Enantioselective Synthesis of γ-Functionalized α-Dehydroamino Esters

Abstract

Copper-catalyzed asymmetric 1,4-addition of diethylzinc to β,γ-unsaturated α-imino esters 1 using a copper-phosphoramidite complex affords enantiomerically enriched γ-functionalized α-dehydroamino esters 2.

Key words

amino acids - asymmetric catalysis - imines - Michael addition - organometallics

References

• Some recent contributions to hydrogenation of α-dehydro­-amino acids:
• 1a Zhang W. Zhang X. J. Org. Chem.  2007,  72:  1020 
• 1b Hu X.-P. Huang J.-D. Zeng Q.-H. Zheng Z. Chem. Commun.  2006,  293 
• 1c Hoen R. Van den Berg M. Bernsmann H. Minnaard AJ. De Vries JG. Feringa BL. Org. Lett.  2004,  6:  1433 
• 2a Cerić H. Kovačević M. Šindler-Kulyk M. Tetrahedron  2000,  56:  3985 
• 2b Hou D. Mas JL. Chan TM. Wong YS. Steinman M. McPhail AT. Bioorg. Med. Chem. Lett.  1993,  3:  2171 
• 2c Farina V. Hauck SI. Walker DG. Synlett  1992,  76 
• 3a El Ashry ESH. Ramadan ES. Abdel Hamid H. Hagar M. Lett. Org. Chem.  2005,  2:  415 
• 3b Cvetovich RJ. Pipik B. Hartner FW. Grabowski EJJ. Tetrahedron Lett.  2003,  44:  5867 
• 3c Nagasaki A. Adachi Y. Yonezawa Y. Shin C.-G. Heterocycles  2003,  60:  321 
• 3d Arnold Z. Synthesis  1990,  39 
• 3e Breslow R. Canary JW. Varney M. Waddell ST. Yang D. J. Am. Chem. Soc.  1990,  112:  5212 
• For reviews about α-dehydroamino acid compounds, see:
• 4a RajanBabu TV. Yan YY. Shin S. Curr. Org. Chem.  2003,  7:  1759 
• 4b Drexler HJ. You J. Zhang S. Fisher C. Bauman W. Spannenberg A. Heller DT. Org. Process Res. Dev.  2003,  7:  355 
• 4c Brunner H. Curr. Org. Chem.  2002,  6:  441 
• 4d Schmidt U. Lieberknecht A. Wild J. Synthesis  1988,  159 
• 5a Broda MA. Siodak D. Rzeszotarska B. J. Pept. Sci.  2005,  11:  546 
• 5b Mathur P. Ramakumar S. Chauhan VS. Biopolymers  2004,  76:  150 
• 5c Vijayaraghavan R. Kumar P. Dey S. Singh TP. J. Pept. Res.  2003,  62:  63 
• 6a Chen D. Guo L. Liu J. Kirtane S. Cannon JF. Li G. Org. Lett.  2005,  7:  921 
• 6b Sai H. Ogiku T. Ohmizu H. Synthesis  2003,  201 
• 6c Ferreira PMT. Maia HLS. Monteiro LS. Sacramento J. J. Chem. Soc., Perkin Trans. 1  1999,  3697 
• 6d Stohlmeyer MM. Tanaka H. Wandless TJ. J. Am. Chem. Soc.  1999,  121:  6100 
• 6e Ferreira PMT. Maia HLS. Montiro LS. Tetrahedron Lett.  1998,  39:  9575 
• 7 Groundwater PW. Sharif T. Arany A. Hibbs DE. Hursthouse MB. Nyerges M. Tetrahedron Lett.  1998,  39:  1433 
• 8 Davis FA. Liu H. Liang C.-H. Venkat Reddy G. Zhang Y. Fang T. Titus DD. J. Org. Chem.  1999,  64:  8929 
• 9 Trost BM. Dake GR. J. Am. Chem. Soc.  1997,  119:  7595 
• 10 Schmidt U. Griesser H. Leitenberger V. Lieberknecht A. Mangold R. Meyer R. Riedl B. Synthesis  1992,  487 
• 11a Palacios F. Vicario J. Maliszewska A. Aparicio D. J. Org. Chem.  2007,  72:  2682 
• 11b Palacios F. Vicario J. Aparicio D. J. Org. Chem.  2006,  71:  7690 
• 11c Palacios F. Alonso C. Rubiales G. Villegas M. Tetrahedron  2005,  61:  2779 
• 11d Palacios F. Ochoa de Retana AM. Pascual S. Oyarzabal J. J. Org. Chem.  2004,  69:  8767 
• 11e Palacios F. Ochoa de Retana AM. Pascual S. Oyarzabal J. Org. Lett.  2002,  4:  769 
• 12 Palacios F. Vicario J. Org. Lett.  2006,  8:  5405 

13

The absolute configuration of the stereogenic center of
α-dehydroamino esters 2 was established by comparison of the rotary power of the known carboxylic acid resulting from ozonolysis and subsequent oxidation of the intermediate aldehyde.

14

The conventional process involves the addition of a solution of 1-azadiene 1 to a toluene solution of diethylzinc together with the copper catalyst.