Synthesis and application of oxadiazines as chiral ligands for the enantioselective addition of diethylzinc to aldehydes

Dean, Melissa A.; Hitchcock, Shawn R.

doi:10.1016/j.tetasy.2010.09.010

Cited by 11 publications

(7 citation statements)

References 22 publications

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“…The phenolic hydrogen is strongly hydrogen bonded to the nearby ester carbonyl oxygen, as can be inferred from the sharp singlet at 12 ppm in 1 H NMR spectrum of 1 . The use of potassium carbonate 21 or tetrabutylammonium hydroxide 22 in DMF produced a reaction, but only elimination instead of substitution (Scheme 1). Dienoates 9 and 10 suggest that the strong bases deprotonated one of the hydrogens on carbon 3 and this led to elimination of the ester attached to carbon 3.…”

Section: Resultsmentioning

confidence: 99%

Isolation, semisynthesis, covalent docking and transforming growth factor beta-activated kinase 1 (TAK1)-inhibitory activities of (5Z)-7-oxozeaenol analogues

Fakhouri

El‐Elimat

Hurst

et al. 2015

Bioorganic & Medicinal Chemistry

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(5Z)-7-Oxozeanol and related analogues were isolated and screened to explore their activity as TAK1 inhibitors. Seven analogues were synthesized and more than a score of natural products isolated that examined the role that different areas of the molecule contribute to TAK1 inhibition. A novel nonaromatic difluoro-derivative was synthesized that had similar potency compared to the lead. This is the first example of a nonaromatic compound in this class to have TAK1 inhibition. Covalent docking for the isolated and synthesized analogues was carried out and found a strong correlation between the observed activities and the calculated binding.

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Section: Resultsmentioning

confidence: 99%

Isolation, semisynthesis, covalent docking and transforming growth factor beta-activated kinase 1 (TAK1)-inhibitory activities of (5Z)-7-oxozeaenol analogues

Fakhouri

El‐Elimat

Hurst

et al. 2015

Bioorganic & Medicinal Chemistry

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“…THF- d 8 (Cambridge Isotopes) was used as received. ( t BuO) 3 WC t Bu, ( t BuO) 3 WCEt, 3-( tert -butyl)-2-hydroxybenzaldehyde, 3-( tert -butyl)-2-methoxybenzaldehyde, and Ph 3 PCH 2 were prepared according to published procedures. All other reagents were purchased from commercial vendors and used without further purification.…”

Section: Methodsmentioning

confidence: 99%

“…Unless specified otherwise, all manipulations were performed under an inert atmosphere using standard Schlenk or glovebox techniques. Pentane, hexanes, toluene, diethyl ether, tetrahydrofuran, and acetonitrile were dried using a Glass- ( t BuO) 3 WC t Bu, 43 ( t BuO) 3 WCEt, 42 3-(tert-butyl)-2hydroxybenzaldehyde, 40 3-(tert-butyl)-2-methoxybenzaldehyde, 58 and Ph 3 PCH 2 50 were prepared according to published procedures. All other reagents were purchased from commercial vendors and used without further purification.…”

Section: ■ Experimental Sectionmentioning

confidence: 99%

New Alkylidyne Complexes Featuring a Flexible Trianionic ONO^3– Pincer-Type Ligand: Inorganic Enamine Effect versus Sterics in Electrophilic Additions

et al. 2015

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Metal−carbon multiple bonds exhibit enhanced nucleophilicity at the α carbon within ONO trianionic pincer alkylidyne complexes. Defined as the inorganic enamine ef fect, this phenomenon is a result of the overlap of the N atom lone pair within the ONO 3− ligand and a π bond from the metal− carbon multiple bond. Treating the proligand. DFT calculations modeling 4-t Bu reveal overlap of the N atom lone pair with a WC π bond. However, 4-t Bu reacts with electrophiles preferentially at the pincer N atom as opposed to the WC α group. Multinuclear NMR spectroscopy, combustion analysis, and single-crystal X-ray crystallography are employed to characterize complexes 3-Et, 3-t Bu anti , and 4-t Bu. ■ INTRODUCTIONTailored ancillary ligands are critical to the further development of homogeneous transition-metal catalysis. 1 Ligand modifications enable exquisite control over the electronic and geometric properties of metal complexes. Among the various classes of ligands available, pincer and pincer-type ligands 2 garner particular attention. Emerging as a class of their own, trianionic pincer ligands, 3 thus far, have been well-suited for stabilizing early transition metals in their high oxidation states. Trianionic [NCN], 4−7 [OCO], 8−20 [NNN], 21−25 [CCC], 26 and [ONO] 27−36 ligands are some of the common donor motifs and in combination with the appropriate metal ion will catalyze nitrene and carbene transfer, 21−23,27,37 aerobic oxidation, 14 ethylene and alkyne polymerization, 5,6,15,16,36 and alkene isomerization. 5 Important structure−bonding relationships 29,33 within trianionic pincer complexes are emerging and serve to elevate the level of electronic and geometric control over metal ions. For example, tungsten−alkylidene and −alkylidyne complexes featuring the [ONO] 3− pincer-type ligand [CF 3 -ONO]H 3 exhibit enhanced nucleophilicity at the metal−carbon multiple bond. 28−30 The enhanced nucleophilicity is a consequence of the "inorganic enamine effect" (Figure 1). 28−30 Analogously to enamines, an inorganic enamine involves constraining a nitrogen atom lone pair to be collinear with a metal−carbon π bond. The interaction accentuates the nucleophilicity by delocalizing electron density from the nitrogen atom lone pair onto the α carbon, and being π* in character, the HOMO orbital is destabilized.The trianionic pincer ligand [CF 3 -ONO] 3− , first used to illustrate the inorganic enamine effect, is relatively rigid and contains a biaryl amido ligand. 28−30 One question to answer is as follows: what influence do the N atom substituents (aryl vs alkyl) and the flexibility of the ligand have on the nucleophilicity of metal−carbon multiple bonds? Described herein is the synthesis of the trianionic pincer ligand precursor [O CH2 N CH2 O]H 3 (2), its metalation with ( t BuO) 3 WCEt and ( t BuO) 3 WC t Bu to afford complexes 3-Et and 3-t Bu anti , access to the trianionic version {[O CH2 N CH2 O]WC t Bu-(O t Bu)}{CH 3 PPh 3 } (4-t Bu), and in situ solution-phase experiments to assess the inorganic enamine effect on 4-...

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“…The analytical data were consistent with those previously reported. 33,34 R f = 0.32 ( petroleum ether-EtOAc + AcOH, 9 : 1 + 1% (v/v)); mp 83 °C; IR (film): 3064,3001,2953,2924,2859,2827,2657,2566,1751,1690,1592,1467,1423,1405,1376,1308,1229,1281,1192,1163,1090,1001,977,916,822,811,765,742, 725 cm −1 ; 1 H NMR: δ = 2.37 (s, 3 H, CH 3 ), 3.92 (s, 3 H, OCH 3 ), 7.17 (dd, J = 7.8, 7.5 Hz, 1 H, 5-H), 7.43 (dd, J = 7.5, 1.3 Hz, 1 H, 4-H), 7.95 (dd, J = 7.8, 1.3 Hz, 1 H, 6-H) ppm; 13 C NMR: δ = 16.1 (CH 3 ), 62.2 (OCH 3 ), 122.2 (C-1), 125.0 (C-5), 130.8 (C-6), 131.9 (C-3), 137.1 (C-4), 158.1 (C-2), 167.2 (COOH) ppm; MS: m/z (%): 166 (47), 149 (18), 148 (37), 137 (30), 133 (53), 119 (100), 105 (37), 93 (29), 91 (76), 78 (27), 77 (64), 65 (17), 51 (31).…”

Section: Synthesis Of the Model Substrate And Reference Compoundsmentioning

confidence: 99%

“…R f = 0.17 ( petroleum ether-EtOAc, 7 : 3); anal. calcd for C 10 H 12 O 4 : C, 61.22; H, 6.16; found: C, 60.79 ± 0.05; H, 6.18 ± 0.01; IR (film): 3432,3076,2999,2951,2872,2835,1712,1593,1465,1433,1424,1365,1298,1267,1230,1193,1134,1085,1061, 1000, 887, 870, 812, 778, 764, 731 cm −1 ; 1 H NMR: δ = 2.32 (brs, 1 H, OH), 3.88 (s, 3 H, OCH 3 ), 3.91 (s, 3 H, COOCH 3 ), 4.75 (d, J = 5.1 Hz, 2 H, CH 2 ), 7.16 (dd, J = 7.8, 7.5 Hz, 1 H, 5-H), 7.56 (dd, J = 7.5, 1.5 Hz, 1 H, 4-H), 7.77 (dd, J = 7.8, 1.5 Hz, 1 H, 6-H); 13 C NMR: δ = 52.4 (COOC̲ H 3 ), 61.0 (CH 2 ), 62.7 (OCH 3 ), 124.0 (C-5), 124.3 (C-1), 131.3 (C-6), 133.1 (C-4), 135.6 (C-3), 158.3 (C-2), 166.6 (C̲ OOCH 3 ) ppm; MS: m/z (%): 196 (16), 181 (23), 165 (34), 149 (100), 135 (75), 119 (27), 105 (23), 91 (16), 77 (36), 65 (17), 51 (10).…”

Section: Characterisation Ofmentioning

confidence: 99%

Benzylic hydroxylation of aromatic compounds by P450 BM3

et al. 2013

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Cytochrome P450 BM3 monooxygenase from Bacillus megaterium and its variants are promising catalysts for organic synthesis. Aiming at the identification of variants for selective hydroxylation of functionalised aromatic compounds, the double mutant F87A L188C showed remarkably improved catalytic activity towards a set of tested toluene derivatives. The apparent catalytic efficiency of this variant towards the model substrate methyl 2-methoxy-3-methylbenzoate was 63.6 s −1 M −1 , which is 535-fold higher compared to that of wild-type BM3. Furthermore, the double mutant selectively catalysed the benzylic hydroxylation of numerous toluene derivatives, especially in the presence of carbonyl-or carboxyl-functions that are directly attached to the aromatic ring. Preparative scale conversion resulted in efficient production of methyl 3-(hydroxymethyl)-2-methoxybenzoate (73% yield) which proved that F87A L188C is a suitable, efficient and sustainable catalyst for the introduction of benzylic hydroxyl groups in general. b

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Synthesis and application of oxadiazines as chiral ligands for the enantioselective addition of diethylzinc to aldehydes

Cited by 11 publications

References 22 publications

Isolation, semisynthesis, covalent docking and transforming growth factor beta-activated kinase 1 (TAK1)-inhibitory activities of (5Z)-7-oxozeaenol analogues

Isolation, semisynthesis, covalent docking and transforming growth factor beta-activated kinase 1 (TAK1)-inhibitory activities of (5Z)-7-oxozeaenol analogues

New Alkylidyne Complexes Featuring a Flexible Trianionic ONO^3– Pincer-Type Ligand: Inorganic Enamine Effect versus Sterics in Electrophilic Additions

Benzylic hydroxylation of aromatic compounds by P450 BM3

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Synthesis and application of oxadiazines as chiral ligands for the enantioselective addition of diethylzinc to aldehydes

Cited by 11 publications

References 22 publications

Isolation, semisynthesis, covalent docking and transforming growth factor beta-activated kinase 1 (TAK1)-inhibitory activities of (5Z)-7-oxozeaenol analogues

Isolation, semisynthesis, covalent docking and transforming growth factor beta-activated kinase 1 (TAK1)-inhibitory activities of (5Z)-7-oxozeaenol analogues

New Alkylidyne Complexes Featuring a Flexible Trianionic ONO3– Pincer-Type Ligand: Inorganic Enamine Effect versus Sterics in Electrophilic Additions

Benzylic hydroxylation of aromatic compounds by P450 BM3

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New Alkylidyne Complexes Featuring a Flexible Trianionic ONO^3– Pincer-Type Ligand: Inorganic Enamine Effect versus Sterics in Electrophilic Additions