Enantioselective Radical Addition Research Articles

Retracted: Enantioselective Radical Addition to Ketimines: A Synthetic Route Towards α,α‐Disubstituted α‐Amino Acids

The title reaction provides a general route for the synthesis of α,α-disubstituted α-amino acids under metal-free conditions.

ChemInform Abstract: Enantioselective Radical Addition Reactions to Imines Using Binaphthol‐Derived Chiral N‐Triflyl Phosphoramides.

AbstractChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.

ChemInform Abstract: Highly Enantioselective Radical Addition to N‐Benzoyl Hydrazones Using Chiral Ammonium Salts.

AbstractChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.

Enantioselective radical addition reactions to imines using binaphthol-derived chiral N-triflyl phosphoramides

Binaphthol-derived chiral phosphoric acid catalysts were applied to enantioselective radical addition reactions of imines and provided chiral amines with good enantioselectivities (73–84% ee). Furthermore, the enantioselectivities were not affected by either electronic properties of phenyl imines or radical precursors.

Radical Addition to C=N Bonds Mediated by Chiral Ammonium Salts

A protonated cinchona alkaloid ­derivative (PC)-mediated enantioselective radical addition of alkyl radicals to the C=N bond of N-benzoyl hydrazones is reported (for a Lewis acid mediated version, see: G. K. Friestad et al. ­Angew. Chem. Int. Ed. 2003, 42, 5061). In the presence of PC, Ph2SiH2, Et3B and air in di­chloromethane, the addition of alkyl radicals generated from alkyl iodides to N-benzoyl hydrazones furnished the adducts in good yields and good to excellent enantioselectivities (90:10 to 99.5:0.5) at -30 ˚C. The employment of diphenylsilane instead of organotin hydrides as the radical chain carrier can avoid such disadvantages as high toxicity and difficulty in purifying the product. Triethylborane is necessary for initiating the reaction at low temperatures.

Highly Enantioselective Radical Addition to N-Benzoyl Hydrazones Using Chiral Ammonium Salts

In the presence of a protonated cinchonine derivative, radical addition reactions proceeded efficiently, affording addition adducts in high yields with an extremely high enantioselectivity. The chiral ammonium salt was recyclable after a simple aqueous workup. The reaction provides environmentally benign reaction conditions.

Enantioselective Radical Addition Reactions to the C=N Bond Utilizing Chiral Quaternary Ammonium Salts of Hypophosphorous Acid in Aqueous Media.

AbstractChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract, please click on HTML or PDF.

Enantioselective Radical Addition of Alkyl Halides to Glyoxylate Oxime Ether

Quaternary ammonia salts of cinchona alkaloids quinine and quinidine and hypophosphorous acid have been employed to provide a chiral environment for the addition of an alkyl radical to glyoxylate oxime ether. The reaction was found to proceed with moderate to good yields and varying degrees of enantioselectivities. The highest enantioselectivity was observed for sterically demanding alkyl halides. The described method offers mild and practical reaction conditions: The glyoxylate oxime ether is generated in situ and the reaction is run at room temperature.

Reactive Ketimino Radical Acceptors: Intermolecular Alkyl Radical Addition to Imines with a Phenolic Hydroxyl Group

Intermolecular carbon radical addition to the carbon-nitrogen double bond of ketimines was studied. In the study on the reactivity of various aldimines, we found that the aldimine 7 having a phenolic hydroxyl group shows an excellent reactivity toward nucleophilic carbon radicals. A remarkable effect of phenolic hydroxyl group is assumed to be the stabilization of intermediate aminyl radical provided by a hydroxyl group. The screening of reactive ketimino acceptors showed that ketimines 15, 17, and 19 having a phenolic hydroxyl group exhibit excellent reactivities. The radical addition to ketimines 15, 17, and 19 took place regioselectively at the imino carbon to give the C-alkylated products without the formation of N-alkylated products. Enantioselective ethyl radical addition to ketimine 15 using chiral box ligand and Zn(OTf)2 gave the diethylated product 30 in 80% ee.

Enantioselective radical addition reactions to the CN bond utilizing chiral quaternary ammonium salts of hypophosphorous acid in aqueous media

An enantioselective addition of alkyl radicals to glyoxylate oxime ether mediated by Cinchona alkaloid derived chiral ammonium salts of hypophosphorous acid, QP and QDP, has been developed.

Enantioselective Radical Addition to N‐Acyl Hydrazones Mediated by Chiral Lewis Acids.

AbstractFor Abstract see ChemInform Abstract in Full Text.

Enantioselective Radical Addition to N‐Acyl Hydrazones Mediated by Chiral Lewis Acids

Radikale Vorgehensweise: In Gegenwart eines chiralen CuII-Bisoxazolin-Komplexes verläuft die Addition von Alkylradikalen (.R2) an achirale N-Acylhydrazone mit hohen Enantioselektivitäten (siehe Schema). Die Beteiligung des Katalysators in diesen ersten katalytischen asymmetrischen Radikaladditionen an CN-Bindungen konnte nachgewiesen werden.

Enantioselective radical addition to N-acyl hydrazones mediated by chiral Lewis acids.

A radical concept: In the presence of chiral CuII–bisoxazoline complexes, the addition of alkyl radicals to achiral N-acyl hydrazones, which have a two-point-binding motif, proceeded with high enantioselectivity. Evidence of catalyst turnover was demonstrated, providing the first example of asymmetric catalysis in radical additions to CN bonds.

Asymmetric synthesis of alpha-amino acids based on carbon radical addition to glyoxylic oxime ether

The first asymmetric synthesis of alpha-amino acids based on diastereoselective carbon radical addition to glyoxylic imine derivatives is reported. The addition of an isopropyl radical, generated from i-PrI, Bu(3)SnH, and Et(3)B in CH(2)Cl(2) at 25 degrees C, to achiral glyoxylic oxime ether 1 proceeded regioselectively at the imino carbon atom of the oxime ether group to give an excellent yield of the C-isopropylated product 2. The competitive reaction using glyoxylic oxime ether 1 and aldoxime ether 4 showed that the reactivity of the glyoxylic oxime ether toward nucleophilic carbon radicals was enhanced by the presence of a neighboring electron-withdrawing substituent. Thus, the alkyl radical addition to glyoxylic oxime ether 1 proceeded smoothly even at -78 degrees C, in contrast to the unactivated aldoxime ether 4. A high degree of stereocontrol in the carbon radical addition to the glyoxylic oxime ether was achieved by using Oppolzer's camphorsultam as a chiral auxiliary. The stannyl radical-mediated reaction of the camphorsultam derivative 6 with an isopropyl radical at -78 degrees C afforded a 96:4 diastereomeric mixture, 7a, of the C-isopropylated product. The reductive removal of the benzyloxy group of the major diastereomer (R)-7a, by treatment with Mo(CO)(6) and the subsequent removal of the sultam auxiliary by standard hydrolysis, afforded the enantiomerically pure D-valine (R)-12 without any loss of stereochemical purity. To evaluate the new methodology, a variety of alkyl radicals were employed in the addition reaction which gave the alkylated products 7 with excellent diastereoselectivity, allowing access to a wide range of enantiomerically pure natural and unnatural alpha-amino acids. Even in the absence of Bu(3)SnH, treatment of 6 with alkyl iodide and Et(3)B at 20 degrees C gave the C-alkylated products 7 with moderate diastereoselectivities. The use of Et(2)Zn as a radical initiator, instead of Et(3)B, was also effective for the radical reaction. The enantioselective isopropyl radical addition to 1 using (R)-(+)-2, 2'-isopropylidenebis(4-phenyl-2-oxazoline) and MgBr(2) gave excellent chemical yield of the valine derivative 2 in 52% ee.