Highly enantioselective copper(I)-fesulphos-catalyzed 1,3-dipolar cycloaddition of azomethine ylides

The catalyst system formed by Cu(CH3CN)4ClO4 and the planar chiral P,S-ligand Fesulphos behaves as a very efficient chiral Lewis acid in the catalytic asymmetric 1,3-dipolar cycloaddition of azomethine ylides. This catalyst shows a remarkable reactivity at low catalyst loading (0.5-3 mol %), affording in good yields the endo adducts with exceptional levels of enantioselectivity (up to >99% ee). This catalytic asymmetric procedure has a broad structural scope with regard to both azomethine and dipolarophile substitution. The first examples of catalytic asymmetric 1,3-dipolar cycloaddition with ketimine-derived azomethines are reported.     

亚甲胺叶立德参与的不对称1,3-偶极环加成构建含连续季碳中心的螺四氢吡咯衍生物

Cu(I)催化的亚甲胺叶立德和亚环丙基乙酸乙酯参与的不对称endo-1,3-偶极环加成反应,高效构建了多官能化、含有多个连续季碳中心的5-氮杂-[2,4]庚烷化合物.此反应具有广泛的底物适用性,α-取代的和α-非取代的亚甲胺叶立德和亚环丙基乙酸乙酯都能很好的参与反应,并以很高的产率、优秀的非对映选择性(95:5–98:2 d.r)和对映选择性(87%–98%ee)生成相应的在2,3,4位上含有连续季碳中心的螺四氢吡咯化合物.     

Asymmetric construction of trifluoromethylated pyrrolidines via Cu(I)-catalyzed 1,3-dipolar cycloaddition of azomethine ylides with 4,4,4-trifluorocrotonates

Trifluoromethylated pyrrolidines have been synthesized via catalytic asymmetric 1,3-dipolar cycloaddition with excellent stereoselectivity for the first time. Epimerization of the endo-pyrrolidines obtained from cis-4,4,4-trifluorocrotonate into the exo-pyrrolidines was also revealed.     

The catalytic asymmetric 1,3-dipolar cycloaddition of ynones with azomethine ylides

The first catalytic asymmetric 1,3-dipolar cycloaddition of electron-deficient carbon-carbon triple bonds with azomethine ylides has been established. This reaction provides an unprecedented approach to access novel 2,5-dihydropyrrole derivatives with potential bioactivities in perfect enantioselectivities of up to >99% ee.     

Synthesis of bioactive fluoropyrrolidines via copper(i)-catalysed asymmetric 1,3-dipolar cycloaddition of azomethine ylides

Chiral pyrrolidinyl units are important building blocks in biologically active natural products and drugs, and the development of efficient methods for the synthesis of diverse structured pyrrolidine derivatives is of great importance. Meanwhile, incorporating fluorine containing groups into small molecules often changes their activities to a great extent due to the special physicochemical properties of fluorine atoms. Herein, we report an efficient route to obtain enantioenriched 3,3-difluoro- and 3,3,4-trifluoropyrrolidinyl derivatives by Cu(i)-catalysed enantioselective 1,3-dipolar cycloaddition of azomethine ylides with less active 1,1-difluoro- and 1,1,2-trifluorostyrenes. A series of new fluorinated pyrrolidines have been prepared in high yields (up to 96%) and with excellent stereoselectivities (up to >20 : 1 dr and 97% ee), and these unique structural blocks could be readily introduced into some natural compounds and pharmaceuticals. Additionally, antifungal activity investigation against four common plant fungi showed that some products possess general and high biological activities; comparison with the low antifungal activities of corresponding nonfluorinated compounds revealed that the fluorine atoms at the pyrrolidinyl rings play a crucial role in the antifungal activity.

Chiral fluoropyrrolidines were synthesized by Cu(i)-catalyzed enantioselective 1,3-dipolar cycloaddition of azomethine ylides with less active fluorinated styrenes, with broad substrate scope and high yield, stereoselectivity and biological activity.     

Cu-Fesulphos complexes: efficient chiral catalysts for asymmetric 1,3-dipolar cycloaddition of azomethine ylides

The Cu^I-Fesulphos catalyst system (≤3 mol %) shows an excellent performance in the asymmetric 1,3-dipolar cycloaddition of azomethine ylides. High to very high levels of reactivity, endo/exo selectivity, and enantioselectivity (69->99% ee) are generally achieved with a very wide range of azomethine ylides and dipolarophiles. Based on experimental and computational studies data, a model that accounts for this high enantiocontrol is proposed.     

Catalytic asymmetric 1,3-dipolar cycloaddition of N-unprotected 2-oxoindolin-3-ylidene derivatives and azomethine ylides for the construction of spirooxindole-pyrrolidines

Asymmetric 1,3-dipolar cycloaddition of N-unprotected 2-oxoindolin-3-ylidene with azomethine ylides for the construction of spirooxindole-pyrrolidines bearing four contiguous stereogenic centers has been achieved with AgOAc/TF-BiphamPhos complexes for the first time. This catalytic system performance well over a broad scope of substrates, providing the synthetically useful adducts in high yields and excellent diastereoselectivities and moderate enantioselectivities.     

Cu-mediated 1,3-dipolar cycloaddition of azomethine ylides with dipolarophiles: a faster access to spirooxindoles of potential pharmacological interest

CuI facilitated three-component reaction of isatin derivatives, l-proline and terminal alkynes containing an amide or ester functional group. The multi-component reaction (MCR) afforded a faster and practical synthesis of spirooxindole derivatives. A range of novel spirooxindoles were synthesized by using this straightforward and one-pot efficient methodology. A representative compound showed significant inhibition of PDE4B enzyme in vitro and good interactions with this protein in silico.     

Formal asymmetric 1,3-dipolar cycloaddition of azomethine ylides to (S)-2-p-tolylsulfinyl-2-cyclopentenone

Azomethine ylides, derived from iminoesters 1 and DBU in the presence of silver salts, react with (S)-2-p-tolylsulfinyl-2-cyclopentenone 2 in a completely regio- and endoselective manner but with a low facial selectivity, affording a mixture of two cycloadducts 3 and 4. When the ylides were prepared with LHMDS, only one diastereoisomer 3 was obtained in an almost quantitative yield. A nucleophilic addition/ring closure process easily accounts for the stereochemical results. Compounds 3 were transformed into optically pure 4-oxocyclopenta[c]dihydropyrroles and tetrahydropyrroles by elimination of the sulfinyl group.     

CuII-catalysed asymmetric 1,3-dipolar cycloaddition of azomethine ylides with a chiral ferrocene-derived P,N-ligand

A ferrocene-derived P,N-heterodonor ligand was effectively used in a Cu(OAc)₂·H₂O-catalysed asymmetric 1,3-dipolar cycloaddition of azomethine ylides with maleate derivatives, affording cycloadducts with high yields (up to 96%), diastereoselectivities (>99 dr), and enantioselectivities (up to 99% ee).     

Cu(I)/DTBM-BIPHEP-catalyzed exo-selective 1,3-dipolar cycloaddition of azomethine ylides with cis-trifluorocrotonate for asymmetric construction of trifluoromethylated pyrrolidines

A direct and facile access to highly substituted exo-pyrrolidines bearing a unique trifluoromethyl group is developed via Cu(I)/DTBM-BIPHEP-catalyzed asymmetric 1,3-dipolar cycloaddition of azomethine ylides with cis-4,4,4-trifluorocrotonate for the first time.     

A novel Fe(II)/diaryl prolinol catalyzed asymmetric 1,3-dipolar cycloaddition of azomethine ylides with alkenes

A novel Fe(II)/diaryl prolinol catalyzed asymmetric 1,3-dipolar cycloaddition of azomethine ylides with alkenes has been developed. In the presence of FeCl₂ (10 mol %) and α,α-bis(3,5-bistrifluoromethylphenyl)prolinol L1 (10 mol %), [3+2] cycloaddition of azomethine ylides with electronic-deficient olefins underwent smoothly in CH₃CN at room temperature to generate the desired endo-adducts in moderate to good yields and enantioselectivities. This is the first example of Fe(II)/N,O-ligand (L1) catalyzed 1,3-dipolar enantioselective cycloaddition reaction of azomethine ylides.     

Axially chiral BINIM and Ni(II)-catalyzed highly enantioselective 1,3-dipolar cycloaddition reactions of azomethine ylides and N-arylmaleimides

Axially chiral BINIM-Ni(II) complexes are effective catalysts in the asymmetric 1,3-dipolar cycloaddition reactions of azomethine ylides and N-arylmaleimides to give the corresponding adducts in good yields and up to 95% enantiomeric excesses.     

Bifunctional AgOAc/ThioClickFerrophos complex-catalyzed asymmetric 1,3-dipolar cycloaddition of azomethine ylides with aryl- and alkylidene malonates

AgOAc/ThioClickFerrophos complex-catalyzed 1,3-dipolar cycloaddition of glycine imino ester, the precursor of azomethine ylide, with aryl- and alkylidene malonates afforded the corresponding exo-cycloadducts, that is, proline ester derivatives in high yields with high enantiomeric excess (up to 99% ee). The reactions proceeded smoothly under base-free conditions demonstrating the bifunctional catalysis of the silver complex.     

Highly enantioselective asymmetric 1,3-dipolar cycloaddition of azomethine ylide catalyzed by a copper(I)/ClickFerrophos complex

A copper(I)/ClickFerrophos complex catalyzed the asymmetric 1,3-dipolar cycloaddition reaction of methyl N-benzylideneglycinate (the source of azomethine ylides) with vinyl sulfone to give the exo-2,4,5-trisubstituted pyrrolidine in good yield with high enantioselectivity (99% ee). The complex also effectively catalyzed reactions of other dipolarophiles such as acrylates, maleate, and maleimides to give the exo-2,4,5-, and 2,3,4,5-substituted pyrrolidine derivatives with high diastereo- and enantioselectivities.     

Intramolecular copper(I)-catalyzed 1,3-dipolar cycloaddition of azido-alkynes: synthesis of triazolo-benzoxazepine derivatives and their biological evaluation

Synthesis of a series of [1,2,3] triazolo [5,1-c] [1,4]benzoxazepine derivatives have been accomplished by the intramolecular Cu(I)-catalyzed cycloaddition of azido-alkynes derived from salicylaldehyde. The biological profile of these heterocyclic structural scaffolds toward anti-bacterial as well as anti-fungal activity has also been illustrated.     

Asymmetric construction of 3-vinylidene-pyrrolidine derivatives containing allene moiety via Ag(I)/TF-BiphamPhos-catalyzed 1,3-dipolar cycloaddition of azomethine ylides with diethyl 2-(3,3-diphenylpropa-1,2-dienylidene) malonate

Catalytic asymmetric 1,3-dipolar cycloaddition of various azomethine ylides with diethyl 2-(3,3-diphenylpropa-1,2-dienylidene)malonate has been developed successfully with good to excellent enantioselectivity for the effcient construction of 3-vinylidene-pyrrolidine derivatives containing a unique allene moiety.     

Stereoselective construction of spiro(butyrolactonepyrrolidines) by highly efficient copper(I)/TF-BiphamPhos-catalyzed asymmetric 1,3-dipolar cycloaddition

Pyrrole into one: The catalytic asymmetric 1,3-dipolar cycloaddition of cyclic aldimino esters has been accomplished for the first time, enabling facile access to spiro(butyrolactonepyrrolidines) containing one spiro quaternary center and three tertiary stereogenic centers (see scheme). The catalytic system performs well with a broad range of substrates, furnishing synthetically useful adducts in high yields, with excellent diastereo- and enantioselectivities under mild conditions.     

Binap-gold(I) trifluoroacetate as a bifunctional catalyst for the synthesis of chiral prolines through 1,3-dipolar cycloaddition of azomethine ylides

Highly enantioselective 1,3-dipolar cycloadditions of amino acid-derived azomethine ylides with alkenes have been performed, for the first time, under gold-catalysis using (S_a)- or (R_a)-Binap-gold(I) trifluoroacetate complexes, with the cationic Binap-gold acting as a Lewis acid and the counteranion as a base. Maleimides and trans-1,2-bis(phenylsulfonyl)ethylene were reacted with imino esters at room temperature in the absence of a base to afford, in very good yields, the corresponding polysubstituted prolines with total endo-diastereoselection and higher enantioselectivities than the Binap-silver trifluoroacetate complex.