A Short and Practical Access to both Enantiomers of 4-Hydroxycyclohexenone Based on a Desymmetrizing CBS Reduction

Abstract

By employing an unprecedented CBS-catalyzed reductive desymmetrization of the readily available meso-diketone 2, both enantiomers of the cyclohexenone precursor 3 can be synthesized in up to 92% yield and 98% ee. From this precursor, 4-hydro­xy­cyclohexenone (1) is easily liberated by a retro Diels-Alder reaction.

asymmetric catalysis - oxazaborolidines - cyclohexen­ones - reduction - desymmetrization

References

<A NAME="RT05606SS-1A">1a</A> Enders D. Breuer K. In Comprehensive Asymmetric Catalysis   Vol. 2:  Jacobsen EN. Pfaltz A. Yamamoto H. Springer; Berlin: 1999.  p.1093 

<A NAME="RT05606SS-1B">1b</A> Yamamoto A. Sudo H. Endo A. Atherosclerosis  1980,  35:  259 

<A NAME="RT05606SS-2A">2a</A> Trost BM. Romero AG. J. Org. Chem.  1986,  51:  2332 

<A NAME="RT05606SS-2B">2b</A> Audia JE. Boisvert L. Patten AD. Villalobos A. Danishefsky SJ. J. Org. Chem.  1989,  54:  3738 

<A NAME="RT05606SS-2C">2c</A> Gebauer O. Brückner R. Liebigs Ann. Chem.  1996,  1559 

<A NAME="RT05606SS-3A">3a</A> Brünjes R. Tilstam U. Winterfeldt E. Chem. Ber.  1991,  124:  1677 

<A NAME="RT05606SS-3B">3b</A> Carreño MC. García Ruano JL. Garrido M. Pilar Ruiz M. Solladié G. Tetrahedron Lett.  1990,  31:  6653 

<A NAME="RT05606SS-3C">3c</A> De March P. Escoda M. Figueredo M. Font J. García-García E. Rodríguez S. Tetrahedron: Asymmetry  2000,  11:  4473 

<A NAME="RT05606SS-4A">4a</A> Morgan BS. Hoenner D. Evans P. Roberts SM. Tetrahedron: Asymmetry  2004,  15:  2807 

<A NAME="RT05606SS-4B">4b</A> Marchand AP. Xing D. Wang Y. Bott SG. Tetrahedron: Asymmetry  1995,  6:  2709 

<A NAME="RT05606SS-4C">4c</A> Kazlauskas RJ. Weissfloch ANE. Rappaport AT. Cuccia LA. J. Org. Chem.  1991,  56:  2656 

<A NAME="RT05606SS-4D">4d</A> Demir AS. Sesenoglu O. Org. Lett.  2002,  4:  2021 

<A NAME="RT05606SS-5">5</A> Suzuki H. Yamazaki N. Kibayashi C. J. Org. Chem.  2001,  66:  1494 

<A NAME="RT05606SS-6">6</A> Hashiguchi S. Fujii A. Haack K.-J. Matsumura K. Ikariya T. Noyori R. Angew. Chem., Int. Ed. Engl.  1997,  36:  288 ; Angew. Chem. 1997, 109, 300

<A NAME="RT05606SS-7">7</A> Bäckvall J.-E. Byström SE. Nordberg RE. J. Org. Chem.  1984,  49:  4619 

<A NAME="RT05606SS-8">8</A> Nising CF. Ohnemüller UK. Bräse S. Angew. Chem. Int. Ed.  2006,  45:  307 ; Angew. Chem. 2006, 118, 313

<A NAME="RT05606SS-9">9</A>

The absolute configuration of diversonol has not yet been determined.

<A NAME="RT05606SS-10">10</A> Oda M. Kawase T. Okada T. Enomoto T. Org. Synth.  1996,  73:  253 

<A NAME="RT05606SS-11A">11a</A> Hiroya K. Kurihara Y. Ogasawara K. Angew. Chem., Int. Ed. Engl.  1995,  34:  2287 ; Angew. Chem. 1995, 107, 2445

<A NAME="RT05606SS-11B">11b</A> Konno H. Ogasawara K. Synlett  1999,  1135 

<A NAME="RT05606SS-11C">11c</A> Mehta G. Islam K. Tetrahedron. Lett.  2003,  44:  6733 

<A NAME="RT05606SS-12">12</A> Corey EJ. Helal CJ. Angew. Chem. Int. Ed.  1998,  37:  1986 ; Angew. Chem. 1998, 110, 2092

<A NAME="RT05606SS-13A">13a</A> Spivey AC. Andrews BI. Brown AD. Frampton CS. Chem. Commun.  1999,  2523 

<A NAME="RT05606SS-13B">13b</A> Dixon RA. Jones S. Tetrahedron: Asymmetry  2002,  13:  1115 

<A NAME="RT05606SS-13C">13c</A> For a review on enzymatic desymmetrizations, see: Garcia-Urdiales E. Alfonso I. Gotor V. Chem. Rev.  2005,  105:  313 

<A NAME="RT05606SS-14">14</A>

This observation might be due to the fact that (R)- and (S)-Me-CBS were received from different suppliers and is being currently investigated in our group.

<A NAME="RT05606SS-15">15</A> The enantiomeric excess of (S)-(-)-4-hydroxycyclohexen-one was determined to be >94% by using the Mosher method: Dale JA. Mosher HS. J. Am. Chem. Soc.  1973,  95:  512