Mukaiyama Aldol-Prins Cyclizations with Ketones

Abstract

The Mukaiyama aldol-Prins (MAP) cyclization with ketones is described. These reactions produce substituted tetrahydropyrans efficiently and in some cases with high stereoselectivity. Cyclizations with E- and Z-alkenes are shown to be stereospecific. These studies extend the scope of the MAP cyclizations promoted by titanium tetrabromide.

Key words

tandem reactions - annulations - aldol reaction - stereo­selective - carbocations

References

• 1a de Meijere A. von Zezschwitz P. Nuske H. Stulgies B. J. Organomet. Chem.  2002,  653:  129 
• 1b Malacria M. Chem. Rev.  1996,  96:  289 
• 1c Heumann A. Reglier M. Tetrahedron  1996,  52:  9289 
• 1d Tietze LF. Chem. Ind.  1995,  453 
• Related cascade cyclizations:
• 2a Frost LM. Smith JD. Berrisford DJ. Tetrahedron Lett.  1999,  40:  2183 
• 2b Wang X. Meng Q. Nation AJ. Leighton JL. J. Am. Chem. Soc.  2002,  124:  10672 
• 3a Kopecky DJ. Rychnovsky SD. J. Am. Chem. Soc.  2001,  123:  8420 
• 3b Patterson B. Marumoto S. Rychnovsky SD. Org. Lett.  2003,  5:  3163 
• 4 Alder RW. Harvey JN. Oakley MT. J. Am. Chem. Soc.  2002,  124:  4960 
• Preparations of ketones in Table 1:
• 5a Entry 5: Nemoto H. Ishibashi H. Nagamochi M. Fukumoto K. J. Org. Chem.  1992,  57:  1707 
• 5b Entry 6: Quimpere M. Ruest L. Deslongchamps P. Synthesis  1992,  132 
• 5c Entry 7: Denmark S. Stavenger R. J. Org. Chem.  1998,  63:  9524 
• 6 Watanabe WH. Conlon LE. J. Am. Chem. Soc.  1957,  79:  2828 
• 7 Nokami J. Nomiyama K. Matsuda S. Imai N. Kataoka K. Angew. Chem. Int. Ed.  2003,  42:  1273 
• 8 For the preparation of analogous E- and Z-homoallylic alcohols, see: Jaber JJ. Mitsui K. Rychnovsky SD. J. Org. Chem.  2001,  66:  4679 

9

The configurations of the stereocenters in 8 and 9 were determined by analysis of the ¹H NMR coupling constants and of the NOESY spectra.