One-Pot Reduction-Aldol Reaction of Esters

Abstract

We have developed a new protocol for making aldol adducts in a one-pot reaction between esters and silyl enol ethers in the presence of DIBALH without isolating the intermediate aldehydes. Lewis acid activation of the initially formed aluminated hemiacetals produces highly reactive electrophilic aldehyde equivalents in situ. Using this protocol, various aldol adducts can be readily obtained in up to 90% yield on a large scale.

aldol reaction - reduction - esters - aldehydes - aluminated hemiacetals - one-pot reaction

References

For reviews, see:

1a Heathcock CH. In Comprehensive Organic Synthesis   Vol. 4:  Trost BM. Fleming I. Pergamon; Oxford: 1991.  p.133-275  

1b Braun M. In Houben-Weyl: Methods of Organic Chemistry   Vol. E21:  Helmchen G. Hoffmann RW. Mulzer J. Schaumann E. George Thieme Verlag; Stuttgart: 1995.  p.1603 

For example, see:

2a Evans DA. Starr JT. J. Am. Chem. Soc.  2003,  125:  13531 

2b Heathcock CH. McLaughlin M. Hubbs JL. Wallace GA. Scott R. Claffey MM. Hayes CJ. Ott GR. J. Am. Chem. Soc.  2003,  125:  12844 

2c Kiyooka S. Shahid KA. Goto F. Okazaki M. Shuto Y. J. Org. Chem.  2003,  68:  7967 

2d Gaul C. Njardarson JT. Danishefsky SJ. J. Am. Chem. Soc.  2003,  125:  6042 

2e Kalesse M. Chary KP. Quitschalle M. Burzlaff A. Kasper C. Scheper T. Chem.-Eur. J.  2003,  9:  1129 

3 Mukaiyama T. Banno K. Narasaka K. J. Am. Chem. Soc.  1974,  96:  7503 

For recent development of the aldol reaction, for example, see:

4a Yanagisawa A. Sekkiguchi T. Tetrahedron Lett.  2003,  44:  7163 

4b Nagasawa T. Fujiwara H. Mukaiyama T. Chem. Lett.  2003,  44:  6187 

4c Calter MA. Orr RK. Tetrahedron Lett.  2003,  44:  5699 

For example, see:

5a Evans DA. Hu E. Burch JD. Jaeschke G. J. Am. Chem. Soc.  2002,  124:  5654 

5b Wong Y.-S. Chem. Commun.  2002,  686 

5c Evans DA. Fitch DM. Smith TE. Cee VJ. J. Am. Chem. Soc.  2000,  122:  10033 

6 For one-pot reaction of lactones to give aldol derivatives, see: Schmitt A. Reissig H.-U. Eur. J. Org. Chem.  2001,  1169 

7 For one-pot reduction-Wittig reaction of esters, see: Takacs JM. Helle MA. Seely FL. Tetrahedron Lett.  1986,  27:  1257 

8 Sasaki M. Yudin AK. J. Am. Chem. Soc.  2003,  125:  14242