The increasing demand for stable isotopically labeled compounds has led to an increased interest in H/D-exchange reactions at carbon centers. Today deuterium-labeled compounds are used as internal standards in mass spectrometry or to help elucidate mechanistic theories. Access to these deuterated compounds takes place significantly more efficiently and more cost effectively by exchange of hydrogen by deuterium in the target molecule than by classical synthesis. This Review will concentrate on the preparative application of the H/D-exchange reaction in the preparation of deuterium-labeled compounds. Advances over the last ten years are brought together and critically evaluated.

The renaissance of H/D exchange.

Organolithium chemistry is broadly integrated and widely applied in studies that bridge inorganic, physical, organic, and theoretical chemistry.1 Reactions with organolithium species as reagents, reactants, or intermediates are so well established that organolithiums are the most widely used organometallics in contemporary organic chemistry. Deprotonative lithiations are commonly used to generate enolates, ylides, and dipole-stabilized, localized sp2 or sp or delocalized carbanions as reactive intermediates for diverse applications.2 A sequence in which a proton on a tetrahedral carbon is replaced by a substituent begins with removal of a proton from 1 to give the formally sp3 organolithium 2. Reaction of 2 with an electrophile subsequently provides 3.

Regioselective, Diastereoselective, and Enantioselective Lithiation−Substitution Sequences: Reaction Pathways and Synthetic Applications

Asymmetric catalysts, either chemical or biological, effect the reactions of enantiomeric substrates at unequal rates, allowing for the kinetic resolution of racemates. The asymmetric reaction of chirally labile compounds capable of undergoing in situ racemization can, in principle, afford a single stereoisomer in 100% ee and in 100% yield. The second-order reaction provides a powerful tool for the stereoselective synthesis of chiral compounds, as exemplified by, among others, the biochemical hydrolysis of hydantoins or oxazolinones and microbial reductions or BINAP–Ru(II) catalyzed hydrogenation of certain α-substituted β-keto esters. Such transformations are characterized by the presence of parallel reactions interrelated by the stereoinversion of the enantiomeric substrates. The efficiency is decisively affected by the kinetic parameters, particularly the relative rates of the stereoinversion and reaction as well as the intrinsic stereochemical parameters of the catalyst and substrate. Such stereoselec...

Stereoselective Organic Synthesis via Dynamic Kinetic Resolution

https://pubs.rsc.org/en/Content/ArticlePDF/2017/CC/C7CC01254C

Stereospecific functionalizations and transformations of secondary and tertiary boronic esters

Chiral tertiary diamines in asymmetric synthesis.

Chiral Lithium‐1‐oxyalkanides by Asymmetric Deprotonation; Enantioselective Synthesis of 2‐Hydroxyalkanoic Acids and Secondary Alkanols

Chirale Lithium-1-oxyalkanide durch asymmetrische Deprotonierung; enantioselektive Synthese von 2-Hydroxyalkansäuren und sekundären Alkanolen

Stereodivergent Enantioselective Synthesis by Exploiting Unusually Large Kinetic H/D Isotope Effects on Deprotonation

The deprotonation of achiral akyl carbamates with sec-butyllithium/(-)sparteine proceeds with a high degree of chiral recognition to form substituted alcohols usually with 2 95 76 ee after reaction with electrophiles followed by deprotection. The stereoselection is kinetically controlled and a qualitative transition state model is proposed. Some studies, concerning the discrimination between both enantiomers of stereogenic akyl carbamates and on its utilization for the kinetic resolution are reported. The competition between external and internal competition was investigated in few cases. Finally, we disclose a short report on the enantioselective electrophilic substitution of 1-methylindene; here the origin of stereoselection is an thermodynamically driven epimerization of diastereomeric indenyllithium sparteine complexes. INTRODUCTION Many methods for the enantioselective synthesis are based on the selection of a chiral reagent or of a reagent under the influence of a chiral catalyst between the enantiotopic faces of a trigonal carbon moiety. In only a few cases, an efficient selection between enantiotopic groups at a tetragonal carbon atom has been verified (Scheme 1). Scheme 1 Select ion between Enant iotopic Faces Select ion between Enant io top ic Groups Widely used in synthesis Impressive examples of the latter type have been reported (ref. 1) independently by the research groups of Koga and Simpkins: CSubstituted cyclohexanones are deprotonated by chiral lithium amides, derived from

Enantioselective synthesis via sparteine-induced asymmetric deprotonation

The title compound was synthesized with 98% ee by enantioselective lithiation and methylation of 1-dodecanol, employing a new protection/activation method for primary alcohols, followed by asymmetric deprotonation of the carbamate

Folker Hintze

Papers

Chiral Lithium‐1‐oxyalkanides by Asymmetric Deprotonation; Enantioselective Synthesis of 2‐Hydroxyalkanoic Acids and Secondary Alkanols

Chirale Lithium-1-oxyalkanide durch asymmetrische Deprotonierung; enantioselektive Synthese von 2-Hydroxyalkansäuren und sekundären Alkanolen

Stereodivergent Enantioselective Synthesis by Exploiting Unusually Large Kinetic H/D Isotope Effects on Deprotonation

Enantioselective synthesis via sparteine-induced asymmetric deprotonation

Enantioselective synthesis of (S)-1-methyldodecyl acetate, a pheromone of Drosophila mulleri, via (−)-sparteine-assisted deprotonation of 1-dodecanol