RESUMO
This density functional theory study explores the detailed mechanism of nickel-catalyzed hydroalkylation of the CâC bond of N-Cbz-protected enamines (Cbz = benzyloxycarbonyl) with alkyl iodides to give chiral α-alkyl amines. The active catalyst (biOx)NiH, a chiral bioxazoline (biOx)-chelated Ni(I) hydride, exhibits chemoselectivity that favors single electron transfer to the alkyl iodide over CâC hydrometalation with the enamine. This generates an alkyl radical and a Ni(II) intermediate, which takes up the enamine substrate CbzNHCHâCH2CH3 via a regio- and enantioselective CâC insertion into the NiII-H bond. The resulting Ni(II) alkyl complex combines with the alkyl radical, forming a Ni(III) intermediate, from which the alkyl-alkyl reductive elimination delivers the chiral amine product. The regioselectivity arises from a combination of orbital and noncovalent interactions, both of which are induced by the Cbz group. Thus, Cbz plays an additional role in controlling regioselectivity. The enantioselectivity stems from the differing distortion energies of CbzNHCHâCH2CH3. The reductive elimination is the rate-determining step (ΔG⧧ = 18.7 kcal/mol). In addition, the calculations show a noninnocent behavior of the biOx ligand induced by the insertion of CbzNHCHâCH2CH3 into the Ni-H bond of (biOx)NiH. These computationally gained insights can have implications for developing new Ni(I)-catalyzed reactions.
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We report a general protocol for the convergent synthesis of 1,4-dicarbonyl Z-alkenes form alkynes using α-diazo sulfonium triflate and water. The CâO, CâC, and C-H bonds are formed under mild conditions with a wide range of functional groups tolerated. The reaction exhibits excellent Z-selectivity and complete regioselectivity. The resulting 1,4-dicarbonyl Z-alkenes can smoothly undergo follow-up conversion to a variety of heteroaromatic scaffolds. Moreover, the reaction also provides a facile access to the corresponding deuterated Z-alkenes and deuterated heteroarenes with a high level of deuterium incorporation (90-97% D-inc.) by directly using D2O, thus rendering the method highly valuable. The comprehensive mechanistic studies indicate that a free carbyne radical intermediate is formed via the photocatalytic single electron transfer process, and KH2PO4 plays a crucial role in significant improvements on yield and selectivity based on density-functional theory calculations, providing a new direction for radical coupling reactions of diazo compounds.
Assuntos
Alcenos , Alcinos , Alcenos/química , Alcinos/química , Catálise , Radicais Livres , ÁguaRESUMO
Reported here is a concise total synthesis of (-)-berkelic acid in eight linear steps. This synthesis features a Catellani reaction/oxa-Michael cascade for the construction of the isochroman scaffold, a one-pot deprotection/spiroacetalization operation for the formation of the tetracyclic core structure, and a late-stage Ni-catalyzed reductive coupling for the introduction of the lateral chain. Notably, four stereocenters are established from a single existing chiral center with excellent stereocontrol during the deprotection/spiroacetalization process. Stereocontrol of the intriguing deprotection/spiroacetalization process is supported by DFT calculations.
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Pt(II) and Au(III)-mediated intermolecular divergent annulations of benzofurazans and ynamides highlighted the N- to O-selectivity of tunable metal carbene intermediates. PtCl2 with a bulky phosphite ligand resulted in the specific synthesis of six-membered quinoxaline N-oxides and successfully suppressed the in-situ deoxygenation of N-oxides. On the other hand, an unique gold(III) catalyst (2,6-di-MeO-PyrAuCl3) led to the five-membered ring products, benzimidazoles. A broad scope of functional groups was well compatible, delivering better yields and selectivities in contrast to conventional gold(I) catalysts. The different behavior of presumed platinum(II) and gold(III) carbenes with respect to chemoselectivity was intensively examined by experiments and DFT calculations. A detailed mechanistic study, based on DFT calculations, revealed that the highly electrophilic carbocation-like gold(III) carbene triggers an oxophilic cyclization, followed by a cascade ring contraction and acyl migration. On the contrary, the Pt carbene species is less cationic, favoring the formation of the six-membered ring via N-attack.
Assuntos
Ouro , Platina , Ciclização , Metano/análogos & derivadosRESUMO
We present a detailed DFT mechanistic study on the first Ni-catalyzed direct carbonyl-Heck coupling of aryl triflates and aldehydes to afford ketones. The precatalyst Ni(COD)2 is activated with the phosphine (phos) ligand, followed by coordination of the substrate PhOTf, to form [Ni(phos)(PhOTf)] for intramolecular PhOTf to Ni(0) oxidative addition. The ensuing phenyl-Ni(ii) triflate complex substitutes benzaldehyde for triflate by an interchange mechanism, leaving the triflate anion in the second coordination sphere held by Coulomb attraction. The Ni(ii) complex cation undergoes benzaldehyde C[double bond, length as m-dash]O insertion into the Ni-Ph bond, followed by ß-hydride elimination, to produce Ni(ii)-bound benzophenone, which is released by interchange with triflate. The resulting neutral Ni(ii) hydride complex leads to regeneration of the active catalyst following base-mediated deprotonation/reduction. The benzaldehyde C[double bond, length as m-dash]O insertion is the rate-determining step. The triflate anion, while remaining in the second sphere, engages in electrostatic interactions with the first sphere, thereby stabilizing the intermediate/transition state and enabling the desired reactivity. This is the first time that such second-sphere interaction and its impact on cross-coupling reactivity has been elucidated. The new insights gained from this study can help better understand and improve Heck-type reactions.
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We report on the basis of DFT computations a plausible and detailed reaction mechanism for the first Pd-catalyzed decarbonylative phosphorylation of amides forming C-P bonds, which reveals, among other things, crucial events in the second coordination sphere, including ion pair and hydrogen bonding interactions as well as proton transfer.
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Ultrashort metal-metal distances (USMMDs, dM-M < 1.900 Å) have been realized computationally between the main group metal beryllium. However, due to their ionic charge state and the insufficient stability of their electronic structures and/or thermodynamic stabilities, the known species with ultrashort Be-Be distances are unsuitable for synthesis in the condensed phase, which deters the applications of these interesting structures from being explored. In the present study, using our previously reported global minima species [XH3-Be2H3-XH3]+ (X = N and P) with ultrashort Be-Be distances and well-defined electronic structures as their parent molecules, we designed a series of neutral polygons retaining ultrashort Be-Be distances. These polygons also possess well-defined electronic structures and good thermodynamic stabilities, which are demonstrated by their large HOMO-LUMO gaps of 6.20-7.68 eV, very high vertical detachment energies (VDEs) of 8.96-11.29 eV, rather low vertical electron affinities (VEAs) of -1.21 to +1.78 eV, and unexpectedly high formation energies relative to the building blocks of E- and Be2H3+ (-105.2 to -153.2 kcal mol-1 for the formation of an E-Be bond). The good stability with regard to their electronic structures and thermochemistry reveal their high feasibility to be synthesized in the condensed phase. Thus, we anticipate experimental studies on these interesting nano-polygons to realize structures with USMMDs between main group metals and explore their possible application.
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A current project in metal-metal bonding chemistry is to achieve ultrashort metal-metal distances (USMMDs, denoted by dM-M < 1.900 Å) between main group metal beryllium atoms. A valid way for achieving such USMMDs is the substitution of a carbon atom in a planar pentacoordinate environment with the isoelectronic Be2 moiety. In the present work, we report our recent findings that a similar substitution can be applied to the carbon atom in a planar hexacoordinate environment. Using species CN3Be3+ and CO3Li3+ and related analogues as the templates, the Be2N3M3+ (M = Be, Mg, Ca) and Be2O3M3+ (M = Li, Na, K) species with axial ultrashort Be-Be distances of 1.627-1.870 Å were designed computationally. The ultrashort Be-Be distances in these species represent a balance between the lengthening effect of axial Be-Be electrostatic interactions and the shortening effects of the strong X-Be bonding and repulsive X-X-X electrostatic interactions. In addition, the shorter axial Be-Be distances were determined firstly by the smaller size of the bridging electronegative X atoms and secondly by the lower electronegativity of the peripheral M atoms, while the stabilities of the newly designed species were closely related to the types of valence electron pairs, whereby the localized two-center two-electron bonds were better for stabilization than the non-bonding valence lone pairs. Among the newly designed species, Be2N3Be3+ and Be2N3Mg3+ were characterized to be the kinetically stable global minima, thereby providing promising targets for the experimental realization of species with USMMDs between main group metals.
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By using a yeast two-hybrid assay, cyclic AMP-response-element-binding protein-related protein (CREB-RP), also called activating transcription factor 6beta (ATF6beta), was identified as a cellular protein that interacts with the NS4B protein of hepatitis C virus. An N-terminal half of NS4B and a central portion of CREB-RP/ATF6beta containing the basic leucine zipper (bZIP) domain were involved in the interaction. The interaction between NS4B and CREB-RP/ATF6beta was demonstrated also in mammalian cells by co-immunoprecipitation and confocal microscopic analyses using specific antibodies. The bZIP domain of ATF6alpha, which shares high sequence similarity with CREB-RP/ATF6beta, was also shown to interact with NS4B in yeast although the interaction was weaker than that between NS4B and CREB-RP/ATF6beta. CREB-RP/ATF6beta and ATF6alpha are known as endoplasmic reticulum (ER) stress-induced transcription factors. Collectively, our results imply the possibility that NS4B modulates certain cellular responses upon ER stress through the physical interaction with CREB-RP/ATF6beta and ATF6alpha.