Synergistic Gold and Iron Dual Catalysis: Preferred Radical Addition Toward Vinyl-Gold Intermediate Over Alkene

Transcription

1 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, , [Fe] t-bu, acetone 2 Mike Wipf Group Page 1 of 17 7/25/2015

2 Why This Paper? 2 S cyclodehydration? 2 2 Currently: S 1. Me 3 Cl 2 S 2. LA Mike Wipf Group Page 2 of 17 7/25/2015

3 Why This Paper? 2 S cyclodehydration? 2 2 Currently: S 1. Me 3 Cl 2 S 2. LA Mike Wipf Group Page 3 of 17 7/25/2015

4 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, rg. Lett. 2012, 14, J. rg. Chem. 2012, 77, J. Am. Chem. Soc. 2011, 133, Mike Wipf Group Page 4 of 17 7/25/2015

5 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, J. Am. Chem. Soc. 2011, 133, Mike Wipf Group Page 5 of 17 7/25/2015

6 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, Angew. Chem. Int. Ed. 2015, 54, Mike Wipf Group Page 6 of 17 7/25/2015

7 Tandem Gold Catalyzed eactions B() 2 (dppm)(aubr) 2 SelectFluor MeC: 2 50 o C 51-90% PAuTf 2 Mo 2 (acac) 2, 3 P, XS C 2 Cl % 2 X X = Br, I 3 tbu PAuTf 2 SelectFluor K 3 P 4 MeC: % 2 3 n 2 BF 4 [u] or [Ir] 3 PAuCl Me:MeC visible light 34-90% n J. Am. Chem. Soc. 2010, 132, rg. Lett. 2010, 12, rg. Lett. 2009, 11, J. Am. Chem. Soc. 2014, 136, Mike Wipf Group Page 7 of 17 7/25/2015

8 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, Mike Wipf Group Page 8 of 17 7/25/2015

9 Title Paper: Screening of Conditions, Fe(acac) 3 solvent 2 A B Entry Solvent TIme (h) Conv. (%) Yield (%A:%B) PAuTf 2 MeC 12 <10 0:0 iprautf 2 MeC <10:85 3 ditbuxos AuTf 2 MeC :65 4 ditbuxos Au(MeC)SbF 6 MeC :45 5 () 3 PAuTf 2 MeC :58 6 JackieosAuTf 2 MeC : PAuTf 2 acetone : PAuTf 2 C 2 Cl : PAuTf 2 Me : PAuTf 2 Dioxane :38 11* 3 PAuTf 2 acetone :-- * 50% t-bu J. Am. Chem. Soc. 2015, 137, Mike Wipf Group Page 9 of 17 7/25/2015

10 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, Mike Wipf Group Page 10 of 17 7/25/2015

11 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, Mike Wipf Group Page 11 of 17 7/25/2015

12 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, Mike Wipf Group Page 12 of 17 7/25/2015

13 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, Mike Wipf Group Page 13 of 17 7/25/2015

14 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 Wipf Group Page 14 of 17 7/25/2015

15 Proposed Mechanism Fe III 2 Fe II Fe III Fe II J. Am. Chem. Soc. 2015, 137, Mike Wipf Group Page 15 of 17 7/25/2015

16 Proposed Mechanism Fe III 2 Fe II Fe III Fe II J. Am. Chem. Soc. 2015, 137, Mike Wipf Group Page 16 of 17 7/25/2015

17 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 Wipf Group Page 17 of 17 7/25/2015