Asymmetric Synthesis of Protected 2-Keto-1,3-diol and 1,2,3-Triol Building Blocks Bearing a Quaternary Stereogenic Center

Abstract

The asymmetric synthesis of protected 2-keto-1,3-diols 5 and 1,2,3-triols 6 bearing a quaternary stereogenic center starting from 2,2-dimethyl-1,3-dioxan-5-one (1) is described. The stereogenic centers are generated by sequential α-alkylation of 1 using the SAMP/RAMP hydrazone method and stereoselective reduction of ketones 5 with l-selectride. The products are obtained in good yields and high diastereomeric and enantiomeric excesses.

Keywords

2-keto-1,3-diols - 1,2,3-triols - asymmetric synthesis - quaternary stereogenic center - SAMP/RAMP hydrazones.

References

• 1 Searle PA. Molinski TF. J. Org. Chem.  1995,  60:  4296 
• 2 Lear MJ. Hirama M. Tetrahedron Lett.  1999,  40:  4897 
• 3 Mulzer J. Angew. Chem., Int. Ed. Engl.  1991,  30:  1452 
• 4a Greven R. Jütten P. Scharf H.-D. Carbohydr. Res.  1995,  275:  83 
• 4b Nicolaou KC. Mitchell HJ. van Delft FL. Rübsam F. Rodriguez RM. Angew. Chem., Int. Ed. Engl.  1998,  37:  1871 
• 4c Nicolaou KC. Mitchell HJ. Jain NF. Winssinger N. Hughes R. Bando T. Angew. Chem., Int. Ed.  1999,  38:  240 
• 5 Nicolaou KC. Boddy CNC. Bräse S. Winssinger N. Angew. Chem., Int. Ed.  1999,  38:  2097 
• Recent reviews:
• 6a Fuji K. Chem. Rev.  1993,  93:  2037 
• 6b Corey EJ. Guzman-Perez A. Angew. Chem., Int. Ed. Engl.  1998,  37:  388 
• 7a Weber B. Seebach D. Angew. Chem., Int. Ed. Engl.  1992,  31:  84 
• 7b Weber B. Seebach D. Tetrahedron  1994,  50:  6117 
• 8 Jacobsen EN. In Catalytic Asymmetric Synthesis   Ojima I. VCH; New York: 1993. 
• 9a Becker H. Sharpless KB. Angew. Chem., Int. Ed. Engl.  1996,  35:  448 
• 9b Kolb HC. Van Nieuwenhze MS. Sharpless KB. Chem. Rev.  1994,  94:  2483 
• 9c Morikawa K. Park J. Andersson PG. Hyshiyama T. Sharpless KB. J. Am. Chem. Soc.  1993,  115:  8463 
• 10 Bockstiegel B. Dissertation   Technical University of Aachen; Germany: 1989. 
• 11a Enders D. In Asymmetric Synthesis   Vol. 3B:  Morrison JD. Academic Press; Orlando: 1984.  p.275 
• 11b Enders D. Klatt M. In Encyclopedia of Reagents for Organic Synthesis   Paquette LA. Wiley; New York: 1995.  p.3368 
• For previous asymmetric syntheses based on 2 see:
• 12a Enders D. Hundertmark T. Tetrahedron Lett.  1999,  40:  4169 
• 12b Enders D. Hundertmark T. Eur. J. Org. Chem.  1999,  751 
• 12c Enders D. Hundertmark T. Lampe C. Jegelka U. Scharfbillig I. Eur. J. Org. Chem.  1998,  2839 
• 12d Enders D. Bockstiegel B. Gatzweiler W. Jegelka U. Dücker B. Wortmann L. Chimica Oggi  1997,  15:  20 
• 12e Enders D. Jegelka U. Tetrahedron Lett.  1993,  34:  2453 
• 12f Enders D. Bockstiegel B. Synthesis  1989,  493 
• 13 Hoppe D. Schmincke H. Kleemann H.-W. Tetrahedron  1989,  45:  687 
• 15 Enders D. Kownatka D. Hundertmark T. Prokopenko OF. Runsink J. Synthesis  1997,  649 

14

The crystal structure has been deposited at the Cambridge Cryst. Data Centre (CCDC 162249), 12 Union Road, Cambridge CB2 1EZ, UK.