123387-66-6Relevant articles and documents
The barrier to enantiomerization of N-Boc-2-lithiopyrrolidine: The effect of chiral and achiral diamines
Yousaf, Taher I.,Williams, Roger L.,Coldham, Iain,Gawley, Robert E.
, p. 97 - 98 (2008)
(-)-Sparteine and TMEDA dramatically lower both enthalpy and entropy of activation for the barrier to enantiomerization of N-Boc-2-lithiopyrrolidine in diethyl ether, whereas N,N′-diisopropylbispidine has little effect; the entropy of activation for enantiomerization is zero in the presence of TMEDA and slightly negative in the presence of sparteine; these data suggest a subtle change in mechanism of enantiomerization in the presence of TMEDA and sparteine. The Royal Society of Chemistry.
Dynamic resolution of N-alkyl-2-lithiopyrrolidines with the chiral ligand (-)-sparteine
Coldham, Iain,Dufour, Samuel,Haxell, Thomas F.N.,Vennall, Graham P.
, p. 3205 - 3220 (2005)
A selection of 2-lithiopyrrolidines with different N-alkyl-substituents were prepared and tested for their dynamic resolution in the presence of the chiral ligand (-)-sparteine. Good yields of the electrophile-quenched products were obtained with enantiomer ratios up to 85:15 using branched N-alkyl derivatives. The major product was shown to have the opposite absolute configuration compared with that obtained in the asymmetric deprotonation of N-Boc-pyrrolidine with (-)-sparteine. The enantioselectivity arises from a dynamic thermodynamic resolution in which the minor diastereomeric complex reacts faster with the electrophile.
An experimental and computational study of the enantioselective lithiation of N-Boc-pyrrolidine using sparteine-like chiral diamines
O'Brien, Peter,Wiberg, Kenneth B.,Bailey, William F.,Hermet, Jean-Paul R.,McGrath, Matthew J.
, p. 15480 - 15489 (2004)
The enantioselective lithiation of N-Boc-pyrrolidine using sec-butyllithium and isopropyllithium in the presence of sparteine-like diamines has been studied experimentally and computationally at various theoretical levels through to B3P86/6-31G*. Of the (-)-cytisine-derived diamines (N-Me, N-Et, N-nBu, N-CH2t-Bu, N-iPr) studied experimentally, the highest enantioselectivity (er 95:5) was observed with the least sterically hindered N-Me-substituted diamine, leading to preferential removal of the pro-R proton i.e., opposite enantioselectivity to (-)-sparteine. The experimental result with the N-Me-substituted diamine correlated well with the computational results: at the B3P86/6-31G* level, the sense of induction was correctly predicted; the lowest energy complex of isopropyllithium/diamine/N-Boc-pyrrolidine also had the lowest activation energy (ΔH? = 11.1 kcal/mol, ΔG? = 11.5 kcal/mol) for proton transfer. The computational results with the N-iPr-substituted diamine identified a transition state for proton transfer with activation energies of ΔH? = 11.7 kcal/mol and ΔG? = 11.8 kcal/mol (at the B3P86/6-31G* level). Although comparable to (-)-sparteine and the N-Me-substituted diamine, these ΔH? and ΔG? values are at odds with the experimental observation that use of the N- iPr-substituted diamine gave no product. It is suggested that steric crowding inhibits formation of the prelithiation complex rather than increasing the activation enthalpy for proton transfer in the transition state. Three other ligands (N-H and O-substituted as well as a five-membered ring analogue) were studied solely using computational methods, and the results predict that the observed enantioselectivity would be modest at best.
Enantioselective deprotonation: The structure and reactivity of an unsymmetrically complexed isopropyllithium/sparteine/Et2O dimer
Gallagher, Donald J.,Kerrick, Shawn T.,Beak, Peter
, p. 5872 - 5873 (1992)
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Evaluation of a sparteine-like diamine for asymmetric synthesis
Harrison,O'Brien,Porter,Smith
, p. 1202 - 1203 (2001)
Evaluation of a sparteine-like diamine indicates that only the ABC rings of sparteine are required for high enantioselectivity in the lithiation-substitution of N-Boc pyrrolidine.
Dynamic kinetic resolution of N-Boc-2-lithiopyrrolidine
Coldham, Iain,Patel, Jignesh J.,Sanchez-Jimenez, Graciela
, p. 3083 - 3085 (2005)
Asymmetric substitution of the organolithium derived either from N-Boc-2-tributylstannylpyrrolidine by tin-lithium exchange or from N-Boc-pyrrolidine by deprotonation occurs in the presence of a commercially available chiral diamine ligand with high levels of enantioselectivity by a dynamic kinetic resolution pathway. The Royal Society of Chemistry 2005.
Silylarene Hydrogenation: A Strategic Approach that Enables Direct Access to Versatile Silylated Saturated Carbo- and Heterocycles
Wiesenfeldt, Mario P.,Knecht, Tobias,Schlepphorst, Christoph,Glorius, Frank
supporting information, p. 8297 - 8300 (2018/06/29)
We report a method to convert readily available silylated arenes into silylated saturated carbo- and heterocycles by arene hydrogenation. The scope includes alkoxy- and halosilyl substituents. Silyl groups can be derivatized into a plethora of functionalities and find application in organic synthesis, materials science, and pharmaceutical, agrochemical, and fragrance research. However, silylated saturated (hetero-) cycles are difficult to access with current technologies. The yield of the hydrogenation depends on the amount of the silica gel additive. This silica effect also enables a significant improvement of a previously disclosed method for the hydrogenation of highly fluorinated arenes (e.g., to all-cis-C6H6F6).
The First Modular Route to Core-Chiral Bispidine Ligands and Their Application in Enantioselective Copper(II)-Catalyzed Henry Reactions
Scharnagel, Dagmar,Müller, Andreas,Prause, Felix,Eck, Martin,Goller, Jessica,Milius, Wolfgang,Breuning, Matthias
supporting information, p. 12488 - 12500 (2015/08/25)
The first modular and flexible synthesis of core-chiral bispidines was achieved by using an "inside-out" strategy. The key intermediate, a NBoc-activated bispidine lactam, was constructed in enantiomerically pure form from a chirally modified β-amino acid and 2-(acetoxymethyl)acrylonitrile in just five steps and good 48% yield. A simple addition-reduction protocol permitted a highly endo-selective introduction of substituents and, thus, a fast and variable access to 2-endo-substituted and 2-endo,N-fused bi- and tricyclic bispidines. The new diamines were evaluated as the chiral ligands in asymmetric Henry reactions. Excellent enantioselectivities of up to 99% ee and good diastereomeric ratios of up to 86:14 were reached with a copper(II) complex modified by a 2-endo,N-(3,3-dimethylpyrrolidine)-annelated bispidine. Its performance is superior to that of the well-known bispidines (-)-sparteine and the (+)-sparteine surrogate.
Silylated pyrrolidines as catalysts for asymmetric Michael additions of aldehydes to nitroolefins
Husmann, Ralph,Joerres, Manuel,Raabe, Gerhard,Bolm, Carsten
supporting information; experimental part, p. 12549 - 12552 (2011/02/22)
Silicon can! A convenient synthesis of enantiopure (S)-2- (diphenylmethylsilyl)pyrrolidine is described and its organocatalytic activity in asymmetric Michael reactions is demonstrated (see scheme). By using 10 mol% of this novel organocatalyst, the addition of aldehydes to nitroolefins affords products with high stereoselectivities (d.r. 97:3 and e.r. 95:5) in yields up to 99%.
