Application of the addition of triorganozincates to N-(tert-butanesulfinyl)imines to the enantioselective synthesis of α-amino acids

Highly enantiomerically enriched N-protected α-amino acids can be easily prepared from optically pure N-(tert-butanesulfinyl)imines by a four-step sequence involving: diastereoselective addition of a triorganozincate to the imine, removal of the sulfinyl group, benzoylation of the nitrogen atom of the obtained primary amine and oxidation of one of the substituents on the carbon atom α to the nitrogen. Using the same configuration in the sulfinyl chiral auxiliary, amino acids with the (R) or the (S) configuration can be prepared by choosing the proper combination of imine and organozincate. α,α-Disubstituted α-amino esters with high optical purity can also be prepared by the diastereoselective addition of trialkylzincates to α-imino esters.     

Native silica nanoparticle catalyzed anti-Markovnikov addition of thiols to inactivated alkenes and alkynes: a new route to linear and vinyl thioethers

A new route for the synthesis of linear and vinyl thioethers has been demonstrated using bare silica nanoparticle as catalyst at room temperature under solvent-free conditions. The catalyst can be reused up to six times without loss of catalytic activity.     

The first ionic liquid-promoted three-component coupling strategy for an expeditious synthesis of β-nitrocarbonitriles/thiocyanates

A novel and convenient three-component coupling reaction of nitromethane, aromatic aldehydes and trimethylsilyl cyanide (TMSCN) or ammonium thiocyanate has been developed for an expeditious synthesis of β-nitrocarbonitriles or β-nitrothiocyanates, respectively, via C-C and C-S bond-forming reactions. The synthetic protocol strategically involves a one-pot sequential Henry reaction and a Michael addition efficiently promoted by the same ionic liquid [bmim]OH. The main advantages of the present approach include the use of inexpensive simple substrates and an ionic liquid as an efficient reaction promoter for the mild synthesis in a one-pot procedure.     

Diastereoselective, large-scale synthesis of β-amino acids via asymmetric aza-Michael addition as α2δ ligands for the treatment of generalized anxiety disorder and insomnia

Scalable synthetic routes to β-amino acids 1 and 2 are presented. These two compounds, which bind to the α2δ subunit of calcium channels and have important medical applications, have been prepared on kilogram scale in our pilot plant through an improved synthesis that avoids the use of highly toxic reagents and hazardous chemistry present in the original Medicinal Chemistry route. The two chiral centers are introduced through asymmetric Michael and aza-Michael reactions with excellent diastereoselectivity.     

Ring-closing metathesis as a tool for the efficient preparation of chiral spirocyclic ethers from homoallylic alcohols

The preparation of chiral spirocyclic ethers via allylic etherification/olefin metathesis of homoallylic alcohols is investigated. This reaction sequence transforms the enantiopure substrate alcohols, synthesized by a one-pot asymmetric rhodium-catalyzed conjugate addition/metal-mediated allylation procedure, into the desired spiro ethers with full conversions and in excellent isolated yields. The synthetic sequence provides an efficient means for a rapid construction of functionalized spiro ethers in a stereoselective manner.     

Enantioselective synthesis of (−)-lasubine II

A highly enantioselective synthesis of lythraceae alkaloid lasubine II has been achieved using organo-catalyzed Mannich reaction, Maruoka allylation, and aza-Michael addition as the key steps.     

Organocatalytic conjugate addition of 1-bromonitroalkanes to α,β-unsaturated aldehydes: synthesis of nitrocyclopropanes

A variety of secondary amines were studied as the catalyst in the conjugate addition of 1-bromonitromethane to α,β-unsaturated aldehydes. Proline was identified as the best catalyst for this reaction. MeOH/AcONa system was found to provide much better yields than CHCl₃/Et₃N system reported before. Good yields of nitrocyclopropane products were obtained with a variety of β-aryl acroleins. Several substituted 1-bromonitromethanes were also examined in the reaction. Both 1-bromonitroethane and 1-phenyl-1-bromonitromethane gave the corresponding nitrocyclopropanes in good yields. The diastereoselectivity of the reaction was strongly affected by the steric hindrance of 1-bromonitroalkanes.     

Unexpected reactivity for the RAFT copolymerization of oligo(ethylene glycol) methacrylates

Homo‐ and copolymers of di(ethylene glycol) methyl ether methacrylate (DEGMA) and oligo(ethyleneglycol) methyl ether methacrylate (OEGMA₁₁₀₀) were synthesized with various chain lengths via reversible addition fragmentation chain transfer (RAFT) polymerization in ethanol using [M]/[RAFT] ratios of 100 and 200. Kinetic investigations on the homo‐ and copolymerization of these monomers were performed using a parallel synthesizer resulting in well‐defined polymers with polydispersity indices mostly below 1.3. The polymerization kinetics are presented and discussed in detail surprisingly revealing that the DEGMA homopolymerization is slower than the OEGMA₁₁₀₀ homopolymerization. Transfer coefficients c were estimated to be ～0.5 for the RAFT polymerization of both DEGMA and OEGMA₁₁₀₀ resulting in hybrid behavior at the beginning of the polymerizations. Subsequent copolymerization also revealed fast incorporation of the OEGMA₁₁₀₀ and relatively slow incorporation of DEGMA resulting in well‐defined copolymers with a molecular weight up to 100 kDa and polydispersities around 1.20. © 2009 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 47: 2811–2820, 2009     

Oxidative Addition Reactions of Element–Hydrogen Bonds with Different Polarities to a Gallium(I) Compound

The gallium(I) derivative [Ga({N(dipp)CMe}₂CH)] ( 1 ; dipp=2,6‐diisopropylphenyl) undergoes facile oxidative addition reactions with various element–hydrogen bonds including N? H, P? H, O? H, Sn? H, and H? H bonds. This was demonstrated by its reaction with triphenyltin hydride, ethanol, water, diethylamine, diphenylphosphane, and dihydrogen. All products were characterized by means of single‐crystal X‐ray structure determination, NMR spectroscopy, IR spectroscopy, and mass spectrometry.     

The Ambident Reactivity of 2,4,6‐Tris(trifluoromethanesulfonyl)anisole in Methanol: Using the SO2CF3 Group as a Tool to Reach the Superelectrophilic Dimension in σ‐Complexation Processes

The kinetics of σ complexation of 2,4,6‐tris(trifluoromethanesulfonyl)anisole ( 7 d ) have been investigated over a large pH range of 2–13.70 at T=20 °C in methanol. Two competitive processes associated with the initial addition of MeO^? at the unsubstituted 3‐position of 7 d to give a 1,3‐dimethoxy adduct ( 9 d ‐Me) and a subsequent and slow conversion of this species into a 1,1‐dimethoxy isomer ( 8 d ‐Me) have been identified. Both adducts 8 d ‐Me and 9 d ‐Me are 10⁵–10⁶ times more stable than the related adducts 8 a ‐Me and 9 a ‐Me of 2,4,6‐trinitroanisole ( 7 a ), a conventional reference aromatic electrophile in Meisenheimer complex chemistry. The high stability of 8 d ‐Me and 9 d ‐Me is shown to derive from greater rates of formation and lower rates of decomposition than previously determined for 8 a ‐Me and 9 a ‐Me, thereby emphasising the especially high activation of a benzene ring by SO₂CF₃ group(s). Analysis of the collected rate and equilibrium data for σ complexation in the anisole series 2,4,6‐tris(SO₂CF₃)‐, 2,6‐bis(SO₂CF₃)‐4‐nitro‐, 4‐SO₂CF₃‐2,6‐dinitro‐ and 2,4,6‐trinitro‐ supports the idea that the especially high capacity of resonance stabilisation of the negative charge of the adducts through an F_π‐type (as defined in ref. 49 ) polarisation effect is a major factor that accounts for the strong activation provided by SO₂CF₃ groups. A most significant result is the finding that the 1,1‐dimethoxy adduct 8 d ‐Me is by far the most stable benzene σ adduct so far reported. With a p value of 7.32, this adduct is formed exclusively through methanol addition up to pH≈10. This is consistent with the location of 7 d in the superelectrophilic region defined by p ≤9.5–10.5. For comparison, the solvent contribution is negligible in the formation of the 1,3‐isomer 9 d ‐Me, the p (10.59) of which is situated on the upper limit of the boundary. Taking advantage of the simple relationship linking pK_a values for σ complexation in methanol and water, a ranking of the triflone 7 d on the general thermodynamic scale constructed for Meisenheimer electrophiles in water is informative. An approximate calibration on the electrophilicity scale kinetically derived by Mayr et al. has also been made.