Concept: Keto-enol tautomerism
The enantioselective allylation of ketones is a problem of fundamental importance in asymmetric reaction design, especially given that only a very small number of methods can generate tertiary carbinols. Despite the vast amount of attention that synthetic chemists have given to this problem, success has generally been limited to just a few simple ketone types. A method for the selective allylation of functionally complex ketones would greatly increase the utility of ketone allylation methods in the chemical synthesis of important targets. Here we describe the operationally simple, direct, regioselective and enantioselective allylation of β-diketones. The strong tendency of β-diketones to act as nucleophilic species was overcome by using their enol form to provide the necessary Brønsted-acid activation. This reaction significantly expands the pool of enantiomerically enriched and functionally complex tertiary carbinols that may be easily accessed. It also overturns more than a century of received wisdom regarding the reactivity of β-diketones.
Although 2-(2'-hydroxyphenyl)imidazo[1,2-a]pyridine (HPIP) is only weakly fluorescent in solution, two of its crystal polymorphs in which molecules are packed as stacked pairs and in nearly coplanar conformation exhibit bright excited-state intramolecular proton transfer (ESIPT) luminescence of different colors (blue-green and yellow). In order to clarify the enhanced and polymorph-dependent luminescence of HPIP in the solid state, the potential energy surfaces (PESs) of HPIP in the ground (S(0)) and excited (S(1)) states were analyzed computationally by means of ab initio quantum chemical calculations. The calculations reproduced the experimental photophysical properties of HPIP in solution, indicating that the coplanar keto form in the first excited (S(1)) state smoothly approaches the S(0)/S(1) conical intersection (CI) coupled with the twisting motion of the central C-C bond. The S(1)-S(0) energy gap of the keto form became sufficiently small at the torsion angle of 60°, and the corresponding CI point was found at 90°. Since a minor role of the proximity effect was indicated experimentally and theoretically, the observed emission enhancement of the HPIP crystals was ascribed to the following two factors: (1) suppression of efficient radiationless decay via the CI by fixing the torsion angle at the nearly coplanar conformation of the molecules in the crystals and (2) inhibition of excimer formation resulting from the lower excited level of the S(1)-keto state compared to the S(0)-S(1) excitation energy in the enol form. However, the fluorescence color difference between the two crystal polymorphs having slightly different torsion angles was not successfully reproduced, even at the MS-CASPT2 level of theory.
The photo-thermal tautomerization processes between enol and keto forms of 4-tert-butyl-4'-methoxydibenzoylmethane (trade name, avobenzone) in acetonitrile has been studied by steady-state and laser flash photolysis. The keto form is produced upon photolysis of the enol in only acetonitrile with a quantum yield of 0.014. The molar absorptivity of the keto form was determined. Phototautomerization from the keto to the enol form was not seen. Laser flash photolysis of the keto form recognized the formation of the triplet state. In the dark, the keto form underwent thermal tautomerization to the enol with a lifetime of 5.1 h at 295 K. The enolization rate in acetonitrile was not accelerated by the presence of alcohols and/or water, but increased with increasing temperature and followed the Arrhenius expression. The activation energy and the frequency factor were determined for the enolization process from the keto to the enol form. Based on the energy states of the tautomers and isomers as estimated by DFT calculations, a schematic energy diagram was determined for the photo-thermal tautomerization processes in acetonitrile.
A new method for ketone enolate C-acylation is described which utilizes alkyl pentafluorophenylcarbonates, thiocarbonates, and thionocarbonates as the reactive acylating agents, and MgBr(2)·Et(2)O, DMAP, and i-Pr(2)NEt as the reagents for enolization. A wide range of ketones have been observed to undergo clean C-acylation via this protocol.
Unmodified racemic sites on heterogeneous chiral catalysts reduce their overall enantioselectivity, but this effect is mitigated in the Orito reaction (methyl pyruvate (MP) hydrogenation to methyl lactate) by an increased hydrogenation reactivity. Here, this effect is explored on a R-1-(1-naphthyl)ethylamine (NEA)-modified Pd(111) model catalyst where temperature-programmed desorption experiments reveal that NEA accelerates the rates of both MP hydrogenation and H/D exchange. NEA+MP docking complexes are imaged using scanning tunnelling microscopy supplemented by density functional theory calculations to allow the most stable docking complexes to be identified. The results show that diastereomeric interactions between NEA and MP occur predominantly by binding of the C=C of the enol tautomer of MP to the surface, while simultaneously optimizing C=O····H2N hydrogen-bonding interactions. The combination of chiral-NEA driven diastereomeric docking with a tautomeric preference enhances the hydrogenation activity since C=C bonds hydrogenate more easily than C=O bonds thus providing a rationale for the catalytic observations.
Importance of 2'-deoxyguanosine-uridine mispair as the most occurring mismatch in transcriptional studies of RNAs from DNAs is multiplied when 5-halo-substituted uridine species cause to serious increase in probability of its occurrence. Many studies relate this higher probability to existence of possible tautomeric and ionic forms of its constituent bases. According to these statements, relative populations of mismatches between 5-fluorouridine and both keto and enol forms of 2'-deoxyguanosine are computed by using conformational search. In order to have a complete scan of all of high probable conformers in a moderate computational time, an extensive conformational search methodology is employed here which benefits from advantages of both molecular dynamics (MD) simulations and quantum mechanics (QM) calculations. Population of enolic tautomer of normal wobble orientation is about 0.057% of that of its keto tautomer, whereas population of enolic tautomer of reverse wobble orientation is about 0.0054% of that of its keto tautomer. Totally, reverse wobble orientation is about six times more populated than normal wobble orientation. Calculated populations are in good agreement with experimental populations of closely related compounds. Reliability of applied methodology is certified in part by good agreement obtained between some experimental data such as NMR parameters and corresponding Boltzmann weighted average (BWA) data of most probable conformers. Validation of this methodology is certified with high accuracy by applying it on the substituted diuridine pairs, where experimental populations are available. Not only calculated populations and NMR parameters of this test are in very good agreement with experimental data, but also they free of ambiguities mentioned by experimentalists.
A palladium-catalyzed decarboxylative coupling of enol carbonates with diarylmethyl electrophiles that are derived from secondary benzylic alcohols has been developed. This method allows the generation of a variety of β-diaryl ketones through an efficient and highly stereospecific coupling. In addition, detailed mechanistic insight into the coupling suggests that the reaction is a rare example of an intramolecular decarboxylative coupling that proceeds without crossover between reactants.
Hydroxyphenyl-benzothiazole (HBT), is a well-known organic system based on its special character of the excited state hydrogen transfer (ESHT) following photoexcitation. However, the capability of this system regarding photochromism and photoswitching has not been addressed yet. In this study, we have investigated this subject by the aim of the MP2, CC2, ADC(2) and CASSCF theoretical methods. Also, we have considered several electron withdrawing groups and investigated their effects on photophysical characters and spectroscopic properties of enol and keto tautomeres of titled system. It has been predicted that the main HBT and its considered substitutions fulfill the essential characters required for photochromism. Also, substitution is an effective idea for tuning the photophysical nature of HBT and its similar systems. Our theoretical results verify that different substitutions alter the UV absorption of HBT systems from 330-351 nm, and also the corresponding absorption wavelength of the γ-forms of 526-545 nm.
Pigment Yellow 101 (PY101) is widely used as a typical pigment due to its excellent excited-state properties. However, the origin of its photostability is still elusive. In this work, we have systematically investigated the photodynamics of PY101 by performing combined electronic structure calculations and trajectory-based nonadiabatic dynamics simulations. On the basis of the results, we have found that upon photoexcitation to the S1state, PY101 undergoes an essentially barrierless excited-state intramolecular single proton transfer generating an S1keto species. In the keto region, there is an energetically accessible S1/S0conical intersection that funnels the system to the S0state quickly. In the S0state, the keto species either goes back to its trans-enol species through a ground-state reverse hydrogen transfer or arrives at the cis-keto region. In addition, we have found an additional excited-state decay channel for the S1enol species, which is directly linked to an S1/S0conical intersection located in the enol region. This mechanism has also been confirmed by our dynamics simulations, in which about 54% of the trajectories decay to the S0state via the enol S1/S0conical intersection; while the remaining ones employ the keto S1/S0conical intersection. The gained mechanistic information helps us understand the photostability of the PY101 chromophore and its variants with the same molecular scaffold.
Enolonium Species, resulting from the umpolung of ketone enolates by Koser’s hypervalent iodine reagents activated by boron trifluoride, react with a variety of nitrogen heterocycles to form α-aminated ketones. The reactions are mild and complete in 4-5 hours. Additionally, α-azidation of the enolonium species takes place using trimethylsilyl azide as a convenient source of azide nucleophile.