Fragmentation of 4-Sulfonylbicyclo[3.1.0]hexan-2-ones as the Key Step in the Enantioselective Synthesis of (1R)-cis-Chrysanthemic Acid Involving Desymmetrization of 3,3,6,6-Tetramethylbicyclo[3.1.0]hexane-2,4-dione

Abstract

t-BuOK-H₂O (7.6:2.3) in THF or DMSO allows the efficient Grob-type fragmentation of 4-sulfonyl-bicyclo[3.1.0]hexan-2-ones which cannot be achieved by potassium hydroxide in DMSO as we originally described.

Key words

ring opening - retro-aldol - nucleophiles - lithiation - chirality

References and Notes

• 1a Krief A. Surleraux D. Frauenrath H. Tetrahedron Lett.  1988,  29:  6157 
• 1b Krief A. Surleraux D. Dumont W. Pasau P. Lecomte P. Pure Appl. Chem.  1990,  62:  1311 
• 1c Krief A. In Stereocontrolled Organic Synthesis, A "Chemistry for the 21st Century" Monograph   Trost BM. International Union of Pure and Applied Chemistry, Blackwell Scientific Publications; Oxford: 1994.  p.337-397  
• 1d

  Readily available from dimethyl dimedone.

• 2 Krief A. Surleraux D. Ropson N. Tetrahedron: Asymmetry  1993,  4:  289 
• 3a Krief A. Swinnen D. Tetrahedron Lett.  1996,  37:  7123 
• 3b Krief A. Swinnen D. Billen D. Tetrahedron Lett.  2002,  43:  5871 
• 4 Krief A. Surleraux D. Robson MJ. Synlett  1991,  4:  276 
• 5 Krief A. Lorvelec G. Jeanmart S. Tetrahedron Lett.  2000,  41:  3871 
• 6 Grob CA. Angew. Chem., Int. Ed. Engl.  1969,  8:  535 
• 9a Gassman PG. Zalar FV. Tetrahedron Lett.  1964,  40:  3031 
• 9b Gassman PG. Zalar FV. Tetrahedron Lett.  1964,  44:  3251 
• 9c Gassman PG. Lumb JT. Zalar FV. J. Am. Chem. Soc.  1967,  946 
• 9d Gassman PG. Schenk WN. J. Org. Chem.  1977,  42:  918 
• 10 Adams DJ. Blake AJ. Cooke PA. Gill CD. Simpkins N. Tetrahedron  2002,  58:  4603 
• 11a

  Compound 10a: [α]_D ²⁰ -20 (c 1.20, CHCl₃).

• 11b

  Compound 11a _exo : [α]_D ²⁰ +12.5 (c 1.22, CHCl₃).

• 11c

  Compound 1a _Ms-exo : [α]_D ²⁰ +55.1 (c 1.11, CHCl₃).

• 11d

  Compound 2a: [α]_D ²⁰ +81.7 (c 1.0, CHCl₃).

• 11e

  Compound 12a _exo : [α]_D ²⁰ +4.9 (c 1.32, MeOH).

• 11f

  Compound 2a: [α]_D ²⁰ +82.2 (c 1.0, CHCl₃).

7

Once we found a good method for the fragmentation reaction, we performed the synthesis of scalemic 2a as originally planned by Prof. Nigel Simpkins and informed him. We thank Prof. Nigel Simpkins, School of Chemistry, University of Nottingham, University Park, Nottingham, NG7 2RD, UK for his kindness.

8

These results as well as those on the whole series of stereoisomers disclosed on Scheme [1] will be reported later. For example, we confirmed that the very labile endo-mesylate 1a _{Ms- endo} does not produce chrysanthemic acid 2a neither under conditions A nor optimized conditions B or C.^1a,4

12

Norberg, B.; Wouters, J.; Krief, A.; Kremer, A. Acta Crystallogr., Sect. C, to be published.