Synthetic Potential of Configurationally Unstable Chiral Carbanions

Abstract

This account summarizes our recent efforts in exploring the synthetic potential of configurationally labile chiral carbanions next to electron-withdrawing groups that have previously been considered to be impossible even to generate. We place particular emphasis on the generation and trapping of chiral α-nitrile carbanions as well as evaluation of the configurational stability of those carbanions and effects of solvent on the stability.

1 Introduction

2 Epoxysilane Rearrangement

2.1 Background

2.2 Chirality Transfer from Epoxide to Carbanion

2.3 Chirality Transfer from an Epoxide by [2,3]-Wittig Rearrangement and Trapping of a Chiral Carbanion

2.4 Solvent Effects on the Configurational Stability of Carbanions

3 Evaluation of the Effects of Substituents on Configurational Stability of a Chiral Carbanion

4 Enantioselective Trapping of an α-Chiral Carbanion of Acyclic Nitrile by a Carbon Electrophile

5 Summary

Key words

carbanions - nitriles - stereoselective synthesis - Brook rearrangement - Wittig rearrangement

• References

• 1 Still WC, Sreekumar C. J. Am. Chem. Soc. 1980; 102: 1201
• 2a Clayden J. Organolithiums: Selectivity for Synthesis. Pergamon; Oxford: 2002
• 2b Gawley RE In Stereochemical Aspects of Organolithium Compounds, Topics in Stereochemistry . Vol. 26. Gawley RE, Siegel J. Chap. 3 Wiley; New York: 2010: 93-133
• 2c Kizirian J.-C In Stereochemical Aspects of Organolithium Compounds, Topics in Stereochemistry . Vol. 26. Gawley RE, Siegel J. Chap. 6 Wiley; New York: 2010: 189-251
• 2d Basu A, Thayumanavan S. Angew. Chem. Int. Ed. 2002; 41: 716
• 3a Hoppe D, Hense T. Angew. Chem., Int. Ed. Engl. 1997; 36: 2282
• 3b Hoppe D In The Chemistry of Organolithium Compounds . Vol. 1. Rappoport Z, Marek I. Wiley; Chichester: 2004: 1055-1164
• 3c Hoppe D, Marr F, Brüggemann M In Organolithiums in Enantioselective Synthesis . Hodgson DM. Springer; New York: 2003: 61-137
• 3d ref. 2c.

For enantioselective deprotoanation/trapping of chiral cyclopropyl nitriles, see:
• 4a Walborsky HM, Motes JM. J. Am. Chem. Soc. 1970; 92: 2445
• 4b Walborsky HM, Motes JM. J. Am. Chem. Soc. 1970; 92: 2445
• 4c Walborsky HM, Youssef AA, Motes JM. J. Am. Chem. Soc. 1962; 84: 2465
• 4d Walborsky HM, Hornyak FM. J. Am. Chem. Soc. 1955; 77: 6026
• 4e Carlier PR, Zhang Y. Org. Lett. 2007; 9: 1319
• 4f Carlier PR. Chirality 2003; 15: 340
• 5a Takeda K, Kawanishi E, Sasaki M, Takahashi Y, Yamaguchi K. Org. Lett. 2002; 4: 1511
• 5b Sasaki M, Kawanishi E, Nakai Y, Matsumoto T, Yamaguchi K, Takeda K. J. Org. Chem. 2003; 68: 9330

For synthetic application of the epoxysilane rearrangement, see:
• 6a Matsumoto T, Masu H, Yamaguchi K, Takeda K. Org. Lett. 2004; 6: 4367
• 6b Sasaki M, Horai MTakeda K. Tetrahedron Lett. 2006; 47: 9271
• 6c Sasaki M, Takeda K. Org. Lett. 2004; 6: 4849
• 6d Tanaka K, Takeda K. Tetrahedron Lett. 2004; 45: 7859
• 6e Okamoto N, Sasaki M, Kawahata MYamaguchi K, Takeda K. Org. Lett. 2006; 8: 1889
• 6f Nakai Y, Kawahata M, Yamaguchi K, Takeda K. J. Org. Chem. 2007; 72: 1379
• 7a Cuadrado P, González-Nogai AM. Tetrahedron Lett. 2000; 41: 1111
• 7b Cuadrado P, González-Nogai AM. Tetrahedron Lett. 1997; 38: 8117
• 8 Sasaki M, Kawanishi E, Shirakawa Y, Kawahata M, Masu H, Yamaguchi K, Takeda K. Eur. J. Org. Chem. 2008; 3061
• 9 Sasaki M, Shirakawa Y, Kawahata M, Yamaguchi K, Takeda K. Chem. Eur. J. 2009; 15: 3363

For reviews on [2,3]-Wittig rearrangement, see:
• 10a Nakai T, Mikami K. Chem. Rev. 1986; 86: 885
• 10b Marshall JA In Comprehensive Organic Synthesis . Vol. 3. Trost BM, Fleming I. Pergamon; Oxford: 1991: 975-1014
• 10c Mikami K, Nakai T. Synthesis 1991; 594
• 10d Nakai T, Mikami K. Org. React. 1994; 46: 105
• 10e Nakai T, Tomooka K. Pure Appl. Chem. 1997; 696: 595
• 10f Hodgson DM, Tomooka K, Gras E In Organolithiums in Enantioselective Synthesis . Hodgson DM. Springer; New York: 2003: 217
• 11 Sasaki M, Higashi M, Masu H, Yamaguchi K, Takeda K. Org. Lett. 2005; 7: 5913
• 12a Curtin DY, Koehl WJ. Jr. J. Am. Chem. Soc. 1962; 84: 1967
• 12b Wu S, Lee S, Beak P. J. Am. Chem. Soc. 1996; 118: 715
• 12c Carstens A, Hoppe D. Tetrahedron 1994; 50: 6097
• 12d Gawley RE, Zhang Q. Tetrahedron 1994; 50: 6077
• 12e Kapeller DC, Hammerschmidt F. J. Org. Chem. 2009; 74: 2380
• 13 Kaumanns O, Appel R, Lemek T, Seeliger F, Mayr H. J. Org. Chem. 2009; 74: 75 and references cited therein
• 14 Ikemoto H, Sasaki M, Takeda K. Eur. J. Org. Chem. 2010; 6643
• 15a Verner EJ, Cohen T. J. Am. Chem. Soc. 1992; 114: 375
• 15b Verner EJ, Cohen T. J. Org. Chem. 1992; 57: 1072
• 15c Hoffmann R, Brückner R. Chem. Ber. 1992; 125: 1957
• 15d Tomooka K, Igarashi T, Nakai T. Tetrahedron 1994; 50: 5927
• 15e Hoffmann R, Rückert T, Brückner R. Tetrahedron Lett. 1993; 34: 297
• 15f Schäfer H, Schöllkopf U, Walter D. Tetrahedron Lett. 1968; 9: 2809
• 15g Evans DA, Baillargeon DJ. Tetrahedron Lett. 1978; 19: 3315
• 15h Azzena U, Denurra T, Melloni G, Piroddi AM. J. Org. Chem. 1990; 55: 5532
• 15i Tomooka K, Yamamoto H, Nakai T. J. Am. Chem. Soc. 1996; 118: 3317
• 15j Tomooka K, Yamamoto H, Nakai T. Liebigs Ann./Recl. 1997; 1275
• 16a Hoffmann RW In Stereochemical Aspects of Organolithium Compounds, Topics in Stereochemistry . Vol. 26. Gawley RE, Siegel J. Chap. 5 Wiley; New York: 2010: 165-188
• 16b Hoffmann RW, Lanz J, Metternich R, Tarara G, Hoppe D. Angew. Chem., Int. Ed. Engl. 1987; 26: 1145
• 16c Hirsch R, Hoffmann RW. Chem. Ber. 1992; 125: 975
• 16d Hoffmann RW, Rühl T, Harbach J. Liebigs Ann. Chem. 1992; 725
• 16e Hoffmann RW, Julius M, Chemla F, Ruhland T, Frenzen G. Tetrahedron 1994; 50: 6049
• 16f Basu A, Gallagher D, Beak P. J. Org. Chem. 1996; 61: 5718
• 16g Beak P, Basu A, Gallagher DJ, Park YS, Thayumanavan S. Acc. Chem. Res. 1996; 29: 552
• 16h see also ref.^2d
• 17 Reich HJ, Sikorski WH, Thompson JL, Sanders AW, Jones AC. Org. Lett. 2006; 8: 4003 ; and references cited therein
• 18 Deora N, Carlier PR. J. Org. Chem. 2010; 75: 1061 ; and references cited therein
• 19 Ott H, Däschlein C, Leusser D, Schildbach D, Seibel T, Stalke D, Strohmann C. J. Am. Chem. Soc. 2008; 130: 11901 ; and references cited therein
• 20 Wu Y.-D, Houk KN, Marshall JA. J. Org. Chem. 1990; 55: 1421
• 21 For participation of dioxane as a bidentate ligand with lithium ions, see: Pasumansky L, Collins CJ, Pratt LM, Nguỹên NV, Ramachandran B, Singaram B. J. Org. Chem. 2007; 72: 971
• 22 Shimizu M. Angew. Chem. Int. Ed. 2011; 50: 5998
• 23 Wolf C. Dynamic Stereochemistry of Chiral Compounds: Principles and Applications. Royal Society of Chemistry; Cambridge: 2008
• 24 Sasaki M, Ikemoto H, Kawahata M, Yamaguchi K, Takeda K. Chem. Eur. J. 2009; 15: 4663
• 25a Denmark SE, Dorow RL. J. Org. Chem. 1990; 55: 5926
• 25b O’Brien P, Powell HR, Raithby PR, Warren S. J. Chem. Soc., Perkin Trans. 1 1997; 1031
• 26a ref.^16d
• 26b Boche G. Angew. Chem., Int. Ed. Engl. 1989; 28: 277
• 26c Gais H.-J, Vollhardt J, Lindner HJ. Angew. Chem., Int. Ed. Engl. 1986; 25: 939
• 26d Gais H.-J, Hellmann G. J. Am. Chem. Soc. 1992; 114: 4439
• 27a Bordwell FG. Acc. Chem. Res. 1998; 31: 456
• 27b Taft RW, Bordwell FG. Acc. Chem. Res. 1998; 31: 463
• 27c Zhang S, Zhang X.-M, Bordwell FG. J. Am. Chem. Soc. 1995; 117: 602
• 28a Fleming FF, Shook BC. Tetrahedron 2002; 58: 1
• 28b Arseniyadis S, Kyler KS, Watt DS. Org. React. 1984; 31: 1
• 28c Fleming FF, Gudipati S, Zhang Z, Liu W, Steward OW. J. Org. Chem. 2005; 70: 3845
• 29 Sasaki M, Takegawa T, Ikemoto H, Kawahata M, Yamaguchi K, Takeda K. Chem. Commun. 2012; 48: 2897