Robert J. Hinkle
Associate Professor of Organic Chemistry,
(757)-221-1501; e-mail: email@example.com
Our research encompasses three distinct areas of chemistry: Algal Biofuels; the Catalytic Use of Bi(III) Compounds for the synthesis of ethers; and the chemistry of Iodonium Salts.
Under the guidance of William & Mary's Vice Provost for Research, Dennis Manos, a group of scientists as well as Blackrock Energy of Williamsburg began to talk about focusing the expertise of our faculty on a project with potential to both ameliorate the nutrient problem in the Chesapeake Bay as well generate biomass for production of fuels. After much planning we received funding from the Norwegian Oil Company, Statoil, for a collaboration between The College of William & Mary, The Virginia Institute of Marine Science (VIMS), The Smithsonian Instititute, The University of Arkansas, the University of Maryland and Blackrock Energy. William & Mary and VIMS are affiliates and both institutions are partially supported by the Commonwealth of Virginia. Scientists at VIMS study the ecology of the Chesapeake Bay and the campus is conveniently located at the mouth of the York River in Gloucester, Virginia. This location on one of the largest estuarine environments in North America is ideal for studying the effects of many variables (e.g., pollutants, overfishing, currents, tides, nutrient levels, oxygen levels, etc.) on the overall health of the bay.
-VIMS: Professors Elizabeth Canuel and Emmett Duffy.
-William and Mary: yours truly, as well as Provost Dennis Manos and Professors William Cooke and Eugene Tracy.
-Smithsonian: Walter Adey, Ph. D., scientist and Curator.
-Arkansas chemical engineers: Professors Jamie Hestekin and Robert Beitle.
-Maryland: Professor Patrick Kangas.
In 2002, we began to work in an area of catalysis in which 5-15 mole percent of bismuth(III) compounds can be used to efficiently synthesize cyclic ethers from acyclic precursors. The initial reactions were conducted while I was on sabbatical in P. Andrew Evans' laboratories at Indiana University. Professor Evans has recently moved to The University of Liverpool where he is the Professor and Heath Harrison Chair of Organic Chemistry. The initial reactions showed that highly diastereoselective reactions can be carried out using allyltimethylsilane as a nucleophile in a Tandem Cyclization-Addition sequence. The stereochemistry of allylation is completely consistent with that known for cyclic six-membered oxocarbenium ions. For definitive work on oxocarbenium ion stereochemistry, see publications listed on Prof. Keith Woerpel's Home page on the University of California, Irvine's chemistry website (UCI website )
Since that initial investigation, we have extended the range of nucleophiles which can participate in this reaction. The use of ketene silyl acetals (reagent in red over lower arrow) provides diastereselective additions, but the addition is much lower than with allylsilane above. These results imply that the diastereoselectivity is inversely proportional to the strength of the pi-nucleophile during addition to the intermediate ion.
We are currently expanding our emphasis to include numerous new electrophiles and nucleophiles in tandem and three-component addition-cyclization reactions with Bi(III) "catalysts." Please see J. Org. Chem. 2006, 71, 7071.
Iodine is a very large element and because of its size as well as great polarizeability, iodine can adopt oxidation states such as -1, +3 and +5. Our Early work in the area of iodonium salts (iodine +3) showed the remarkable leaving group ability of the hypervalent iodine moiety found in alkenyl(aryl)iodonium salts. Under very mild conditions, the salts, (E)-7a-c, fragment into three vinyl triflates as well as iodobenzene (eq 1).
We originally interpreted this fragmentation as evidence for the formation of a primary vinyl cation, which had been unobserved in solution. Further work from our labs as well as a lab in Japan (Okuyama's lab) indicated that the primary vinyl cation (A) shown in Scheme 2 is, indeed, not necessary to interpret the results of this thermal reaction.
More recently we have become much more interested in compounds which contain both iodonium and diazo functional groups in the same molecule. We are currently developing reactions in which the phenyliodonio (red) moiety can selectively be replaced while the diazo group (N2) remains. Both of these functionalities are quite useful in organic synthesis.
Chem. 150W Beyond Petroleum as a Fuel (Fall T/Th 11:00)
Chem 457/657 Organic Synthesis (Fall, T/Th 12:30)
Chem 252, Introductory Organic Chemistry Laboratory, I: (W, Th, Spring)
Chem 353 Introductory Organic Chemistry Laboratory, II: (M, T, Fall)
Academic Year 2009-2010
Shane Lewis (M. S. 2010)
Travis J. Grubbs (B. S. 2010)
Rob Ziegler (B. S. 2010)
R. Frederick Lambert (B. S. 2011)
Stephen E. Ammann (B. S. 2011)
Emily E. Stephens (B. S. 2012)
Allison Kennington (B. S. 2013)
Academic Year 2008-2009
Lee C. Speight (B. S. 2009)
Christopher Katilie (B. S. 2009)
Andrew Midland (B. S. 2009)
Academic Year 2007-2008
Lauren A. Katkish (B. S. 2008)
Joshua Pahng (B. S. 2008)
Academic Year 2006-2007
Kristie Schmidt (M. S. 2007)
Heather E. Stevenson (B. S. 2007)
H. Danielle Johnson (B. S. 2007)
Christine Forgues (B. S. 2007)
Elizabeth J. Cline (B. S. 2007)
Academic Year 2005-2006
Timothy J. Brown (B. S. 2006)
Yajing Lian (M. S. 2005)
Melissa Sprachman (B.S. 2006) **Beckman Scholar**
Kristie Schmidt (M. S. 2007)
Tim Brown (B. S. 2006)
Camille and Henry Dreyfus Foundation--Henry Drefus Teacher-Scholar Award (2002-2007)
Arnold and Mabel Beckman Foundation (Beckman Scholarships to Melissa Sprachman (B.S. 2006), Ann Mikowski (B.S. 2003) and Anne McNeil (B. S. 1999)
Eli Lilly Pharmaceutical Corporation (Summer Fellowship for M. Christa Mattern--B.S. 2005)
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William and Mary Undergraduate Students are in Bold
1) Hinkle, R. J.; Lian, Y.; Speight, L. C.; Stevenson, H. E.; Sprachman, M. M.; Katkish, L. A.; Mattern, M. C. ” Synthesis of 2,6-Disubstituted Dihydropyrans via an Efficient BiBr3-initiated Three Component, One-pot Cascade,” Tetrahedron. 2009, 65, 6834–6839.
2) Lian, Y.; Hinkle, R. J. ”BiBr3-Initiated Tandem Addition/Silyl-Prins Reactions to 2,6-Disubstituted Dihydropyrans,” J. Org. Chem. 2006, 71, 7071-7074.
3) Robert J. Hinkle, Lian, Y.; Litvinas, N. D.; Jenkins, A. T.; Burnette, D. C. "Bismuth(III) Bromide Initiated Cyclization-Addition Reactions: Effect of Nucleophile and Total Synthesis of (+)-(S,S)-(cis-6-methyltetrahydropyran-2-yl)acetic Acid and its trans-Diastereomer," Tetrahedron 2005, 61, 11679-11685
4 ) Evans, P. A.; Cui, J.; Gharpure, S. J; Hinkle, R. J. “ Stereoselective Construction of Cyclic Ethers using a Tandem Two-Component Etherification: Elucidation of the Role of Bismuth Tribromide,” J. Am. Chem. Soc. 2003, 125,11456-11457.
5) Hinkle, R. J. "Mikowski, A.M. "Kinetics of Stereoisomeric 2-Methyl-1-butenyl(aryl)iodonium triflates," Included in a special issue of ARKIVOC 2003, vi, 201-212, published 25 July 2003: http://www.arkatusa.org/ark/journal/2003/Varvoglis/AV745A/745A.pdf.
6) Tykwinski, R. R. †; Kamada, K. ‡; Bykowski, D. †; Hegmann, F. A. †; Hinkle, R. J. "Nonlinear Optical Properties of Thienyl and Bithienyl Iodonium Salts as Measured by the Z-scan Technique," J. Opt. A: Pure Appl. Opt. 2002, 4, S202-206. .
7) Bykowski, D. †; McDonald, R. †; Hinkle, R. J.; Tykwinski, R. R. † "Structural and Electronic Characteristics of Thienyl(aryl)iodonium Triflates," J. Org. Chem., 2002, 67, 2798-2804.
8) Hinkle, R. J.; McDonald, R. †, "(Z)-2-Methyl-1-buten-1-yl(aryl)iodonium Triflates Containing Electron-Withdrawing Groups on the Aryl Moiety." Acta Cryst. C. 2002, C58, o117-o121.
9) McNeil, A. J. ; Hinkle, R. J.; Rouse, E. A.; Thomas, Q. A.; Thomas, D. B. "Vinyl Carbocations: Solution Studies of Alkenyl(aryl)iodonium Triflate Fragmentations," J. Org. Chem. 2001 , 66, 5556-5565.
10) Hinkle, R. J.; Leri, A. C.; David, G. A.; Erwin, W. M. "Addition of Benzylzinc Halides to Alkenyl(phenyl)iodonium Triflates: Stereoselective Synthesis of Trisubstituted Alkenes," Org. Lett. 2000, 2, 1521-1523.
11) Hinkle, R. J.; McNeil, A. J.; Thomas, Q. A.; Andrews, M. N. “Vinyl Cations in Solution: Kinetics and Products of Alkenyl(aryl)iodonium Salt Fragmentations,” J. Am. Chem. Soc. 1999, 121, 7437-7438.
12) Hinkle, R. J.; Thomas, D. B. “Facile Fragmentations of Alkenyl(aryl)iodonium Triflates,” J. Org. Chem. 1997, 62, 7534-7535.
13) Hinkle, R. J.; Stang, P. J. "Stereospecific Synthesis of Trisubstituted Alkenyl-(phenyl)iodonium Salts from Vinylstannanes" Synthesis 1994, 313.
14) Hinkle, R. J.; Poulter, G. T.; Stang, P. J. "Palladium(II) and Copper(I) Co-Catalyzed Coupling of Stereodefined Alkenyl(phenyl)iodonium Salts and Unsaturated Tri-n-butylstannanes" J. Am. Chem. Soc. 1993, 115, 11626.
15) Hinkle, R. J.; Stang, P. J.; Arif, A. M. "Vinylplatinum Carbenes and Nitriles, Platinoxa-cyclic Complexes and Heck-Type Coupling Products Formed Via Reaction of ( sigma-2-propenyl)bis(triphenylphosphine)platinum(II) Triflate with Alkynols, Nitriles, and Acrylate Esters. Molecular Structure of [(PPh3)2PtCH2C(O)OCH3][OTf]" Organometallics 1993, 12, 3510.
16) Zhong, Z.; Hinkle, R. J.; Arif, A. M.; Stang, P. J. "Novel Synthesis of eta-3-Allyl)platinum(II) Complexes from Enol Triflates and Simple Olefins and Their Regiospecific Deprotonation" J. Am. Chem. Soc. 1991, 113, 6196.
17) Hinkle, R. J.; Stang, P. J.; Kowalski, M. H. "Vinylphosphonium Salts: Stereoselective Palladium-Catalyzed Vinylation of Triphenylphosphine with Vinyl Triflates" J. Org. Chem. 1990, 55, 5033.
18) Kowalski, M. H.; Hinkle, R. J.; Stang, P. J. "A Simple Highly Stereospecific Preparation of Vinylphosphonium Salts: Palladium-Catalyzed Vinylation of Triphenyphosphine via Vinyl Triflates" J. Org. Chem. 1989, 54, 2783.
19) Pike, R. M.; Mayo, D. W.; Butcher, S. S.; Butcher, D. J.; Hinkle, R. J., "Microscale Organic Laboratory IV: A Simple and Rapid Procedure for Carrying Out Wittig Reactions " J. Chem. Ed. 1986, 63, 917.
† University of Alberta, Edmonton, Alberta, Canada
1) Robert J. Hinkle,* 2008 NSF Workshop on Organic Synthesis and Natural Products Chemistry, June 19-22, 2008. The Minary Center in Holderness, NH. I was the only undergraduate faculty member invited to this prestigious workshop.
2) Robert J. Hinkle,* Kristie M. Schmidt, Yajing Lian and Heather Stevenson, , “One-Pot, Three-Component Mukaiyama Aldol/Silyl-Prins Reactions to Dihydropyrans,” Presented at the Gordon Research Conference: Organic Reactions and Processes, Smithfield, RI, 15-20 July 2007. Invited Oral Presentation based on Poster Award, Thursday, 20 July 2007..
3) Robert J. Hinkle,* Yajing Lian, Kristie M. Schmidt, Heather Stevenson, and H. Danielle Johnson, “Bi(III)-Initiated Two- and Three-component Addition/silyl-Prins Reactions Toward cis-2,6-Disubstituted Dihydropyrans,” Presented at the 58 th Southeastern Regional Meeting of the American Chemical Society, Augusta, GA, November 01-04, 2006. Oral Presentation 227.
4) Timothy J. Brown, Robert J. Hinkle,* Melissa M. Sprachman, Mamio C. Mattern, Yajing Lian, “ Investigations of p- Nucleophiles in the Synthesis of 2-6 Disubstituted Tetrahydropyrans,” Presented at the 58 th Southeastern Regional Meeting of the American Chemical Society, Augusta, GA, November 01-04, 2006. Poster Presentation 439.
5) Timothy J. Brown, Robert J. Hinkle, Melissa M. Sprachman, M. Christa Mattern, Yajing, Lian. Investigations of pi -nucleophiles in the synthesis of 2,6-disubstituted tetrahydropyrans. Abstracts, 38th Middle Atlantic Regional Meeting of the American Chemical Society, Hershey, PA, United States, June 4-7 (2006), Poster Presentation.
6) Robert J. Hinkle, Yajing Lian, Y, M. Christa Mattern, Melissa M. Sprachman, “Bimuth(III)-Initiated Diastereoselective Cyclization-Addition Reactions toward 2,6-Disubstituted Tetrahydropyrans, 230 th ACS National Meeting, 28 August to 01 September 2005, Oral Presentation 538
7) Yajing Lian, Robert J. Hinkle, “Etherification reactions initiated by BiBr3: Total Synthesis of (+)-(S,S)-(cis-6-methyltetrahydropyran-2-yl)acetic Acid and its trans-Diastereomer,” 230 th ACS National Meeting, 28 August to 01 September 2005 , Poster Presentation 115.
8) Melissa M. Sprachman, M. Christa Mattern, Yajing Lian, Robert J. Hinkle, “Selective Tandem Cyclization-Addition Reactions Using catalytic Quantities of BiBr3 and π-Nucleophiles,” 230 th ACS National Meeting, 28 August to 01 September 2005, Poster Presentation 116.
9) Melissa M. Sprachman; Robert J. Hinkle,“The Use of Bismuth Compounds in the Non-Toxic Syntheses of Natural Products,” Arnold and Mabel Beckman Scholars Symposium, Irvine , CA , July 2005. Poster Presentation.
10) Robert J. Hinkle, Yajng Lian; Nichole D. Litvinas; Alex T. JenkinsJenkins; Daniel C. Burnette," BiBr3 Initiated Cyclization-Addition Reactions: Total Synthesis of (+) -(S,S)-(cis-6- Methyltetrahydropyran-2-yl)acetic Acid, its trans-Diastereomer and Effect of Nucleophile on Oxocarbenium Ion Additions, Presented at the National Organic Symposium, Salt Lake City, Utah, June 12-16, 2005. Poster Presentation B21.
11) Robert J. Hinkle, M. Christa Mattern, Melissa M. Sprachman and Nichole D. Litvinas, "Bismuth(III) Initiated Diastereoselective Cyclization-Addition Reactions Toward 2,6- Disubstituted Tetrahydropyrans," Presented at the 56 th Southeastern Regional Meeting of the American Chemical Society, Durham, NC, November 10-13, 2004. Oral Presentation 2004.
12) Yajing Lian, Robert J. Hinkle, Ann M. Mikowski, Michael C. Brochu, Robert R. Knowles, , "Isotope Effects and Mechanism(s) of Fragmentation of Alkenyl Iodonium Triflate Salts," Presented at the 56 th Southeastern Regional Meeting of the American Chemical Society, Durham, NC, November 10-13, 2004. Poster Presentation 255.
13) Melissa M. Sprachman, Nichole D. Litvinas, M. Christa Mattern, Robert J. Hinkle, Alex T. Jenkins, Daniel C. Burnette, "Stereoselective Tandem Cyclization-Addition Reactions Using Catalytic BiBr3," Presented at the 56th Southeastern Regional Meeting of the American Chemical Society, Durham, NC, November 10-13, 2004. Poster Presentation 800.
14) Santosh J. Gharpure, Robert J. Hinkle, Jian Cui, P. Andrew Evans,"Bismuth Catalyzed Diastereo- selective Etherification Reactions: Application to the Synthesis of Non-Adjacent and Fused Polycyclic Ethers," Presented at the National Organic Symposium, Bloomington, IN June 8-12, 2003. Poster Presentation C94.
15) Robert J. Hinkle, P. Andrew Evans, Jian Cui, Benedicte D. Delouvrie, “Diastereoselective Syntheses of Di– and Trisubstituted Cyclic Ethers via Tandem Cyclization-Addition Reactions,” Presented at the 225th American Chemical Society Meeting, New Orleans, LA, March 23-27, 2003. Oral Presentation 666.
Professor Ram Mohan, Bismuth Expert
Professor P. Andrew Evans, Bismuth Expert
Colonial Road Runners (CRR) running club of Williamsburg
© 2006, Robert J. Hinkle and College of William & Mary