Regioselectivity in the ring opening of 2-alkylcyclopropylmethyl radicals: the effect of electronegative substituents

Ratier, Max; Pereyre, Michel; Davies, Alwyn G.; Sutcliffe, R.

doi:10.1039/p29840001907

Cited by 29 publications

(9 citation statements)

References 7 publications

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“…120 8C (ref. [39] 118-122 8C); GC (50 8C, isothermic): t R = 8.77 min, analysis did not show any traces of (Z)-isomer; 1 General procedure for synthesis of acetates 2 a-c: [42] The allylic alcohol (4.4 mmol) was dissolved in dichloromethane (10 mL) and cooled to 0 8C under stirring. Acetyl chloride (0.34 mL, 4.8 mmol) and pyridine (0.38 mL, 4.7 mmol) were added and the reaction was monitored by TLC.…”

Section: Products Were Identified Bymentioning

confidence: 99%

Deconvoluting the Memory Effect in Pd‐Catalyzed Allylic Alkylation: Effect of Leaving Group and Added Chloride

Fristrup

Jensen

Hoppe

et al. 2006

Chemistry A European J

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An analysis of product distributions in the Tsuji-Trost reaction indicates that several instances of reported "memory effects" can be attributed to slow interconversion of the initially formed syn- and anti-[Pd(eta3-allyl)] complexes. Addition of chloride triggers a true memory effect, in which the allylic terminus originally bearing the leaving group has a higher reactivity. The latter effect, termed regioretention, can be rationalized by ionization from a palladium complex bearing a chloride ion, forming an unsymmetrically substituted [Pd(eta3-allyl)] complex. DFT calculations verify that the position trans to the phosphine ligand is more reactive both in the initial ionization and in the subsequent nucleophilic attack.

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Section: Products Were Identified Bymentioning

confidence: 99%

Deconvoluting the Memory Effect in Pd‐Catalyzed Allylic Alkylation: Effect of Leaving Group and Added Chloride

Fristrup

Jensen

Hoppe

et al. 2006

Chemistry A European J

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“…However, with powdered sodium borohydride in diethyl ether, the conversion of 20 was quantitative, and the yield of 21 was excellent (98%). In the final step, the attempted 1,3-dehydrotosylation of 22 with potassium tert -butoxide, when carried out in dimethyl sulfoxide as reported [ 26 – 27 ], compound 23 as an intermolecular condensation product of the expected ethyl trans -(2-trifluoromethyl)cyclopropanecarboxylate with DMSO was obtained in 74% yield. Among several other base/solvent combinations tested – NaOEt/EtOH, NaOMe/MeOH, t -BuOK/ t -BuOH, NaH/THF, t -BuOK/THF under reflux – the last one gave the best results with up to 47% yield of the trans -(2-trifluoromethyl)cyclopropanecarboxylic acid ( 24 ).…”

Section: Resultsmentioning

confidence: 99%

“…Therefore, an alternative approach to trans -(2-trifluoromethyl)cyclopropanecarboxylic acid 23 by way of the Claisen condensation product of ethyl trifluoroacetate ( 17 ) with diethyl succinate ( 18 ) [ 25 ] was used. The conditions for two of the known further steps [ 26 – 27 ] ( Scheme 2 ) had to be modified to achieve acceptable yields. The reduction of the ketoester 20 to the hydroxyester 21 under the previously described conditions (H 2 /PtO 2 ) proceeded very slowly, and in several runs (2 h, 24 h, 72 h) the yield of 21 was never better than 60% with up to 25% recovered ketoester 20 .…”

Section: Resultsmentioning

confidence: 99%

(2R,1'S,2'R)- and (2S,1'S,2'R)-3-[2-Mono(di,tri)fluoromethylcyclopropyl]alanines and their incorporation into hormaomycin analogues

Meijere¹,

Kozhushkov²,

Yufit³

et al. 2014

Beilstein J. Org. Chem.

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SummaryEfficient and scalable syntheses of enantiomerically pure (2R,1'S,2'R)- and (2S,1'S,2'R)-3-[2-mono(di,tri)fluoromethylcyclopropyl]alanines 9a–c, as well as allo-D-threonine (4) and (2S,3R)-β-methylphenylalanine (3), using the Belokon' approach with (S)- and (R)-2-[(N-benzylprolyl)amino]benzophenone [(S)- and (R)-10] as reusable chiral auxiliaries have been developed. Three new fluoromethyl analogues of the naturally occurring octadepsipeptide hormaomycin (1) with (fluoromethylcyclopropyl)alanine moieties have been synthesized and subjected to preliminary tests of their antibiotic activity.

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“…An alternative route to trans-2-(trifluoromethyl)cyclopropylmethanol is by way of the Claisen condensation product of diethyl succinate with ethyl trifluoroacetate [63] according to known procedure. However, the previously used conditions were modified for two of the four steps in order to achieve a better overall yield [64] (Scheme 7). Surprisingly, the reduction of the ketoester 35 to the hydroxyester 36 proceeded very slowly under the previously described conditions (H 2 /PtO 2 ) -in several attempts (2 h, 24 h and 72 h) the yield of 36 was never better than 60%, and about 25% of the ketoester 35 was recovered.…”

Section: Development Of a General Protocolmentioning

confidence: 99%

Total Synthesis of Various Hormaomycin Analogues with Modified Amino Acid Residues

Raev¹

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AM 250 (250 MHz), Varian Unity 300 (300 MHz), Inova 500 (500 MHz), Inova 600 (600 MHz). 1 H chemical shifts are reported in ppm relative to residual peaks of deuterated solvents: δ (ppm) = 2.49 for [D 5 ]DMSO, 4.65 for HOD in D 2 O, 7.26 for CHCl 3 , 1.73 and 3.55 for [D 7 ]THF, 3.35 for CHD 2 OD. Higher-order NMR spectra were approximately interpreted as first-order spectra, if possible. For the characterization of the observed signal multiplicities the following abbreviations have been applied: s = singlet, d = doublet, t = triplet, q = quartet, quin = quintet, m = multiplet, as well as b = broad. 13 C NMR [additional DEPT (Distortionless Enhancement by Polarization Transfer) or APT (Attached Proton Test)]: Bruker AM 250 (62.9 MHz), AMX 300 (75.5 MHz) or Varian Unity 300 (75.5 MHz), Inova 500 (125.7 MHz), Inova 600 (125.7 MHz) instruments. 13 BORWIN HSS-2000, column Nucleodur ® C18 (250 mm × 20 mm, 5 µm, 100 Å), flow rate 18.0 ml/min. Optical rotations: Perkin-Elmer 241 digital polarimeter, 1-dm cell; optical rotation values are given in 10 -1 deg cm 2 g -1 ; concentrations (c) are given in g/100 mL. M.p.: Büchi 510 capillary melting point apparatus, uncorrected values. TLC: Macherey-Nagel pre-coated sheets, 0.25 mm Sil G/UV254. The chromatograms were viewed under UV light and/or by treatment with phosphomolybdic acid (10% in ethanol), or ninhydrine (0.2% in ethanol), or I 2 vapor. Column chromatography: Merck silica gel, grade 60, 230-400 mesh and Baker silica gel, 40-140 mesh. Elemental analyses: Mikroanalytisches Laboratorium des Instituts für Organische und Biomolekulare Chemie der Universität Göttingen.Starting materials: Anhydrous solvents were prepared according to standard methods by distillation over drying agents and were stored under nitrogen. All other solvents were distilled before use.All reactions were carried out with magnetic stirring and, when employing air-or moisturesensitive materials, in flame-dried glassware under argon or nitrogen. 7.General synthetic protocols Deprotection of N-Fmoc-protected peptides (GP 1)The respective protected peptide (1 mmol) was taken up with acetonitrile or THF (2 mL), diethylamine (2 mL) was added, and the resulting mixture left at ambient temperature for 40 min. All volatiles were evaporated under reduced pressure, the residue was taken up with toluene (2 × 5 mL), which was evaporated under reduced pressure to remove the last traces of diethylamine. The obtained crude N-deprotected peptide was directly used in the next condensation step. Peptide condensation step for the preparation of peptides using EDC/HOAt -mediated coupling (GP 2)EDC (1.03 mmol) and HOAt (1.05 mmol) were added to a cooled (4 °C) solution of the respective N-protected amino acid (1 mmol) in anhydrous CH 2 Cl 2 (3 mL). After 20 min, the solution of the appropriate crude N-deprotected peptide (0.97 mmol) and TMP (3 mmol) in

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Regioselectivity in the ring opening of 2-alkylcyclopropylmethyl radicals: the effect of electronegative substituents

Abstract: The regioselectivity of the ring-opening of the trans-2-alkylcyclopropylmethyl radical A t o give the primary alkyl radicals B, or the secondary alkyl radicals C, has been investigated, where the groups R

Cited by 29 publications

References 7 publications

Deconvoluting the Memory Effect in Pd‐Catalyzed Allylic Alkylation: Effect of Leaving Group and Added Chloride

Deconvoluting the Memory Effect in Pd‐Catalyzed Allylic Alkylation: Effect of Leaving Group and Added Chloride

(2R,1'S,2'R)- and (2S,1'S,2'R)-3-[2-Mono(di,tri)fluoromethylcyclopropyl]alanines and their incorporation into hormaomycin analogues

Total Synthesis of Various Hormaomycin Analogues with Modified Amino Acid Residues

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