Stereospecific DearomatisingCyclisation of Tertiary α-Amidoorganolithiums

Abstract

Lithiation of benzamides derived from a chiral and enantiomericallypure α-methylbenzylamine leads to diastereoselective andregioselective dearomatising cyclisations with overall conservationof the stereochemistry of the starting stereogenic centre.

Key words

amide; - lithiation - cyclisation - stereospecificity - dearomatisation

References

• 1 Basu A. Thayumanavan S. Angew. Chem. Int. Ed.  2002,  41:  716 
• 2 Carstens A. Hoppe D. Tetrahedron  1994,  50:  6097 
• 3 For discussions concerning configurationalstability and stereospecificity in the reactions of organolithium compounds,see: Clayden J. Organolithiums:Selectivity for Synthesis   Pergamon; Oxford: 2002. 
• 4 Hammerschmidt F. Hanninger A. Chem. Ber.  1995,  128:  1069 
• 5 Faibish NC. Park YS. Lee S. Beak P. J. Am. Chem. Soc.  1997,  119:  11561 
• 6 Derwing C. Frank H. Hoppe D. Eur.J. Org. Chem.  1999,  3519 
• 7 Hoppe D. Kaiser K. Stratmann O. Fröhlich R. Meyer O. Hoppe D. Angew. Chem. Int. Ed.  1997,  36:  2784 
• 8 Hoppe D. Kaiser B. Stratmann O. Frohlich R. Angew. Chem. Int. Ed.  1998,  36:  2784 
• 9 Stratmann O. Kaiser B. Frohlich R. Meyer O. Hoppe D. Chem.-Eur.J.  2001,  7:  423 
• 10 Gawley RE. Low E. Zhang Q. Harrris R. J. Am. Chem. Soc.  2000,  122:  3344 
• 11 Gawley RE. TetrahedronLett.  1999,  40:  4297 
• 12a Chiralamido-substituted secondary organolithiumshave been made previously, principally by deprotonation of N-benzyl amides under the influence ofa nearby stereogenic centre or axis (diastereoselective deprotonation:see refs. and: Bragg RA. Clayden J. Menet CJ. Tetrahedron Lett.  2002,  43:  1955 
• 12b The use of a chiral base: Clayden J. Menet CJ. Mansfield DJ. Chem. Commun.  2002,  38 ; or by stereospecific kinetic-isotope-directedlithiation or tin-lithium exchange
• 13 Ahmed A. Clayden J. Yasin SA. Chem.Commun.  1999,  231 
• 14 Clayden J. Menet CJ. Mansfield DJ. Org. Lett.  2000,  2:  4229 
• 15 Clayden J. Tchabanenko K. Yasin SA. Turnbull MD. Synlett  2001,  302 
• 16 For an example of lithiated carbamate unstable towards a stereospecificrearrangement, see: Hara O. Ito M. Hamada Y. TetrahedronLett.  1998,  39:  5537 
• 18 The cyclisation can be interpretedas a nucleophilic attack by the organolithium centre on the aromaticring or as an electrocyclic ring closure, see: Clayden J. Purewal S. Helliwell M. Mantell SJ. Angew. Chem. Int.Ed.  2002,  41:  1091 
• 20 Bragg RA. Clayden J. Tetrahedron Lett.  1999,  40:  8323 
• 21 Bragg RA. Clayden J. Tetrahedron Lett.  1999,  40:  8327 
• 22 Fuji K. Kawabata T. Chem.-Eur. J.  1998,  373 
• 23 Cuyegkeng MA. Mannschreck A. Chem. Ber.  1987,  120:  803 
• 24 Bowles P. Clayden J. Helliwell M. McCarthy C. Tomkinson M. Westlund N. J. Chem. Soc., Perkin Trans. 1  1997,  2607 
• 25 Ahmed A. Bragg RA. Clayden J. Lai LW. McCarthy C. Pink JH. Westlund N. Yasin SA. Tetrahedron  1998,  54:  13277 
• 26 Clayden J. Knowles FE. Menet CJ. Tetrahedron Lett.  2003,  44:  3397 

17

The X-ray crystal structure of a relatedcyclisation product (see ref. [26] )allows us confidence in assigning both absolute and relative stereochemistryas shown.

19

Clayden, J.; Menet, C. J. Tetrahedron Lett., inpress.