Synthesis of Unsymmetrical Polysubstituted Pyridines from β-Sulfonylvinylamines via 1-Aza-Allyl Anion Intermediates

Abstract

A modular synthesis of highly functionalized unsymmetrical pyridines has been developed from reacting β-sulfonylvinylamines with α,β-unsaturated systems in the presence of base via the formation of 1-aza-allyl anion intermediates.

Key words

β-sulfonylvinylamines - 2,4,6-triarylpyridines - 1-aza-allyl anions - α,β-unsaturated ketones - cascade reactions

References

• Applications as anticancer agents:
• 1a Basnet A. Thapa P. Karki R. Na Y. Jahng Y. Jeong BS. Jeong TC. Lee CS. Lee ES. Bioorg. Med. Chem.  2007,  15:  4351 
• 1b Zhao LX. Moon YS. Basnet A. Kim EK. Cho WJ. Jahng Y. Park JG. Jeong TC. Cho WJ. Choi SU. Lee CO. Lee SY. Lee CS. Lee ES. Bioorg. Med. Chem. Lett.  2004,  14:  1333 
• 1c Zhao LX. Kim TS. Ahn SH. Kim TH. Kim EK. Cho WJ. Choi H. Lee CS. Kim JA. Jeong TC. Chang CJ. Lee ES. Bioorg. Med. Chem. Lett.  2001,  11:  2659 
• 1d Carter PJ. Cheng CC. Thorp HH. J. Am. Chem. Soc.  1998,  120:  632 
• Applications as chemosensors:
• 2a Yang QZ. Wu LZ. Zhang H. Chen B. Wu ZX. Zhang LP. Tung CH. Inorg. Chem.  2004,  43:  5195 
• 2b Siu PKM. Lai SW. Lu W. Zhu N. Che CM. Eur. J. Inorg. Chem.  2003,  2749 
• 2c Wong KH. Chan MCW. Che CM. Chem. Eur. J.  1999,  5:  2845 
• Applications as optoelectronic devices:
• 3a Liu R. Chang J. Xiao Q. Li Y. Chen H. Zhu H. Dyes Pigm.  2011,  88:  88 
• 3b Chen JL. Chang SY. Chi Y. Chen K. Cheng YM. Lin CW. Lee GH. Chou PT. Wu CH. Shih PI. Shu CF. Chem. Asian J.  2008,  3:  2112 
• 3c Williams JAG. Top. Curr. Chem.  2007,  281:  205 
• 3d Chou PT. Chi Y. Chem. Eur. J.  2007,  13:  380 
• 3e Yan BP. Cheung CCC. Kui SCF. Xiang HF. Roy VAL. Xu SJ. Che CM. Adv. Mater.  2007,  19:  3599 
• 3f Yan BP. Cheung CCC. Kui SCF. Roy VAL. Che CM. Xu SJ. Appl. Phys. Lett.  2007,  91:  63508 
• 3g Chou PT. Chi Y. Eur. J. Inorg. Chem.  2006,  3319 
• 3h Sun W. Zhu H. Barron PM. Chem. Mater.  2006,  18:  2602 
• Applications as semi-conductors:
• 4a Lu W. Roy VAL. Che CM. Chem. Commun.  2006,  3972 
• 4b Kaes C. Katz A. Hosseini MW. Chem. Rev.  2000,  100:  3553 
• 5a Carrasco AC. Pidko EA. Masdeu-Bulto AM. Lutz M. Spek AL. Vogt D. Müller C. New J. Chem.  2010,  34:  1547 
• 5b Eryazici I. Moorefield CN. Durmus S. Newkome GR. J. Org. Chem.  2006,  71:  1009 
• Condensation of 1,5-diketones with formamide-formic acid:
• 6a Chubb F. Hay AS. Sandin RB. J. Am. Chem. Soc.  1953,  75:  6042 
• Chichibabin method:
• 6b Dilthey W. J. Prakt. Chem.  1921,  102:  209 
• 6c Lombard R. Stephen JP. Bull. Soc. Chim. Fr.  1958,  1458 
• 6d Zecher W. Kröhnke F. Chem. Ber.  1961,  94:  690 
• 6e Frank RL. Steven RP. J. Am. Chem. Soc.  1949,  71:  2629 
• Reaction of N-phenacylpyridinium salts and α,β-unsaturated ketones:
• 6f Kröhnke F. Zecher W. Angew. Chem., Int. Ed. Engl.  1962,  1:  626 
• 6g Kröhnke F. Synthesis  1976,  1 
• Reaction of N-phosphinylethanimines with aldehydes:
• 6h Kobayashi T. Kakiuchi H. Kato H. Bull. Chem. Soc. Jpn.  1991,  64:  392 
• Reaction of lithiated β-enaminophos-phonates with chalcones:
• 6i Palacios F. Retana de A. MO. Oyarzabal J. Tetrahedron Lett.  1996,  37:  4577 
• Reaction of acetophenones, benzaldehydes, and NH₄OAc under solvent-free or microwave conditions:
• 6j Cave GWV. Raston CL. Chem. Commun.  2000,  2199 
• 6k Tu S. Li T. Shi F. Fang F. Zhu S. Wei X. Zong Z. Chem. Lett.  2005,  34:  732 
• Reaction of pyridinium salts and α,β-unsaturated ketones:
• 7a Yan C.-G. Cai X.-M. Wang Q.-F. Wang T.-Y. Zheng M. Org. Biomol. Chem.  2007,  5:  945 
• 7b Malik S. Pandey K. J. Chem. Eng. Data  1983,  28:  430 
• 7c

  Also see refs. 1a,b. Lewis acid catalyzed reaction of ω-pyrrolidino-acetophenone with chalcone under microwave conditions:

• 7d Borthakur M. Dutta M. Gogoi S. Bouruah RC. Synlett  2008,  3125 
• Reaction of α,β-unsaturated imines with sodium enolates of methyl aryl ketones:
• 7e Kiselyov AS. Tetrahedron Lett.  1995,  36:  9297 
• Diels-Alder reaction:
• 7f Diring S. Retailleau P. Ziessel R. J. Org. Chem.  2007,  72:  10181 
• 8 Tsui GC. Glenadel Q. Lau C. Lautens M. Org. Lett.  2011,  13:  208 
• 9 Feringa BL. J. Chem. Soc., Chem Commun.  1985,  466 
• References outlining the importance of 1-aza-allyl anions and applications in heterocyclic synthesis:
• 10a Enamines: Their Synthesis, Structure and Reactions   Cook AG. Marcel Dekker; New York: 1969. 
• 10b House HO. Modern Synthetic Reactions   2nd ed:  W. A. Benjamin, Inc.; Menlo Park: 1972. 
• 10c Mangelinckx S. Giubellina N. Kimpe ND. Chem. Rev.  2004,  104:  2353 
• 10d Job A. Janeck CF. Bettray W. Peters R. Enders D. Tetrahedron  2002,  58:  2253 
• 10e Caro CF. Lappert MF. Merle PG. Coord. Chem. Rev.  2001,  605:  219 
• 10f Semmelhack MF. In Comprehensive Organic Synthesis   Vol. 2:  Trost BM. Fleming I. Pergamon Press; Oxford: 1991. 
• 10g Whitesell JK. Whitesell MA. Synthesis  1983,  517 
• 10h Hickmott PW. Tetrahedron  1982,  38:  3363 

11

Initial C-alkylation at the β-carbon of 1-aza-allyl anions is typically observed over N-alkylation; see ref. 10c.

12

See Supporting Information for additional details relating to the optimization process.