Hans J. Reich

Selenium stabilized carbanions. Preparation of .alpha.-lithio selenides and applications to the synthesis of olefins by reductive elimination of .beta.-hydroxy selenides and selenoxide syn elimination

The deprotonation of several alkyl aryl selenides with lithium amide bases has been studied. The kinetic acidity of methyl m-trifluoromethylphenyl selenide was found to be 1 / 3 3 that of the sulfur analogue. The introduction of a m-trifluoromethyl substituent into methyl phenyl sulfide increased the kinetic acidity by a factor of 22.4. A variety of @-hydroxy selenides have been prepared by the reduction of a-phenylseleno ketones and the addition of a-lithio selenides (prepared by deprotonation of benzyl phenyl selenide, bis(phenylseleno)methane, methoxymethyl m-trifluoromethylphenyl selenide, and phenylselenoacetic acid, and by n-butyllithium cleavage of bis(pheny1seleno)methane) to carbonyl compounds. These @-hydroxy selenides are converted to olefins on treatment with rnethanesulfonyl chloride and triethylamine. This reductive elimination proceeds exclusively or predominantly with anti stereochemistry. Simple olefins, styrenes, cinnamic acids, vinyl ethers, and vinyl selenides have been prepared using this technique. Attempts to carry out the syn reductive elimination of @-hydroxy selenoxides or related compounds have not been successful. a-Li thio selenides can also be alkylated, and the derived selenides converted to olefins by selenoxide syn elimination. The unique chemical properties of organoselenium compounds have been successfully exploited for a variety of olefin-forming proce~ses .~ The synthetic utility of these reactions is amplified by the capacity of the selenium function to serve as an activating group for carbon-carbon bond formation, in addition to its role in the introduction of the double bond. The preparation, properties, and reactions of a-lithio selenides will be the subject of this paper. The following paper4 describes our work on the chemistry of a-lithio selenoxides. All of the standard procedures for the preparation of alkyllithium reagents are, in principle, applicable to the preparation of a-lithio selenides. In practice, only two methods have been used widely: the n-butyllithium cleavage of selenoacetals and -ketals5s6 and the deprotonation of selenides using strong b a s e ~ . l ~ % ~ . ~ The former procedure developed by Seebach and c o w ~ r k e r s ~ . ~ ~ , ~ is generally applicable to systems 1 where Rl and Rl can be hydrogen or an alkyl or aryl group. The resulting lithium reagents 2 have high nucleophilicity; they react with

What’s Going on with These Lithium Reagents?

This Perspective describes a series of research projects that led the author from an interest in lithium reagents as synthetically valuable building blocks to studies aimed at understanding the science behind the empirical art developed by synthetic chemists trying to impose their will on these reactive species. Understanding lithium reagent behavior is not an easy task; since many are mixtures of aggregates, various solvates are present, and frequently new mixed aggregates are formed during their reactions with electrophiles. All of these species are typically in fast exchange at temperatures above -78 °C. Described are multinuclear NMR experiments at very low temperatures aimed at defining solution structures and dynamics and some kinetic studies, both using classic techniques as well as the rapid inject NMR (RINMR) technique, which can in favorable cases operate on multispecies solutions without the masking effect of the Curtin-Hammett principle.

Silyl ketone chemistry : Preparation and reactions of unsaturated silyl ketones

Abstract A series of silyl ketones has been prepared by appropriate manipulation of ⇌-silylated allenol ethers. Among the compounds prepared were alkenyl, alkynyl and acyl silyl ketones. The spectroscopic properties of representative members of these classes of compounds have been measured, and some of their chemical reactions studied Diels-Alder cycloadditions of vinyl and alkynyl silyl ketones proceed smoothly, and can be used to prepare new types of silyl ketones. Several examples of reactions with organolithium reagents are given; the process can be an effective route to enol silyl ethers with absolute regiochemical control.

Nanowires Enabling Signal‐Enhanced Nanoscale Raman Spectroscopy

Silicon nanowires grown by the vapor-liquid-solid (VLS) mechanism catalyzed by gold show gold caps (droplets) approximately 20-500 nm in diameter with a half spherical towards almost spherical shape. These gold droplets are well suited to exploit the surface-enhanced Raman scattering (SERS) effect and could be used for tip-enhanced Raman spectroscopy (TERS). The gold droplet of a nanowire attached to an atomic force microscopy (AFM) tip could locally enhance the Raman signal and increase the spatial resolution. Used as a SERS template, an ensemble of self-organizing nanowires grown bottom up on a silicon substrate could allow highly sensitive signal-enhanced Raman spectroscopy of materials that show a characteristic Raman signature. A combination of a nanowire-based TERS probe and a nanowire-based SERS substrate promises optimized signal enhancement so that the detection of highly dilute species, even single molecules or single bacteria or DNA strands, and other soft matter is within reach. Potential applications of this novel nanowire-based SERS and TERS solution lie in the fields of biomedical and life sciences, as well as security and solid-state research such as silicon technology.

Rigid cyclophanes that illustrate stereochemical principles

Abstract All of the point groups common to organic chemistry except two are illustrated by known compounds that are rigid [2.2]paracyclophane derivatives. Examples are given of transannular directing effects by acetyl, nitro, and acetoxyl substituents attached to [2.2]paracyclophane. In bromination or chloromethylation, proton loss of a sigma complex is rate-determining, and the oxygens already in the molecule remove the proton being substituted. The synthesis of [2.2.2](1,2,4)cyclophane and [3.2.2](1,2,5)cyclophane, and their unusual chemical properties are described. Transannular hydride shifts out of methyl groups due to proximity effects are reported. Torsional racemizations and epimerizations of [2.2]paracyclophane derivatives are reviewed. The diradical intermediates formed have been intercepted by either H· donors, or by addition to substituted olefins. To account for the stereochemical course of addition and substitution reactions in the side-chains of [2.2]- and [4,2]paracyclophanes, new types of bridged carbonium ions are suggested. Conformational equilibria in the four-carbon side-chain of [4.2]paracyclophane derivatives are discussed.

Reactivity of the Triple Ion and Separated Ion Pair of Tris(trimethylsilyl)methyllithium with Aldehydes : A RINMR Study

Low-temperature rapid-injection NMR (RINMR) experiments were performed on tris(trimethylsilyl)methyllithium. In THF/Me2O solutions, the separated ion (1S) reacted faster than can be measured at -130 degrees C with MeI and substituted benzaldehydes (k >/= 2 s -1), whereas the contact ion (1C) dissociated to 1S before reacting. Unexpectedly, the triple ion reacted faster with electron-rich benzaldehydes relative to electron-deficient ones. The addition of HMPA had no effect on the rate of reaction of the triple ion with p-diethylaminobenzaldehyde, and the immediate product of the reaction was the HMPA-solvated separated ion 1S, with the Peterson product forming only slowly. Thus, the aldehyde is catalyzing the dissociation of the triple ion. HMPA greatly decelerated the reaction of 1S (<10 -10), providing an estimate of the Lewis acid activating effect of a THF-solvated lithium cation in an organolithium addition to an aldehyde.

“Stable” selenenic acids

Abstract Two of the stable selenenic acids reported in the literature are actually other materials.

Mechanism of the Lithium-Tellurium, Lithium-Iodine and Lithium-Mercury Exchange Reactions: Hypervalent Tellurium and Iodine Ate Complexes

Abstract The lithium-tellurium exchange is among the fastest of the lithium-metalloid exchange reactions; only the lithium-iodine exchange is slightly faster. Tellurium, iodine and mercury ate complexes are formed when diphenyl telluride, iodobenzene or diphenylmercury are treated with phenyllithium in THF. The mechanism of the lithium-tellurium exchange, (as well as the Li/I and Li/Hg) proceeds through such ate complex intermediates. Monomeric phenyllithium is the reactive form of phenyllithium (the dimer does not participate detectably). Tetraphenyltellurium and triphenyliodine also form hypervalent ate complexes under suitable conditions.

Mechanistic studies of the lithium enolate of 4-fluoroacetophenone: rapid-injection NMR study of enolate formation, dynamics, and aldol reactivity.

Lithium enolates are widely used nucleophiles with a complicated and only partially understood solution chemistry. Deprotonation of 4-fluoroacetophenone in THF with lithium diisopropylamide occurs through direct reaction of the amide dimer to yield a mixed enolate-amide dimer (3), then an enolate homodimer (1-Li)(2), and finally an enolate tetramer (1-Li)(4), the equilibrium structure. Aldol reactions of both the metastable dimer and the stable tetramer of the enolate were investigated. Each reacted directly with the aldehyde to give a mixed enolate-aldolate aggregate, with the dimer only about 20 times as reactive as the tetramer at -120 °C.

Solution Structures of Lithium Enolates of Cyclopentanone, Cyclohexanone, Acetophenones, and Benzyl Ketones. Triple Ions and Higher Lithiate Complexes

Multinuclear NMR spectroscopic studies at low temperature (-110 to -150 degrees C) revealed that lithium p-fluorophenolate and the lithium enolates of cyclohexanone, cyclopentanone and 4-fluoroacetophenone have tetrameric structures in THF/Et(2)O and THF/Et(2)O-HMPA by study of the effects of the addition of HMPA. The Z and E isomers of the lithium enolate of 1,3-bis-(4-fluorophenyl)-2-propanone (5F-Li) show divergent behavior. The Z isomer is completely dimeric in pure diethyl ether, and mostly dimeric in 3:2 THF/ether, where monomer could be detected in small amounts. TMTAN and PMDTA convert Z-5F-Li to a monomeric amine complex, and HMPA converts it partially to monomers, and partially to lithiate species (RO)(2)Li(-) and (RO)(3)Li(2-). Better characterized solutions of these lithiates were prepared by addition of phosphazenium enolates (using P4-(t)Bu base) to the lithium enolate in 1:1 ratio to form triple ion (RO)(2)Li(-) P4H(+), or 2:1 ratio to form the higher lithiate (RO)(3)Li(2-) (P4H(+))(2)) (quadruple ions). The E isomer of 5F-Li is also dimeric in 3:2 THF/Et(2)O solution, but is not detectably converted to monomer either by PMDTA or HMPA. In contrast to Z-5F-Li, the E isomer is tetrameric in diethyl ether even in the presence of excess HMPA. Thus for the two isomers of 5F six different enolate structures were characterized: tetramer, dimer, CIP-monomer, SIP-monomer, triple ion, and quadruple ion.