Career Summary

Xiaopeng Yin The Wulff Group

Michigan State University 6/6/2014

Eric N. Jacobsen

About Eric N. Jacobsen

PERSONAL Born February 22, 1960, New York, N.Y. Married to Virginia Estevez on May 17, 1997. Three daughters (Adriana, Isabel, and Emilia) EDUCATION 1978-1982: New York University, New York, New York.

Degree awarded: B.S. in Chemistry Research advisor (1981-1982): Professor Yorke E. Rhodes

1982-1986: University of California, Berkeley, California. Degree awarded: Ph.D. Research advisor: Professor Robert G. Bergman

1986-1988: National Institutes of Health Postdoctoral Fellow Massachusetts Institute of Technology, Cambridge, Massachusetts. Research advisor: Professor K. Barry Sharpless Development of the osmium-catalyzed asymmetric dihydroxylation reaction.

EMPLOYMENT 1988-1993: University of Illinois at Urbana-Champaign

Assistant Professor (June 1988-September 1991) Associate Professor (September 1991-June 1993)

1993-present: Harvard University Professor (July 1993-June 2001) Sheldon Emery Professor of Chemistry (July 2001-present)

Group Members Present Graduate Students: 9 Postdocs: 11 Past Ph.D Students: 37 Postdocs: 80

Mini Group Reunion in summer 2011

Publications

1983-2014 186 research articles (70 JACS, 27 Angew, 2 Science, 1 Nature, 1 Natrue Chem.) 23 reviews 16 patents

Citations

Sum of Times Cited without self-citations : 28014 Citing Articles without self- citations: 15081 Average Citations per Item: 158.21

Top 3 cited research articles: 1.  Zhang, W.; Loebach, J. L.; Wilson, S. R.; Jacobsen, E. N. "Enantioselective Epoxidation of

Unfunctionalized Olefins Catalyzed by (salen)Manganese Complexes," J. Am. Chem. Soc. 1990, 112, 2801–2803 (1243, 50/y)

2.  Tokunaga, M.; Larrow, J.F.; Kakiuchi, F.; Jacobsen, E.N. "Asymmetric Catalysis with Water: Efficient Kinetic Resolution of Terminal Epoxides by Means of Catalytic Hydrolysis," Science 1997, 277, 936–938. (900, 50/y)

3.  Schaus, S. E.; Brandes, B. D; Larrow, J. F.; Tokunaga, M.; Hansen, K. B.; Gould, A. E.; Furrow, M. E.; Jacobsen, E. N. "Highly Selective Hydrolytic Kinetic Resolution of Terminal Epoxides Catalyzed by Chiral (salen)Cobalt(III)-Complexes. Practical Synthesis of Enantioenriched Terminal Epoxides and 1,2-Diols," J. Am. Chem. Soc. 2002, 124, 1307–1315. (616, 47/y)

Catalysts*

79

39

16 17

Salen Complexes H-bond Donors (Schiff Base)Cr Complex Other

* Summarized from 151 Independent research papers in selected journals

Metal of Salen Complexes *

26

23

16

11 3

Co Mn Cr Al Cu

* Summarized from 151 Independent research papers in selected journals

H-bond Donors*

32

4 3

thiourea urea guanidinium

* Summarized from 151 Independent research papers in selected journals

Reaction*

20

31

4

10 10 7 6

23

5

8 7 12 8

Epoxidation Epoxides Ring Opening Aziridinization Conjugate Addition Cycloadditions C=C functionalization C=O functionalization C=N functionalization C=O α-functionalization Mechanism Study Catalyst Study Total Synthesis other

* Summarized from 151 Independent research papers in selected journals

Jacobsen Asymmetric Epoxidation of Olefins

Zhang, W.; Loebach, J. L.; Wilson, S. R.; Jacobsen, E. N. J. Am. Chem. Soc. 1990, 112, 2801–2803 Jacobsen, E. N.; Zhang, W.; Muci, A. R.; Ecker, J. R.; Deng, L. J. Am. Chem. Soc. 1991, 113, 7063–7064

9 substrates, 36-75% yield, 20-93% ee, only cis-alkene gave good results

6 cis-alkene substrates, 63-96% yield, 89-98% ee

Preparation of Catalyst

Palucki, M.; Finney, N.S.; Pospisil, P.J.; Güler, M.L.; Ishida, T.; Jacobsen, E.N. J. Am. Chem. Soc. 1998, 120, 948–954

“Side on” Mechanism

Jacobsen, E. N.; Zhang, W.; Muci, A. R.; Ecker, J. R.; Deng, L. J. Am. Chem. Soc. 1991, 113, 7063–7064 Palucki, M.; Finney, N.S.; Pospisil, P.J.; Güler, M.L.; Ishida, T.; Jacobsen, E.N. J. Am. Chem. Soc. 1998, 120, 948–954

Substrate limitation

Properties favoring high enantioselectivity

Jacobsen, E. N.; Deng, L.; Furukawa, Y.; Martínez, L. E. Tetrahedron 1994, 50, 4323–4334 Palucki, M.; Pospisil, P. J.; Zhang, W.; Jacobsen, E. N. J. Am. Chem. Soc. 1994, 116, 9333–9334

Terminal alkenes

mCPBA, -78°C, 30 min, Catalyst 3 88% yield, 86% ee

Substrate limitation

Brandes, B. D.; Jacobsen, E. N. J. Org. Chem. 1994, 59, 4378–4380 Brandes, B. D.; Jacobsen, E. N. Tetrahedron Lett. 1995, 36, 5123–5126

Trisubstituted alkenes

6 substrates, 61-97% yield, 86-95% ee,

Tetrasubstituted alkenes

Catalyst 2, 84% yield, 96% ee Catalyst 2, 81% yield, 97% ee

Catalyst 3, 45% yield, 65% ee Catalyst 3, 37% yield, 35% ee

Trans Epoxides

Zhang, W.; Lee, N. H.; Jacobsen, E. N. J. Am. Chem. Soc. 1994, 116, 425–426 Chang, S.; Lee, N. H.; Jacobsen, E. N. J. Org. Chem. 1993, 58, 6939–6941 Chang, S.; Galvin, J. M.; Jacobsen, E. N. J. Am. Chem. Soc. 1994, 116, 6937–6938

65% yield, t/c = 5:1 98% ee 58% yield, t/c = 7:1 83% ee 81% yield, t/c = 9:1 87% ee

Cis-enynes and cis-dienes

Chiral Quaternary Ammonium Salts additives

Ring Opening of Epoxides

Martínez, L. E.; Leighton, J. L.; Carsten, D. H.; Jacobsen, E. N. J. Am. Chem. Soc. 1995, 117, 5897–5898

Kinetic Resolution with TMSN3

Larrow, J.F.; Schaus, S.E.; Jacobsen, E.N. J. Am. Chem. Soc. 1996, 118, 7420–7421

Hydrolytic Kinetic Resolution (HKR)

Tokunaga, M.; Larrow, J.F.; Kakiuchi, F.; Jacobsen, E.N. Science 1997, 277, 936–938

Mechanism and Improvement

Nielsen, L. C. P.; Stevenson, C. P.; Blackmond, D.G.; Jacobsen, E. N. J. Am. Chem. Soc. 2004, 126, 1360–1362 Nielsen, L. P. C.; Zuend, S. J.; Ford, D. D.; Jacobsen, E. N. J. Org. Chem., 2012, 77, 2486–2495

Method A: X = OAc Method B: X = OTs

Mechanism and Improvement

Ready, J. R.; Jacobsen, E. N. Angew. Chem. Int. Ed. 2002, 41, 1374–1377. Breinbauer, R.; Jacobsen, E. N. Angew. Chem. Int. Ed. 2000, 39, 3604–3607

Stereochemical Communication Between Catalysts

Ford, D. D.; Nielsen, L. P. C.; Zuend, S. J.; Musgrave, C. B.; Jacobsen, E. N. J. Am. Chem. Soc. 2013, 135, 15595–15608

Phenolytic Kinetic Resolution (PKR)

Ready, J. M.; Jacobsen, E. N. J. Am. Chem. Soc. 1999, 121, 6086–6087

Asymmetric Alkene Aziridination

Li, Z.; Conser, K. R.; Jacobsen, E. N. J. Am. Chem. Soc. 1993, 115, 5326–5327 Li, Z.; Quan, R. W.; Jacobsen, E. N. J. Am. Chem. Soc. 1995, 117, 5889–5890

Enantioselective Michael Additions

Enantioselective Michael Additions

Myers, J. K.; Jacobsen, E. N. J. Am. Chem. Soc. 1999, 121, 8959–8960 Sammis, G. M.; Jacobsen, E. N. J. Am. Chem. Soc. 2003, 125, 4442–4443

Enantioselective Michael Additions

Sammis, G. M.; Danjo, H.; Jacobsen, E. N. J. Am. Chem. Soc. 2004, 126, 9928–9929

Cooperative Dual Catalysis

Enantioselective Michael Additions

Taylor, M. S.; Jacobsen, E. N. J. Am. Chem. Soc. 2003, 125, 11204–11205

Enantioselective Michael Additions

Taylor, M. S.; Zalatan, D. N.; Lerchner, A. M.; Jacobsen, E. N. J. Am. Chem. Soc. 2005, 127, 1313–1317

9 examples, 76-93% yield, 75-96% ee,

8 examples, 70-90% yield, 88-95% ee,

7 examples, 72-97% yield, 61-94% ee,

Asymmetric Hetero-Diels-Alder Reactions

Schaus, S.E.; Brånalt, J.E.; Jacobsen, E.N. J. Org. Chem. 1998, 63, 403–405

Asymmetric Hetero-Diels-Alder Reactions

Dossetter, A. G.; Jamison, T. F.; Jacobsen, E. N. "Angew. Chem. Int. Ed. 1999, 38, 2398–2400

14 examples, 50-97% yield, 81-99% ee,

Total Synthesis of FR901464

Thompson, C. F.; Jamison, T. F.; Jacobsen, E. N. J. Am. Chem. Soc. 2000, 122, 10482–10483 Thompson, C. F.; Jamison, T. F.; Jacobsen, E. N. J. Am. Chem. Soc. 2001, 123, 9974–9983.

Total Synthesis of (+)-Ambruticin

Liu, P.; Jacobsen, E. N. J. Am. Chem. Soc. 2001, 123, 10772–10773

Synthesis of the Catalyst

Schaus, S.E.; Brånalt, J.E.; Jacobsen, E.N. J. Org. Chem. 1998, 63, 403–405

Inverse Electron Demand Hetero-Diels–Alder Reactions

Gademann, K.; Chavez, D. E.; Jacobsen, E. N. Angew. Chem. Int. Ed. 2002, 41, 3059–3061 Chavez, D. E.; Jacobsen, E. N. Org. Lett. 2003, 5, 2563–2565

Quinone Diels–Alder Reactions and Application

Jarvo, E. R.; Lawrence, B. M.; Jacobsen, E. N. Angew. Chem. Int. Ed. 2005, 44, 6043–6046 Boezio, A. A.; Jarvo, E. R.; Lawrence, B. M.; Jacobsen, E. N. Angew. Chem. Int. Ed. 2005, 44, 6046–6050

Hetero-Ene Reactions

Ruck, R. T.; Jacobsen, E. N. J. Am. Chem. Soc. 2002, 124, 2882–2883 Ruck, R. T.; Jacobsen, E. N. Angew. Chem. Int. Ed. 2003, 42, 4771–4774 Jacobsen, E. N. Angew. Chem., Int. Ed. 2008, 47, 1469–1472

18 examples, 50-98% yield, 70-96% ee

6 examples, 47-90% yield, 87-93% ee

42% yield, 93% ee, dr>30:1

Asymmetric Strecker Reaction

Sigman, M.S.; Jacobsen, E.N. J. Am. Chem. Soc. 1998, 120, 5315–5316 Sigman, M.S.; Jacobsen, E.N. J. Am. Chem. Soc. 1998, 120, 4901–4902

R= Ar, 7 examples, 91-99 % yield, 79-95% ee R= Alkyl, 2 examples, 69-77 % yield, 37-57% ee

M = Al(III)Cl

Thiourea Catalyst

Sigman, M.S.; Jacobsen, E.N. J. Am. Chem. Soc. 1998, 120, 4901–4902

6 examples, 65-92 % yield, 70-91% ee

Mode of Activation

Vachal, P.; Jacobsen, E. N. J. Am. Chem. Soc. 2002, 124, 10012–10014

Mode of Activation

Zuend, S. J.; Coughlin, M. P.; Lalonde, M. P.; Jacobsen, E. N. Nature 2009, 461, 968–970 Zuend, S. J., Jacobsen, E. N. J. Am. Chem. Soc. 2009, 131, 15358–15374

Activation of Imines

Wenzel, A. G.; Jacobsen, E. N. J. Am. Chem. Soc. 2002, 124, 12964–12965 Joly, G. D.; Jacobsen, E. N. J. Am. Chem. Soc. 2004, 126, 4102–4103

R= Ar, 14 examples, 84-99 % yield, 86-98% ee

Hydrophosphonylation

18 examples, 52-93 % yield, 81-99% ee

Mannich Reactions

Activation of Imines and Ketones

Xu, H.; Zuend, S. J.; Woll, M. P.; Tao, Y.; Jacobsen, E. N. Science 2010, 327, 986–990 Fuerst, D. E.; Jacobsen, E. N. J. Am. Chem. Soc. 2005, 127, 8964–8965

Cyanosilylation of Ketones

18 examples, 81-98 % yield, 86-98% ee

Povarov Reactions

H-bonding Anion Stabilization

Taylor, M. S.; Jacobsen, E. N. J. Am. Chem. Soc. 2004, 126, 10558–10559 Brown, A. R.; Uyeda, C.; Raheem, I. T.; Thiara, P. V.; Peterson, E. A.; Jacobsen, E. N. J. Am. Chem. Soc. 2007, 129, 13404–13405

Acyl-Pictet-Spengler Reactions

Pictet-Spengler-Type Cyclizations

7 examples, 65-81 % yield, 85-95% ee

15 examples, 51-94 % yield, 81-99% ee

H-bonding Anion Stabilization

Raheem, I. T.; Thiara, P. V.; Peterson, E. A.; Jacobsen, E. N. J. Am. Chem. Soc. 2007, 129, 13404–13405

H-bonding Anion Stabilization

Reisman, S. E.; Doyle, A. G.; Jacobsen, E. N. J. Am. Chem. Soc. 2008, 130, 7198–7199

Additions to Oxocarbenium Ions

6 examples, 71-96 % yield, 74-90% ee

H-bonding Anion Stabilization

Knowles, R. R.; Lin, S.: Jacobsen, E. N. J. Am. Chem. Soc. 2010, 132, 5030–5032 Veitch, G. E.; Jacobsen, E. N. Angew. Chem. Int. Ed. 2010, 49, 7332–7335

Cationic Polycyclizations

Iodolactonization

9 examples, 71-96 % yield, 48-96% ee

7 examples, 51-77 % yield, 89-94% ee

H-bonding Anion Stabilization

Brown, A. R.; Kuo, H.-S.; Jacobsen, E. N. J. Am. Chem. Soc. 2010, 132, 9286–9288 Burns, N. Z.; Witten, M. G.; Jacobsen, E. N. J. Am. Chem. Soc. 2011, 133, 14578–14581

α-Alkylation of Aldehydes

9 examples, 52-770% yield, 85-94% ee

[5+2] Pyrylium Cycloadditions

H-bonding TS Stabilization

Uyeda, C.; Jacobsen, E. N. J. Am. Chem. Soc. 2008, 130, 9228–9229 Brown, A. R.; Uyeda, C.; Brotherton, C. A.; Jacobsen, E. N. J. Am. Chem. Soc. 2013, 135, 6747–6749

Guanidinium Catalysts

Claisen Rearrangements

Cope-Type Hydroamination