Mechanism of Asymmetric Homologation of Alkenylboronic Acids with CF3-Diazomethane via Borotropic Rearrangement.

Density functional theory calculations have been performed to investigate the mechanism for the BINOL-catalyzed asymmetric homologation of alkenylboronic acids with CF3-diazomethane. The reaction proceeds via a chiral BINOL ester of the alkenylboronic acid substrate. The calculations reveal a complex scenario for the formation of the chiral BINOL-alkenylboronate species, which is the key intermediate in the catalytic process. The aliphatic alcohol additive plays an important role in the reaction. This study provides a rationalization of the stereoinduction step of the reaction, and the enantioselectivity is mainly attributed to the steric repulsion between the CF3 group of the diazomethane reagent and the γ-substituent of the BINOL catalyst. The complex potential energy surface obtained by the calculations is analyzed by means of microkinetic simulations.

Three-Component Approach to Densely Functionalized Trifluoromethyl Allenols by Asymmetric Organocatalysis.

We have developed a new three-component catalytic coupling reaction of alkynyl boronates, diazomethanes, and aliphatic/aromatic ketones in the presence of BINOL derivatives. The reaction proceeds with a remarkably high enantio- and diastereoselectivity (up to three contiguous stereocenters) affording tertiary CF3-allenols in a single operational step. The reaction proceeds under mild, neutral, metal-free conditions, which leads to a high level of functional group tolerance.

Catalytic Homologation-Allylboration Sequence for Diastereo- and Enantioselective Synthesis of Densely Functionalized ß-Fluorohydrins with Tertiary Fluoride Stereocenters.

Homologation of trisubstituted fluoroalkenes followed by allylboration of aldehyde, ketone and imine substrates is suitable for synthesis of ß-fluorohydrin and amine products. In the presence of (R)-iodo-BINOL catalyst enantioselectivities up to 99 % can be achieved by formation of a single stereoisomer with adjacent stereocenters, of which one is a tertiary C-F center.

The Biblical Job Against Zeno the Stoic: Living Purposively Versus Dying for Meaning.

Zeno the Stoic and the biblical Job react very differently to stressors in their lives. While Zeno succumbs to a relatively minor accident and takes his life, Job withstands cataclysmic losses, survives, and ultimately is restored. While Zeno's search for meaning ends in his suicide, Job's sense of purpose enables him to survive and ultimately thrive. The essential difference is that while Zeno greatly catastrophizes a relatively minor stressor in a desperate search for meaning, Job lives a life of purpose which gives his life intrinsic meaning. This distinction may be most relevant in today's chaotic world, with so many young people striving to "find themselves" in often the most destructive ways. While Job is resilient, Zeno is not. Job's biblical faith provides the grounding for his self-knowledge. Zeno the Stoic does not seem to have this foundational self-knowledge and is searching for signs that he is not adrift in an indifferent world. For some people, at least, biblical religion seems to provide a healthy foundational view which gives life essential purpose.

Eating and Drinking Narratives in Biblical-Rabbinic Versus Graeco-Roman Writings.

The writings of ancient Greece and Rome and of biblical Israel are filled with descriptions of food. The narratives in Greek and Roman mythology and poetry often describe violent and repulsive behavior associated with food. The biblical narratives, in contrast, tend to view food in a respectful and purposeful manner. We compare and contrast some of these stories with regard to the specific themes: restraint, respect, purpose, and order. In each comparison, patterns of eating described in biblical laws and narratives will be contrasted with those emerging from Graeco-Roman stories and customs.

Sulfenofunctionalization of Chiral α-Trifluoromethyl Allylboronic Acids: Asymmetric Synthesis of SCF3 , SCF2 R, SCN and SAr Compounds.

We report herein a new method for the synthesis of densely functionalized chiral allyl SCF3 , SCF2 R, SCN and SAr species with a separate CF3 functionality. The synthetic approach is based on selenium-catalyzed sulfenofunctionalization of chiral α-CF3 allylboronic acids. The reactions proceeded with remarkably high stereo-, diastereo- and site-selectivity, based on the formation of a stable thiiranium ion followed by rapid deborylative ring opening.

Asymmetric Organocatalytic Homologation: Access to Diverse Chiral Trifluoromethyl Organoboron Species.

A broad range of aliphatic, aromatic, and heterocyclic boronic acids were successfully homologated using trifluorodiazoethane in the presence of BINOL derivatives to provide the corresponding chiral trifluoromethyl containing boronic acid derivatives in high yields and excellent enantioselectivity. The in situ conversion of the chiral transient boronic acids to the corresponding alcohols or ß-CF3 carboxylates are also demonstrated.

Electrophilic Fluorination of Alkenes via Bora-Wagner-Meerwein Rearrangement. Access to ß-Difluoroalkyl Boronates.

The electrophilic fluorination of geminal alkyl substituted vinyl-Bmida derivatives proceeds via bora-Wagner-Meerwein rearrangement. According to DFT modelling studies this rearrangement occurs with a low activation barrier via a bora-cyclopropane shaped TS. The Bmida group has a larger migration aptitude than the alkyl moiety in the Wagner-Meerwein rearrangement of the presented electrophilic fluorination reactions.

Base-catalysed 18F-labelling of trifluoromethyl ketones. Application to the synthesis of 18F-labelled neutrophil elastase inhibitors.

A new method for the fluorine-18 labelling of trifluoromethyl ketones has been developed. This method is based on the conversion of a-COCF3 functional group to a difluoro enol silyl ether followed by halogenation and fluorine-18 labelling. The utility of this new method was demonstrated by the synthesis of fluorine-18 labelled neutrophil elastase inhibitors, which are potentially useful for detection of inflammatory disorders.

Organocatalytic Synthesis of α-Trifluoromethyl Allylboronic Acids by Enantioselective 1,2-Borotropic Migration.

Chiral α-substituted allylboronic acids were synthesized by asymmetric homologation of alkenylboronic acids using CF3/TMS-diazomethanes in the presence of BINOL catalyst and ethanol. The chiral α-substituted allylboronic acids were reacted with aldehydes or oxidized to alcohols in situ with a high degree of chirality transfer. The oxygen-sensitive allylboronic acids can be purified via their isolated diaminonaphthalene (DanH)-protected derivatives. The highly reactive purified allylboronic acids reacted in a self-catalyzed reaction at room temperature with ketones, imines, and indoles to give congested trifluoromethylated homoallylic alcohols/amines with up to three contiguous stereocenters.

Enantioselective Construction of Tertiary Fluoride Stereocenters by Organocatalytic Fluorocyclization.

1,1-Disubstituted styrenes with internal oxygen and nitrogen nucleophiles undergo oxidative fluorocyclization reactions with in situ generated chiral iodine(III)-catalysts. The resulting fluorinated tetrahydrofurans and pyrrolidines contain a tertiary carbon-fluorine stereocenter. Application of a new 1-naphthyllactic acid-based iodine(III)-catalyst allows the control of tertiary carbon-fluorine stereocenters with up to 96% ee. Density functional theory calculations are performed to investigate the details of the mechanism and the factors governing the stereoselectivity of the reaction.

Mechanisms of Formation and Rearrangement of Benziodoxole-Based CF3 and SCF3 Transfer Reagents.

Togni's benziodoxole-based reagents are widely used in trifluoromethylation reactions. It has been established that the kinetically stable hypervalent iodine form (I-CF3) of the reagents is thermodynamically less stable than its acyclic ether isomer (O-CF3). On the other hand, the trifluoromethylthio analogue exists in the thermodynamically stable thioperoxide form (O-SCF3), and the hypervalent form (I-SCF3) has been elusive. Despite the importance of these reagents, very little is known about the reaction mechanisms of their syntheses, which has hampered the development of new reagents of the same family. Herein, we use density functional theory calculations to understand the reasons for the divergent behaviors between the CF3 and SCF3 reagents. We demonstrate that they follow different mechanisms of formation and that the metals involved in the syntheses (potassium in the case of the trifluoromethyl reagent and silver in the trifluoromethylthio analogue) play key roles in the mechanisms and greatly influence the possibility of their rearrangements from the hypervalent (I-CF3, I-SCF3) to the corresponding ether-type form (O-CF3, O-SCF3).

Trifluoromethylthiolation, Trifluoromethylation, and Arylation Reactions of Difluoro Enol Silyl Ethers.

This study reports a new application area of difluoro enol silyl ethers, which can be easily obtained from trifluoromethyl ketones. The main focus has been directed to the electrophilic fluoroalkylation and arylation methods. The trifluoromethylthiolation of difluoro enol silyl ethers can be used for the construction of a novel trifluoromethylthio-α,α-difluoroketone (-COCF2SCF3) functionality. The -CF2SCF3 moiety has interesting properties due to the electron-withdrawing, albeit lipophilic, character of the SCF3 group, which can be combined with the high electrophilicity of the difluoroketone motif. The methodology could also be extended to difluoro homologation of the trifluoromethyl ketones using the Togni reagent. In addition, we presented a method for transition-metal-free arylation of difluoro enol silyl ethers based on hypervalent iodines.

Rhodium-mediated 18F-oxyfluorination of diazoketones using a fluorine-18-containing hypervalent iodine reagent.

Geminal 18F-oxyfluorination of diazoketones was performed in the presence of rhodium mediators. The reactions were performed using a hypervalent iodine-based [18F]fluoro-benziodoxole reagent. By this methodology various α-[18F]fluoro ethers were obtained in high radiochemical yield (up to 98%) and molar activity (216 GBq µmol-1).

Trifluoromethylthiolation-arylation of diazocarbonyl compounds by modified Hooz multicomponent coupling.

A new Zn-mediated trifluoromethylthiolation-based bifunctionalization reaction is developed. In this process, simultaneous C-SCF3 and C-C bond formation takes place in a multicomponent reaction, in which an aryl and a SCF3 group arise from different reagents. Our studies show that the reaction mechanism is similar to the Hooz multicomponent coupling. The process involves in situ generation of BAr3, which reacts with a diazocarbonyl compound, and the reaction is terminated by an electrophilic SCF3 transfer. The reaction can also be extended to fluorination based bifunctionalization which proceeds with somewhat lower yield than the analogous trifluoromethylthiolation reaction.

Social Status and Suicidal Activity Among Psychiatric Patients: Moderating Effects of Gender, Race and Psychiatric Diagnosis.

The relationship between suicide and social class has proved to be complex. Durkheim predicted suicide rates would increase with social status, while others thought the opposite. Results have been mixed. In some studies, suicidality has increased with increasing social status, and in other studies, the two variables have had an inverse relationship. These studies have been primarily conducted on general non-psychiatric populations The present study, in contrast, examines this relationship on a 20-year prospective longitudinal sample of 400 psychiatric patients (differentiated by psychiatric diagnosis) after index hospitalization. Of these, 160 patients show some sign of suicide risk (87 cases of suicidal ideation, 41 of suicide attempts, and 32 suicide completions). A complicated pattern emerges across psychiatric diagnosis, gender, and race. The great majority of patients show no statistically significant relationship between social status and suicide risk. At the maximally different extremes, however, a dramatic difference does emerge. White women diagnosed with nonpsychotic depression show a positive relationship between social status and suicide risk (p < .01) while black men diagnosed with schizophrenia show a negative relationship between these 2 variables (p < .02). The relationship between social status and suicidality among psychiatric patients varies across race, gender, and psychiatric diagnosis. More research needs to be done on this complex and important topic, especially with regard to samples of psychiatric patients. The role of anomie should be studied.

Mechanisms of Rh-Catalyzed Oxyaminofluorination and Oxyaminotrifluoromethylthiolation of Diazocarbonyl Compounds with Electrophilic Reagents.

Density functional theory calculations were performed to study the detailed reaction mechanisms of rhodium-catalyzed oxyaminofluorination and oxyaminotrifluoromethylthiolation of diazocarbonyl compounds with electrophilic N-F and N-SCF3-based reagents. The calculations show that the operating mechanisms for the two reactions are identical. The catalytic cycle starts with N2 dissociation to provide a rhodium-carbene intermediate, followed by nucleophilic attack of tetrahydrofuran on the carbene and a rhodium coordination change generating a rhodium-enolate intermediate. Subsequent electrophilic attack introduces the fluorine or the SCF3 moiety, and it is followed by nucleophilic attack of the remaining amino group to yield the final product.

Catalytic asymmetric propargyl- and allylboration of hydrazonoesters: a metal-free approach to sterically encumbered chiral α-amino acid derivatives.

A new asymmetric catalytic propargyl- and allylboration of hydrazonoesters is reported. The reactions utilize allenyl- and allylboronic acids in the presence of the inexpensive parent BINOL catalyst. The reactions can be performed under mild conditions (0 °C) without any metal catalyst or other additives affording sterically encumbered chiral α-amino acids. This is the first metal-free method for the asymmetric propargyl- and allylboration of hydrazonoesters.

Copper-catalyzed synthesis of allenylboronic acids. Access to sterically encumbered homopropargylic alcohols and amines by propargylboration.

Tri- and tetrasubstituted allenylboronic acids were prepared via a new versatile copper-catalyzed methodology. The densely functionalized allenylboronic acids readily undergo propargylboration reactions with ketones and imines without any additives. Catalytic asymmetric propargylborylation of ketones is demonstrated with high stereoselectivity allowing for the synthesis of highly enantioenriched tertiary homopropargyl alcohols. The reaction is suitable for kinetic resolution of racemic allenylboronic acids affording alkynes with adjacent quaternary stereocenters.

Synthesis of Densely Substituted Conjugated Dienes by Transition-Metal-Free Reductive Coupling of Allenylboronic Acids and Tosylhydrazones.

Tosylhydrazones and allenylboronic acids underwent a transition-metal-free reductive coupling reaction. This process is suitable for synthesis of tetra- and pentasubstituted conjugated dienes. The corresponding allenyl-Bpin substrate showed a very poor reactivity. The reaction is suggested to involve coupling of the in situ formed diazo compound and allenylboronic acid. The intermediate formed in this coupling undergoes allenyl migration followed by protodeboronation to furnish a conjugated diene as major product.