Applications of adical eactions in Asymmetric Synthesis Brandon Meyers Michigan State University Department of Chemistry ovember 19, 2008
utline Introduction Importance of radical reactions Challenges of stereochemistry Methods employed to achieve asymmetric control Chiral Auxiliary Chiral Acid rganocatalysis
General Bond Forming Conditions Acidic (Cationic) - F 3 B! F 3 B! n Basic (Anionic) a I!! I I a eutral (adical) 3 C Br 3 C Br Clayden, J.; Greeves,.; Warren, S.; Wothers, P. rganic Chemistry. xford: University Press. 2001
eversal of eactivity eterolytic Cleavage I electrophilic carbocation I omolytic Cleavage I nucleophilic radical LDA LDA! nucleophilic carbanion Bu 3 Sn AIB Bu 3 Sn!Br electrophilic radical Br Giese, B.; Tetrahedron, 1985, 41, 4025
adicals Stabilized by Electron Donating Groups ucleophilic adical adical SM Energy nonbonding lone pairs Parsons, A.F. An Introduction to Free adical Chemistry, xford: Blackwell Science, 2000, p. 40
adicals Stabilized by Electron Withdrawing Groups adical SM!" Energy Electrophilic adical nonbonding lone pairs!! Parsons, A.F. An Introduction to Free adical Chemistry, xford: Blackwell Science, 2000, p. 40
Early Problems of Stereochemistry Synthesis of Sativene & Capocamphene Br Bu 3 Sn C 3 tbu, h! benzene X X = (37%) X = C 2 - Sativene X X = (25%) X = C 2 - Capocamphene Bakuzis, P.; Campos,..S.; Bakuzis, M.L.F. J. rg. Chem., 1976, 41, 3261
Methods for Asymmetric Control Chiral Auxiliary, X C X C 1 X C * 1 Chiral Acid, A C A C 1 A C 1 * rganocatalysis 1!LG * 1
Sultam & xazolidinone Auxiliaries S ' M * * ' Dipole-dipole control Lewis acid chelation
Dipole-Dipole Chiral Auxiliary Me glyoxylic oxime ether Bn S 1.0 eq. Me 3 Al Cl(C 2 ) 2 Cl reflux 0.67 eq. (1)-(+)-2,10-camphorsultam Bn S 2 90% yield S 2 Bn 5.0 eq. -I, C 2 Cl 2 2.5 eq. Bu 3 Sn 2.0 eq. BF 3 Et 2 5.0 eq. Et 3 B, -78 C S 2 Bn aito, T; Miyabe,.; Ushiro, C.; Ueda, M.; Yamakawa, K. J. rg. Chem., 2000, 65, 176-185
Mechanism Bu 3 Sn I! Bu 3 Sn!I S Bn S Bn S Bn SnBu 3 S Bn
Substrate Scope S 2 Bn 5.0 eq. -I, C 2 Cl 2 2.5 eq. Bu 3 Sn 2.0 eq. BF 3 Et 2 5.0 eq. Et 3 B, -78 C S 2 1 Bn Entry I Product Isolated Yield (%) dr of 1 1 i-pr-i 1a 80 096 : 4 2 Et-I 1b 80 095 : 5 3 t-bu-i 1c 83 >98 : 2 4 i-bu-i 1d 83 097 : 3 5 c-ex-i 1e 86 096 : 4 aito, T; Miyabe,.; Ushiro, C.; Ueda, M.; Yamakawa, K. J. rg. Chem., 2000, 65, 176-185
Preferred Site of Addition ote: = S Bn anti, s-cis S Bn S Bn anti, s-trans syn, s-cis syn, s-trans Bn S aito, T; Miyabe,.; Ushiro, C.; Ueda, M.; Yamakawa, K. J. rg. Chem., 2000, 65, 176-185
eduction of xime Ether and emoval of Chiral Auxiliary Bn 0.7 eq. Mo(C) 6 S 2 2, MeC, reflux S 2 2 = i-pr, 88% yield S 2 2 1 Li-TF (1:4) 2 = i-pr, 88% yield Synthesis of D-Valine 55% overall yield, 4 steps aito, T; Miyabe,.; Ushiro, C.; Ueda, M.; Yamakawa, K. J. rg. Chem., 2000, 65, 176-185
Lewis Acid Chelation to Chiral Auxiliary C 2 Et 1. (CCl) 2, TF 2. C 2 Et n-buli, -78 C 87% yield, two steps C 2 Et i-pr!i (10 eq) Sm(Tf) 3 (1.0 eq) Bu 3 Sn (6.0 eq) C 2 Et Et 3 B (3.0 eq), 2 C 2 Cl 2 /TF (4:1), -78 C 95% yield dr = 29:1 Sibi, M.P.; Liu, P.; Ji, J.; ajra, S.; Chen, J.-X. J. rg. Chem., 2002, 67, 1738-1745
Stereoselective Model Activates!"carbon to imide carbonyl Tf Tf Sm Tf i-pr C 2 Et Blocks Si-face i-pr Sibi, M.P.; Liu, P.; Ji, J.; ajra, S.; Chen, J.-X. J. rg. Chem., 2002, 67, 1738-1745
Synthetic Application: ( )-Enterolactone Previous Synthesis: Chenevert,.; et al. 7 steps, 35% yield Key Step: Enzyme-catalyzed esterification Chenevert,.; Mohammadi-Ziarani, G.; Caron, D.; Dasser, M.; Can. J. Chem., 1999, 77, 223
Lewis Acid Chelation to Chiral Auxiliary Me C 2 Et Br C 3 (10 eq) Sm(Tf) 3 (1.0 eq) Bu 3 Sn (6.0 eq) Et 3 B (3.0 eq), 2 C 2 Cl 2 /TF (4:1), -78 C C 2 Et 71% yield BEt 3 2 Et 2 B Et Et C 2 Et 17% yield Sibi, M.P.; Liu, P.; Ji, J.; ajra, S.; Chen, J.-X. J. rg. Chem., 2002, 67, 1738-1745
Total Synthesis of ( )-Enterolactone Me Me Me C 2 Et 3-MeC6 4 -C 2 I amds, TF -78 C to -54 C C 2 Et Li 2 2 C2 Et 1 Me 50% yield 88% yield Me 1.1.5 eq. B 3 /TF -15 C 2. PPTS, reflux Me 4.0 eq. BBr 3 0 C to -18 C Me 78% yield, two steps 88% yield Sibi, M.P.; Liu, P.; Ji, J.; ajra, S.; Chen, J.-X. J. rg. Chem., 2002, 67, 1738-1745
Methods for Asymmetric Control Chiral Auxiliary, X C X C 1 X C * 1 Chiral Acid, A C A C 1 A C 1 * rganocatalysis 1!LG * 1
Types of Chiral Acids Lewis Acids MgI 2 MgBr 2 Brønsted Acid C 3 2 P 2 Quinine, QP
Chiral Lewis Acid Chelation S 2 Bn 5.0 eq. -I, C 2 Cl 2 2.5 eq. Bu 3 Sn 2.0 eq. BF 3 Et 2 5.0 eq. Et 3 B, -78 C S 2 Bn = i-pr 80% yield, dr = 96:4 Me Bn MgBr 2 i-pr-i, Bu 3 Sn BEt 3, -78 C Me Bn 97% yield, 52% ee aito, T; Miyabe,.; Ushiro, C.; Ueda, M.; Yamakawa, K. J. rg. Chem., 2000, 65, 176-185
Model for Selectivity Mg Bn Me e-face open aito, T; Miyabe,.; Ushiro, C.; Ueda, M.; Yamakawa, K. J. rg. Chem., 2000, 65, 176-185
Chiral Brønsted Acids Quaternary Ammonium Salts of ypophosphorous Acid C 3 C 3 2 P 2 2 P 2 Quinine, QP Quinidine, QDP Cho, D.K.; Jang, D.. Chem. Commun., 2006, 5045-5047
Quinine esults Bn 2 eq. QP, 5 eq. -I 0.5 eq. BEt 3, 2 C 2 Cl 2 / 2 (1:1) 4 h, rt Bn Et Bn 1 2 2a Entry I Product Isolated Yield (%) 2a Yield (%) er of 2 : S C 3 1 i-pr-i 2b 83 7 21 : 79 2 c-ex-i 2c 80 10 21 : 79 3 t-bu-i 2d 60 30 01 : >99 4 1-Ad-I 2e 45 35 01 : >99 5 n-ct-i 2f 50 25 40 : 60 2 P 2 Quinine, QP Cho, D.K.; Jang, D.. Chem. Commun., 2006, 5045-5047
Quinidine esults Bn 2 eq. QDP, 5 eq. -I 0.5 eq. BEt 3, 2 C 2 Cl 2 / 2 (1:1) 4 h, rt Bn Et Bn 1 2 2a Entry I Product Isolated Yield (%) 2a Yield (%) er of 2 : S 1 i-pr-i 2b 82 10 >62 : 38 2 c-ex-i 2c 82 9 >72 : 28 3 t-bu-i 2d 62 27 >99 : 1 4 1-Ad-I 2e 47 37 >99 : 1 5 n-ct-i 2f 48 30 >58 : 42 C 3 Quinidine, QDP 2 P 2 Cho, D.K.; Jang, D.. Chem. Commun., 2006, 5045-5047
Model for Enantioselectivity Quinine versus Quinidine C 3 C 3 2 P 2 2 P 2 Si-face open e-face open Cho, D.K.; Jang, D.. Chem. Commun., 2006, 5045-5047
Conjugate adical Addition Enantioselective addition to α'-hydroxy enone I 0.3 eq. Chiral L.A. 2.0 eq. Bu 3 Sn 3.0 eq. Et 3 B/ 2 C 2 Cl 2, -78 0 C, 24 h 66% yield, 75% ee Mg(Tf 2 ) 2 Chiral Lewis Acid Sibi, M.P.; Lee, S.; Lim, C.J.; Kim, S.; Subramaniam,.; Zimmerman, J. rg. Lett., 2006, 8, 4311-4313
Scope of α'-ydroxy Enone and Alkyl alide Substrates 1 5.0 eq. 2 -I 0.3 eq. Chiral L.A. 2.0 eq. Bu 3 Sn 3.0 eq. Et 3 B/ 2 C 2 Cl 2, -78 0 C, 24 h 2 1 1 = C 2 C 2 2 = 1a-d 2a-d Entry 1 2 Product Isolated Yield (%) ee (%) 1 C 2 C 2 t-bu 1a 66 75 2 C 2 C 2 i-pr 1b 85 68 3 C 2 C 2 n-pr 1c 63 72 4 C 2 C 2 Et 1d 87 72 5 t-bu 2a 90 78 6 i-pr 2b 78 78 7 n-pr 2c 68 86 8 Et 2d 82 80 Mg(Tf 2 ) 2 Chiral Lewis Acid Sibi, M.P.; Lee, S.; Lim, C.J.; Kim, S.; Subramaniam,.; Zimmerman, J. rg. Lett., 2006, 8, 4311-4313
Model for Enantioselectivity 2 Mg X X 1 e-face open X=Tf 2 Sibi, M.P.; Lee, S.; Lim, C.J.; Kim, S.; Subramaniam,.; Zimmerman, J. rg. Lett., 2006, 8, 4311-4313
Synthetic Application: (+)-icciocarpin A Previous Synthesis: Krishe, M.; Agapiou, K. 6 steps, 14% yield Key step: Michael cycloisomerization (+)-icciocarpin A Agapiou, K.; Krishe, M. rg. Lett., 2003, 5, 1737-1740
adical Conjugate Addition MgI 2 Cl Bn Bn 5.0 eq. Cl Br 5.0 eq. Bu 3 Sn 5.0 eq. Et 3 B / 2, -78 C 84% yield, 97% ee Mg Bn icciocarpin A Sibi, M.P.; e, L. rg. Lett., 2004, 6, 1749-1752
Preparation of Aldehyde Intermediate Cl Sm(Tf) 3 C 3 Cl Bn 95% Me Bn ai Acetone I Me LiMDS -78 C to rt Me 98% Bn 97% Bn 1. Pd() 2 / 2, ex/etac, -10 C 2. TEMP, KBr, acl, std. ac 3, 0 C 76% over two steps C Me icciocarpin A Sibi, M.P.; e, L. rg. Lett., 2004, 6, 1749-1752
Synthesis of icciocarpin A Me (i-pr) 3 Ti 2.0 eq. C Solvent, -78 C 2.0 eq. s-buli 85% icciocarpin A 41% overall yield 5.7 : 1 Sibi, M.P.; e, L. rg. Lett., 2004, 6, 1749-1752
Methods for Asymmetric Control Chiral Auxiliary, X C X C 1 X C * 1 Chiral Acid, A C A C 1 A C 1 * rganocatalysis 1!LG * 1
MacMillan Enamine Chemistry Me 1 2 Me 1 2 SET Me 1 2 Me 1 2 Me 1 2 TMS * Beeson, T.D.; Mastracchio, A.; ong, J.B.; Ashton, K.; MacMillan, D.W.C. Science, 2007, 316, 582-585
Previous rganocatalytic esearch Iminium & Enamine rganocatalysis Enamine Activation M catalysis Iminium Activation LUM catalysis - 2-2 e - aldehyde amine catalyst These two modes of catalyst activation have provided more than 60 asymmetric metric methodologies over the past 7 years. - Dr. David MacMillan Beeson, T.D.; Mastracchio, A.; ong, J.B.; Ashton, K.; MacMillan, D.W.C. Science, 2007, 316, 582-585
ypothesis - SM Activation Et SET Butanal IP = 9.8 ev Pyrrolidine IP = 8.8 ev Et Enamine IP = 7.2 ev Et SM-activated Me Me Beeson, T.D.; Mastracchio, A.; ong, J.B.; Ashton, K.; MacMillan, D.W.C. Science, 2007, 316, 582-585
ypothesis - Enantioselectivity Density Functional Theory Model of Imidazolidinone Catalyst Me Beeson, T.D.; Mastracchio, A.; ong, J.B.; Ashton, K.; MacMillan, D.W.C. Science, 2007, 316, 582-585
Applications of SM-rganocatalysis α-substitution of Aldehydes Allylation Enolation * 1 xyamination Alkylation Vinylation
α-allylation of Aldehydes General eaction aldehyde 1 SiMe 3 CA (2.5 equiv.) ac 3, 24 h DME, -20 C 2.5 equiv. CF 3 C allylsilane 20 mol% cat. 1 product 1 CA = Ceric Ammonium itrate ( 4 ) 2 Ce( 3 ) 6 Beeson, T.D.; Mastracchio, A.; ong, J.B.; Ashton, K.; MacMillan, D.W.C. Science, 2007, 316, 582-585
rganocatalytic Allylation: Scope of Aldehyde Substrate 20 mol% SiMe 3 TFA CA (2.5 eq.), -20 C ac 3, DME, 24 h 81% yield, 91% ee 75% yield, 92% ee 72% yield, 87% ee Bz Boc 75% yield, 94% ee 72% yield, 95% ee 70% yield, 93% ee Beeson, T.D.; Mastracchio, A.; ong, J.B.; Ashton, K.; MacMillan, D.W.C. Science, 2007, 316, 582-585
rganocatalytic Allylation: Scope of Allylsilane Substrate 1 TFA 20 mol% C 6 13 SiMe 3 CA (2.5 eq.), -20 C ac 3, DME, 24 h 1 C 6 13 C 6 13 C 6 13 C 6 13 C 2 Et 88% yield, 91% ee 77% yield, 88% ee 87% yield, 90% ee 81% yield, 90% ee Beeson, T.D.; Mastracchio, A.; ong, J.B.; Ashton, K.; MacMillan, D.W.C. Science, 2007, 316, 582-585
α-eteroarylation & lefin Cyclization of Aldehydes C 6 13 + Boc 20 mol% TFA CA (2.5 eq.), -20 C ac 3, DME, 24 h Boc 85% yield 84% ee TFA 20 mol% CA (2.5 eq.), -10 C LiCl, TF, 24 h Cl 85% yield dr >8:1 95% ee Beeson, T.D.; Mastracchio, A.; ong, J.B.; Ashton, K.; MacMillan, D.W.C. Science, 2007, 316, 582-585
Mechanistic Investigation Bn t-bu radical Bn t-bu C 6 13 C 6 13 Me Me 2.5 equiv. cation Bn t-bu C 6 13 Me Beeson, T.D.; Mastracchio, A.; ong, J.B.; Ashton, K.; MacMillan, D.W.C. Science, 2007, 316, 582-585
Mechanistic Investigation Bn t-bu radical Bn t-bu C 6 13 2 C 6 13 Me C 6 13 Me 65% yield Me Bn t-bu C 6 13 Me cation Bn t-bu C 6 13 Me C 6 13 2 Me not observed Beeson, T.D.; Mastracchio, A.; ong, J.B.; Ashton, K.; MacMillan, D.W.C. Science, 2007, 316, 582-585
Applications of SM-rganocatalysis α-substitution of Aldehydes Allylation Enolation * 1 xyamination Alkylation Vinylation
α-xyamination of Aldehydes 4.0 eq. 1. Catalyst, Cp 2 FeBF 4 2. ab 4, rt Zn(Ac) 2 enantioselective 1,2-diol synthesis Sibi, M.P.; asegawa, M. J. Am. Chem. Soc., 2007, 129, 4124-4125
Catalyst ptimization 4.0 eq. 1. Catalyst, TF (1.0 M), rt 1.0 eq. Cp 2 FeBF 4 2. 2.0 eq. ab 4, rt TEMP BF 4 1 2 3 4 Tf C 2 Entry Catalyst mol % time, h Isolated Yield (%) ee (%) 1 none 24 79 2 1 100 1 61 3 2 100 1 63 76 4 2 20 1 78 64 5 3 20 1 87 80 6 4 20 1 71-3 Sibi, M.P.; asegawa, M. J. Am. Chem. Soc., 2007, 129, 4124-4125
Scope of Aldehydes 4.0 eq. 1. 20 mol% 3, DMF (1.0 M) 0.1 eq. FeCl 3, 0.3 eq. a 2 temp., time 2. 2.0 eq. ab 4, rt TEMP Entry Temp, C time, h Isolated Yield (%) ee (%) 1 C 6 5 r.t. 2 74 32 2 C 6 5 C 2 r.t. 2 80 71 3-10 24 68 82 4 C 6 5 C 2 C 2 r.t. 2 78 60 5-10 24 64 84 6 4-Me-C 6 4 C 2 C 2 r.t. 2 77 81 7-10 24 64 86 8 4-2 -C 6 4 C 2 C 2 r.t. 2 74 75 9-10 24 75 82 10 (C 3 ) 2 C r.t. 24 74 0 BF 4 3 Sibi, M.P.; asegawa, M. J. Am. Chem. Soc., 2007, 129, 4124-4125
Model for Enantioselectivity Si-face open Sibi, M.P.; asegawa, M. J. Am. Chem. Soc., 2007, 129, 4124-4125
Applications of SM-rganocatalysis α-substitution of Aldehydes Allylation Vinylation * 1 xyamination Alkylation Enolation * 1
α-enolation of Aldehydes TMS 1 1!-substituted 1,4-dicarbonyl Importance of eaction: ne step reaction to form umpolung polarity without going through anionic mechanism Jang,.Y.; ong, J.B.; MacMillan, D.W.C. J. Am. Chem. Soc., 2007, 129, 7004-7005
rganocatalytic Enolation: Scope of Aldehyde Substrate TMS 20 mol% CA (2 eq.), DTBP (2 eq.) acetone, 2, 24 h, -20 C TFA hexyl 85% yield 90% ee 7 92% yield 92% ee 74% yield 93% ee 77% yield 91% ee 2 71% yield 90% ee 84% yield 95% ee Bn Boc Jang,.Y.; ong, J.B.; MacMillan, D.W.C. J. Am. Chem. Soc., 2007, 129, 7004-7005
rganocatalytic Enolation: Scope of Enolsilane Substrate TFA hexyl Si 3 1 20 mol% CA (2 eq.), DTBP (2 eq.) DME, 2, 24 h, -20 C hexyl 1 Enolsilane Product Enolsilane Product TMS hexyl 77% yield 92% ee TBS t-bu hexyl t-bu 74% yield 96% ee TMS hexyl 77% yield 92% ee TBS t-bu hexyl 55% yield 92% ee Jang,.Y.; ong, J.B.; MacMillan, D.W.C. J. Am. Chem. Soc., 2007, 129, 7004-7005
Applications of SM-rganocatalysis α-substitution of Aldehydes Allylation Vinylation * 1 xyamination Alkylation 1 Enolation * 1
rganocatalytic α-vinylation of Aldehydes KF 3 B 1 20 mol% TFA 1 aldehyde vinyl-bf 3 K enantioenriched!-vinyl aldehyde Importance of eaction: Form β,γ-unsaturated aldehydes without olefin transpostion Kim,.; MacMillan, D.W.C. J. Am. Chem. Soc., 2008, 130, 398-399
rganocatalytic Vinylation of Aldehydes KF 3 B 1 20 mol% TFA 1 aldehyde vinyl-bf 3 K enantioenriched!-vinyl aldehyde BF 3 K - 1 e - 1 KF 3 B 1 KF 3 B 1 Kim,.; MacMillan, D.W.C. J. Am. Chem. Soc., 2008, 130, 398-399
rganocatalytic Vinylation: Scope of Aldehyde Substrate KF 3 B 20 mol% CA (2.5 eq.), -50 C ac 3, DME, 2, 24 h TFA Me 72% yield 94% ee 4 78% yield 95% ee 82% yield 96% ee Et 79% yield 93% ee 2 78% yield 93% ee 76% yield 96% ee Bn Boc Kim,.; MacMillan, D.W.C. J. Am. Chem. Soc., 2008, 130, 398-399
rganocatalytic Vinylation: Scope of Vinyl Trifluoroborate Salt hexyl KF 3 B 1 1 =, Me 20 mol% CA (2.5 eq.), -50 C ac 3, DME, 2, 24 h TFA hexyl 1 hexyl 81% yield 94% ee hexyl Me 78% yield 95% ee hexyl 6 82% yield 89% ee Cl Me hexyl 77% yield 95% ee hexyl 61% yield 95% ee hexyl 84% yield 90% ee Kim,.; MacMillan, D.W.C. J. Am. Chem. Soc., 2008, 130, 398-399
Applications of SM-rganocatalysis α-substitution of Aldehydes Allylation Enolation * 1 xyamination Alkylation * * 1 1 * 2 Vinylation 1
α-alkylation of Aldehydes Br 1 2 rganocatalysis otoredox Catalysis 1 2 aldehyde racemic!-bromocarbonyl enantioenriched!-alkylated "-ketoaldehyde Me Tf Me Me Me Me u 2+ rganocatalyst otoredox Catalyst icewicz, D.A.; MacMillan, D.W.C. Science, 2008, 322, 77-80
Catalytic Cycles 1 ()C 1 5 4 Br! Br SET u(bpy) 3 + (3) reductant 1 10 1 t-bu 11 catalyst 6 t-bu aldehyde 7 u(bpy) 3 2+ photoredox catalyst 1 otoredox Catalytic Cycle SET rganocatalytic Cycle 8 t-bu photon source * u(bpy) 3 2+ (2) oxidant 1 9 t-bu 1 5 3 C Si-face open icewicz, D.A.; MacMillan, D.W.C. Science, 2008, 322, 77-80
2.0 eq. rganocatalytic Alkylation: Scope of Aldehyde Substrate hexyl Et C 2 Et C 2 Et Br 93% yield 90% ee Et 20 mol% Et C 2 Et 4 C 2 Et Me TFA Me 86% yield 90% ee Me Me Me 0.5 mol% u(bpy) 3 Cl 2 2.0 eq 2,6-lutidine, DMF fluorescent light, 23 C C 2 Et C 2 Et C 2 Et C 2 Et 83% yield 95% ee C 2 Et C 2 Et C 2 Et C 2 Et 92% yield 90% ee C 2 Et 63% yield 93% ee C 2 Et 66% yield 91% ee Boc icewicz, D.A.; MacMillan, D.W.C. Science, 2008, 322, 77-80
rganocatalytic Alkylation: Scope of α-bromocarbonyl Substrate ex 2.0 eq. Br 1 20 mol% Me TFA Me Me Me Me 0.5 mol% u(bpy) 3 Cl 2 2.0 eq 2,6-lutidine, DMF fluorescent light, 23 C ex 1 ex 84% yield 96% ee ex C 2 CF 3 80% yield 92% ee ex C 2 Et C 2 Et 80% yield 88% ee 2 Me t-bu 2 C ex 84% yield 95% ee ex 87% yield 96% ee ex 70% yield 5:1 dr, 99% ee icewicz, D.A.; MacMillan, D.W.C. Science, 2008, 322, 77-80
To Sum Up Asymmetric control is difficult in radical synthesis Fast reactivity Planar structure Methods that have been used to control asymmetry Chiral Auxiliary Chiral Acid Chelation rganocatalysis
Acknowledgements Dr. Jetze Tepe Dr. Babak Borhan Group Membes: Brandon, Chris, Daljinder, Jason, Mike, ahman, Samantha, Thu, Amanda Arvind, Camille, Carmin