Efficient, direct α-methylenation of carbonyls mediated by diisopropylammonium trifluoroacetate

Bugarin, Alejandro; Jones, K.; Connell, Brian T.

doi:10.1039/b924577d

Cited by 81 publications

(62 citation statements)

References 42 publications

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“…However, NO 2 or CN substituted derivatives (12, AC 50 = 4.39 µM; 13, AC 50 = 2.76 µM) showed 2-3 fold increase of activities compared with lead compound 8, which could be explained by the function of hydrogen bond receptor of them. Notably, when the benzene ring in compound 8 was replaced with the heterocycles, we observed the similar trend that only the heterocyle derivatives containing hydrogen bond receptor (25,28,29,32) showed remarkable activities (AC 50 = 4.30, 3.56, 3.70, 1.00 µM). More interestingly, the activity of the azaindole derivatives 32 (AC 50 = 1.00 µM) is greatly higher than that of indole derivatives 31 (AC 50 > 20 µM).…”

Section: Biological Evaluations In Vitrosupporting

confidence: 68%

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New pyridin-3-ylmethyl carbamodithioic esters activate pyruvate kinase M2 and potential anticancer lead compounds

Zhang

Liu

et al. 2015

Bioorganic & Medicinal Chemistry

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Section: Biological Evaluations In Vitrosupporting

confidence: 68%

“…Various aryl or hetroaryl ketones reacted respectively with paraformaldehyde catalyzed by diisopropylammonium trifluoroacetate to form the intermediates acryloyl arenes, 25 which were followed by the addition of dithiocarbamates from CS 2 and 3-(aminomethyl)pyridine to afford the corresponding target compounds 9-35. 26 …”

Section: Chemistrymentioning

confidence: 99%

New pyridin-3-ylmethyl carbamodithioic esters activate pyruvate kinase M2 and potential anticancer lead compounds

Zhang

Liu

et al. 2015

Bioorganic & Medicinal Chemistry

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“…Turning to the metathesis strategy, we began investigating α-methylenation protocols. Using the conditions recently reported by Connell and coworkers, treatment of 30 with (HCHO) n and diisopropylammonium trifluoroacetate 30 afforded the undesired Diels-Alder adduct 31 , effectively rendering our RCM approach unfeasible. These results cast doubt as to whether our proposed C2-furan approach would provide access to 1 .…”

Section: Resultsmentioning

confidence: 99%

Asymmetric Synthesis of the Aminocyclitol Pactamycin, a Universal Translocation Inhibitor

2013

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An asymmetric total synthesis of the aminocyclopentitol pactamycin is described, which delivers the title compound in 15 steps from 2,4-pentanedione. Critical to this approach was the exploitation of a complex symmetry-breaking reduction strategy to assemble the C1, C2, and C7 relative stereochemistry within the first four steps of the synthesis. Multiple iterations of this reduction strategy are described, and a thorough analysis of stereochemical outcomes is detailed. In the final case, an asymmetric Mannich reaction was developed to install a protected amine directly at the C2 position. Symmetry-breaking reduction of this material gave way to a remarkable series of stereochemical outcomes leading to the title compound without recourse to non-strategic downstream manipulations. This synthesis is immediately accommodating to the facile preparation of structural analogs.

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“…[29] Diisopropylammonium trifluoroacetate mediated α-methylenation [30] of acetophenone 6a with paraformaldehyde did produce enone 11, but suffered from low (≈ 60 %) conversions. [29] Diisopropylammonium trifluoroacetate mediated α-methylenation [30] of acetophenone 6a with paraformaldehyde did produce enone 11, but suffered from low (≈ 60 %) conversions.…”

Section: Resultsmentioning

confidence: 99%

Enantioselective Ring Opening of meso‐Epoxides with Silicon Tetrachloride Catalyzed by Pyridine N‐Oxides Fused with the Bicyclo[3.3.1]nonane Framework

Neniškis

Stončius

2015

Eur J Org Chem

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The synthesis of new chiral Lewis basic organocatalysts that contain pyridine N-oxide moieties fused with the bicyclo-[3.3.1]nonane framework is reported. The obtained pyridine N-oxides were employed as catalysts in the enantioselective ring opening of meso-epoxides with silicon tetrachloride. Derivative 1b endowed with two 2,4-diaryl-substituted pyridine N-oxide moieties proved to be a particularly effective cata-6359 lyst for desymmetrization of norbornene oxide 16i to furnish Wagner-Meerwein rearrangement product 20i in unprecedented 96 % ee. Difunctional congener 3, which is striped of the 4-aryl substituents, exhibited moderate to high levels of asymmetric induction (47-88 % ee) with alicyclic epoxide substrates.N,NЈ-dioxide L3, [8] helical chiral N-oxide L4, [9] bipyridine N-monooxide L5 (PINDOX), [10] as well as dipyridylmethane, [11] bis(tetrahydroisoquinoline) [12] and bipyridine [13] N,NЈ-dioxides promote enantioselective chlorohydrin formation. Figure 1. Selected Lewis basic pyridine-type N-oxide and phosphine oxide organocatalysts.Chiral phosphine oxides, such as axially chiral L6 (BI-NAPO), [14] its heteroaromatic congeners, [15] or allene-derived bisphosphine oxide L7, [16] have been also shown to A. Neniškis, S. Stončius FULL PAPERcatalyze enantioselective ring-opening of meso-epoxides with SiCl 4 . Nevertheless, the Lewis basic catalysts developed so far proved to be rather fastidious with respect to the epoxide substrate. As a rule, the ability to impart high levels of enantioselection is limited to the derivatives of cisstilbene oxide (87-97 % ee with catalysts L1-L4, L6, and L7), whereas in the case of the less sterically demanding aliphatic substrates and, in particular, with cyclic epoxides, the enantioselectivity drops to moderate levels. Pinene-derived N-monooxide PINDOX [10] (L5; Figure 1), which is most effective with saturated cyclic substrates that contain more than seven carbon atoms and norbornene oxide (87-90 % ee) but inefficient with cis-stilbene oxide (16 % ee), is a notable exception.Desymmetrization of meso-epoxides is an attractive strategy for asymmetric synthesis as two contiguous stereogenic centers can be unveiled through a single transformation. [17] Therefore further development, which enhances the catalyst efficiency and broadens the scope of such reactions is desirable. Herein we present the synthesis of new Lewis bases that feature a pyridine N-oxide fragment attached to a chiral bicyclo[3.3.1]nonane backbone, and their application in enantioselective ring opening of meso-epoxides with silicon tetrachloride. www.eurjoc.org 6361 Scheme 2. Reagents and conditions: (a) TiCl 4 , Cl(CH 2 ) 2 COCl, 1,2-DCE; (b) TEA, CH 2 Cl 2 (18-43 %); (c) (i) DMF, POCl 3 , 0°C (98 %), (ii) H 2 C=CHMgBr, THF, 0°C (80 %); (d) IBX, THF/ DMSO, room temp. (67 %); (e) Me 2 NH 2 Cl, iPrOH, Δ (91 %); (f) 4, TEA, 180°C, then NH 2 OH·HCl, EtOH, Δ (30 %); (g) m-CPBA, K 2 CO 3 , CH 2 Cl 2 , room temp. (38 %).

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Efficient, direct α-methylenation of carbonyls mediated by diisopropylammonium trifluoroacetate

Abstract: A very efficient method for the direct alpha-methylenation of carbonyl compounds, with yields up to 99%, utilizing paraformaldehyde, diisopropylammonium trifluoroacetate, and catalytic acid or base, is presented.

Cited by 81 publications

References 42 publications

New pyridin-3-ylmethyl carbamodithioic esters activate pyruvate kinase M2 and potential anticancer lead compounds

New pyridin-3-ylmethyl carbamodithioic esters activate pyruvate kinase M2 and potential anticancer lead compounds

Asymmetric Synthesis of the Aminocyclitol Pactamycin, a Universal Translocation Inhibitor

Enantioselective Ring Opening of meso‐Epoxides with Silicon Tetrachloride Catalyzed by Pyridine N‐Oxides Fused with the Bicyclo[3.3.1]nonane Framework

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