Evidence for the Role of Tetramethylethylenediamine in Aqueous Negishi Cross-Coupling: Synthesis of Nonproteinogenic Phenylalanine Derivatives on Water

TitleEvidence for the Role of Tetramethylethylenediamine in Aqueous Negishi Cross-Coupling: Synthesis of Nonproteinogenic Phenylalanine Derivatives on Water
Publication TypeJournal Article
Year of Publication2011
AuthorsA.J Ross, F. Dreiocker, M. Schafer, J. Oomens, A Meijer, B.T Pickup, R.FW Jackson
JournalJournal of Organic Chemistry
Volume76
Number5
Pagination1727-1734
Date PublishedMar
Type of ArticleArticle
ISBN Number0022-3263
Accession NumberISI:000288142800024
KeywordsCATIONS, chemistry, COMPLEXES, DIMETHYLFORMAMIDE, ELECTROSPRAY MASS-SPECTROMETRY, FACILITY, GAS-PHASE, INFRARED-SPECTROSCOPY, ORGANOZINCATE ANIONS, PSEUDOPOTENTIALS
Abstract

The structure of the alkylzinc-tetramethylethylenediamine (TMEDA) cluster cation 3 has been determined in the gas phase by a combination of tandem mass spectrometry, infrared multiphoton dissociation (IRMPD) spectroscopy, and DFT calculations. Both sets of experimental results establish the existence of a strongly stabilizing interaction of TMEDA with the zinc cation. High-level DFT calculations on the cluster cation 3 allowed the identification of two low energy conformers, each featuring a four-coordinate zinc atom with a bidentate TMEDA ligand, and internal coordination from the carbonyl group of the Boc group to zinc. The experimental IRMPD spectrum is reproduced with an appropriately weighted combination of the IR spectra of the two conformers identified by theory. DFT calculations on the structure of the allcylzinc halide 2 with coordinated TMEDA using the PCM model of water solvent suggest that TMEDA can promote ionization of the zinc-iodine bond in organozinc iodides under aqueous conditions, providing a credible explanation for the role of TMEDA in stabilizing the carbon-zinc bond. Reaction of the serine-derived iodide 1 with aryl iodides "on water", promoted by nano zinc in the presence of PdCl2(Amphos)(2) (5 mol %) and TMEDA, leads to the formation of protected phenylalanine derivatives 4 in reasonable yields. In the case of ortho-substituted aryl iodides and aryl iodides that are solids at room temperature, conducting the reaction at 65 degrees C gives unproved results. In all cases, the product 5 of reductive dimerization of the iodide 1 is also isolated.

URL<Go to ISI>://000288142800024
Division

GUTHz

Department

Molecular Dynamics

PID

d1c47fea1135016a68b9f8e6bc202327

Alternate TitleJ. Org. Chem.

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