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A ‘principles and practice’ tutorial-style review of the application of solution-phase NMR in the analysis of the mechanisms of homogeneous organic and organometallic reactions and processes. This review of 345 references summarises why solution-phase NMR spectroscopy is uniquely effective in such studies, allowing non-destructive, quantitative analysis of the wide range of nuclei common to organic and organometallic reactions, providing exquisite structural detail, and using instrumentation that is routinely available in most chemistry research facilities. The review is in two parts. The first comprises an introduction to general techniques and equipment, and guidelines for their selection and application. Topics include practical aspects of the reaction itself, reaction monitoring techniques, NMR data acquisition and processing, analysis of temporal concentration data, NMR titrations, DOSY, and the use of isotopes. The second part comprises a series of 15 'Case Studies', each selected to illustrate specific techniques and approaches discussed in the first part, including in situ NMR (1/2H, 10/11B, 13C, 15N, 19F, 29Si, 31P), kinetic and equilibrium isotope effects, isotope entrainment, isotope shifts, isotopes at natural abundance, scalar coupling, kinetic analysis (VTNA, RPKA, simulation, steady-state), stopped-flow NMR, flow NMR, rapid injection NMR, pure shift NMR, dynamic nuclear polarisation, 1H/19F DOSY NMR, and in situ illumination-NMR

The mechanism of anion-catalyzed C–H silylation by R3SiCF3 reagents has been investigated using homogeneous TBAT-initiation, in situ and stopped-flow 19F NMR spectroscopy 2H-KIE, LFER, deuterium-labeled crossover, structure-selectivity quantitation (TMSCF3/TESCF3), carbene trapping, and DFT-calculations. Analysis of the kinetics of reactions of 1,3-difluorobenzenes (2), and the generation of ArSiMe3 and Me3SiF as a function of the concentration of [2], [TMSCF3], and [TBAT], show that a CF3-anionoid is the active intermediate. The CF3-anionoid is reversibly released from siliconate [(CF3)2SiMe3]− and undergoes partitioning through rate-limiting arene deprotonation (1H/2H KIE 9.5) to generate ArSiMe3 (via a transient aryl anionoid) and fluoroform (CF3H), in competition with F-anion transfer to TMSCF3 to generate CF2 and TMSF. The [2]/[TMSCF3] concentration ratio directly and proportionally controls the kinetics of the partition, in favor of C–H deprotonation. Higher concentrations of TBAT and lower concentrations of TMSCF3 lead to faster rates of ArSiMe3 generation. Use of the homologous TESCF3 reagent leads to faster rates of anion catalysis and an increased selectivity toward C–H deprotonation. Perfluoroalkenes, generated in situ from CF2, capture the CF3-anionoid leading to progressive inhibition of the anion-catalysis. Inhibition is suppressed by using a styrene additive to trap the CF2 and the efficiency of the process enhanced by slow-addition of TMSCF3 (1) to maintain a high concentration ratio [2]/[1].

ConspectusReagent instability reduces the efficiency of chemical processes, and while much effort is devoted to reaction optimization, less attention is paid to the mechanistic causes of reagent decomposition. Indeed, the response is often to simply use an excess of the reagent. Two reaction classes with ubiquitous examples of this are the Suzuki–Miyaura cross-coupling of boronic acids/esters and the transfer of CF3 or CF2 from the Ruppert–Prakash reagent, TMSCF3. This Account describes some of the overarching features of our mechanistic investigations into their decomposition. In the first section we summarize how specific examples of (hetero)arylboronic acids can decompose via aqueous protodeboronation processes: Ar–B(OH)2 + H2O → ArH + B(OH)3. Key to the analysis was the development of a kinetic model in which pH controls boron speciation and heterocycle protonation states. This method revealed six different protodeboronation pathways, including self-catalysis when the pH is close to the pKa of the boronic acid, and protodeboronation via a transient aryl anionoid pathway for highly electron-deficient arenes. The degree of “protection” of boronic acids by diol-esterification is shown to be very dependent on the diol identity, with six-membered ring esters resulting in faster protodeboronation than the parent boronic acid. In the second section of the Account we describe 19F NMR spectroscopic analysis of the kinetics of the reaction of TMSCF3 with ketones, fluoroarenes, and alkenes. Processes initiated by substoichiometric “TBAT” ([Ph3SiF2][Bu4N]) involve anionic chain reactions in which low concentrations of [CF3]− are rapidly and reversibly liberated from a siliconate reservoir, [TMS(CF3)2][Bu4N]. Increased TMSCF3 concentrations reduce the [CF3]− concentration and thus inhibit the rates of CF3 transfer. Computation and kinetics reveal that the TMSCF3 intermolecularly abstracts fluoride from [CF3]− to generate the CF2, in what would otherwise be an endergonic α-fluoride elimination. Starting from [CF3]− and CF2, a cascade involving perfluoroalkene homologation results in the generation of a hindered perfluorocarbanion, [C11F23]−, and inhibition. The generation of CF2 from TMSCF3 is much more efficiently mediated by NaI, and in contrast to TBAT, the process undergoes autoacceleration. The process involves NaI-mediated α-fluoride elimination from [CF3][Na] to generate CF2 and a [NaI·NaF] chain carrier. Chain-branching, by [(CF2)3I][Na] generated in situ (CF2 + TFE + NaI), causes autoacceleration. Alkenes that efficiently capture CF2 attenuate the chain-branching, suppress autoacceleration, and lead to less rapid difluorocyclopropanation. The Account also highlights how a collaborative approach to experiment and computation enables mechanistic insight for control of processes.

The kinetics of quinuclidine displacement of BH

The kinetics of quinuclidine displacement of BH3 from a wide range of Lewis base borane adducts have been measured. Parameterization of these rates has enabled the development of a nucleofugality scale (NFB), shown to quantify and predict the leaving group ability of a range of other Lewis bases. Additivity observed across a number of series R′3–nRnX (X = P, N; R′ = aryl, alkyl) has allowed the formulation of related substituent parameters (nfPB, nfAB), providing a means of calculating NFB values for a range of Lewis bases that extends far beyond those experimentally derived. The utility of the nucleofugality parameter is explored by the correlation of the substituent parameter nfPB with the hydrolyses rates of a series of alkyl and aryl MIDA boronates under neutral conditions. This has allowed the identification of MIDA boronates with heteroatoms proximal to the reacting center, showing unusual kinetic lability or stability to hydrolysis.

The potential of merging photoredox and nickel catalysis to perform multicomponent alkene difunctionalizations under visible-light irradiation is demonstrated here. Secondary and tertiary alkyl groups, as well as sulfonyl moieties can be added to the terminal position of the double bond with simultaneous arylation of the internal carbon atom in a single step under mild reaction conditions. The process, devoid of stoichiometric additives, benefits from the use of bench-stable and easy-to-handle reagents, is operationally simple, and tolerates a wide variety of functional groups.

Background. The mussel Modiolus capax is a commercially important resource in the northwest of Mexico; however few studies evaluate its reproduction. Goals. The reproductive activity and the gonadosomatic index of were used to describe the seasonal variations in the reproductive cycle of the M. capax and the relationship with the environmental changes. Methods. Approximately 24 specimens were collected per month in two localities at La Paz inlet, Baja California Sur, Mexico, between October 2008 and December 2010. Relationships between gonad developmental states and size were estimated; also, its relationships with temperature and chlorophyll-a. Results. The results indicated a synchronous spawning between males and females in March in one locality and in January in the other. In both localities, ripe and post-spawning females showed follicular atresia, in up to 82% of all females in one locality. The smallest organisms were found in the early gametogenesis stage; the largest, in the spawning stage. The gonadosomatic index differed between localities, and was positively correlated with the increase in chlorophyll-a. A significant relationship was observed between temperature and the frequencies of the gametogenesis and ripening stages. Conclusions. The study of the reproduction of M. capax revealed that environmental changes affect on the activity and reproductive status and favored the development of follicular atresia.

El mejillon Modiolus capax es una especie de importancia comercial en el noroeste de Mexico; sin embargo existen pocos trabajos que evaluan su reproduccion. Objetivos: Comparar el ciclo reproductivo de M. capax en dos bancos ubicados a diferentes profundidades en la Ensenada de La Paz, B.C.S., Mexico, y sus relaciones con las variables ambientales. La talla de primera madurez (L50) se estimo utilizando un modelo logistico para obtener el valor de longitud en el que el 50% de la poblacion se encuentran maduros. Metodos: Se recolectaron aproximadamente 25 (± 4.5) especimenes, entre octubre de 2008 y diciembre de 2010, en un banco poco profundo de la zona intermareal (Banco A) y 23 (± 4) en un banco superficial profundo (Banco B). El tamano en la primera madurez sexual (L50) se estimo utilizando un modelo logistico para obtener el tamano en un 50% de madurez. Las evaluaciones mensuales de la informacion biologica individual se complementaron con el analisis histologico de las gonadas, en diferentes momentos del ciclo reproductivo. Se estimo la relacion entre los estadios de desarrollo gonadal y el indice gonadosomatico, tambien su relacion con la temperatura y la clorofila. Resultados: Los resultados indican que ocurrio un pico de desove en marzo (Banco A) y en enero en el otro (Banco B). En ambas localidades, las hembras maduras y en post-desove presentaron atresia folicular, hasta el 82% en el banco B. La L50 fue de 74.12 mm para el banco A y 71.74 mm para el B. El indice gonadosomatico difirio entre bancos y se correlaciono positivamente con el aumento de clorofila-a (Banco A). Se observo una relacion negativa significativa entre la temperatura y el estadio de madurez (Banco A). Conclusiones: El estudio de la reproduccion de M. capax revelo que los bancos analizados presentan una periodicidad reproductiva diferente y que los cambios ambientales afectan la actividad reproductiva, favorecieron el desarr

The mechanism of CF2 transfer from TMSCF3 ( 1 ), mediated by TBAT (2–12 mol %) or by NaI (5–20 mol %), has been investigated by in situ/stopped-flow 19F NMR spectroscopic analysis of the kinetics of alkene difluorocyclopropanation and competing TFE/c-C3F6/homologous perfluoroanion generation, 13C/2H KIEs, LFERs, CF2 transfer efficiency and selectivity, the effect of inhibitors, and density functional theory (DFT) calculations. The reactions evolve with profoundly different kinetics, undergoing autoinhibition (TBAT) or quasi-stochastic autoacceleration (NaI) and cogenerating perfluoroalkene side products. An overarching mechanism involving direct and indirect fluoride transfer from a CF3 anionoid to TMSCF3 ( 1 ) has been elucidated. It allows rationalization of why the NaI-mediated process is more effective for less-reactive alkenes and alkynes, why a large excess of TMSCF3 ( 1 ) is required in all cases, and why slow-addition protocols can be of benefit. Issues relating to exothermicity, toxicity, and scale-up are also noted. Postprint

The mechanism of CF

Alkene dicarbofunctionalizations enable the streamlined construction of aliphatic structures and have thus been the subject of intense research efforts. Despite significant progress, catalytic asymmetric variants remain scarce. Inspired by the advantages of reductive cross-coupling approaches, we present here a highly efficient asymmetric intermolecular Ni-catalyzed reductive dicarbofunctionalization of alkenes. Two distinct readily available electrophiles, namely, Csp2- and Csp3-halides, are added simultaneously across a variety of olefins (vinyl amides, vinyl boranes, vinyl phosphonates) at room temperature in a highly regio- and enantioselective manner. The reaction, devoid of sensitive organometallic reagents, takes advantage of an in situ generated chiral alkyl Ni(III)-intermediate to ensure a stereodefined outcome in the Csp3-Csp2 bond-forming reaction. An (l)-(+)-isoleucine chiral bisoxazoline ligand and the presence of coordinating sites on the alkene are key for the successful outcome in these "asymmetric radical relayed reductive couplings" (ARRRCs). Further, multiple transformations of the chiral amides obtained in this process showcase the potential of this new methodology for the straightforward assembly of chiral building blocks such as primary and secondary amines and oxazolines, highlighting its synthetic utility.

β,β-Disubstituted vinyl sulfones were obtained with complete regio- and stereocontrol in a multicomponent reaction involving alkynes, organoboronic acids, and sulfonyl chlorides in the presence of a nickel catalyst. The reaction proceeds via sulfonyl radicals generated in situ under mild reaction conditions.

An intermolecular, three-component reductive dicarbofunctionalization of alkenes is presented here. The combination of Ni catalysis with TDAE as final reductant enables the direct formation of Csp3–Csp3 and Csp3–Csp2 bonds across a variety of π-systems using two different electrophiles that are sequentially activated with exquisite selectivity under mild reaction conditions.

The kinetics of the nominally irreversible reaction of the third generation Grubbs catalyst G-III-Br (4.6 μM) with ethyl vinyl ether (EVE) in toluene at 5 °C have been re-visited. There is a rapid equilibrium between the bispyridyl form of G-III-Br, 1, and its monopyridyl form, 2 (K ≈ 0.001 M). The empirical rate constants (kobs.) for the reaction with EVE, determined UV-vis spectrophotometrically under optimised anaerobic stopped-flow conditions, are found by testing the quality of fit of a series of steady-state approximations. The kinetics do not correlate with solely dissociative or associative pathways, but do correlate with a mechanism where these pathways converge at an alkene complex primed to undergo metathesis. In the presence of traces of air there is a marked increased in the rate of decay of G-III-Br due to competing oxidation to yield benzaldehyde; a process that appears to be very efficiently catalysed by trace metal contaminants. The apparent acceleration of the initiation process may account for the rates determined herein being over an order of magnitude lower than previously estimated.

Olefins devoid of directing or activating groups have been dicarbofunctionalized here with two electrophilic carbon sources under reductive conditions. Simultaneous formation of one C(sp3)-C(sp3) and one C(sp3)-C(sp2) bond across a variety of unbiased π-systems proceeds with exquisite selectivity by the combination of a Ni catalyst with TDAE as sacrificial reductant. Control experiments and computational studies revealed the feasibility of a radical-based mechanism involving, formally, two interconnected Ni(I)/Ni(III) processes and demonstrated the different ability of Ni(I) species (Ni(I)I vs PhNi(I)) to reduce the C(sp3)-I bond. The role of the reductant was also investigated in depth, suggesting that a one-electron reduction of Ni(II) species to Ni(I) is thermodynamically favored. Further, the preferential activation of alkyl vs aryl halides by ArNi(I) complexes as well as the high affinity of ArNi(II) for secondary over tertiary C-centered radicals explains the lack of undesired homo- and direct coupling products (Ar-Ar, Ar-Alk) in these transformations.

A nickel-catalyzed three-component reaction involving terminal alkynes, boronic acids, and alkyl halides is presented herein. Trisubstituted alkenes can be obtained in a highly regio- and stereocontrolled manner by the simultaneous addition of both aryl and alkyl groups across the triple bond in a radical-mediated process. The reaction, devoid of air- and moisture-sensitive organometallic reagents and catalysts, is operationally simple and offers a broad scope and functional-group tolerance.

Herein we present the first example of a three-component dicarbofunctionalization of olefins under reductive conditions. Our strategy takes advantage of nickel catalysis to add aryl and alkyl groups across the double bond with remarkable selectivity. The reaction shows broad functional group compatibility and more importantly, it proves to be general in terms of the alkenes that can be functionalized compared to previous dicarbofunctionalization methods. Initial control experiments reveal different activation modes for both electrophiles and the involvement of alkyl radicals throughout the reaction.

A Pd-catalyzed three component reaction involving terminal alkynes, boronic acids, and perfluoroalkyl iodides is presented here. Trisubstituted perfluoroalkenes can be obtained in a highly regio- and stereocontrolled manner by the simultaneous addition of both aryl and CnFm groups across the triple bond in a radical-mediated process. The reaction is operationally simple offering a broad scope and functional group tolerance.

A nickel-catalyzed three-component reaction involving terminal alkynes, boronic acids, and alkyl halides is presented herein. Trisubstituted alkenes can be obtained in a highly regio- and stereocontrolled manner by the simultaneous addition of both aryl and alkyl groups across the triple bond in a radical-mediated process. The reaction, devoid of air- and moisture-sensitive organometallic reagents and catalysts, is operationally simple and offers a broad scope and functional-group tolerance.

A Pd-catalyzed three component reaction involving terminal alkynes, boronic acids, and perfluoroalkyl iodides is presented here. Trisubstituted perfluoroalkenes can be obtained in a highly regio- and stereocontrolled manner by the simultaneous addition of both aryl and CnFm groups across the triple bond in a radical-mediated process. The reaction is operationally simple offering a broad scope and functional group tolerance.

Through histological analyses, this investigation reveals an unusual high incidence of hermaphroditism in Megapitaria squalida, a gonochoric species. A total of 684 specimens were sampled at monthly intervals from February 2007 to January 2008 at Bahia de La Paz and Bahia Magdalena, Baja California Sur, Mexico. Microscopic examination showed that 21.8% of specimens from Bahia de La Paz and 23.5% from Bahia Magdalena were hermaphroditic; in both areas, hermaphroditism was found throughout the year, although in variable proportions. In general, a significantly higher number of females relative to males (chi-square, P < 0.05) were observed in both areas. Our findings indicate that this unusual incidence of hermaphroditism was likely caused by the low population density resulting from overfishing.

Two highly stereoselective radical-mediated syntheses of densely functionalized indanes and dibenzocycloheptadienes from ortho-vinyl- and ortho-vinylaryl-substituted N-(arylsulfonyl)-acrylamides, respectively, are presented.

Two highly stereoselective radical-mediated syntheses of densely functionalized indanes and dibenzocycloheptadienes from ortho-vinyl- and ortho-vinylaryl-substituted N-(arylsulfonyl)-acrylamides, respectively, are presented here. The chemoselective addition of in situ generated radicals (X(·)) onto the styrene moieties triggers an unprecedented reaction cascade, resulting in the formation of one new C-X bond and two new C-C bonds, a formal 1,4-aryl migration, and the extrusion of SO2 to generate an amidyl radical intermediate. This intermediate, upon H abstraction, leads to the observed 5- and 7-membered ring carbocyclic products, respectively, in a highly efficient manner.

The cannonball jellyfish Stomolophus meleagris is regarded as a fishery resource with high commercial value, but with scarce biological information. With the aim to generate preliminary information on reproductive aspects, the present study analyzes its fecundity, based on the estimated number of vitellogenic oocytes in the gonad; in addition, we evaluated its relationship with the jellyfish body length, diameter and wet weight; and we established the relationship of the gonadosomatic index (IGS) with the jellyfish diameter and length. For this, a total of 30 specimens were collected, measured and weighed in a monthly basis, in Las Guasimas lagoon from January to May 2006. In order to estimate the gonad volume, 60 mature females were analyzed and their gonads were extracted and stained with hematoxylin-eosin. Gonad images from histological preparations were analyzed and the number of vitellogenic and previtellogenic oocytes obtained. We used catch data from The Guasimas for population recruitment analysis, that was estimated with FISAT II. Among results, we found that fecundity increased with jellyfish length, diameter and total wet weight. The lower fecundity rates occured on February and the highest during May (11 873 071 and 37 528 197 millions of vitellogenic oocytes per gonad, respectively). The IGS increased with length and diameter of the specimens, at its maximum value of 3.7% was observed in May. A continuous production of previtellogenic oocytes were observed during the full collection period. The maximum recruitment was observed in July and November (37.50% and 28.01% respectively). The high fecundity observed in S meleagris, suggests a high population reproductive potential that may support the possibility of an important fishery consolidation on this jellyfish.

Facultad de Medicina Veterinaria y Zootecnia