OrganobismuthChemistryGraduate Seminar Presentation by Brennan Murphy

Brock University 03/27/14

1

Overview

• Properties of bismuth• Refining & toxicity

• Bismuth as a Lewis acid• Methodology• Use in total synthesis

• Bismuth reagents• Bi(III) compounds• Bi(V) compounds• Use in total synthesis

• Conclusion

2

The Element-Bismuth

• Discovered in Germany-end of the fifteenth century by an unknown alchemist.

• German root: “bisemutum” meaning “white mass.”

• Physical data• Melting point: 271 °C

• Density: 9.8 g/mL

• Electron configuration: [Xe] 4f145d106s26p3

• Most stable isotope: 209Bi

• Half-life: > 2 x 1018 years

• Toxicity: 4 mg/L of blood

3

Smith, J. D. The Chemistry of Arsenic, Antimony, and Bismuth Pergamon Press: Oxford, 1973; 553;

Mendis, A. H.W.; Marshall, B. J. Biological Chemistry of Arsenic, Antimony and Bismuth; H. Sun;

Wiley, 2011; 253.

Isolation & Refining

• By-product of copper electrowinning.

• Co-occurrence with lead in electrowon cathodicslimes.

• Separated in its pure form by the Betterton-Kroll process, pyrorefining, and roasting over coke.

4

Smith, J. D. The Chemistry of Arsenic, Antimony, and Bismuth; Pergamon Press: Oxford, 1973;

pp 554-555.

Bismuth Toxicity

Compound LD50 (g/kg) Species and Route

Bismuth oxide (Bi2O3) 5 Rat, oral

10 Mouse, oral

Bismuth oxychloride (BiOCl) 22 Rat, oral

Bismuth nitrate (Bi(NO3)3) <2.5 Mouse, intraperitoneal

Bismuth vanadate (BiVO4) <5 Rat, oral

Bismuth sodium thioglycollate (Bi(C2O2H2SNa)3) 47.2 Child (20 kg), oral

Trimethylbismuthine (BiMe3) 0.484 Rabbit, oral

0.182 Rabbit, subcutaneous

Triphenylbismuthine (BiPh3) 12 Dog, intravenous

180 Dog, oral

5Suzuki, H.; Matano Y. Organobismuth Chemistry Elsevier Science B.V., 2001; pp 20.

Bismuth for better chemistry

• Non-toxic

• Environmentally safe

• Catalytic

• Relatively unknown

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Appel-type halogenation

7Labrouillère, M.; Le Roux, C.; Gaspard-Iloughmane, H.; Dubac, J. Synlett 1994, 723.

Palladium-free Suzuki coupling

8Malik, P.; Joseph, D.; Chakraborty, D. Appl. Organomet. Chem. 2013, 27, 519.

Selective oxidations

9Salvador, J. A. R.; Silvestre, S. M.; Pinto, R. M. A. Molecules 2011, 16, 2884.

Thioacetal protection

10

Komatsu, N.; Uda, M.; Suzuki, H. Synlett 1995, 984; Komatsu, N.; Taniguchi, A.; Uda, M.;

Suzuki, H. Chem. Commun. 1996, 1847.

Thiirane preparation

11Baltork, M.; Aliyan, H. Synth. Commun. 1998, 28, 3943.

Epoxide rearrangement

12Bhatia, K. A.; Eash, K. J.; Leonard, N. M.; Oswald, M. C.; Mohan, R. S. Tetrahedron Lett. 2001, 42,

8129.

Epoxide opening

13Ogawa, C.; Azoulay, S.; Kobayashi, S. Heterocycles 2005, 66, 201.

Selective reduction

14Borah, H. N.; Prajapati, D.; Sandhu, J. S. J. Chem. Res. (S) 1994, 228.

Catalytic allenylation of hydrazones

15Kobayashi, S.; Kitanosono, T.; Ueno, M. Synlett 2010, 2033.

Hydroamination

16

Qin, H.; Yamagiwa, N.; Matsunaga, S.; Shibasaki, M. J. Am. Chem. Soc., 2006, 128, 1611;

Qin, H.; Yamagiwa, N.; Matsunaga, S.; Shibasaki, M. Chem.–Asian J., 2007, 2, 150;

Mathia, F.; Szolcsanyi, P. Org. Biomol. Chem., 2012, 10, 2830.

Stepwise alkylation/hydroamination

17Komeyama, K.; Kouya, Y.; Ohama, Y.; Takaki, K. Chem. Commun. 2011, 47, 5031.

Substitution of conjugated alcohols

18Qin, H.; Yamagiwa, N.; Matsunaga, S.; Shibasaki, M. Angew. Chem. Int. Ed. 2007, 46, 409.

Catalytic SN`

19

Csatayova, K.; Davies, S. G.; Lee, J. A.; Ling, K. B.; Roberts, P. M.; Russell, A. J.; Thomson, J. E.

Org. Lett., 2010, 12, 3152; Kawai, N.; Abe, R.; Uenishi, J. Tetrahedron Lett., 2009, 50, 6580.

Catalytic benzylation

20Rueping, M.; Nachtsheim, B. J.; Ieawsuwan, W. Adv. Synth. Catal. 2006, 348, 1033.

Catalytic hydroarylation (azonazine)

21

Komeyama, K.; Yamada, T.; Igawa, R.; Takaki, K. Chem. Commun. 2012, 48, 6372;

Ghosh, S.; Kinthada, L. K.; Bhunia, S.; Bisai, A. Chem. Commun. 2012, 48, 10132.

Catalytic β-Dicarbonyl Alkylation

22Rueping, M.; Nachtsheim, B. J.; Kuenkel, A. Org. Lett. 2007, 9, 825.

Hydroxycoumarin benzylation

23Rueping, M.; Nachtsheim, B. J.; Sugiono, E. Synlett 2010, 1549.

Allylic alcohol annulation

24

Bonrath, W.; Dittel, C.; Giraudi, L.; Netscher, T.; Pabst, T.; 7th International symposium on

catalysis applied to fine chemicals (7th CAFC). Elsevier Science, Bingen, 2005, pp 65.

Suggested mechanism

25

Catalytic prenylation

26

Ollevier, T.; M, Topwe. Synthesis 2006, 3963; Judd, K. E.; Caggiano, L. Org. Biomol. Chem. 2011,

9, 5201.

Domino Heck coupling/hydroamination

27Kamisaki, H.; Nanjo, T.; Tsukano, C.; Takemoto, Y. Chem.–Eur. J. 2011, 17, 626.

Heck mechanism part one

28Kamisaki, H.; Nanjo, T.; Tsukano, C.; Takemoto, Y. Chem.–Eur. J. 2011, 17, 626.

Heck mechanism part two

29Kamisaki, H.; Nanjo, T.; Tsukano, C.; Takemoto, Y. Chem.–Eur. J. 2011, 17, 626.

Bismuth hydroamination

30Kamisaki, H.; Nanjo, T.; Tsukano, C.; Takemoto, Y. Chem.–Eur. J. 2011, 17, 626.

Formal synthesis of (-)-platensimycin

31Eey, S. T.; Lear, M. J. Org. Lett. 2010, 12, 5510.

Dehydrative arylation mechanism

32Eey, S. T.; Lear, M. J. Org. Lett. 2010, 12, 5510.

Carbobismuthination of Alkynes

33Nishimoto, Y.; Takeuchi, M.; Yasuda, M.; Baba, A. Angew. Chem. Int. Ed. 2012, 51, 1051.

Asymmetric Mukiayama aldolcondensation

34

Kobayashi, S.; Ogino, T.; Shimizu, H.; Ishikawa, S.; Hamada, T.; Manabe, K. Org. Lett. 2005, 7, 4729.

Unusual Mukiayama aldol condensation

35

Ollevier, T.; Bouchard, J. E.; Desyroy, V. J. Org. Chem. 2008, 73, 331;

Attanasi, O. A.; Favi, G.; Giorgi, G.; Mantellini, F.; Karapetyan, V.; Langer, P. Tetrahedron 2009, 65,

5456.

Mechanism on next slide

Suggested mechanism

36Tetrahedron 2009, 65, 5456.

Epoxide opening/Prins cyclization

37

Lambert, R. F.; Hinkle, R. J.; Ammann, S. E.; Lian, Y.; Liu, J.; Lewis, S. E.; Pike, R. D. J. Org. Chem.

2011, 76, 9269.

Suggested mechanism

38

Lambert, R. F.; Hinkle, R. J.; Ammann, S. E.; Lian, Y.; Liu, J.; Lewis, S. E.; Pike, R. D. J. Org. Chem.

2011, 76, 9269.

Sakurai cyclization

39Leroy, B.; Marko, I. E. Tetrahedron Lett. 2001, 42, 8685.

40

Biomimetic cationic etherification

Fotiadou, A. D.; Zografos, A. L. Org. Lett. 2011, 13, 4592.

Catalytic Enyne cyclization

41

Wang, Z.; Fang, S. Eur. J. Org. Chem. 2009, 5505;

Komeyama, K.; Miyagi, M.; Takaki, K. Chem. Lett.

2009, 38, 224.

Cascade azaenynol cyclization

42Komeyama, K.; Saigo, N.; Miyagi, M.; Takaki, K. Angew. Chem. Int. Ed. 2009, 48, 9875.

Catalytic enyne cyclization

43Wang, L.; Fan, R. Org. Lett. 2012, 14, 3596.

Biomimetic triene cycloisomerization

44Godeau, J.; Fontaine-Vive, F.; Antoniotti, S.; Dunach, E. Chem.–Eur. J. 2012, 18, 16815.

Mixed Bi(III) organylhalides

45Akiba, K. Organo Main Group Chemistry, Wiley: New Jersey, 2001; pp 144.

Bi(III) Cyclopropyl transfer

46

Gagnon, A.; Duplessis, M.; Alsabeh, P.; Barabe, F. J. Am. Chem. Soc. 2007, 129, 44;

Gagnon, A.; St. Onge, M.; Little, K.; Duplessis, M; Barabe, F. J. Org. Chem. 2008, 73, 3604.

Preparation of Bi(V) reagents

47Akiba, K. Organo Main Group Chemistry, Wiley: New Jersey, 2001; pp 144.

Bi(V) Reagent reactivity

48Bismuth-Mediated Organic Reactions Springer-Verlag Berlin Heidelberg: 2012, pp 22.

.

Alkylation with bismuthonium salts

49

Matano, Y.; Imahori, H. J. Org. Chem. 2004, 69, 5505.

Barton, D. H. R.; Bhatnagar, N. Y.; Blazejewski, J. C.; Charpiot, B.; Finet, J. P.; Lester, D. J.;

Motherwel, W. B.; Papoula, M. T. B.; Stanforth, S. P. J. Chem. Soc. Perkin Trans. 1. 1985, 2657.

Approach toward maoecrystal V

50

Krawczuk, P. J.; Schone, N.; Baran, P. S. Org. Lett., 2009, 11, 4774.

Barton, D. H. R.; Blazejewski, J. C.; Charpiot, B.; Finet, J. P.; Motherwel, W. B.; Papoula, M. T. B.;

Stanforth, S. P. J. Chem. Soc. Perkin Trans. 1. 1985, 2667.

Conclusion

• Non-toxic

• Water compatible

• Catalytic

• Unique reactivity

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Reviews

• Org. Biomol. Chem. 2013, 11, 2740.

• Chem. Eur. J. 2013, 19, 3270.

• Bismuth-Mediated Organic Reactions 2012, Springer-Verlag Berlin Heidelberg.

• Biological Chemistry of Arsenic, Antimony, and Bismuth 2011, John Wiley & Sons Ltd.

• Chem. Soc. Rev. 2011, 40, 4649.

• Eur. J. Org. Chem. 2004, 2517.

• Tetrahedron 2002, 58, 8373.

• Organobismuth Chemistry 2001, Elsevier Science B.V.

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