Practical Chloromanganese-Salen-Catalyzed Enantioselective Reformatsky Reaction with Ketones

Abstract

The first catalytic enantioselective Reformatsky reaction is realized by a controlled transmetalation of an α-iodo ester with di­methylzinc in the presence of a chloromanganese-Salen complex (20 mol%) as catalyst and 4-phenylpyridine N-oxide (25 mol%) as additive. The zinc enolate is formed under mild conditions at room temperature; it undergoes enantioselective addition to ketones. The reaction shows broad scope and moderate to good stereoselection and it allows the straightforward preparation of quaternary stereogenic centers.

Key words

Reformatsky reaction - enantioselective - catalysis - chloromanganese-Salen complex - dimethylzinc

References

• For recent reviews, see:
• 1a Ocampo R. Dolbier WR. Tetrahedron  2004,  60:  9325 
• 1b Fürstner A. Synthesis  1989,  571 
• 1c Fürstner A. In Organozinc Reagents   Knochel P. Jones P. Oxford University Press; New York: 1999.  p.287 
• 1d Marshall JA. Chemtracts  2000,  13:  705 
• 2 Rieke RD. Uhm SJ. Synthesis  1975,  452 
• 3 Santaniello E. Manzocchi A. Synthesis  1977,  698 
• 4a Kanai K. Wakabayashi H. Honda T. Org. Lett.  2000,  2:  2549 
• 4b Kanai K. Wakabayashi H. Honda T. Heterocycles  2002,  58:  47 
• 5 Adrian JC. Snapper ML. J. Org. Chem.  2003,  68:  2143 
• 6a Otaka A. Watanabe J. Yukimasa A. Sasaki Y. Watanabe H. Kinoshita T. Oishi S. Tamamura H. Fujii N. J. Org. Chem.  2004,  69:  1634 
• 6b Obringer M. Colobert F. Neugnot B. Solladie G. Org. Lett.  2003,  5:  629 
• 7 Cozzi PG. Rivalta E. Angew. Chem. Int. Ed.  2005,  44:  3600 
• 8 Fischer C. Fu GC. J. Am. Chem. Soc.  2005,  127:  4594 
• 10a Krasovskiy A. Krasovskaya V. Knochel P. Angew. Chem. Int. Ed.  2006,  45:  2958 
• 10b Krasovskiy A. Straub BF. Knochel P. Angew. Chem. Int. Ed.  2006,  45:  159 
• 10c Krasovskiy A. Knochel P. Angew. Chem. Int. Ed.  2004,  43:  3333 
• 11 Vettel S. Vaupel A. Knochel P. J. Org. Chem.  1996,  61:  7473 
• 12 Maruoka K. Hirayama N. Yamamoto H. Polyhedron  1990,  9:  223 
• 13 Sato I. Takizawa Y. Soai K. Bull. Chem. Soc. Jpn.  2000,  73:  2825 
• 14 Ukaji Y. Takenaka S. Horita Y. Inomata K. Chem. Lett.  2001,  254 
• 15 Cozzi PG. Angew. Chem. Int. Ed.  2006,  45:  2951 
• 16 Cozzi PG. Chem. Soc. Rev.  2004,  33:  410 
• 17 ClMn(Salen) can act as a Lewis acid, see: Kim SS. Lee SH. Kwak JM. Tetrahedron: Asymmetry  2006,  17:  1165 
• 18 Palucki M. Finney NS. Pospisil PJ. Guler ML. Ishida T. Jacobsen EN. J. Am. Chem. Soc.  1998,  120:  948 
• 20 Solari E. Corazza F. Floriani C. Chiesi-Villa A. Guastini C. J. Chem. Soc., Dalton Trans.  1990,  1345 
• 21 Chipperfield JR. Clayton J. Siraj KA. Woodward S. J. Chem. Soc., Dalton Trans.  2000,  1087 ; and references cited therein
• 22 Oisaki K. Zhao D. Kanai M. Shibasaki M. J. Am. Chem. Soc.  2006,  128:  7164 
• 23 Finney NS. Pospisil PJ. Chang S. Palucki M. Konsler RG. Hansen KB. Jacobsen EN. Angew. Chem. Int. Ed.  1997,  36:  1720 
• 24 Epstein WW. Sonntag AC. J. Org. Chem.  1967,  32:  3390 

9

Cozzi P. G., unpublished results.

19

The combination of ClMn(Salen) with Me₂Zn, in the absence of iodoacetate and ketones, gives a rapid development of a yellow color, indicating the presence of Zn(Salen). In addition, by quenching the reaction with water, free Salen ligand is observed by TLC analysis. ClMn(Salen) is quite stable in the presence of water.