Addition of Lithiated Tertiary Aromatic Amides to Epoxides and Aziridines: Asymmetric Synthesis of (S)-(+)-Mellein

Abstract

Addition of ortholithiated or laterally lithiated amides to epoxides or aziridines provides, in some cases stereoselectively, products which may cyclise to yield benzopyranones in good enantiomeric excess.

Key words

lithiation - directed metallation - synthesis - epoxide - benzopyranone - isochromanone

References and Notes

• 1a Gschwend HW. Rodriguez HR. Org. React.  1979,  26:  1 
• 1b Narasimhan NS. Mali RS. Synthesis  1983,  957 
• 2 Snieckus V. Chem. Rev.  1990,  90:  879 
• 3 Clark RD. Jahangir A. Org. React.  1995,  47:  1 
• 4 Clayden J. Stimson CC. Keenan M. Synlett  2005,  1716 
• 5 Fuji K. Kawabata T. Chem. Eur. J.  1998,  373 
• 6 Ahmed A. Bragg RA. Clayden J. Lai LW. McCarthy C. Pink JH. Westlund N. Yasin SA. Tetrahedron  1998,  54:  13277 
• 7 Watanabe M. Sahara M. Kubo M. Furukawa S. Billedeau RJ. Snieckus V. J. Org. Chem.  1984,  49:  742 
• 8 Comins DL. Brown JD. J. Org. Chem.  1986,  51:  3566 
• 9 Clayden J. Stimson CC. Keenan M. Wheatley AEH. Chem. Commun.  2004,  228 
• Asymmetry was introduced into a comparable reaction of 2-alkylbenzoate esters by the use of a chiral lithium amide base, see:
• 10a Regan AC. Staunton J. J. Chem. Soc., Chem. Commun.  1987,  520 
• 10b Regan AC. Staunton J. J. Chem. Soc., Chem. Commun.  1983,  764 
• 11 For a comparable strategy using secondary amides, see: Narasimhan NS. Bhide BH. Tetrahedron  1971,  27:  6171 
• 12 A previous report had indicated lack of reactivity between lithiated tertiary amides and epoxides in the absence of BF₃, see: Choukchou-Braham N. Asakawa Y. Lepoittevin J.-P. Tetrahedron Lett.  1994,  35:  3949 
• 13 The synthesis of alcohols 3 by addition of lithiated amides to aldehydes is in contrast stereoselective with respect to the axis and the benzylic stereogenic centre, but non stereoselective with regard to the relationship between the two centers, see: Clayden J. Pink JH. Westlund N. Frampton CS. J. Chem. Soc., Perkin. Trans. 1  2002,  901 
• 15a Williams AC. Camp N. Science of Synthesis   Vol. 14:  Thieme; Stuttgart: 2003.  p.347 
• 15b Napolitano E. Org. Prep. Proced. Int.  1997,  29:  631 
• 15c Hill RA. Prog. Chem. Org. Nat. Prod.  1986,  49:  1 
• 16 See: Dimitriadis C. Gill M. Harte MF. Tetrahedron: Asymmetry  1997,  8:  2153 ; and references cited therein
• 17 Koshino H. Yoshihara T. Okuno M. Sakamura S. Tajimi A. Shimanuki T. Biosci., Biotechnol., Biochem.  1992,  56:  1096 
• 18 Clayden J. Mitjans D. Youssef LH. J. Am. Chem. Soc.  2002,  124:  5266 
• 19 Andersen KK. Tetrahedron Lett.  1962,  93 
• 20 Solladié G. Hutt J. Girardin A. Synlett  1987,  1731 

14

X-ray crystallographic data have been deposited with the Cambridge Crystallographic Database, reference 288095.

21

Additions of ortholithiated amides to aziridines failed even in the presence of Lewis acids.

22

Crystallographic data have been deposited with the Cambridge Crystallographic database, reference 288094.