氮氧双功能salen催化剂在酮的不对称硅氰化反应中的应用

通过在催化剂的不同位置同时引入LALB（Lewis acid/Lewis base）双功能基团（包括氮氧偶极基团和金属钛中心）来改善其催化活性和立体控制能力,合成基于salen骨架结构的新型氮氧双功能催化剂.在相对温和的条件下成功的将该类双功能催化剂应用于酮的不对称硅氰化反应,表现出了中等程度的选择性和非常高的反应活性...     

Enantioselective epoxidation of alpha,beta-enones promoted by alpha,alpha-diphenyl-L-prolinol as bifunctional organocatalyst

[reaction: see text] An operationally simple and mild protocol for the catalytic enantioselective epoxidation of alpha,beta-unsaturated ketones has been estabilished using commercially available alpha,alpha-diphenyl-l-prolinol as bifunctional organocatalyst and tert-butyl hydroperoxide (TBHP) as oxidant. The epoxides have been obtained in good yields and with up to 80% ee.     

Enantioselective aza-Henry reaction catalyzed by a bifunctional organocatalyst

[reaction: see text] The aza-Henry reaction of imines with nitroalkanes was promoted by chiral thiourea with an N,N-dimethylamino group to give beta-nitroamines with good enantioselectivity. Various N-protected imines were examined as substrates. N-Phosphinoylimine gave the best result in terms of chemical yield and enantioselectivity (up to 91% yield, up to 76% ee).     

Enantioselective cyanosilylation of ketones catalyzed by a chiral oxazaborolidinium ion

The chiral oxazaborolidinium salt 1 (X = TfO) is an excellent catalyst for the cyanosilylation of methyl ketones promoted by trimethylsilyl cyanide and diphenylmethyl phosphine oxide as co-reactants (to generate Ph(2)MePOTMS(N=C:) as a reactive intermediate). The face selectivity of this reaction parallels that previously observed for the corresponding reaction of aldehydes. A unifying and rational mechanistic explanation is provided for these enantioselective reactions. Evidence is presented to support the importance of alpha-C-H...O hydrogen bonding, pi,pi-interaction of the complexed ketonic carbonyl with the mexyl group of 1, and an early transition state for high enantioselectivity. The cyanosilylation reaction described herein provides access to many useful chiral compounds.     

Enantioselective cyanosilylation of ketones catalyzed by double-activation catalysts with N-oxides

Enantioselective addition of trimethylsilyl cyanide to ketones by a catalytic double-activation method is described. By combinatorially using 2.0 mol% of a chiral salen-titanium complex and 1.0 mol% of an achiral tertiary amine N-oxide, aromatic, aliphatic and α,β-unsaturated ketones are converted into corresponding cyanohydrin trimethylsilyl ethers with 50-93% yield and 59-86% ee. The effects of ligand structure, catalyst loading and substrate concentration, solvents, the nature of Lewis base, counter ion and other additives, temperature, and substrate structure on the enantioselectivity are discussed. Three possible paths to achieve the asymmetric version of double-activation catalysis and two independent examples of it are proposed.     

Enantioselective cyanosilylation of ketones catalyzed by Mn(salen)/Ph3PO

TMSCN asymmetrically adds to a variety of ketones by catalysis with 1/Ph₃PO. This is a double activation where 1 acts as a Lewis acid and Ph₃PO as a Lewis base. Various ketones were subjected to the enantioselective addition to give up to 85% ee.     

Highly enantioselective cyanosilylation of ketones catalyzed by a bifunctional Ti(IV) complex

A bifunctional catalyst system composed of (S)-prolinamide (2a), titanium(IV) isopropoxide, and phenolic N-oxide (3f) exhibited high catalytic efficiency in the enantioselective cyanosilylation of ketones. In the presence of 2.5 mol % catalyst, a variety of aromatic and aliphatic ketones were converted into the corresponding tertiary cyanohydrin O-TMS ethers in excellent yields (up to 96%) and high enantioselectivities (up to 96% ee). A proposed catalytic cycle was illustrated to explain the origin of the asymmetric induction.     

Enantioselective cyanosilylation of ketones by a catalytic double-activation method with an aluminium complex and an N-oxide

Double-activation catalysis promises high catalytic efficiency in the enantioselective cyanosilylation of ketones through the combined use of a Lewis acid and a Lewis base. Catalyst systems composed of a chiral salen-Al complex and an N-oxide have high catalytic turnovers (200 for aromatic ketones, 1000 for aliphatic ones). With these catalysts, a wide range of aliphatic and aromatic ketones were converted under mild conditions into tertiary cyanohydrin O-TMS ethers in excellent yields and with high enantioselectivities (94% ee for aromatic ketones, 90% ee for aliphatic ones). Preliminary mechanistic studies revealed that the salen-Al complex played the role of a Lewis acid to activate the ketone and the N-oxide that of a Lewis base to activate TMSCN; that is, double activation.     

A mild and efficient cyanosilylation of ketones catalyzed by a Lewis acid-Lewis base bifunctional catalyst

A new family of bifunctional catalysts (N-oxides-Ti(OⁱPr)₄ (2:1)) containing a Lewis acid and a Lewis base was developed and applied to the catalytic cyanosilylation of ketones. Utilizing rac((1R,2S) and (1S,2R))-1-(2′-pyridylmethyl)-2-diphenylhydroxymethylpyrrolidine N-oxide-titanium (2:1) complex and N-benzyl-diethanolamine N-oxide-titanium (2:1) complex as catalysts, the cyanosilylation products were obtained in 42-97% yield. Based on experimental phenomena and kinetic studies, a catalytic cycle was proposed to explain the remarkable activities of these catalysts. Investigations indicated that rac((1R,2S) and (1S,2R))-1-(2′-pyridylmethyl)-2-diphenylhydroxymethylpyrrolidine N-oxide-titanium (2:1) complex and N-benzyl-diethanolamine N-oxide-titanium (2:1) complex should promote the reaction via a dual activation of the ketone by the titanium and TMSCN by the N-oxide.     

Enantioselective cyanosilylation of ketones by a catalytic double-activation method employing chiral Lewis acid and achiral N-oxide catalysts

[reaction: see text] Enantioselective addition of TMSCN to ketones is achieved by a catalytic double-activation method using 1a-Ti(IV) complex as the Lewis acid and achiral N-oxide 2 as the Lewis base to activate ketones and TMSCN, respectively.     

Enantioselective Michael addition of cyclic ketones to nitroolefins catalyzed by a novel fluorine-insertion organocatalyst

A novel fluorine-insertion organocatalyst, which was designed based on the fluorine–ammonium ion gauche effect, was synthesized and used successfully to catalyze the asymmetric Michael addition of cyclic ketones to nitroolefins. High yields and excellent diastereo- and enantioselectivities were achieved under mild conditions. A possible stereochemical model is also proposed.     

Enantioselective Michael addition of alpha-substituted cyanoacetates to vinyl ketones catalyzed by bifunctional organocatalysts

A highly enantioselective Michael addition of alpha-substituted cyanoacetates to vinyl ketones was accomplished in the presence of simple bifunctional thiourea/tertiary amine organocatalysts. A number of alpha-aryl or alkyl cyanoacetates have been successfully applied to give multifunctional compounds with an all-carbon-substituted quaternary stereocenter in excellent enantioselectivities (82-97 % ee) and yields (61-99 %). The optical pure adducts could be smoothly converted to variously structured beta(2,2)-amino acid esters. Moreover, an interesting reaction model involving multiple hydrogen-bonding interactions amongst the thiourea/tertiary amine catalyst and the reactants has been proposed based on the absolute configuration of the adduct and computational studies.     

Polystyrene-supported TBD as an efficient and reusable organocatalyst for cyanosilylation of aldehydes, ketones, and imines

Polystyrene-supported TBD (PS-TBD) catalyzes cyanosilylation of both aldehydes and ketones using TMSCN to give the corresponding products in high yields. Imines were also converted into the desired α-cyanoanimes under the same conditions. PS-TBD was easily recovered and reused without significant loss of catalytic activity.     

Enantioselective construction of quaternary carbon centre catalysed by bifunctional organocatalyst

The bifunctional thiourea-tertiary amine derivatives of simple chiral diamines serve as highly enantioselective catalysts for the Michael addition of alpha-substituted cyanoacetates to vinyl sulfones, giving an efficient protocol for the construction of an all-carbon substituted quaternary stereocentre.     

Enantioselective Michael addition of 3-aryl-substituted oxindoles to methyl vinyl ketone catalyzed by a binaphthyl-modified bifunctional organocatalyst

The enantioselective conjugate addition reaction of 3-aryl-substituted oxindoles with methyl vinyl ketone promoted by binaphthyl-modified bifunctional organocatalysts was investigated. The corresponding Michael adducts, containing a quaternary center at the C3-position of the oxindoles, were generally obtained in high yields with excellent enantioselectivities (up to 91% ee).     

Enantioselective allylation of aldehydes catalyzed by new bifunctional bisoxazoline-metal complexes

The asymmetric allylation reactions of aldehydes catalyzed by a 10 mol % bisoxazoline complex bearing a phosphine oxide moiety, which was newly designed and synthesized from l-serine, afforded the corresponding homoallylic alcohols in 48-74% yields with 39-86% ee. The reaction proceeds with the dual activation of the aldehyde and allylsilane by the Lewis acid and base of the catalyst. The evidence for the activation of the allylsilane was clarified by the ³¹P NMR spectra.     

Asymmetric cyanosilylation of ketones catalyzed by recyclable polymer-supported copper(II) salen complexes

Various ketones have undergone asymmetric trimethylsilylcyanation at room temperature with (CH₃)₃SiCN (TMSCN) in the presence of a chiral-supported Cu(salen) complex and Ph₃PO as the catalyst. Aromatic, aliphatic, and heterocyclic ketones have been converted into the corresponding cyanohydrin trimethylsilyl ethers in 83?96% yields with 52?84% ee. Several factors concerning the reactivity and enantioselectivity have been discussed. A double activation where Cu(salen) plays the role of Lewis acid and Ph₃PO acts as a Lewis base is reported. Poly(ethylene glycol) monomethyl ether (MeO-PEG) has been used as a soluble support while JandaJel (JJ) and Merrifield (MF) resins served as insoluble supports. Each polymer is linked to the salen catalyst through a glutarate spacer. The soluble catalysts were recovered by precipitation with a suitable solvent while the insoluble catalysts were simply filtered from the reaction mixture. The JandaJel-attached Cu(salen) catalyst could be used for five cycles with the retention of efficiency and the Merrifield-bound Cu(salen) catalyst was found to loose activity with each use.