Fall l 2008 CC Chemical Compositions The Magazine of The Department of Chemistry and Biochemistry The University of Texas at Austin O OH O O O O O O O H N H O N 1. nBuLi O OTBS O N ∆ Br Br MeO2C N 2. R"X R R" O OH Pd Enolate N 2 CO2H S S N Me R' R" N N H Me Arylation N R R' R' Lewis Acid Mediated Me Me R N S S N Me O Coupling H O O OH 1 3 4 OH NH2 OAc O OH O O OH O H H H O Allylic TMS i. 4Å MS, CH3CN MeO2C (-)-gliotoxin MeO2C MeO2C ii. TFA, -45 °C to rt O O O Alkylation O + O OMe HO N N N OMe N Me Me Me H N NH iii. NaCN aq., CH2Cl2 emestrin 5 6 7 N 1. nBuLi N ∆ 2 N 2. R"X OMe CN 1-pot R R" 89% (88:12) NCbz O R R' R' Cbz R R" e.g. N O BnO N R' NH2 O R1 H HO H Cl R2 1 2 R O + R N N O Ts OH H Br M R Ar R N N Ar O Me OH Cl Me OH Me H Br N Me N N H NH Me p-toluenesulfonic acid H Me O Me HO o O H 0 C O Me (-)-epimyrtine (±)-tashiromine CN Me N 30 min Ts (-)-Caryophyllene Oxide 30% Br (HO) OP O ∆G ∆H T∆S 2 (HO)2OP O Compounda -1 Ka (M ) (kcal/mol) (kcal/mol) (kcal/mol) 1 [1.0 ± 0.1] x 106 -8.2 ± 0.1 -7.0 ± 0.1 1.2 ± 0.03 2 [4.4 ± 0.4] x 105 -7.7 ± 0.1 -5.3 ± 0.1 2.4 ± 0.06 O Acyclic O 7 O Control O 3 [8.5 ± 0.3] x 105 -8.1 ± 0.1 -6.2 ± 0.02 1.9 ± 0.02 N N Acyclic 2 H H 5 Control HN O HN (3) ([5.6 ± 0.2] x 10 ) (-7.9 ± 0.1) (-4.9 ± 0.02) (3.0 ± 0.02) HN R R R R Macro- 4 [9.9 ± 2.9] x 106 -9.5 ± 0.2 -4.8 ± 0.1 4.7 ± 0.2 HN O cyclization O HN O N N N N NH HN (4) ([6.5 ± 0.9] x 106) (-9.3 ± 0.1) (-6.4 ± 0.04) (2.9 ± 0.1) Macro- cyclization H O N N O a Results in parentheses refer to corresponding acyclic controls. M M M O C ONH2 C ONH 2 (HO)2OP O (HO)2OP O 3 4 N N N N n O O Flexible R R R R Control O O NH O O NH H 2 H 2 N NH N NH N N 2 N N 2 H H H H O O O O 1 2 HO O O Br Rh(COD)2OTf (2 mol%) N - R'' H H A Ph3CCO2H (2 mol%) + H H H R'' A- NH H N R' NH HN N N N N R N N N N R (R)-xylyl-WALPHOS (2 mol%) HO R' N N H H O o N H DCE, H2 (1 atm), 40 C CH3 1 R' = H, Alkyl R'' = Alkyl, Aryl 65-93% Yield H 90 - 99% ee 1 2 1 C A N-Hetereocyclic aromatic aldehydes and ketones, which are structurally similar to vicinal C+ C+ O OR OR dicarbonyl compounds are coupled to conjugated enynes using chirally modified rhodium N OR OR N Julia-Kocienski Me N OR OR Me EtO Olefination Fragment C catalyst in the presence of a bronsted acid co-catalyst with good to excellent yields and S N + I RO H H C+ RO RO OR H H - Me O O RO OR A - O Heck Me enantioselectivities. N N N H H H A Me Coupling OH A- N H N H H Me OTES N N H H N OTES Fragment B Rh(COD)2BARF (5 mol%) N N N I HO2C NHTs +- or N * R = TBDMS 2-Fur P (12 mol%) C - Fragment A NTs 3 C+ OH OH R N R N R' R' Na SO (200 mol%) "Oxidation" Me 2 4 Yamaguchi Me o Me SpnJ, FAD 15 DCM, H2 (1 atm), 25 C Macrolactonization 15 HO HO O HO OH OH O O o 57 - 99% Yield Me 21 11 TrisHCl, pH 8, 29 C Me R = Alkyl, Aryl R''= Alkyl, Aryl O O 3:1-12:1 dr "Cross-bridging Reactions" SpnF, SpnL, SpnM Me O Me N OH 2 O OMe N-Hetereocyclic vinylarenes , which are structurally similar to enones, are coupled to N-tosyl Me Me Me O OMe OMe aldimines using a rhodium catalyst and monodentate phosphine lignad with good to excellent H H Glycosylations O OH O O O O Me yields and acceptable levels of diastereoselectivities. The synthesis of unnatural β-methyl-α- Me O O H H H H aminoacids via this methodology is under investigation. Spinosyn A Spinosyn Aglycone R' R' R' R' R' R' N H H2N NH2 N N H H N N+ N N+ + H H O O HC l air, TE A C l- C l- MeOH NH HN acetone NH HN NH HN R H R H N R N R R H N R 1•HC l 2•HC l Allylation with allenes H OH OH O R2 cat. IrLn cat. IrLn R2 H R R1 R 1 i-PrOH H R1 R 3 H R2 R3 3 2 R Allylation with 1,3-dienes R 1 = H MeO2C C O O OH MeO2C OH O 2 cat. IrLn or RuLn cat. IrLn or RuLn 2 2 R R R R H R 1 1 1 i-PrOH H R1 1 [R h(C O)2C l]2 MeO2C R = E -c-P r MeO2C H R OLG + R 1 H MeO2C MeO2C Propargylation with Enynes MeO2C C O2Me R 2 R 2 = H, Me, Ph R 1 = Z-E t MeO2C R R2 OH R 2 OH cat. RuLn cat. RuLn O 2 MeO2C H R R1 H 1 i-PrOH H R1 CH2H Li O O Redox complimentary, byproduct free carbonyl addition from the aldehyde or alcohol oxidation level R Ti(OiPr) [R hC l((R )-Tol-BINAP )] , TMS Cl, 4 2 R O 2-cyclopentenone R = Alkyl, H, C H2OP G R R N N OMe O O O O Me O O Me Me O MeO Me O 1: R = (E)-CH-CHEt, 3: R = (E)-CH-CHEt, didehydrostemofoline isodidehydrostemofoline (asparagamine A) 2: R = nBu, stemofoline 4: R = nBu, isostemofoline Me O OTMS Me N MeO Me O N O O O 5 O 4 O Me O Me MeO Me didehydrostemofoline (1) R O R Me MeO N N 8 N R 14 H O OMe O OMe Me Me O 2n+ O O O S S N N N N N N S N N O -2n H S N N O Ru O Ru - O N N -2n e N N N N 2PF6 n thank you to our1 supportersPoly-1 Student abstracts from the Spring Symposium 2008, p.24. For a complete list of donors, see pp. 20-21. CONTENTS Chemical Compositions l Fall 2008 From the Chair For members of our community who are interested in and 4 Letters from the Chairs support teaching and research in chemistry and biochem- istry, Chemical Compositions provides a guide to the past, Research present, and future activities of the Department of Chemistry 6 Got Chemistry? and Biochemistry at the University of Texas at Austin. A Profile of Chris Bielawski 7 State-of-the-Heart Chip On the Cover: Electrogenerated chemiluminescence (ECL) for clinical 8 CEC: Renewable Energy analysis was largely developed at UT and is now used worldwide. Image shows ECL from the reduction of 9,10-diphenyl anthracene at the lower surface of a rotating ring-disk electrode immersed in acetonitrile (from Faculty J.T. Maloy’s UT dissertation, 1970). In addition to renewable energy 9 Lara Mahal technologies the Center for Electrochemistry (CEC) (article, page 8) also 10 Everybody WINS! carries out research in the fields of bioelectrochemistry and ultrasensitive 11 Honors and Awards biosensor probes where electrochemistry plays a key role in the 12 Welcome New Faculty electroanalytical characterization of living systems. 14 Joseph J. Lagowski Retires 17 In Memoriam Giving 18 The Faulkner Chair 20 Donors Students 13 New Graduate Students 14 Scholarships & Fellowships 24 Spring Symposium 25 Undergraduate Research Department 26 Staff Excellence 27 Staff Profile 28 Calendar Chemical Compositions 3 FORMER CHAIR’S LETTER It is truly amazing how quickly time flies when you are busy and hav- Chair ing fun. Indeed, I can scarcely believe that it has been four years since I Richard M. Crooks accepted the position as Chair of the Department, and my “retiring” from this position is bittersweet. I am eager to be able to devote more time to Associate Department teaching and research, but I shall miss the exciting opportunities the Chair Chair has to advance the Department. As I look back over these past four years, Dean R. Appling I believe the Department has made considerable progress toward its goal Associate Director of being amongst the top ten chemistry and biochemistry departments in Dr. Richard B. Quy the country. We weathered the attacks of a number of predatory departments and Administrative Manager retained a large number of vital members of our faculty.