Radical Addition Approach to Asymmetric Amine Synthesis: Design, Implementation, and Comparison of Chiral N-Acylhydrazones
- 7 July 2005
- journal article
- research article
- Published by American Chemical Society (ACS) in The Journal of Organic Chemistry
- Vol. 70 (16) , 6330-6338
- https://doi.org/10.1021/jo050756m
Abstract
Intermolecular radical addition to CN 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 CN 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 CN 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.Keywords
This publication has 17 references indexed in Scilit:
- Radical addition to oxime ethers for asymmetric synthesis of β-amino acid derivativesOrganic & Biomolecular Chemistry, 2002
- Diethylzinc: A Chain-Transfer Agent in Intermolecular Radical Additions. A Parallel with TriethylboraneThe Journal of Organic Chemistry, 1999
- Highly Diastereoselective Radical Addition to Oxime Ethers: Asymmetric Synthesis of β-Amino AcidsOrganic Letters, 1999
- Novel Synthesis of α-Amino Acid Derivatives through Triethylborane-Induced Solid-Phase Radical ReactionsThe Journal of Organic Chemistry, 1999
- Enantioselective Free Radical ReactionsAccounts of Chemical Research, 1998
- Samarium(II) Iodide Induced Radical Cyclizations of Halo- and CarbonylhydrazonesJournal of the American Chemical Society, 1994
- Enantioselective Synthesis of α‐Substituted Primary Amines by Nucleophilic Addition to Aldehyde‐SAMP HydrazonesAngewandte Chemie International Edition in English, 1986
- Chiral 1,4-dihydropyridine equivalents: a new approach to the asymmetric synthesis of alkaloids. The enantiospecific synthesis of (+)- and (-)-coniine and dihydropinidineJournal of the American Chemical Society, 1983
- Selective trapping of dienes by benzylideneacetoneiron tricarbonyl. Synthetic and mechanistic studies of the reactions of 1,3,5-cyclooctatriene and its derivatives with benzylideneacetoneiron tricarbonylJournal of the American Chemical Society, 1977
- A New Method for the Alkylation of Ketones and Aldehydes: the C-Alkylation of the Magnesium Salts of N-Substituted IminesJournal of the American Chemical Society, 1963