntese química , Amidas/química , Técnicas de Química Sintética , Compostos Heterocíclicos/química , Indicadores e Reagentes/química , Metano/química , Pirróis/química , Estereoisomerismo , Especificidade por Substrato
17.
Nat Chem ; 5(9): 768-74, 2013 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-23965679

RESUMO

Catalytic enantioselective monosilylations of diols and polyols furnish valuable alcohol-containing molecules in high enantiomeric purity. These transformations, however, require high catalyst loadings (20-30 mol%) and long reaction times (2-5 days). Here, we report that a counterintuitive strategy involving the use of an achiral co-catalyst structurally similar to the chiral catalyst provides an effective solution to this problem. A combination of seemingly competitive Lewis basic molecules can function in concert such that one serves as an achiral nucleophilic promoter and the other performs as a chiral Brønsted base. On the addition of 7.5-20 mol% of a commercially available N-heterocycle (5-ethylthiotetrazole), reactions typically proceed within one hour, and deliver the desired products in high yields and enantiomeric ratios. In some instances, there is no reaction in the absence of the achiral base, yet the presence of the achiral co-catalyst gives rise to facile formation of products in high enantiomeric purity.


Assuntos
Álcoois/química , Bases de Lewis/química , Silício/química , Catálise , Cinética , Ácidos de Lewis/química , Estereoisomerismo , Tetrazóis/química
18.
Angew Chem Int Ed Engl ; 52(30): 7694-9, 2013 Jul 22.
Artigo em Inglês | MEDLINE | ID: mdl-23864395

RESUMO

All-catalytic route to trisubstituted allenes: The first examples of catalytic enantioselective allylic substitution reactions that involve alkyne-based nucleophiles and lead to products having tertiary stereogenic centers are followed by an exceptionally stereospecific amine-catalyzed isomerization to trisubstituted allenes (see picture; NHC = N-heterocyclic carbene).


Assuntos
Alcadienos/química , Alquinos/química , Compostos Alílicos/química , Compostos de Alumínio/química , Cobre/química , Metano/análogos & derivados , Catálise , Metano/química , Estereoisomerismo
19.
J Am Chem Soc ; 135(30): 11222-31, 2013 Jul 31.
Artigo em Inglês | MEDLINE | ID: mdl-23862690

RESUMO

The Pt-catalyzed enantioselective diboration of terminal alkenes can be accomplished in an enantioselective fashion in the presence of chiral phosphonite ligands. Optimal procedures and the substrate scope of this transformation are fully investigated. Reaction progress kinetic analysis and kinetic isotope effects suggest that the stereodefining step in the catalytic cycle is olefin migratory insertion into a Pt-B bond. Density functional theory analysis, combined with other experimental data, suggests that the insertion reaction positions platinum at the internal carbon of the substrate. A stereochemical model for this reaction is advanced that is in line both with these features and with the crystal structure of a Pt-ligand complex.


Assuntos
Alcenos/química , Boratos/química , Platina/química , Catálise , Cinética , Ligantes , Modelos Moleculares , Conformação Molecular , Oxirredução , Estereoisomerismo , Especificidade por Substrato
20.
Org Lett ; 15(6): 1414-7, 2013 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-23461762

RESUMO

Two types of NHC-Cu complexes catalyze protoborations of terminal allenes to afford valuable 1,1- or trisubstituted vinylboron species with high site selectivity and stereoselectivity. The scope of the method, application to natural product synthesis, and mechanistic basis for the observed selectivity trends are presented.


Assuntos
Alcadienos/química , Cobre/química , Compostos Heterocíclicos/química , Metano/análogos & derivados , Compostos Organometálicos/química , Catálise , Ligantes , Metano/química , Estrutura Molecular , Estereoisomerismo
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...