- Reaction of diethyl dibromomalonate with methoxide: Evidence for a novel bromophilic attack
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Reaction of diethyl dibromomalonate (1) with sodium methoxide in cyclohexene yields dibromonorcarane (2) as the major product. This product forms via the capture of dibromocarbene (4) by cyclohexene. Dibromocarbene, in turn, is generated from ethyl tribromoacetate (6) which evidence suggests arises via a bromophilic attack between the carboethoxydibromomethyl carbanion (7) and diethyldibromomalonate (1).
- Mebane, Robert C.,Smith, Keegan M.,Rucker, Darlene R.,Foster, Michael P.
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p. 1459 - 1462
(2007/10/03)
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- Synthesis of isotopically labelled L-phenylalanine and L-tyrosine
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A synthetic route to stable-isotope-substituted L-phenylalanine is presented, which allows the introduction of 13C, 15N, and deuterium labels at any position or combination of positions. For labelling of the aromatic ring, a synthetic route to ethyl benzoate (or benzonitrile) has been developed, based on the electrocyclic ring-closure of a 1,6-disubstituted hexatriene system, with in situ aromatization by elimination of one (amino) substituent. Several important (highly isotopically enriched) synthons have been prepared, namely benzonitrile, benzaldehyde, ethyl benzoate, and ethyl diphenyloxyacetate. Labelled L-phenylalanines have been synthesized from both aromatic precursors by initial conversion into sodium phenylpyruvate and subsequent transformation of this intermediate into the L-α-amino acid by an enzymatic reductive amination reaction. In this manner, highly enriched phenylalanines are obtained on the 10-gram scale and with high enantiomeric purities (≥ 99% ee). The method has been validated by the synthesis of [1'13C]-L-Phe and [2-D]-L-Phe. In addition, two methods are described for the introduction of isotopes into L-tyrosine starting from the isotopically enriched precursors benzonitrile and ethyl benzoate.
- Raap, Jan,Nieuwenhuis, Saskia,Creemers, Alain,Hexspoor, Sander,Kragl, Udo,Lugtenburg, Johan
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p. 2609 - 2621
(2007/10/03)
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- Vinylic Substitution of 1,2-Dibromo-1,2-difluoroethylene and Tribromofluoroethylene. An Intramolecular kBr/kF Element Effect and Apparent Inversion of Configuration in SNV Reactions
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The reactions of (E/Z)-1,2-dibromo-1,2-difluoroethylene(1) and of tribromofluoroethylene (2) with alkoxide ions and of 1 with p-toluenethiolate ion give multiplicity of products.The reaction of 1 with 1 equiv of NaOMe gives mainly a 2:1 mixture of the product of one bromine displacement, together with methyl dimethoxyacetate (3), methyl bromofluoroacetate (4), 1,1,2-trifluoro-2-bromoethyl ether (7), and 1,1-difluoro-1,2,2-trimethoxyethane (8).With 2 equiv of MeO(1-) 3 and 4 are the main products, and at 130 deg C, dimethyl ether 5 is also formed.With EtOCH2CH2O(1-) 1 gave 2-ethoxyethyl bromofluoroacetate (9), bis(2-ethoxyethyl) ether (10), and E/Z mixtures of the substitution products EtOCH2CH2OC(F)=C(F)Br (12) and EtOCH2CH2OC(Br)=C(F)Br (13).Reaction of 2 with excess RO(1-) (R = Me, Et) gives alkyl dibromoacetates, while with 1 equiv of RO(1-) only a bromine from the =C(F)Br carbon is displaced.Reaction of 1 with p-TolSNa in MeOH gives the reduction-substitution product p-TolSC(F)=CHF (18), together with (P-TolS)2 (16) and p-TolSMe (17).The same reaction in DMSO gives E/Z mixtures of the product of displacement of one bromine (19) or two bromines (20).Formation of the products is rationalized by an initial nucleophilic attack on the vinylic carbon followed by leaving group expulsion, giving, e.g., 12, 13, 19, or 20.Hydrolysis of the intermediate or addition of HF to the initial substition product gives saturated products, e.g., 3, 4, 7, or 8, while SN2 reactions on the ether oxygen give ethers 5 and 10.A bromophilic reaction gives the reduction-substitution product 18, while hydrolysis-decarboxylation leads to 17.The regiospecificity of the nucleophilic addition is due to polar and hyperconjugative effects.An intramolecular element effect kBr/kF of > 10 is reported for the first time in the reaction of 1 with EtOCH2CH2O(1-).This value and the absence of such effects in other reactions are consistent with a much higher nucleofugality from a (1-)CC(F)Br system of Br(1-) compared with F(1-).The E/Z compositions of 18-20 indicates an apparent inversion in their formation, but it is not known whether these compositions are thermodynamically or kinetically controlled.
- Shainyan, Bagrat A.,Rappoport, Zvi
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p. 3421 - 3428
(2007/10/02)
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- REACTION OF DIALKOXYPHOSPHORYL- AND THIOPHOSPHORYLSULFENYL BROMIDES WITH DIAZO COMPOUNDS
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Reaction of dialkoxyphosphoryl- and thiophosphorylsulfenyl bromides with diazocompounds leads to the insertion of methylene or substituted methylene groups at the S-Br bond of the sulfenylbromide.In the reaction of dialkoxyphosphorylsulfenyl bromides with ethyl diazoacetate, insertion of an ethoxycarbonyl group at the S-Br bond of the sulfenyl bromide is accompanied by phosphoryl/thiophosphoryl rearrangement.
- Khaskin, B. A.,Torgasheva, N. A.,Ishmuratov, A. S.
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p. 989 - 993
(2007/10/02)
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