Date: 28th August 2009Seminar onVinyl PhosphonateByMr. Santosh V. NalageDept.Organic Chemistry NMU, Jalgaon

* Content * 1. Introduction2. Synthesis of Vinyl Phosphonate By Various methods3. Applications4. Reactions 5. References 6. Conclusion

1. Introduction*Useful intermediates in organic transformation1* Important application as they undergo Michael addition* enantioselective organocatalytic conjugate additiona)b)c)A= carbonyl, cyano, sulfonyl, sulfinyl, alkoxycarbonyl, phosphoryl etc.

2. Synthesis of Vinyl Phosphonate By Various methods* Metalation of readily available 1-alkylphosphonates * By lithium salts* Arbusov reaction * The Heck reaction * Olefination reaction * Radical trapping

3. ApplicationsVinyl phosphonates are compound that have a wide range of applications in many areas *Co-polymers, *Polymer additives, *Flame retardants, *Intermediates for drug*Agrochemicals *Biologically important molecules* Transformation into carbocyclic, heterocyclic and many products .2b

4. ReactionsAlexakis et al. reported the first enantioselective organocatalytic conjugate addition of aldehydes to vinyl phosphonates using various organocatalyst with high yields up to 97% ee.3Org. Lett. 2007, 9, 3749

B) Michael reaction of electron rich hydroxyarenes with 3-aryl-2- diethoxyphosphoryl acrylic acids 1 followed by lactonization to obtain 4-aryl-3- diethoxyphosphorylchromanones 3. The HWE reaction of chromanones 3 with paraformaldehyde allowed the facile preparation of 3-methylidene-chromanones 4.4Tetrahedron 2007, 63, 12583

C) An enantioselective organocatalytic approach to another class of biologically important molecules, namely α-methylene-δ-lactones and δ-lactams was presented by Jorgensen and co-workers.5 J. Org. Chem. 2008, 73, 8337

D) Total Synthesis of (-)-myrtine: Asymmetric synthesis of trans-2,6-disubstituted 1,2,5,6 tetrahydropyridines , which are valuable building blocks for the synthesis of ring functionalized tran’s-2, 6-disubstituted piperidines. Davis et al. show that the enantioselective addition of organocuprates to 3-dimethoxyphosphoryl dihydropyridinones gave trans-2, 6-disubstituted piperidines.6J. Org. Chem. 2007, 72, 2046

E) 2-diethoxyphosphoryl-2-alkenoates 5 were used as Michael acceptor’s in the reaction with N-methyl hydroxylamine hydrochloride. Adducts 6 were not isolated but instead were lactonized to the trans-configured 7.7a These compounds turned out to be very potent against several leukemia cell lines and thus more specific biological evaluations of the most promising compounds were performed.7bMed.Chem. Lett. 2006, 16, 1430.Eur. J. Med. Chem.2007, 42,248

F) Reaction with nitroalkane provides key intermediate in the synthesis of heterocyclic rings.8a-ca) Synthesis 2001, 403b) Synlett 2004, 2685

G) Very recently, Cullen and Rovis9 developed an intramolecular stetter reaction of vinylphosphine oxides and vinylphosphonates.Org. Lett. 2008, 10, 3141

H) An efficient synthesis of 1, 3-diaryl-2-cyanobuta-1, 3-dienes 14 from 2- diethoxyphosphoryl-3-arylacrylonitrile 11 was very recently reported by Chowdhury and Gosh10. This goal was achieved using a one-pot domino process involving michael addition of dimsyllithium to 11, HWE reaction of resulting anion 12 with aromatic aldehydes and a base-induced hydrosulfinylmethane elimination from olefin 13. J. Org. Chem. 2008, 3868.

5. References 1) a) Minami, T.; Motoyoshiya, J. Synthesis1992, 333. (b) Mikoljczyk, M.; Balczewski, P. Top. Curr. Chem, 2003, 223, 162. 2) (a) Ben-Valid, S.; Qunter, A.; Srebnik, M. J. Org. Chem. 2005, 70,3554. (References Therein) (b) Minami, T.; Okauchi, T.; Kouno, R. Synthesis2001, 349. 3) Sulzer-M, S.; Tissot, M.; Alexakis, A.; Org. Lett. 2007,9, 3749. 4) Krawezyk, H.; Albrecht, L.; Wojciechowski, J.; Wolf, W. M. Tetrahedron 2007, 63, 12583. 5) Albrecht, L.; Richter, B.; Krawezyk, H.; Jorgensen, K. A. J. Org. Chem. 2008, 73, 8337. 6) Davis, F. A.; Xu, H.; Zhang, J. J. Org. Chem. 2007, 72, 2046. 7) (a) Janecki, T.; Wasek, T.; Rozalski, M.; Krajewska, U.; Studzian, K.; Kanecka, A. Bioorg. Med.Chem. Lett. 2006, 16, 1430. (b) Rozalski, M.; Krajewska, U.; Panczyk, M.; Rozalski, B.; Wasek, T.; Janecki, T. Eur. J. Med. Chem.2007, 42,248. 8) (a) Janecki, T.; Blaszczyk, E. Synthesis2001, 403. (b) Janecki, T.; Blaszczyk, E.; Krajewska, H.Synlett 2004, 2685. (c) Krajewska, H.; Albrecht, L.;Wojciechowski, J.; Wolf, W.Tetrahedron2006, 62, 908. 9) Cullen, S. C.; Rovis, T. Org. Lett. 2008, 10, 3141.(10) Chowdhury, R.; Ghosh, S.K. J. Org. Chem. 2008, 3868.

6. Conclusion The Micheal addition reactions to vinyl phosphonates emphasizes the enormous synthetic potential of these organophosphorous reagents. They are readily available and allow the synthesis of a wide variety of chemically and biologically important compounds.

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