First Stereoselective Synthesis of the C(1)-C(13) Fragment of Dolabelides Using Ruthenium-SYNPHOS^®-Catalyzed Asymmetric Hydrogenation Reactions

Abstract

The first stereocontrolled synthesis of the C(1)-C(13) fragment of cytotoxic macrolides dolabelides is reported. The C(3), C(7), C(9) and C(11) hydroxyl-bearing stereocenters were installed using ruthenium-mediated asymmetric hydrogenation reactions of the adequate β-keto esters and β-hydroxy ketone.

Key words

asymmetric catalysis - hydrogenation - ruthenium - total synthesis - natural products

References

• 1 Ojika M. Nagoya T. Shibata T. Yamada K. Tetrahedron Lett.  1995,  36:  7491 
• 2 Suenaga K. Nagoya T. Shibata T. Kigoshi H. Yamada K. J. Nat. Prod.  1997,  60:  155 
• 3 Phansavath P. Duprat de Paule S. Ratovelomanana-Vidal V. Genêt J.-P. Eur. J. Org. Chem.  2000,  3903 
• 4 Lavergne D. Mordant C. Ratovelomanana-Vidal V. Genêt J.-P. Org. Lett.  2001,  3:  1909 
• 5 Labeeuw O. Phansavath P. Genêt J.-P. Tetrahedron: Asymmetry  2004,  15:  1899 
• 6a Duprat de Paule S. Jeulin S. Ratovelomanana-Vidal V. Genêt J.-P. Champion N. Dellis P. Tetrahedron Lett.  2003,  44:  823 
• 6b Duprat de Paule S. Jeulin S. Ratovelomanana-Vidal V. Genêt J.-P. Champion N. Dellis P. Eur. J. Org. Chem.  2003,  1931 
• 6c

  Both antipodes of SYNPHOS^® {[2,3,2′,3′-tetrahydro-5,5′-bi(1,4-benzodioxin)-6,6′-diyl]bis(diphenylphosphane)} are commercially available from Strem Chemicals.

• 7 Grimaud L. de Mesmay R. Prunet J. Org. Lett.  2002,  4:  419 
• 8 Desroy N. Le Roux R. Phansavath P. Chiummiento L. Bonini C. Genêt J.-P. Tetrahedron Lett.  2003,  44:  1763 
• 9 Schmidt DR. Park PK. Leighton JL. Org. Lett.  2003,  5:  3535 
• Reviews:
• 10a Genêt J.-P. In Reductions in Organic Synthesis   Magid A. ACS Symposium Series 641, American Chemical Society; Washington DC: 1996.  p.31-51  
• 10b Genêt J.-P. Acc. Chem. Res.  2003,  36:  908 
• 11 Noyori R. Acta Chem. Scand.  1996,  50:  380 
• 12 Walkup RD. Kane RR. Boatman PD. Cunningham RT. Tetrahedron Lett.  1990,  31:  7587 
• 13 Rathke MW. Lindert A. J. Am. Chem. Soc.  1971,  93:  2318 
• 14 Genêt J.-P. Pinel C. Ratovelomanana-Vidal V. Mallart S. Caño de Andrade MC. Laffite J.-A. Tetrahedron: Asymmetry  1994,  5:  665 
• 15 Genêt J.-P. Ratovelomanana-Vidal V. J. Organomet. Chem.  1998,  567:  163 
• 16 Fráter G. Helv. Chim. Acta  1979,  62:  2825 
• 17 Seebach D. Wasmuth D. Helv. Chim. Acta  1980,  63:  197 
• 18 Paterson I. Smith JD. Ward RA. Tetrahedron  1995,  51:  9413 
• 19 Claffey MM. Hayes CJ. Heathcock CH. J. Org. Chem.  1999,  64:  8267 
• 20 Ikariya T. Ishii Y. Kawano H. Arai T. Saburi M. Yoshikawa S. Akutagawa S. J. Chem. Soc., Chem. Commun.  1985,  922 
• 21 Ohta T. Tonomura Y. Nozaki K. Takaya H. Mashima K. Organometallics  1996,  15:  1521 
• 22 Mashima K. Nakamura T. Matsuo Y. Tani K. J. Organomet. Chem.  2000,  607:  51 
• 24 For the use of this type of catalyst in total synthesis, see: Fürstner A. Dierkes T. Thiel OR. Blanda G. Chem.-Eur. J.  2001,  7:  5286 
• 25 Blanchette MA. Choy W. Davis JT. Essenfeld AP. Masamune S. Roush WR. Sakai T. Tetrahedron Lett.  1984,  25:  2183 
• 26 Rychnovsky SD. Skalitzky DJ. Tetrahedron Lett.  1990,  31:  945 

23

Typical Procedure for the Synthesis of Ikariya-Mashima’s Catalyst with ( S )-SYNPHOS ^® 10.
A mixture of [RuCl₂(η⁶-benzene)]₂ (25 mg, 0.05 mmol), (S)-SYNPHOS^® (64 mg, 0.1 mmol) and dimethylammonium chloride (8 mg, 0.1 mmol) were introduced in a 50 mL round bottom tube equipped with a magnetic stirring bar and a condenser. The mixture was degassed by three vacuum/argon cycles at r.t. Degassed anhyd THF (6 mL) was added. The orange mixture was refluxed overnight and then cooled to r.t. The solvents were evaporated under vacuum and the brown solid 10 was used as crude catalyst for the hydrogenation reaction without further purification.
Typical Procedure for the Hydrogenation Reaction with Ikariya-Mashima’s Catalyst 10.
A solution of b-keto ester 9 (110 mg, 0.30 mmol) in degassed MeOH (2.0 mL) was added to Ikariya-Mashima’s catalyst 10 (6.0 mg, 0.004 mmol) in a round bottom tube via cannula. The reaction vessel was placed in a stainless steel autoclave, which was purged with hydrogen and pressurized to 80 bar. After stirring for 8 h at r.t., hydrogen was vented and the reaction mixture was concentrated in vacuo. The residue was purified by flash chromatography (C₆H₁₂-EtOAc = 8.5:1.5) to give 11 (102 mg, 0.28 mmol, 93%, de = 98%) as a pale yellow oil.