Stereoselective TiCl₄-Promoted Nucleophilic Substitution at C-2 of (4S,5S)-2-Alkyl-4-methyl-5-trifluoromethyl-1,3-dioxolanes

Abstract

TiCl₄-mediated nucleophilic ring-opening reactions of chiral acetals derived from (2S,3S)-1,1,1-trifluorobutane-2,3-diol proceed in a completely regioselective manner, leading to the break of the O1-C2 bond accompanied by a high degree of stereoselectivity. The use of triethylsilyl deuteride or allyltributyltin as nucleophiles gives access, after removal of the chiral auxiliary, to stereoselectively deuterated primary alcohols or homoallylic secondary alcohols, respectively, with high enantiomeric excesses.

Key words

Acetals - ring opening - chiral auxiliary - allylations - stereoselectivity

References

• 1a Seebach D. Imwinkeheid R. Weber T. In Modern Synthetic Methods   Scheffold R. Vol. 4:  Springer-Verlag; Berlin: 1986.  p.125 
• 1b Mori A. Fujiwara J. Yamamoto H. J. Organomet. Chem.  1985,  285:  83 
• For example, see:
• 2a McNamara JM. Kishi Y. J. Am. Chem. Soc.  1982,  104:  7371 
• 2b Sekizaki H. Jung M. McNamara JM. Kishi Y. J. Am. Chem. Soc.  1982,  104:  7372 
• 2c Johnson WS. Chan MF. J. Org. Chem.  1985,  50:  2598 
• 3a Ishihara K. Mori A. Yamamoto H. Tetrahedron  1990,  46:  4595 
• 3b Mori I. Ishihara K. Flippin LA. Nozaki K. Yamamoto H. Bartlett PA. Heathcock CH. J. Org. Chem.  1990,  55:  6107 
• 3c Denmark SE. Almstead NG. J. Am. Chem. Soc.  1991,  113:  8089 
• 3d Harada T. Nakamura T. Kinugasa M. Oku A. J. Org. Chem.  1999,  64:  7594 
• 3e Morelli CF. Fornili A. Sironi M. Durì L. Speranza G. Manitto P. Tetrahedron: Asymmetry  2002,  13:  2609 
• 4 Morelli CF. Speranza G. Durì L. Manitto P. Org. Prep. Proc. Int.  2002,  34:  103 
• 5 Stein J. Lewis LN. Gao Y. Scott RA. J. Am. Chem. Soc.  1999,  121:  3693 
• 6 Brosch D. Kirmse W. J. Org. Chem.  1993,  58:  1118 
• 7 Althouse VE. Feigl DM. Sanderson WA. Mosher HS. J. Am. Chem. Soc.  1966,  88:  3595 
• 8 Imwinkelried R. Seebach D. Angew. Chem., Int. Ed. Engl.  1985,  24:  765