299216-14-1Relevant articles and documents
Mn-mediated coupling of alkyl iodides and chiral N-acylhydrazones: Optimization, scope, and evidence for a radical mechanism
Friestad, Gregory K.,Marie, Jean-Charles,Suh, YoungSung,Qin, Jun
, p. 7016 - 7027 (2007/10/03)
Stereoselective radical additions have excellent potential as mild, nonbasic carbon-carbon bond constructions for direct asymmetric amine synthesis. Efficient intermolecular radical addition to C=N bonds with acyclic stereocontrol has previously been limited mainly to secondary and tertiary radicals, a serious limitation from the perspective of synthetic applications. Here, we provide full details of the use of photolysis with manganese carbonyl to mediate stereoselective intermolecular radical addition to N-acylhydrazones. Photolysis (300 nm) of alkyl halides and hydrazones in the presence of Mn 2(CO)10 and InCl3 as a Lewis acid led to reductive radical addition; diastereomer ratios ranged from 93:7 to 98:2 at ca. 35 °C. The reaction tolerates additional functionality in either reactant, enabling subsequent transformations as shown in an efficient asymmetric synthesis of coniine. A series of hydrazones bearing different substituents on the oxazolidinone auxiliary were compared; consistently high diastereocontrol revealed that the identity of the substituent had little practical effect on the diastereoselectivity. Further mechanistic control experiments confirmed the intermediacy of radicals and showed that independently prepared alkyl- or acylmanganese pentacarbonyl compounds do not undergo efficient addition to the N-acylhydrazones under thermal or photolytic (300 nm) conditions. These Mn-mediated conditions avoid toxic tin reagents and enable stereoselective intermolecular radical additions to C=N bonds with the broadest range of alkyl halides yet reported, including previously ineffective primary alkyl halides.
Radical addition approach to asymmetric amine synthesis: Design, implementation, and comparison of chiral N-acylhydrazones
Friestad, Gregory K.,Draghici, Cristian,Soukri, Mustapha,Qin, Jun
, p. 6330 - 6338 (2007/10/03)
Intermolecular radical addition to C=N bonds with acyclic stereocontrol offers excellent potential as a mild, nonbasic carbon-carbon bond construction approach to chiral amines. Here, complete details of the first radical additions to chiral N-acylhydrazones as an approach to asymmetric amine synthesis are disclosed. Novel N-acylhydrazones were designed as chiral C=N radical acceptors with Lewis acid activation, restriction of conformational mobility, and commercial availability of precursors. Amination of 4-alkyl-2-oxazolidinones with O-(mesitylenesulfonyl)hydroxylamine or O-(p-nitrobenzoyl)hydroxylamine afforded N-aminooxazolidinones which were condensed with aldehydes to afford N-acylhydrazones 3-8. Three synthetic methods were developed, implementing these N-acylhydrazones in Lewis acid-promoted intermolecular radical additions to C=N bonds. First, additions of various secondary and tertiary alkyl iodides to propionaldehyde and benzaldehyde hydrazones (3 and 7) under tin hydride radical chain conditions in the presence of ZnCl2 gave N-acylhydrazine adducts with diastereomeric ratios ranging from 93:7 to 99:1. Radical additions to a series of N-acylhydrazones with different substituents on the oxazolidinone revealed that benzyl and diphenylmethyl were more effective stereocontrol elements than those with the aromatic ring directly attached to the oxazolidinone. Second, a tin-free method, exploiting dual functions of triethylborane for both initiation and chain propagation, enabled improved yields in addition of secondary alkyl iodides. Third, under photolytic conditions with hexamethylditin, primary radical addition could be achieved with ethyl iodide in the presence of diethyl ether as cosolvent; the 1-ethoxyethyl adduct was observed as a minor product. Chloromethyl addition was achieved under both the tin-free and photolytic conditions; in this case, the adduct bears alkyl chloride functionality with potential for further elaboration.
Intermolecular alkyl radical addition to chiral N-acylhydrazones mediated by manganese carbonyl [14]
Friestad,Qin
, p. 9922 - 9923 (2007/10/03)
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