Efficient route to 6-CF3-substituted nicotinic acid derivatives

Nenajdenko, Valentine G.; Druzhinin, S. I.; Баленкова, Е. С.

doi:10.1016/j.jfluchem.2006.03.007

Cited by 12 publications

(2 citation statements)

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“…In contrast with α-hydroxy-tetrahydro-pyrindines, which smoothly eliminated water to form the corresponding 1,4-dihydropyridines, [13] the products 4 were unaffected by boiling concd. H 2 SO 4 , by P 2 O 5 or by POCl 3 /Py in toluene as solvent.…”

Section: Resultsmentioning

confidence: 95%

Simple Synthesis of 6‐(Trifluoromethyl)‐2,4,5,6‐tetrahydropyrazolo[3,4‐b]pyran Derivatives by One‐Pot, Three‐Component Reactions

Song

et al. 2007

Eur J Org Chem

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One‐pot, three‐component condensation reactions of aromatic aldehydes 1, 3‐methylpyrazol‐5‐one (2) and ethyl trifluoroacetoacetate (3) provided an efficient methodology for the preparation of ethyl (4S*,5R*)‐4‐aryl‐6‐hydroxy‐3‐methyl‐6‐(trifluoromethyl)‐2,4,5,6‐tetrahydropyrazolo[3,4‐b]pyran‐5‐carboxylate derivatives (4). The reactions gave moderate to good yields under mild conditions. These new products 4 were fully characterized by spectral methods and single‐crystal X‐ray diffraction analysis. A plausible reaction pathway for the formation of 4 is presented. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2007)

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Section: Resultsmentioning

confidence: 95%

Simple Synthesis of 6‐(Trifluoromethyl)‐2,4,5,6‐tetrahydropyrazolo[3,4‐b]pyran Derivatives by One‐Pot, Three‐Component Reactions

Song

et al. 2007

Eur J Org Chem

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“…Finally, we have shown that the Michael adducts can be transformed into hexahydroquinolines with negligible loss of optical activity. Reaction of 3b (96% ee) with ammonium acetate yields hexahydroquinoline 12 (94% ee) (Scheme ) …”

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confidence: 99%

Catalytic, Asymmetric Michael Reactions of Cyclic Diketones with β,γ-Unsaturated α-Ketoesters

Calter

Wang

2009

Org. Lett.

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Newly synthesized cinchona alkaloid-derived pyrimidines function as effective asymmetric catalysts for the Michael reaction between cyclic diketones and β,γ-unsaturated-α-ketoesters. The reactions of electrophiles with either aryl or alkyl γ-substituents give 64−99% yields and 94−99% ee.The Michael reaction stands as one of the fundamental methods for creating carbon-carbon bonds. As this reaction also often results in the creation of stereocenters, much effort has focused on the discovery of catalytic, asymmetric versions of the Michael reaction. 1 Several excellent methods using metal complexes 2 or organic molecules as catalysts have emerged; 3 however, these methods all apply only to certain substrate classes. We were particularly interested in the addition of cyclic diones to enones, as the product of such a Michael reaction could potentially provide an advanced intermediate in the synthesis of the hexahydroquinoline class of calcium channel blockers (Scheme 1). 4 Although Itoh et al. have reported high enantioselectivities for the related addition of diones to unsaturated pyrazole amides, 2d the highest enantioselectivity reported for the addition of diones to enones is 45%. 3d Therefore, we set out to maximize the asymmetric induction of this type of reaction.Our results with the catalytic, asymmetric, interrupted Feist-Bénary (IFB) reaction strongly influenced our exploration of the Michael reaction. 5 The IFB reaction employs a dione nucleophile, and an α-ketoester electrophile. In order to maximize the similarity between the IFB and Michael reactions, we chose β,γ-unsaturated-α-ketoesters as the electrophiles for the E-mail: mcalter@wesleyan.edu. Supporting Information Available. Complete experimental details and characterization data for all new compounds, along with the details of the X-ray structure of 3d. This material is available free of charge via the Internet at http://pubs.acs.org. Michael reaction. As we had found that pyrimidine-bis-cinchona alkaloid derivatives provide the highest enantioselectivity in the IFB reaction, we first tested these compounds as catalysts for the Michael reaction. NIH Public AccessWe used the reaction between dimedone (1a) and β,γ-unsaturated-α-ketoester 2a to screen for the optimal catalyst (Table 1). The product of this reaction cyclizes to form lactol 3a as an equilibrating mixture of anomers. These anomers equilibrate slowly enough that they show up as separate compounds by 1 H and 13 C NMR, but quickly enough that they do not resolve by chromatography. The trace of racemic 3a on a Chiralpak AD HPLC column shows only two peaks for the two enantiomers. By screening catalysts previously synthesized in our group, 5 we immediately found a promising catalyst, 4d, which gives 84% ee. We also observed that increasing the bulk of the pyrimidine C 5 -substituent led to more dramatic increases in enantioselectivity than increasing the size of the C 2 -substituent (5 to 4c vs. 5 to 4b). We therefore postulated that converting the C 5 -tBu substituent into a trieth...

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Highly Enantioselective Conjugate Addition of Cyclic Diketones to β,γ‐Unsaturated α‐Ketoesters Catalyzed by an N,N′‐Dioxide‐Cu(OTf)₂ Complex

Dong

Feng

et al. 2011

Chemistry A European J

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Efficient route to 6-CF3-substituted nicotinic acid derivatives

Cited by 12 publications

References 20 publications

Simple Synthesis of 6‐(Trifluoromethyl)‐2,4,5,6‐tetrahydropyrazolo[3,4‐b]pyran Derivatives by One‐Pot, Three‐Component Reactions

Simple Synthesis of 6‐(Trifluoromethyl)‐2,4,5,6‐tetrahydropyrazolo[3,4‐b]pyran Derivatives by One‐Pot, Three‐Component Reactions

Catalytic, Asymmetric Michael Reactions of Cyclic Diketones with β,γ-Unsaturated α-Ketoesters

Highly Enantioselective Conjugate Addition of Cyclic Diketones to β,γ‐Unsaturated α‐Ketoesters Catalyzed by an N,N′‐Dioxide‐Cu(OTf)₂ Complex

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Efficient route to 6-CF3-substituted nicotinic acid derivatives

Cited by 12 publications

References 20 publications

Simple Synthesis of 6‐(Trifluoromethyl)‐2,4,5,6‐tetrahydropyrazolo[3,4‐b]pyran Derivatives by One‐Pot, Three‐Component Reactions

Simple Synthesis of 6‐(Trifluoromethyl)‐2,4,5,6‐tetrahydropyrazolo[3,4‐b]pyran Derivatives by One‐Pot, Three‐Component Reactions

Catalytic, Asymmetric Michael Reactions of Cyclic Diketones with β,γ-Unsaturated α-Ketoesters

Highly Enantioselective Conjugate Addition of Cyclic Diketones to β,γ‐Unsaturated α‐Ketoesters Catalyzed by an N,N′‐Dioxide‐Cu(OTf)2 Complex

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Highly Enantioselective Conjugate Addition of Cyclic Diketones to β,γ‐Unsaturated α‐Ketoesters Catalyzed by an N,N′‐Dioxide‐Cu(OTf)₂ Complex