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1.
We developed a decarboxylative aldol reaction using α,α-difluoro-β-ketocarboxylate salt, carbonyl compounds, and ZnCl2/N,N,N′,N′-tetramethylethylenediamine. The generation of difluoroenolate proceeded smoothly under mild heating to provide α,α-difluoro-β-hydroxy ketones in good to excellent yield (up to 99%). The α,α-difluoro-β-ketocarboxylate salt was bench stable and easy to handle under air, which realizes a convenient and environmentally friendly methodology for synthesis of difluoromethylene compounds.A ZnCl2/N,N,N′,N′-tetramethylethylenediamine complex promoted decarboxylative aldol reaction of α,α-difluoro-β-ketocarboxylate salt with carbonyl compounds has been developed. 相似文献
2.
Readily available lanthanide amides Ln[N(SiMe3)2]3 (Ln = Nd (1), Sm (2), Eu (3), Yb (4), La (5)), combined with chiral salen ligands H2La ((S,S)-N,N′-di-(3,5-disubstituted-salicylidene)-1,2-cyclohexanediamine) and H2Lb ((S,S)-N,N′-di-(3,5-disubstituted-salicylidene)-1,2-diphenyl-1,2-ethanediamine) were employed in the enantioselective epoxidation of α,β-unsaturated ketones. It was found that the salen–La complex shows the highest efficiency and enantioselectivity. A relatively broad scope of α,β-unsaturated ketones was investigated, and excellent yields (up to 99%) and moderate to good enantioselectivities (37–87%) of the target molecules were achieved.The enantioselective epoxidation of α,β-unsaturated ketones was catalysed by readily available lanthanide amides La[N(SiMe3)2]3 combined with chiral salen ligands. 相似文献
3.
N α-benzenesulfonylhistamine, a new semi-synthetic β-glucosidase inhibitor, was obtained by bioactivity-guided isolation from a chemically engineered extract of Urtica urens L. prepared by reaction with benzenesulfonyl chloride. In order to identify better β-glucosidase inhibitors, a new series of Nα,Nτ-di-arylsulfonyl and Nα-arylsulfonyl histamine derivatives was prepared. Biological studies revealed that the β-glucosidase inhibition was in a micromolar range for several Nα-arylsulfonyl histamine compounds of the series, Nα-4-fluorobenzenesulfonyl histamine being the most powerful compound. Besides, this reversible and competitive inhibitor presented a good selectivity for β-glucosidase with respect to other target enzymes including α-glucosidase.A selective β-glucosidase inhibitor was discovered using the chemically engineered extracts approach. 相似文献
4.
The β-selective asymmetric addition of γ-butyrolactam with cyclic imino esters catalyzed by a bifunctional chiral tertiary amine has been developed, which provides an efficient access to optically active β-position functionalized pyrrolidin-2-one derivatives in both high yield and enantioselectivity (up to 78% yield and 95 : 5 er). This is the first catalytic method to access chiral β-functionalized pyrrolidin-2-one via a direct organocatalytic approach.The asymmetric addition of γ-butyrolactam with cyclic imino esters catalyzed by (DHQD)2AQN has been developed, which provides an access to β-position functionalized pyrrolidin-2-one derivatives in high levels yield and enantioselectivity.Metal-free organocatalytic asymmetric transformations have successfully captured considerable enthusiasm of chemists as powerful methods for the synthesis of various kinds of useful chiral compounds ranging from the preparation of biologically important molecules through to novel materials.1 Chiral pyrrolidin-2-ones have been recognized as important structural motifs that are frequently encountered in a variety of biologically active natural and synthetic compounds.2 In particular, the β-position functionalized pyrrolidin-2-one backbones, which can serve as key synthetic precursors for inhibitory neurotransmitters γ-aminobutyric acids (GABA),3 selective GABAB receptor agonists4 as well as antidepressant rolipram analogues,5 have attracted a great deal of attention. Therefore, the development of highly efficient, environmentally friendly and convenient asymmetric synthetic methods to access these versatile frameworks is particularly appealing.As a direct precursor to pyrrolidin-2-one derivatives, recently, α,β-unsaturated γ-butyrolactam has emerged as the most attractive reactant in asymmetric organometallic or organocatalytic reactions for the synthesis of chiral γ-position functionalized pyrrolidin-2-ones (Scheme 1). These elegant developments have been achieved in the research area of catalytic asymmetric vinylogous aldol,6 Mannich,7 Michael8 and annulation reactions9 in the presence of either metal catalysts or organocatalysts (a, Scheme 1). These well-developed catalytic asymmetric methods have been related to the γ-functionalized α,β-unsaturated γ-butyrolactam to date. However, in sharp contrast, the approaches toward introducing C-3 chirality at the β-position of butyrolactam through a direct catalytic manner are underdeveloped (b, Scheme 1)10 in spite of the fact that β-selective chiral functionalization of butyrolactam can directly build up α,β-functionalized pyrrolidin-2-one frameworks.Open in a separate windowScheme 1Different reactive position of α,β-unsaturated γ-butyrolactam in catalytic asymmetric reactions.So far, only a few metal-catalytic enantioselective β-selective functionalized reactions have been reported. For examples, a rhodium/diene complex catalyzed efficient asymmetric β-selective arylation10a and alkenylation10b have been reported by Lin group (a, Scheme 2). Procter and co-workers reported an efficient Cu(i)–NHC-catalyzed asymmetric silylation of unsaturated lactams (b, Scheme 2).10c Despite these creative works, considerable challenges still exist in the catalytic asymmetric β-selective functionalization of γ-butyrolactam. First, the scope of nucleophiles is limited to arylboronic acids, potassium alkenyltrifluoroborates and PhMe2SiBpin reagents. Second, the catalytic system and activation mode is restricted to metal/chiral ligands. To our knowledge, an efficient catalytic method to access chiral β-functionalized pyrrolidin-2-one via a direct organocatalytic approach has not yet been established. Therefore, the development of organocatalytic asymmetric β-selective functionalization of γ-butyrolactam are highly desirable. In conjunction with our continuing efforts in building upon chiral precedents by using chiral tertiary amine catalytic system,11 we rationalized that the activated α,β-unsaturated γ-butyrolactam might serve as a β-position electron-deficient electrophile. This γ-butyrolactam may react with a properly designed electron-rich nucleophile to conduct an expected β-selective functionalized reaction of γ-butyrolactam under a bifunctional organocatalytic fashion, while avoiding the direct γ-selective vinylogous addition reaction or β,γ-selective annulation as outlined in Scheme 2. Herein we report the β-selective asymmetric addition of γ-butyrolactam with cyclic imino esters12 catalyzed by a bifunctional chiral tertiary amine, which provides an efficient and facile access to optically active β-position functionalized pyrrolidin-2-one derivatives with both high diastereoselectivity and enantioselectivity.Open in a separate windowScheme 2β-Selective functionalization of γ-butyrolactam via metal- (previous work) or organo- (this work) catalytic approach.To begin our initial investigation, several bifunctional organocatalysts13 were firstly screened to evaluate their ability to promote the β-selective asymmetric addition of γ-butyrolactam 2a with cyclic imino ester 3a in the presence of 15 mol% of catalyst loading at room temperature in CH2Cl2 (entries 1–6, Entry Cat. Solvent Yielde erf 1 1a CH2Cl2 70% 40 : 60 2 1b CH2Cl2 <5% 57 : 43 3 1c CH2Cl2 70% 65 : 35 4 1d CH2Cl2 68% 70 : 30 5 1e CH2Cl2 58% 63 : 47 6 1f CH2Cl2 71% 77 : 23 7 1f DCE 72% 80 : 20 8 1f CHCl3 70% 80 : 20 9 1f MTBE 68% 79 : 21 10 1f Toluene 63% 78 : 22 11 1f THF 45% 76 : 24 12 1f MeOH 32% 62 : 38 13b 1f DCE : MTBE 75% 87 : 13 14c 1f DCE : MTBE 72% 87 : 13 15d 1f DCE : MTBE 70% 85 : 15