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DOI: 10.1055/s-2008-1042695
Enantioselective Aldol Synthesis via Radical Addition to Cyclic Enones
Contributor(s):Mark Lautens, Valentina AureggiNorth Dakota State University, Fargo, USA
Enantioselective Radical Reactions: Stereoselective Aldol Synthesis from Cyclic Ketones
Angew. Chem. Int. Ed. 2007, 46: 9231-9234
Publication History
Publication Date:
21 February 2008 (online)
Key words
chiral Lewis acids - ketone aldols - radical addition
Significance
The development of a chiral Lewis acid mediated radical conjugate addition to cyclic enones is reported. This versatile method provides cyclic anti-aldol products of various ring sizes in high yields and excellent diastereo- and enantioselectivities. It constitutes not only a new example (among the rare enantioselective radical addition reactions), but also an efficient alternative to the classical aldol synthetic methods via anionic intermediates, especially for the difficult coupling of bulky aldehyde counterparts with cyclic ketones.
Comment
The authors disclose herein an extension of their previously described enantioselective radical conjugate addition to cyclic enones with a fixed s-trans geometry (M. P. Sibi, J. Zimmerman J. Am. Chem. Soc. 2006, 128, 13346). The reported method involves the transfer of a broad variety of radicals to s-cis cyclic enones from five- to seven-membered rings, mediated by commercially available salen-derived Lewis acid. A variety of aldol products are efficiently obtained with outstanding diastereoselectivities and good to excellent levels of enantioselectivity with a single exception. The relative and absolute stereochemistry was determined for one example through comparative HPLC analysis with a known product.