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DOI: 10.1055/s-2008-1042739
Multicomponent One-Pot Synthesis of Aminals and Thioaminals
Contributor(s):Paul Knochel, Tobias ThalerUniversity of Pittsburgh, USA
Multicomponent Approach to the Synthesis of Oxidized Amides through Nitrile Hydrozirconation
Org. Lett. 2007, 9: 5385-5388
Publication History
Publication Date:
21 February 2008 (online)
Key words
oxidized amides - Schwartz’ reagent - hydrozirconation - multicomponent reaction
Significance
This one-pot multi-component reaction offers a convenient and fast access to ‘oxidized’ amides, including acyl aminals and acyl thioaminals. If nitriles with an ether group at the α-carbon are employed, the formation of the respective aminal is observed to proceed with some diastereoselection. Hereby, the reaction may pass through two different pathways, one involving addition via chelation leading to the anti isomer and the other via an attack in accordance with the Felkin-Anh model leading to the syn isomer. The diastereoselectivity can be increased in favor of the syn products when non-chelating thiols are used, whereas the application of phenol increases the diastereoselectivity in favor of the anti products.
Comment
‘Oxidized’ amides, including aminals and hemiaminals, are important constituents in a range of biologically active natural products, including cytotoxins and protein synthesis inhibitors. This method is of great use to the facile and rapid construction of novel substituted acyl aminals. An improvement of the diastereoselectivities of this reaction in favor of either pathway will increase the significance of this multicomponent reaction.