A Stereoselective Oxy-Michael Approach to THP*-Protected β-Hydroxy Esters

Abstract

The ‘naked’ anion of (S)-6-methyl δ-lactol undergoes efficient oxy-Michael addition to α,β-unsaturated methyl sulfones to give the corresponding adducts with excellent (up to 99% de) stereo­control at the newly formed stereogenic β-centre. The successive reductive desulfonylation using excess samarium(II) iodide under mild reaction conditions affords the THP*-protected β-hydroxy esters as single diastereoisomers after chromatography on silica gel.

Key words

asymmetric synthesis - oxy-Michael additions - samarium(II) iodide - protodesulfonylation - β-hydroxy esters

References

• For selected examples of β-hydroxy esters being employed for the synthesis of natural products, see:
• 1a Lau CK. Crumpler S. Macfarlane K. Lee F. Berthelette C. Synlett  2004,  2281 
• 1b Ritter T. Zarotti P. Carreira EM. Org. Lett.  2004,  6:  4371 
• 1c Kusaka S. Dohi S. Doi T. Takahashi T. Tetrahedron Lett.  2003,  44:  8857 
• 1d Thakur VV. Nikalje MD. Sudalai A. Tetrahedron: Asymmetry  2003,  14:  581 
• 1e Garbaccio RM. Stachel SJ. Baeschlin DK. Danishefsky SJ. J. Am. Chem. Soc.  2001,  123:  10903 
• 1f Cohen F. Overman LE. J. Am. Chem. Soc.  2001,  123:  10782 
• 1g Kobayashi Y. Kumar GB. Kurachi T. Acharya HP. Yamazaki T. Kitazume T. J. Org. Chem.  2001,  66:  2011 
• 1h Ham W.-H. Oh C.-Y. Lee Y.-S. Jeong J.-H. J. Org. Chem.  2000,  65:  8372 
• 1i Kobayashi Y. Matsuumi M. J. Org. Chem.  2000,  65:  7221 
• 2a Noyori R. Ohkuma T. Kitamura M. J. Am. Chem. Soc.  1994,  109:  5856 
• 2b Noyori R. Angew. Chem. Int. Ed.  2002,  41:  2008 ; and references cited therein
• 2c Zhou Y.-G. Tang W. Wang W.-B. Li W. Zhang X. J. Am. Chem. Soc.  2002,  124:  4952 
• 2d Hu A. Ngo HL. Lin W. Angew. Chem. Int. Ed.  2003,  42:  6000 
• For a leading example of catalytic asymmetric aldol approaches to β-hydroxy esters, see:
• 3a Carreira EM. Singer RA. Lee WS. J. Am. Chem. Soc.  1994,  116:  8837 
• For references of organocatalytic asymmetric aldol approaches to β-hydroxy esters, see:
• 3b Berkessel A. Gröger H. Asymmetric Organocatalysis   VCH-Wiley; Weinheim: 2005.  Chap. 6. p.140-166  
• 4a Hinterding K. Jacobsen EN. J. Org. Chem.  1999,  64:  2164 
• 4b Ruck RT. Jacobsen EN. J. Am. Chem. Soc.  2002,  124:  2882 
• 4c Vanderwal CD. Jacobsen EN. J. Am. Chem. Soc.  2004,  126:  14724 
• 5a Adderley NJ. Buchanan DJ. Dixon DJ. Lainé DI. Angew. Chem. Int. Ed.  2003,  42:  4241 
• 5b Buchanan DJ. Dixon DJ. Hernández-Juan FA. Org. Biomol. Chem.  2004,  2:  2932 
• For related reactions, see:
• 5c Enders D. Haertwig A. Raabe G. Runsink J. Angew. Chem., Int. Ed. Engl.  1996,  35:  2388 
• 5d Enders D. Haertwig A. Raabe G. Runsink J. Eur. J. Org. Chem.  1998,  1771 
• 6a Buchanan DJ. Dixon DJ. Scott MS. Lainé DI. Tetrahedron: Asymmetry  2004,  15:  195 
• 6b Buchanan DJ. Dixon DJ. Looker BE. Synlett  2005,  1948 
• 7 Buchanan DJ. Dixon DJ. Hernández-Juan FA. Org. Lett.  2004,  6:  1357 
• 10a Happer DA. Steenson BE. Synthesis  1980,  806 
• 10b Trost BM. Weber L. Strege P. Fullerton TJ. Dietsche TJ. J. Am. Chem. Soc.  1978,  100:  3426 
• 11For a review, see:
• 11 Molander GA. Org. React.  1994,  46:  211 

8

Studies by us have indicated that the direct stereoselective oxy-Michael addition to α,β-unsaturated esters (such as tert-butyl crotonate) was not a viable way to synthesise protected aldol products owing to the low natural reactivity of the two components.

9

All the sulfone-derived Michael acceptors 2 and 5 were obtained as a mixture of Z/E isomers with the predominant E configuration assigned by NOE.