Intramolecular hetero-Michael addition of beta-hydroxyenones for the preparation of highly substituted tetrahydropyranones.

Abstract

Structurally diverse beta-hydroxyenones are shown to undergo nonoxidative 6-endo-trig ring closure to form highly substituted tetrahydropyranones. Amberlyst-15, Al(ClO(4))(3) x 9 H(2)O and [Pd(MeCN)(4)](BF(4))(2) were found to be suitable catalysts for these intramolecular conjugate additions, preventing side reactions, such as dehydration or retroaldolisation. The use of [Pd(MeCN)(4)](BF(4))(2) is particularly effective, as this palladium-mediated reaction is under kinetic control and generates tri- and tetrasubstituted tetrahydropyranones with high levels of diastereocontrol. In the presence of the Lewis acid Al(ClO(4))(3) x 9 H(2)O, the reaction proceeded with a similar level of diastereocontrol; however, in contrast to [Pd(MeCN)(4)](BF(4))(2), this catalyst can promote enolisation. The palladium-mediated reaction was also found to be compatible with an enantioenriched beta-hydroxyenone substrate, giving no loss of enantiopurity upon ring closure. The most distinctive synthetic development to emerge from this new chemistry is the possibility to access tri- and tetrasubstituted 2,6-anti-tetrahydropyranones from anti-aldol precursors. These compounds are particularly difficult to access by using alternative methodologies. Two modes of activation were envisaged for the ring closure, involving metal coordination to either the C=C or C=O functional groups. Experimental results suggest that C=O coordination was the preferred mode of activation for reactions performed in the presence of Al(ClO(4))(3) x 9 H(2)O or [Pd(MeCN)(4)](BF(4))(2).

• Authors: Maud Reiter, Hazel Turner, Véronique Gouverneur
• Journal: Chemistry (Weinheim an der Bergstrasse, Germany) (Chemistry) Vol. 12 Issue 27 Pg. 7190-203 (Sep 18 2006) ISSN: 0947-6539 [Print] Germany
• PMID: 16819725 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Alkenes
• Ketones
• Pyrans

Topics

• Alkenes (chemistry)
• Cyclization
• Ketones (chemistry)
• Oxidation-Reduction
• Pyrans (chemical synthesis, chemistry)