Synergistic Gold and Iron Dual Catalysis: Preferred adical Addition Toward Vinyl-Gold Intermediate ver Alkene aihui Peng, ovruz G. Akhmedov, Yu-Feng Liang, ing Jiao, and Xiaodong Shi J. Am. Chem. Soc. 2015, 137, 8912-8915., [Fe] t-bu, acetone 2 Mike Frasso @ Wipf Group Page 1 of 17 7/25/2015
Why This Paper? 2 S cyclodehydration? 2 2 Currently: S 1. Me 3 Cl 2 S 2. LA Mike Frasso @ Wipf Group Page 2 of 17 7/25/2015
Why This Paper? 2 S cyclodehydration? 2 2 Currently: S 1. Me 3 Cl 2 S 2. LA Mike Frasso @ Wipf Group Page 3 of 17 7/25/2015
Selected Syntheses of 2-5-Disubstitued xazoles 2 2 C 2 I 2 (cat.) xone, DMS, 95 o C 41-80% 2 2 CuBr 2, ethyl nicotinate TBAB, K 2 S 2 8, MeC 22-90% 2 BS DCE, 100 o C 53-88% Br 3 [Cu] CCl 3, 40 o C 17-82% J. rg. Chem. 2013, 78, 6065-6074 rg. Lett. 2012, 14, 4766-4769 J. rg. Chem. 2012, 77, 7526-7537 J. Am. Chem. Soc. 2011, 133, 191-193 Mike Frasso @ Wipf Group Page 4 of 17 7/25/2015
Mechanism of Cu Catalyzed xazole Formation 3 [Cu] CCl 3, 40 o C 17-82% - 2 -[Cu] [Cu] [Cu] Cu D [Cu] D 50% 3 Tol CCl 3, 40 o C Tol 41% Chem. Eur. J. 2014, 20, 3463-3474 J. Am. Chem. Soc. 2011, 133, 191-193 Mike Frasso @ Wipf Group Page 5 of 17 7/25/2015
α-xo Gold Transformations A 2 3 PAuTf 2 60 o C 59-93% 2 A = [LAuCl], A abaf L = PAd 2 2 DCE, -20 o C 2 TBS TBS Key Intermediate J. Am. Chem. Soc. 2011, 133, 8482-8485 Angew. Chem. Int. Ed. 2015, 54, 1245-1249 Mike Frasso @ Wipf Group Page 6 of 17 7/25/2015
Tandem Gold Catalyzed eactions B() 2 (dppm)(aubr) 2 SelectFluor MeC: 2 50 o C 51-90% 2 2 3 3 PAuTf 2 Mo 2 (acac) 2, 3 P, XS C 2 Cl 2 71-98% 2 X X = Br, I 3 tbu 2 3 3 PAuTf 2 SelectFluor K 3 P 4 MeC: 2 17-94% 2 3 n 2 BF 4 [u] or [Ir] 3 PAuCl Me:MeC visible light 34-90% n J. Am. Chem. Soc. 2010, 132, 8885-8887 rg. Lett. 2010, 12, 4904-4907 rg. Lett. 2009, 11, 3646-3649 J. Am. Chem. Soc. 2014, 136, 5844-5847 Mike Frasso @ Wipf Group Page 7 of 17 7/25/2015
Title Paper: Three Preliminary Transformations Ag 3, TMS 3 71% 3 FeCl 2 Togni's reagent 55% CF 3 TF, 2 50 o C 82% Known CuI, S 2 83% S 2 J. Am. Chem. Soc. 2015, 137, 8912-8915 Mike Frasso @ Wipf Group Page 8 of 17 7/25/2015
Title Paper: Screening of Conditions, Fe(acac) 3 solvent 2 A B Entry Solvent TIme (h) Conv. (%) Yield (%A:%B) 1 2 3 PAuTf 2 MeC 12 <10 0:0 iprautf 2 MeC 8 100 <10:85 3 ditbuxos AuTf 2 MeC 8 100 17:65 4 ditbuxos Au(MeC)SbF 6 MeC 8 100 33:45 5 () 3 PAuTf 2 MeC 8 100 11:58 6 JackieosAuTf 2 MeC 8 100 15:71 7 3 PAuTf 2 acetone 8 100 43:38 8 3 PAuTf 2 C 2 Cl 2 8 100 25:65 9 3 PAuTf 2 Me 8 100 29:69 10 3 PAuTf 2 Dioxane 8 100 45:38 11* 3 PAuTf 2 acetone 2 100 83:-- * 50% t-bu J. Am. Chem. Soc. 2015, 137, 8912-8915 Mike Frasso @ Wipf Group Page 9 of 17 7/25/2015
Title Paper: eaction Scope 3 PAuTf 2, Fe(acac) 3 t-bu, acetone 2 F 85% 81% 83% 77% F 3 C Br S Br 71% 75% 69% 61% Me Me Boc 75% 46% 59% 73% Boc Boc Ac 61% 39% 61% J. Am. Chem. Soc. 2015, 137, 8912-8915 Mike Frasso @ Wipf Group Page 10 of 17 7/25/2015
Synergistic or Sequential Catalysis? Slow conversion of 2e to 5e with Fe(acac) 3 Slow conversion of 1e to 5e with 3 PAuTf 2 1e to 5e faster with and [Fe] Suggests that [] occurs on vinyl Au, not alkene J. Am. Chem. Soc. 2015, 137, 8912-8915 Mike Frasso @ Wipf Group Page 11 of 17 7/25/2015
Competency of Vinyl Gold Intermediate F 3 C F 3 C F 3 C IPrAuTf 2, Fe(acac) 3 t-bu, acetone 2,.T. A 77% B <10% IPrAuTf 2, Ag F 3 C Fe(acac) 3, t-bu, 2, acetone-d6 50 o C A B trace 30% AuIPr w/o Fe(acac) 3.T. trace 0% 3 PAuTf 2 analog not isolable 1 eq. TEMP inhibits reaction Questionable reaction temperatures J. Am. Chem. Soc. 2015, 137, 8912-8915 Mike Frasso @ Wipf Group Page 12 of 17 7/25/2015
Slow Protodeauration?, [Fe] acetone, 50 o C 2 53%, [Fe] solvent, 50 o C 2 13%, [Fe] solvent, 50 o C 2 Messy The major challenge for this synthetic route was the slow protodeauration, which led to the poor yields of the cyclizaiton products. J. Am. Chem. Soc. 2015, 137, 8912-8915 Mike Frasso @ Wipf Group Page 13 of 17 7/25/2015
Indole and Benzofuran Scope, FeCl 2 X solvent, 50 o C 2 X F Br p-tol Cl 78% 83% 71% 66% 72% F n-pent Cl 45% 83% 58% 53% 70% Cl Cl Br Cl 57% 75% 71% 77% 78% X Conditions ditbuxosau(mec)sbf 6, EtAc JackieosAuTf 2, dioxane <5% Mike Frasso @ Wipf Group Page 14 of 17 7/25/2015
Proposed Mechanism Fe III 2 Fe II Fe III Fe II J. Am. Chem. Soc. 2015, 137, 8912-8915 Mike Frasso @ Wipf Group Page 15 of 17 7/25/2015
Proposed Mechanism Fe III 2 Fe II Fe III Fe II J. Am. Chem. Soc. 2015, 137, 8912-8915 Mike Frasso @ Wipf Group Page 16 of 17 7/25/2015
Conclusions Experiments suggest oxidation of a vinyl gold intermediate Sloppiness of the rest of the paper and supporting information raises questions about what was done and why Mike Frasso @ Wipf Group Page 17 of 17 7/25/2015