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.

"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.

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.

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.

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.