Nucleophilic Addition Reactions of 1,4-Diketones Derived from Tartaric Acid: Synthesis of TADDOL Analogues

Abstract

A systematic investigation of the reduction and Grignard reagents addition to 1,4-diketones derived from tartaric acid was carried out. It was found that the reduction proceeded with high selectivity using K-Selectride as the reducing agent; while Grignard reagent addition was highly dependent on structure of the dione as well as on the Grignard reagent. The resultant 1,4-diols represent a series of novel TADDOL analogues.

asymmetric synthesis - TADDOL - stereoselective addition

References

1a Nicaloau KC. Sorensen EJ. Classics in Total Synthesis   Wiley-VCH; Weinheim: 1996. 

1b Corey EJ. Cheng X.-M. Logic of Chemical Synthesis   Wiley Interscience; New York: 1995. 

2a Blaser H.-U. Chem. Rev.  1992,  92:  935 

2b Blaser H.-U. Chem. Commun.  2003,  293 

2c Asymmetric Catalysis on Industrial Scale. Challenges, Approaches and Solutions   Blaser H.-U. Schmidt E. Wiley-VCH; Weinheim: 2004.  p.55-70  

2d Breuer M. Ditrich K. Habicher T. Hauer B. Keßeler M. Sturmer R. Zelinski T. Angew. Chem. Int. Ed.  2004,  43:  788 

3 Seebach D. Beck AK. Heckel A. Angew. Chem. Int. Ed.  2001,  40:  92 

4 Jacobsen EN. Yoon TP. Science  2003,  299:  1691 

For the synthesis of TADDOL analogues by addition of MeMgBr and ArMgBr to the diketone 3a, see:

5a Ito YN. Ariza X. Beck AK. Bohac A. Ganter C. Gawley RE. Kuhnle FNM. Tuleja J. Wang YM. Seebach D. Helv. Chim. Acta  1994,  77:  2071 

5b Haase C. Sarko CR. DiMare M. J. Org. Chem.  1995,  60:  1777 

A multistep synthesis of 1,4-diol 4f from mannitol has been reported, see:

5c Yan Y.-Y. RajanBabu TV. Org. Lett.  2000,  2:  4137 

5d Li W. Zhang Z. Xiao D. Zhang X. J. Org. Chem.  2000,  65:  3489 

5e Horita K. Inoue T. Tanaka K. Yonemitsu O. Tetrahedron  1996,  52:  531 

6 Preliminary communication: Prasad KR. Chandrakumar A. Tetrahedron: Asymmetry  2005,  16:  1897 

7a Nugiel DA. Jakobs K. Worley T. Patel M. Kaltenbach RF. Meyer DT. Jadhav PK. De Lucca GV. Smyser TE. Klabe RM. Bacheler LT. Rayner MM. Seitz SP. J. Med. Chem.  1996,  39:  2156 

7b McNulty J. Grunner V. Mao J. Tetrahedron Lett.  2001,  42:  5609 

8

The low selectivity (dr 4a:5a = 67:33) observed in the reduction of diketone 3a with L-Selectride can be explained by the chelation of lithium ion which has a propensity to chelate to a greater extent.

9 Synthesis of compounds 6 and 8 (Scheme 9), see also:

9 Prasad KR. Gholap SL. Synlett  2005,  2260 

10 Vijaya GB. Gravel M. Rawal VH. Org. Lett.  2005,  7:  5657 

11 Bayer A. Murszat P. Thewalt U. Rieger B. Eur. J. Inorg. Chem.  2002,  2614