Solution Structures of the Mixed Aggregates Derived from Lithium Acetylides and a Camphor-Derived Amino Alkoxide

Abstract

Low-temperature (6)Li, (13)C, and (15)N NMR spectroscopies reveal that mixtures of lithium cyclopropylacetylide or lithium phenylacetylide (RCCLi) and a vicinal amino alkoxide derived from camphor (R*OLi) in THF/pentane afford an asymmetric (RCCLi)(3)(R*OLi) mixed tetramer and a C(2)-symmetric (RCCLi)(2)(R*OLi)(2) mixed tetramer depending on the stoichiometries. The corresponding (RCCLi)(R*OLi)(3) mixed tetramer is not observed. R*OLi-mediated additions of PhCCLi to benzaldehyde proceed with up to an 8:1 enantiomeric ratio that depend on both the choice of R*OLi and the PhCCLi/R*OLi stoichiometries. The results are considered in light of a previously proposed mechanism for the 1,2-addition to a trifluoromethyl ketone.

Lobocyclamide B from Lyngbya confervoides. Configuration and Asymmetric Synthesis of β-Hydroxy-α-amino Acids by (−)-Sparteine-Mediated Aldol Addition

“…Although several asymmetric (−)-sparteine-mediated reactions have been rationalized by mechanisms involving enantioselective removal of enantiotopic protons and alkylation of the resultant “chiral” sp 3 hybridized anions, − this mechanism seems unlikely in the present case as a stabilized enolate is generated from 4 and expected to adopt planar sp 2 enolate geometry. The low polarity of the solvent and ability of C 2 symmetric (−)-sparteine to coordinate the lithium counterion suggests another mechanism based on π-face selection mediated by a complex chiral amine-coordinated lithium enolate rather than a chiral base mechanism . Such an alternate reaction pathway is consistent with the observed reversal of diastereoselectivity in the aldol addition of lithium enolate of 4 in the presence of (−)-sparteine, together with induction of a consistent level of asymmetry in the product that is only weakly dependent upon the structure of the aldehyde .…”

Structure of Mixed Alkyllithium/Lithium Alkoxide Aggregates in Ethereal Solvents. Insights from Combined QM/MM Molecular Dynamics Simulations

“…Experimental studies for n-BuLi, n-BuOLi, and tert-BuOLi in THF solution have been reported by McGarrity et al 1,71 The alkyl aggregates exist as a dimer/tetramer equilibrium, whereas mixed alkyl/alkoxide aggregates seem to prefer tetrameric forms. Collum and co-workers 72,73 have reported another study with related systems in which they show that symmetric 2:2 aggregates are the major product in stoichiometric solutions though nonsymmetric aggregates are detected, too. From the theoretical point of view, Pratt et al 41 have reported a study confirming the higher stability of tetramers over dimers.…”

Organolithiums in Enantioselective Additions to π* and σ* Carbon-Oxygen Electrophiles

“…-78°C. 54 Variations of the alkoxide-to-acetylide ratio revealed changes in the sense of enantioselectivity, and the highest enantioselectivity (78% ee) was observed at a ratio of 1:3.…”