Stereoselective Synthesis of Pyrrolidines and Pyrrolizidines by Intramolecular Carbolithiation

Abstract

Methods for the preparation of substituted homoallylic amines and their conversion to pyrrolidines or pyrrolizidines are described. N-Alkylation of a variety of homoallylic secondary amines with (tributylstannyl)methyl methanesulfonate and subsequent tin-lithium exchange, generates organolithium species that undergo intramolecular carbolithiation (anionic cyclization). High stereoselectivities in the cyclization, particularly for the formation of 2,4-disubstituted pyrrolidines, are obtained.

Key words

amines - carbanions - cyclizations - lithiation - heterocycles

References

• 1 Bailey WF. Ovaska TV. Advances in Detailed Reaction Mechanisms  1994,  3:  251 
• 2 Bailey WF. Khanolkar AD. Gavaskar K. Ovaska TV. Rossi K. Thiel Y. Wiberg KB. J. Am. Chem. Soc.  1991,  113:  5720 
• 3a Broka CA. Lee WJ. Shen T. J. Org. Chem.  1988,  53:  1336 
• 3b Broka CA. Shen T. J. Am. Chem. Soc.  1989,  111:  2981 
• 4a Barluenga J. Sanz R. Granados A. Fañanás FJ. J. Am. Chem. Soc.  1998,  120:  4865 
• 4b Nishiyama H. Sakata N. Sugimoto H. Motoyama Y. Wakita H. Nagase H. Synlett  1998,  930 
• 4c Comins DL. Zhang Y. J. Am. Chem. Soc.  1996,  118:  12248 
• 4d Zhang D. Liebeskind LS. J. Org. Chem.  1996,  61:  2594 
• 4e Bailey WF. Jiang X.-L. J. Org. Chem.  1996,  61:  2596 
• 5a Woltering MJ. Fröhlich R. Wibbeling B. Hoppe D. Synlett  1998,  797 
• 5b Ahmed A. Clayden J. Rowley M. Tetrahedron Lett.  1998,  39:  6103 
• 5c Bragg RA. Clayden J. Tetrahedron Lett.  1999,  40:  8327 
• 5d Clayden J. Tchabanenko K. Chem. Commun.  2000,  317 
• 6a Coldham I. Hufton R. Tetrahedron  1996,  52:  12541 
• 6b Coldham I. Fernàndez J.-C. Snowden DJ. Tetrahedron Lett.  1999,  40:  1819 
• 7 Lautens M. Kumanovic S. J. Am. Chem. Soc.  1995,  117:  1954 
• 8 Seyferth D. Andrews SB. J. Organomet. Chem.  1971,  30:  151 
• 9 Seitz DE. Carroll JJ. Cartata CP. Lee S.-H. Zapata A. Synth. Commun.  1983,  13:  129 
• 10a Quintard J.-P. Elissondo B. Jousseaume B. Synthesis  1984,  495 
• 10b Pearson WH. Lindbeck AC. Kampf JW. J. Am. Chem. Soc.  1993,  115:  2622 
• 10c Pearson WH. Stevens EP. Synthesis  1994,  904 
• 10d Katritzky AR. Chang H.-I. Wu J. Synthesis  1994,  907 
• 11 Beak P. Basu A. Gallagher DJ. Park YS. Acc. Chem. Res.  1996,  29:  552 
• 12 Beak P. Kerrick ST. Wu S. Chu J. J. Am. Chem. Soc.  1994,  116:  3231 
• 13 Coldham I. Hufton R. Snowden DJ. J. Am. Chem. Soc.  1996,  118:  5322 
• 14 Some of these results have been reported as a preliminary communication: Coldham I. Hufton R. Rathmell RE. Tetrahedron Lett.  1997,  38:  7617 
• 15a Dondoni A. Franco S. Junquera F. Merchan F. Merino P. Tejero T. Synth. Commun.  1994,  24:  2537 
• 15b Funk RL. Daggett JU. Heterocycles  1987,  26:  2175 
• 15c Mancini F. Piazza MG. Trombini C. J. Org. Chem.  1991,  56:  4246 
• 16 Reich HJ. Borst JP. Coplien MB. Phillips NH. J. Am. Chem. Soc.  1992,  114:  6577 
• 17 Beak P. Lee WK. J. Org. Chem.  1993,  58:  1109 
• 18 Meyers AI. Burgess LE. J. Org. Chem.  1991,  56:  2294 
• 20a Karoyan P. Chassaing G. Tetrahedron Lett.  1997,  38:  85 
• 20b Lorthiois E. Marek I. Normant J.-F. J. Org. Chem.  1998,  63:  2442 
• 20c Galeazzi R. Geremia S. Mobbili G. Orena M. Tetrahedron: Asymmetry  1996,  7:  79 
• 21 Andrés C. Duque-Soladana JP. Iglesias JM. Pedrosa R. Tetrahedron Lett.  1996,  37:  9085 
• 22 Agami C. Couty F. Poursoulis M. Vaissermann J. Tetrahedron  1992,  48:  431 
• 23a Bailey WF. Mealy MJ. J. Am. Chem. Soc.  2000,  122:  6787 
• 23b Gil GS. Groth UM. J. Am. Chem. Soc.  2000,  122:  6789 
• 23c Marek I. J. Chem. Soc., Perkin Trans. 1  1999,  535 
• 24a Pirkle WH. Burlingome TG. Beare SD. Tetrahedron Lett.  1968,  5849 
• 24b Benson SC. Cai P. Colon M. Haiza MA. Tokles M. Snyder JK. J. Org. Chem.  1988,  53:  5335 
• 25 Coldham I. Collis AJ. Mould RJ. Robinson DE. Synthesis  1995,  1147 
• 26a Hoffmann RW. Eichler G. Endesfelder A. Liebigs Ann. Chem.  1983,  2000 
• 26b Wuts PGM. Jung Y.-W. J. Org. Chem.  1991,  56:  365 
• 26c Kuznetsov VV. Lantsetov SV. Aliev AE. Varlamov AV. Prostakov NS. J. Org. Chem. USSR  1992,  28:  61 
• 27 Newcomb M. Marquardt DJ. Deeb TM. Tetrahedron  1990,  46:  2329 
• 28 Karoyan P. Chassaing G. Tetrahedron: Asymmetry  1997,  8:  2025 
• 29 Fletcher DA. McMeeking RF. Parkin D. J. Chem. Inf. Comput. Sci.  1996,  36:  746 

19

The ratio of diastereomers of the picrate salts of 15 and 16 in the crystals was 60:40 by ¹H NMR and 54:46 by X-ray, such that confirmation of the major diastereomer by X-ray structure analysis was not certain.