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

Chiral tertiary diamines in asymmetric synthesis.

Planar-Chiral Ferrocenes: Synthetic Methods and Applications

Enantioselective desymmetrisation of achiral epoxides

Indolizidine and quinolizidine alkaloids

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

Chiral akyl carbamates, bearing hetero-substituents in the or y-position, are deprotonated by sec-butyllithiunVlMEDA with efficient selection between the diastereotopic a-methylene protons. Depending on the substitution pattern and the reaction conditions, either steric or chelate effects act as stereodirecting devices. In several cases, this substrate-induced stereoselectivity is enhanced or is ovenidden by means of sec-butyl~~uml(-)-sparteine, which exhibits a strong preference for the abstraction of the pro4 proton. Altogether, an efficient and simple protocol for the stereoselective generation of synthetic equivalents for hetero-substituted a-oxy- alkanide synthons is presented. Following the ideas of chelate stabilization and of proximity effects (ref. 1) to be powerful devices for directed deprotonation, we discovered in 1979 the strongly activating influence of N,N- dialkylcarbamoyloxy groups in the removal of adjacent protons of weak CH-acids by alkyllithium (ref. 2,3). 2-Alkenyl (ref. 2), benzyl (ref. 4) and 2-akynyl (ref. 5) N,N-diisopropylcarbarnates are deprotonated with great ease by n-butyllithium at low temperatures leading to stable five-membered chelate complexes (ref. 6), which smoothly react with several types of electrophiles. As it can be concluded from mechanistic studies on related systems (ref. 7), a complex is formed from the carbamate ester, butyllithium and the complexing diamine, eg. N,N,N:N'-tetramethylethylendiam~e (TMEDA). The method was also successfully applied to aryl (ref. 8), 1-alkenyl (ref. 9) and 12-ahdienyl (ref. 10) carbarnates by Sniechs et aL, by Kocienski et al., and by our group. Even primary akyl carbamates, derived from saturated alkanols, which lack of further carbanion-stabilizing groups, are deprotonated by sec-butyllithiwdTMEDA (ref. 11). For the latter purpose we developed the 2,2,4,4-tetrarnethyl-1,3-oxazolidine-3-ylcarbonyl group (ref. 11). Here, a steric shielding, similar to that of the N,N-di-tert.-butylcarbamoyl group is wmanted, but the acid-labile amino aced moiety serves as the point of attack for the smooth deprotection to yield the racemic a-substituted alkanol. Overall, a very general protocol for the preparation of synthetic equivalents of a-hydroxy carbanions has been made possible. As we reported in 1990 (ref. ll), replacing the diarnine TMEDA by the naturally occurring alkaloid (-)-spamine, which was introduced to organometallic chemistry in 1968 by Nozaki and Noyori (ref. 12), an efficient selection between the enantiotopic protons of the methylene group in the carbamate takes place (Scheme I). Obviously, the proton transfer in the complex, preformed (ref. 7) from the akyl carbamate, sec-butyllithium and (-)-sparteine, proceeds intramolecularly, resulting in a high difference in AW of the competing diastereomorphic transition states. Since the formed ion pairs are configurationally stable at the reaction conditions, trapping of these leads to substitution products with 2 95 % ee. The enantiomeric

S. Kolczewski

Papers

Enantioselective synthesis via sparteine-induced asymmetric deprotonation

Heteroatom-directed lithiations of chiral alkyl carbamates: A powerful tool for enantioselective synthesis

Enantioselective Synthesis via Sparteine-Induced Asymmetric Deprotonation

Heteroatom-Directed Lithiations of Chiral Alkyl Carbamates: A Powerful Tool for Enantioselective Synthesis