Nucleofugal behavior of a ß-shielded α-cyanovinyl carbanion.

Sterically well-shielded against unsolicited Michael addition and polymerization reactions, α-metalated α-(1,1,3,3-tetramethylindan-2-ylidene)acetonitriles added reversibly to three small aldehydes and two bulky ketones at room temperature. Experimental conditions were determined for transfer of the nucleofugal title carbanion unit between different carbonyl compounds. These readily occurring retro-additions via C-C(O) bond fission may also be used to generate different metal derivatives of the nucleofugal anions as equilibrium components. Fluoride-catalyzed, metal-free desilylation admitted carbonyl addition but blocked the retro-addition.

"Conducted Tour" Migration of Li+ during the cis/trans Stereoinversion of α-Arylvinyllithiums.

A "conducted tour" migration keeps a mobile client on a profitable route even though an occasional side-step may seem attractive. A stereochemical manifestation of such a migration had been suggested by Donald J. Cram (1964), and we present now a different example that concerns the cis/trans stereoinversion of monomeric H2 C=C(Li)-aryl compounds: Upon tetrahydrofuran (THF)-assisted heterolysis of the Li-C bond with formation of a solvent-separated ion pair (SSIP), the unchained "mobile client" Li+ (THF)4 is proposed to surmount the rim of the electronically fixed aryl group and to disdain the less encumbered pathways across the H2 C=C region. This interpretation is based on knowledge from a previously published series of monomeric α-arylalkenyllithiums in combination with two new members: 4-(α-lithiovinyl)-2,2-dimethylbenz[f]indane (1) revealed both a barrier against α-aryl rotation and a route-distinguishing retardation as compared with the corresponding migration-dependent cis/trans stereoinversion rate constant of 1-(α-lithiovinyl)naphthalene (2). Monomeric and dimeric ground states of 1 and 2 and their microsolvation numbers were determined by using the recently developed primary and secondary NMR criteria.

Doubly Diastereoconvergent Preparation and Microsolvation-Controlled Properties of (Z)- and (E)-1'-Lithio-1'-(2,6-dimethylphenyl)propenes.

A doubly diastereoconvergent reaction can ad libitum generate either one or the other of two diastereomeric products with complete consumption of the diastereomeric precorsors or their mixtures. Thus, the preparation of configurationally pure (Z)-1'-lithio-1'-(2,6-dimethylphenyl)propene [(Z)-1] from any Z,E mixture of the corresponding bromoalkenes with n-butyllithium succeeded by means of a user-friendly (E)-1 → (Z)-1 configurational interconversion. The subsequent treatment of (Z)-1 with a minimum amount of THF afforded exclusively (E)-1 as the other diastereomeric product and was mediated by a beneficial (Z)-1 → (E)-1 interconversion. This behavior provided microsolvation-controlled choices of highly diastereoselective derivatizations of 1. Low-temperature 13C NMR spectra established that (Z)-1 was dissolved as a trisolvated monomer in THF but as a disolvated dimer in monodentate, ethereal, non-THF solvents, whereas (E)-1 was always monomeric. Backed by such knowledge, kinetic experiments indicated that the electrophiles 1-bromobutane or ClSiMe3 in Et2O reacted at 32 °C with the tiny (NMR-invisible) population of monomeric (Z)-1 that was formed in a mobile equilibrium from the inactive, predominantly dimeric (Z)-1. The equilibration of monomeric (Z)-1 and (E)-1 in THF as the solvent was fast (seconds on the 1H NMR time scale), whereas the corresponding stereoinversion of both solvated and unsolvated (E)-1 → (Z)-1 in non-THF solvents occurred on the laboratory time scale (minutes at ambient temperatures). Dicyclopropyl ketone added rapidly to the monomers (Z)-1&3THF and (E)-1&3THF with a rate ratio of at least 14:1 in THF at -78 °C. Di-tert-butyl ketone added less rapidly to the less shielded (Z)-1 [but never to (E)-1]; this singly diastereoconvergent process was much more slowly reversible in THF.

Kinetics of α-(2,6-Dimethylphenl)vinyllithium: How To Control Errors Caused by Inefficient Mixing with Pairs of Rapidly Competing Ketones.

Kinetic studies are a suitable tool to disclose the role of tiny reagent fractions. The title compound 2 reacted in a kinetic reaction order of 0.5 (square root of its concentration) with an excess of the electrophiles ClSiMe3, 1-bromobutane (n-BuBr), or 1-iodobutane (n-BuI) at 32 °C in Et2O or in hydrocarbon solvents. This revealed that the tiny (NMR-invisible) amount of a deaggregated equilibrium component (presumably monomeric 2) was the reactive species, whereas the disolvated dimer 2 was only indirectly involved as a supply depot. Selectivity data (relative rate constants κobs) were collected from competition experiments with the faster reactions of 2 in THF and the addition reactions of 2 to carbonyl compounds. This provided the rate sequences of Et2C═O > dicyclopropyl ketone > t-Bu-C(═O)-Ph > diisopropyl ketone ≫ t-Bu2C═O > ClSiMe3 > n-BuI > n-BuBr ≈ (bromomethyl)cyclopropane (but t-Bu2C═O < ClSiMe3 in THF only) and also of cyclopropanecarbaldehyde > acetone ≥ t-Bu-CH═O. It is suggested that a deceivingly depressed selectivity (1 < κobs < kA/kB), caused by inefficient microscopic mixing of a reagent X with two competing substrates A and B, may become evident toward zero deviation from the correlation line of the usual inverse (1/T) linear temperature dependence of ln κobs.

Unusual traits of cis and trans-2,3-dibromo-1,1-dimethylindane on the way from 1,1-dimethylindene to 2-bromo-, 3-bromo-, and 2,3-dibromo-1,1-dimethylindene.

Do not rely on the widely accepted rule that vicinal, sp(3)-positioned protons in cyclopentene moieties should always have more positive (3) J NMR coupling constants for the cis than for the trans arrangement: Unrecognized exceptions might misguide one to wrong stereochemical assignments and thence to erroneous mechanistic conclusions. We show here that two structurally innocent-looking 2,3-dibromo-1,1-dimethylindanes violate the rule by means of their values of (3) J(cis) = 6.1 Hz and (3) J(trans) = 8.4 Hz. The stereoselective formation of the trans diastereomer from 1,1-dimethylindene was improved with the tribromide anion (Br3 (-)) as the brominating agent in place of elemental bromine; the ensuing, regiospecific HBr elimination afforded 3-bromo-1,1-dimethylindene. The addition of elemental bromine to the latter compound, followed by thermal HBr elimination, furnished 2,3-dibromo-1,1-dimethylindene, whose Br/Li interchange reaction, precipitation, and subsequent protolysis yielded only 2-bromo-1,1-dimethylindene.

How Microsolvation Numbers at Li Control Aggregation Modes, sp(2)-Stereoinversion, and NMR Coupling Constants (2)JH,H of H2C═C in α-(2,6-Dimethylphenyl)vinyllithium.

The title compound 4 is a trisolvated monomer 4&3THF in THF solution and dimerizes endothermically to form (4&THF)2 with a strongly positive (!) dimerization entropy in toluene as the solvent. In the absence of electron-pair donor ligands, 4 aggregates (>dimer) in hydrocarbon solutions. These results followed from the (13)C-α splitting patterns and the magnitudes of the one-bond (13)C,(6)Li NMR coupling constants in combination with lithiation NMR shifts as secondary NMR criteria. The rate constants of cis/trans sp(2)-stereoinversion could be measured on the (1)H NMR time scale in THF, in which solvent the preinversion lifetime is 0.24 s at 25 °C. This inversion proceeds according to the pseudomonomolecular, ionic mechanism with the typical, strongly negative pseudoactivation entropy. In a different mechanism, the lifetimes are much longer at 25 °C for the dimer (4&t-BuOMe)2 in toluene (ca. 2.5 min) and for donor-free, aggregated 4 in hexane solution (roughly 1 min). The olefinic interproton two-bond coupling constants (2)JH,H of the H2C═CLi part are proposed as an indicator of microsolvation at Li, because they were found to increase linearly with the "explicit" solvation of α-arylvinyllithiums by 0, 1, 2, and 3 electron-pair donor ligands.

Microsolvation and sp(2)-stereoinversion of monomeric α-(2,6-di-tert-butylphenyl)vinyllithium as measured by NMR.

The ß-unsubstituted title compound dissolves in THF as a uniformly trisolvated monomer, whereas it forms exclusively disolvated monomers in tert-butyl methyl ether, Et2O, TMEDA, or toluene with TMEDA (1.4 equiv). This was established at low temperatures through the observation of separated NMR signals for free and lithium-coordinated ligands and/or through the patterns and magnitudes of (13)C,(6)Li NMR coupling constants. An aggregated form was observed only with Et2O (2 equiv) in toluene as the solvent. The olefinic geminal interproton coupling constants of the H2C= part can be used as a secondary criterion to differentiate between these differently solvated ground-states (3, 2, or <2 coordinated ligands per Li). Due to a kinetic trisolvation privilege of THF, the cis/trans sp(2)-stereoinversion rates could be measured through analyses of (1)H NMR line broadening and coalescence only in THF as the solvent: The pseudomonomolecular (because THF-catalyzed), ionic mechanism is initialized by a C-Li bond heterolysis with the transient immobilization of one additional THF ligand, followed by stereoinversion of the quasi-sp(2)-hybridized carbanionic center in cooperation with a "conducted tour" migration of Li(+)(THF)4 along the α-aryl group within the solvent-separated ion pair.

Carbenoid-mediated nucleophilic "hydrolysis" of 2-(dichloromethylidene)-1,1,3,3-tetramethylindane with DMSO participation, affording access to one-sidedly overcrowded ketone and bromoalkene descendants(§).

2-(Dichloromethylidene)-1,1,3,3-tetramethylindane was "hydrolyzed" by solid KOH in DMSO as the solvent at ≥100 °C through an initial chlorine particle transfer to give a Cl,K-carbenoid. This short-lived intermediate disclosed its occurrence through a reversible proton transfer which competed with an oxygen transfer from DMSO that created dimethyl sulfide. The presumably resultant transitory ketene incorporated KOH to afford the potassium salt of 1,1,3,3-tetramethylindan-2-carboxylic acid (the product of a formal hydrolysis). The lithium salt of this key acid is able to acylate aryllithium compounds, furnishing one-sidedly overcrowded ketones along with the corresponding tertiary alcohols. The latter side-products (ca. 10%) were formed against a substantially increasing repulsive resistance, as testified through the diminished rotational mobility of their aryl groups. As a less troublesome further side-product, the dianion of the above key acid was recognized through carboxylation which afforded 1,1,3,3-tetramethylindan-2,2-dicarboxylic acid. Brominative deoxygenation of the ketones furnished two one-sidedly overcrowded bromoalkenes. Some presently relevant properties of the above Cl,K-carbenoid are provided in Supporting Information File 1.

Deuterium quantification through deuterium-induced remote 1H and 13C†NMR shifts.

Partial labeling by deuterium may be quantified through simple integrations of those (1)H (200 or 400 MHz) and (13)C (100.6 MHz) NMR resonances that are split into pairs by chemical shifts (n)Δ = δ(deuterated) - δ(nondeuterated) as induced by deuterium across n>2 chemical bonds. The relative intensities of the two components of a pair are shown to be influenced to practically equal degrees by relaxation effects, so that a deuterium fraction may be determined from (1)H and (13)C integral pairs at more remote molecular positions under the routine conditions of fast accumulative spectral acquisition.

Microsolvation and 13C-Li NMR coupling.

The empirical expression (1)J(CLi) = L[n(a + d)](-1) is proposed; it claims a reciprocal dependence of the NMR coupling constant (1)J((13)C, Li) in a C-Li compound on two factors: (i) the number n of lithium nuclei in bonding contact with the observed carbanion center and (ii) the sum (a + d) of the numbers a of anions and d of donor ligands coordinated at the Li nucleus that generates the observed (1)J(CLi) value. The expression was derived from integrations of separate NMR resonances of coordinated and free monodentate donor ligands (t-BuOMe, Et2O, or THF) in toluene solutions of dimeric and monomeric 2-(alpha-aryl-alpha-lithiomethylidene)-1,1,3,3-tetramethylindan at moderately low temperatures. This unusually slow ligand interchange is ascribed to steric congestion in these compounds, which is further characterized by measurements of nuclear Overhauser correlations and by solid-state structures of the dimers bearing only one donor per lithium atom (d = 1). Increasing microsolvation numbers d are also accompanied by typical changes of the NMR chemical shifts delta (positive for the carbanionic (13)C(alpha), negative for C(para) and p-H). The aforementioned empirical expression for (1)J(CLi) appears to be applicable to other cases of solvated monomeric, dimeric, or tetrameric C-Li compounds (alkyl, alkenyl, alkynyl, and aryl) and even to unsolvated (d approximately 0) trimeric, tetrameric, or hexameric organolithium aggregates, indicating that (1)J(CLi) might serve as a tool for assessing unknown microsolvation numbers. The importance of obtaining evidence about the (13)C NMR C-Li multiplet splitting of both the nonfluxional and fluxional aggregates is emphasized.

Unpaired spin densities from NMR shifts and magnetic anisotropies of pseudotetrahedral cobalt(II) and nickel(II) vinamidine bis(chelates).

The distribution of unpaired electron spin over all regions of the organic ligands was extracted from the large positive and negative 1H and 13C NMR paramagnetic shifts of the title complexes. Owing to benevolent line broadening and to very high sensitivities of approximately 254,000 and approximately 201,000 ppm/(unpaired electron spin) for Co(II) and Ni(II), respectively, at 298 K in these pseudotetrahedral bis(N,N'-chelates), spin transmission through the sigma- (and orthogonal pi)-bonding system of the ligands could be traced from the chelate ring over five to nine sigma bonds. Most of those "experimental" spin densities DeltarhoN (situated at the observed nuclei) agree reasonably well with quantum chemical DeltarhoDFT (DFT = density functional theory) values and provide an unsurpassed number of benchmark values for the quality of certain types of modern density functionals. The extraction of DeltarhoN became possible through the unequivocal separation of the nuclear Fermi contact shift components from the metal-centered pseudocontact shifts, which are proportional to the anisotropy Deltachi of the magnetic susceptibility: Experimental Deltachi values were obtained in solution from measured deuterium quadrupole splittings in the 2H NMR spectra of two deuterated model complexes and were found to be nonlinear functions of the reciprocal temperature. This provided the reliable basis for predicting metal-centered pseudocontact shifts for any position of a topologically well-defined ligand at varying temperatures. The related ligand-centered pseudocontact shifts were sought by using the criterion of their expected nonlinear dependence on the reciprocal temperature. However, their contributions could not be differentiated from other small effects close to the metal center; otherwise, they appeared to be smaller than the experimental uncertainties. The free activation energy of N-aryl rotation past a vicinal tert-butyl substituent in the Ni(II) vinamidine bis(N,N'-chelates) is DeltaG++(+74 degrees C) approximately 17.0 kcal/mol and past a vicinal methyl group DeltaG++(-6 degrees C) approximately 13.1 kcal/mol.

Carbenoid chain reactions through proton, deuteron, or bromine transfer from unactivated 1-bromo-1-alkenes to organolithium compounds.

The deceptively simple vinylic substitution reactions Alk2C=CA-Br + RLi --> Alk2C=CA-R + LiBr (A = H, D, or Br) occur via an alkylidenecarbenoid chain mechanism (three steps) without transition metal catalysis. 2-(Bromomethylidene)-1,1,3,3-tetramethylindan (Alk2C=CH-Br, 2a) is deprotonated (step 1) by phenyllithium (PhLi) to give the Br,Li-alkylidenecarbenoid Alk2C=CLi-Br (3). In the ensuing chain cycle, 3 and PhLi (step 2) form the observable alkenyllithium intermediate Alk2C=CLi-Ph that characterizes the carbenoid mechanism in Et2O and is able to propagate the chain (step 3) through deprotonation of 2a, furnishing carbenoid 3 and the product Alk2C=CH-Ph. The related 2-(dibromomethylidene)-1,1,3,3-tetramethylindan (Alk2C=CBr2, 2c) and methyllithium (MeLi) generate carbenoid 3 (step 1), which incorporates MeLi (step 2) to give Alk2C=CLi-CH3, which reacts with 2c by bromine transfer producing Alk2C=CBr-CH3 and carbenoid 3 (step 3). PhCCLi cannot carry out step 1, but MeLi can initiate (step 1) the carbenoid chain cycle (steps 2 and 3) of 2c with PhC[triple bond]CLi leading to Alk2C=CBr-C[triple bond]C-Ph. Reagent 2a may perform both proton and bromine transfer toward Alk2C=CLi-CH3, feeding two coupled carbenoid chain processes in a ratio that depends on the solvent and on a primary kinetic H/D isotope effect.

Carbenoid chain reactions: substitutions by organolithium compounds at unactivated 1-chloro-1-alkenes.

The deceptively simple "cross-coupling" reactions Alk(2)C=CA-Cl + RLi --> Alk(2)C=CA-R + LiCl (A = H, D, or Cl) occur via an alkylidenecarbenoid chain mechanism in three steps without a transition metal catalyst. In the initiating step 1, the sterically shielded 2-(chloromethylidene)-1,1,3,3-tetramethylindans 2a-c (Alk(2)C=CA-Cl) generate a Cl,Li-alkylidenecarbenoid (Alk(2)C=CLi-Cl, 6) through the transfer of atom A to RLi (methyllithium, n-butyllithium, or aryllithium). The chain cycle consists of the following two steps: (i) A fast vinylic substitution reaction of these RLi at carbenoid 6 (step 2) with formation of the chain carrier Alk(2)C=CLi-R (8), and (ii) a rate-limiting transfer of atom A (step 3) from reagent 2 to the chain carrier 8 with formation of the product Alk(2)C=CA-R (4) and with regeneration of carbenoid 6. This chain propagation step 3 was sufficiently slow to allow steady-state concentrations of Alk(2)C=CLi-Aryl to be observed (by NMR) with RLi = C6H5Li (in Et2O) and with 4-(Me3Si)C6H4Li (in t-BuOMe), whereas these chain processes were much faster in THF solution. PhC[triple bond]CLi cannot perform step 1, but its carbenoid chain processes with reagents 2a and 2c may be started with MeLi, whereafter LiC[triple bond]CPh reacts faster than MeLi in the product-determining step 2 to generate the chain carrier Alk(2)C=CLi-C[triple bond]CPh (8g), which completes its chain cycle through the slower step 3. The sterically congested products were formed with surprising ease even with RLi as bulky as 2,6-dimethylphenyllithium and 2,4,6-tri-tert-butylphenyllithium.