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.

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 

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

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).

12

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