137496-67-4

Upstream product

• 75-77-4 chloro-trimethyl-silane 
• 86953-79-9 tert-butyl pyrrolidine-1-carboxylate 
• 154874-88-1 (±)-tert-butyl-2-phenylpyrrolidine-1-carboxylate 
• 75400-57-6 N-(tert-butoxycarbonyl)-2-(trimethylsilyl)pyrrole 
• 24424-99-5 di-tert-butyl dicarbonate 
• 870-46-2 t-butoxycarbonylhydrazine 
• 1070-19-5 N-(tert-butyloxycarbonyl) azide 

Downstream Products

• 154344-51-1 2,5-bis(trimethylsilyl)-N-benzylpyrrolidine 

Relevant academic research and scientific papers

Silylarene Hydrogenation: A Strategic Approach that Enables Direct Access to Versatile Silylated Saturated Carbo- and Heterocycles

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 search for an easily-prepared sparteine surrogate

(?)-Sparteine has proven itself to be a highly efficient and versatile ligand. However, in recent years it has become difficult to source. In addition the (+)-enantiomer is also not readily available. Here we report a suite of chiral diamines as potential sparteine surrogates. Chiral trans-1,2-diaminocyclohexane is commercially available in both enantiomeric forms and the parent structure can be easily modified. New (and known) chiral diamines have been tested in the asymmetric silylation of N-Boc pyrrolidine, N-Boc piperidine, the α-alkylation of dimethylhydrazones and in the rearrangement of meso-epoxides. While none match the selectivity of the highly evolved natural product, there is certainly potential for this class of diamine ligands to perform in a diverse set of asymmetric transformations.

The First Modular Route to Core-Chiral Bispidine Ligands and Their Application in Enantioselective Copper(II)-Catalyzed Henry Reactions

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.

Evaluation of the chiral DIANANE backbone as ligand for organolithium reagents

Novel endo,endo-2,5-diaminonorbonane-derived tertiary C2- symmetrical diamines were synthesized via the one-pot reductive amination of enantiomerically pure norbornane-2,5-dione. These ligands were applied to various catalytic reactions such as asymmetric deprotonation, asymmetric bromine-lithium exchange, and enantioselective addition of aryl- and allkylithium reagents to aromatic aldimines. Copyright

Silylated pyrrolidines as catalysts for asymmetric Michael additions of aldehydes to nitroolefins

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%.

Diamine-free lithiation-trapping of N-Boc heterocycles using s-BuLi in THF

A diamine-free protocol for the s-BuLi-mediated lithiation-trapping of N-Boc heterocycles has been developed. In the optimized procedure, lithiation is accomplished using s-BuLi in THF at -30 °C for only 5 or 10 min. Subsequent electrophilic trapping or transmetalation-Negishi coupling delivered a range of functionalized pyrrolidines, imidazolidines, and piperazines in 43-83% yield.

Catalytic asymmetric synthesis of piperidines from pyrrolidine: Concisesynthesis of L-733,060

Catalytic asymmetric deprotonation-aldehyde trapping-ring expansion from a 5- to a 6-ring delivers a concise route to each stereoisomer of -hydroxy piperidines starting from W-Boc pyrrolidine. The methodology is utilized in a 5-step catalytic asymmetric synthesis of the neorokinin-1 receptor antagonist, (+)-L-733,060.

The barrier to enantiomerization of N-Boc-2-lithiopyrrolidine: The effect of chiral and achiral diamines

(-)-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.

On the two-ligand catalytic asymmetric deprotonation of N-Boc pyrrolidine: Probing the effect of the stoichiometric ligand

(Chemical Equation Presented) To map out the stoichiometric ligand requirements in the two-ligand catalytic asymmetric deprotonation of N-Boc pyrrolidine, 24 different ligands have been evaluated; the highest enantioselectivity (90:10 er) was obtained by using s-BuLi in the presence of 0.3 equiv of (-)-sparteine and 1.3 equiv of a cyclohexanediamine-derived ligand.

A new sparteine surrogate for asymmetric deprotonation of N-Boc pyrrolidine

(Chemical Equation Presented) The s-BuLi complex of a cyclohexane-derived diamine is as efficient as s-BuLi/(-)-sparteine for the asymmetric deprotonation of N-Boc pyrrolidine. This is the first example of high enantioselectivity using a non-sparteine-like diamine in such reactions. The ( S, S)-diamine is a useful (+)-sparteine surrogate and was utilized in short syntheses of (-)-indolizidine 167B and an intermediate for the synthesis of the CCK antagonist (+)-RP 66803.