Allylic Alkylation versus Michael Induced Ring Closure:  Chelated Enolates as Versatile Nucleophiles

Pohlman, Matthias; Kazmaier, Uli; Lindner, T.

doi:10.1021/jo049036q

Cited by 28 publications

(16 citation statements)

References 27 publications

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“…These enolates are on one hand thermally rather stable because of chelate complex formation, but on the other hand they show the high reactivity of metal enolates. The enolates undergo a wide range of reactions, such as alkylations, aldol or Michael additions, epoxide opening or transition metal catalyzed allylic alkylations, allowing the introduction of almost “every“ side chain, often in a highly selective fashion. If the reactions are carried out with peptide esters or amides, the stereochemical outcome can be controlled by the stereogenic centres in the peptide chain .…”

Section: Resultsmentioning

confidence: 99%

Synthesis and Biological Evaluation of Modified Miuraenamides

et al. 2018

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Miuraenamides, secondary metabolites of the marine myxobacterium Paraliomyxa miuraensis do not only show a high structural similarity to other cyclodepsipeptides isolated from sponges or terrestrial myxobacteria but they also exhibit a similar mode of action. They accelerate nucleation and polymerization of actin, and therefore interfere with cell division processes, at concentrations in the low nanomolar range. A late stage peptide modification allows the synthesis of a library of (simplified) miuraenamide derivatives with different halogenation and substitution pattern. Detailed SAR studies indicate, that bromination of the central tyrosine is essential for good biological activity, while the side chain of the C‐terminal amino acid can be varied or can even be removed.

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Section: Resultsmentioning

confidence: 99%

Synthesis and Biological Evaluation of Modified Miuraenamides

et al. 2018

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“…(dd, J 9,10 = 7.3 Hz, J 9,11 = 1.3 Hz, 1 H, 9-H), 7.23 (d, J N-H,3 = 7.6 Hz, 1 H, NH), 7.30 (td, J 10,9 = J 10,11 = 7.6 Hz, J 10,12 = 1.5 Hz, 1 H, 10-H). 13…”

Section: Methodsmentioning

confidence: 99%

“…1 H NMR (500 MHz): d = 1.01 (s, 9 H, 9-H), 1.44 (s, 9 H, 6-H), 2.87 (ddd, J 7,10a = 9.8 Hz, J 7,10b = 4.1 Hz, J 7,3 = 1.6 Hz, 1 H, 7-H), 4.41 (dd, J 10a,10b = 12.7 Hz, J 10a,7 = 9.8 Hz, 1 H, 10-H a ), 4.56 (dd, J 10b,10a = 12.7 Hz, J 10b,7 = 4.1 Hz, 1 H, 10-H b ), 4.98 (dd, J 3,N-H = 9.8 Hz, J 3,7 = 1.3 Hz, 1 H, 3-H), 7.06 (d, J N-H,3 = 9.5 Hz, 1 H, NH). 13 C NMR (125 MHz): d = 27.6, 27.6 (6 × q, C-6, C-9), 33.8 (s, C-8), 48.7 (d, C-7), 51.1 (d, C-3), 73.7 (t, C-10), 84.4 (s, C-5), 115.6 (q, J 1,F = 286.1 Hz, C-1), 157.5 (q, J 2,F = 38.1 Hz, C-2), 168.7 (s, C-4).…”

Section: Syn-3aementioning

confidence: 99%

“…Our group has been involved in amino acid synthesis for several years, using chelated amino acid ester enolates as nucleophiles for a wide range of reactions such as Claisen rearrangements, 11 palladium-catalyzed allylic alkylations 12 and Michael additions towards a,b-unsaturated esters. 13 Because of the high synthetic potential of nitro groups, we turned our attention also to the Michael addition towards nitroalkenes.…”

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Diastereoselective Michael Additions of Chelated Enolates towards Nitroalkenes

Mendler¹,

Kazmaier²

2005

Synthesis

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Highly reactive chelated enolates are versatile nucleophiles that underwent Michael additions towards nitroalkenes. The yields and selectivities obtained depend on the protecting groups and metal salts used. Zinc enolates in general give the best yields and the selectivities are high with tosylated glycinates. The best selectivities are obtained using tin enolates in combination with the TFA-protecting groups.Michael additions belong to the most popular C-C bond forming reactions, which might be explained by the high variability of the reaction partners. Very attractive Michael acceptors are nitroalkenes, 1 especially because the strong electron-withdrawing nitro group can be converted into a wide range of other functionalities. 2 Typical examples are the Nef reaction 3 (conversion into aldehydes) or reductions to oximes 4 and amines. 5 Oximes can be further transformed into nitriles, 6 which can also be obtained from nitro compounds directly. 7,8 Schöllkopf et al. investigated Michael additions of bislactim ethers towards nitro alkenes, and obtained best results using the corresponding titanium enolates. 9 This is in good agreement with the observations made by Seebach et al. using N-acyl oxazolidinones as nucleophiles. 10 Reduction of the nitro group gives rise to g-amino acids which are interesting building blocks.Our group has been involved in amino acid synthesis for several years, using chelated amino acid ester enolates as nucleophiles for a wide range of reactions such as Claisen rearrangements, 11 palladium-catalyzed allylic alkylations 12 and Michael additions towards a,b-unsaturated esters. 13 Because of the high synthetic potential of nitro groups, we turned our attention also to the Michael addition towards nitroalkenes.Based on the good results obtained in palladium-catalyzed reactions and Michael additions, we choose the zinc enolate of trifluoroacetyl (TFA)-protected Gly-Ot-Bu (1a) as nucleophile and commercially available (E)-nitrostyrene (2a) as Michael acceptor (Scheme 1). 8 The nitroalkene was added to the enolate at -78 °C and the reaction was monitored by TLC. Complete consumption of the nitroalkene was observed after 2 hours at this temperature and the Michael adduct 3aa was obtained in excellent yield but as a diastereomeric mixture with moderate selectivity. The anti-product was formed preferentially. Obviously the zinc enolates are highly reactive as expected, but with respect to selectivity, the results obtained were far from optimal.Therefore we varied the metal salt and the relative amount used ( Table 1). The reaction mixtures were allowed to warm to room temperature overnight. Increasing the amount of ZnCl 2 to 2.5 equivalents (entry 2) had no significant effect on either yield or selectivity. This observation was also confirmed with the other metal salts used. Magnesium enolates (entries 3 and 4) showed a comparable selectivity but the syn-product was formed preferentially with this and all other salts investigated. Slightly better selectivities were obtained with ClTi(Oi-Pr) 3 as...

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“…Palladium‐catalyzed transformations of allylic compounds have demonstrated powerful and well‐established synthetic procedures for carbon–carbon and carbon–heteroatom (N, O, S) bond formation . With respect to the reaction mechanism, palladium‐catalyzed allylation proceeds via π‐allyl palladium complexes . Most of the mechanistic studies focus on either the elimination of the leaving group or the attack of the amine…”

Section: Introductionmentioning

confidence: 99%

PEG‐4000‐promoted palladium‐catalyzed N‐allylation in water: aminonaphthalene as an example

Shih

Shue

Yang

2012

Applied Organom Chemis

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An environmentally friendly, efficient catalytic process using palladium associated with ligands in a PEG4000–water system leading to N‐allylation was described in this study. PEG‐4000 was found to improve the palladium‐catalyzed allylic amination of allylic acetates with aminonaphthalenes and gave overall good to high yields of the corresponding N‐allylic aminonaphthalenes. Copyright © 2012 John Wiley & Sons, Ltd.

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Allylic Alkylation versus Michael Induced Ring Closure: Chelated Enolates as Versatile Nucleophiles

Cited by 28 publications

References 27 publications

Synthesis and Biological Evaluation of Modified Miuraenamides

Synthesis and Biological Evaluation of Modified Miuraenamides

Diastereoselective Michael Additions of Chelated Enolates towards Nitroalkenes

PEG‐4000‐promoted palladium‐catalyzed N‐allylation in water: aminonaphthalene as an example

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