Palladium-Catalyzed Oxygenation of Unactivated sp 3 C-H Bonds

Transcription

1 Palladium-Catalyzed xygenation of Unactivated sp 3 C- Bonds Pd(Ac) 2 5 mol% PhI(Ac) eq. Pd 2 Ac Desai, L. P.; ull, K. L.; Sanford *, M. S. University of Michigan J. Am. Chem. Soc. 2004, 126, ASAP (Web Release 16 th July 2004) David Wipf Group 1 Current Literature 24 th July /29/04

2 xidation of Unactivated sp 3 C- Bonds: A Challenge in rganic Synthesis - REACTIVITY ( C- bond dissociation energy in methane 104 kcal mol -1 ) - SELECTIVITY ( C- bond dissociation energy in methanol: 93 kcal mol -1 ). while in ature Mycobacterium phlei Stearic acid leic acid Rhizopus nigricans David Wipf Group 2 Current Literature 24 th July /29/04

3 Chemical Routes for the Intramolecular xidative Functionalization of Unactivated sp 3 C- Bond a) Reactions based on heteroatom centered radicals b) Reactions based on Rhodium-mediated carbene and nitrene sp 3 C- bond insertions c) Reactions based on transition metal-mediated sp 3 C- bond activation David Wipf Group 3 Current Literature 24 th July /29/04

4 Reactions Based on eteroatom-centered Radicals offmann-loeffler-freytag Reaction R 1 Cl R 2 1., Δ 2. R 1 R2 offmann, A. W. Ber. 1883, 16, 558. Corey, E. J.; ertler, W. R. J. Am. Chem. Soc. 1958, 80, Arigoni, D. and coworkers J.Am. Chem. Soc. 1958, 80, Barton`s itrite Photolysis Ac Ac hν Barton, D.. R. and coworkers J.Am. Chem. Soc. 1960, 82, 2640 Breslow`s Remote xidation hν Breslow, R. and coworkers J. Am. Chem. 1973, 95, 3251 Jung, M. E.: Johnson, T. W. J. Am. Chem. Soc. 1997, 119, David Wipf Group 4 Current Literature 24 th July /29/04

5 Reactions Based on Rhodium-Mediated Carbene and itrene sp 3 C- Bond Insertions 2 TBS Rh 2 (CCPh 3 ) mol% TBS Cl 2 A B C Rh 2 (CCF 3 ) 4 10 mol% PhI(Ac) 2, Mg Cl 2 D (-)-Tetrodotoxin inman, A.; Du Bois, J. J. Am. Chem. Soc. 2003, 125, Espino, C. G.; Du Bois, J. Angew. Chem., Int. Ed. 2001, 40, 598. For a Review on the Use of Rh-Mediated Intramolecular C- Insertion in atural Products Syntheses see: Taber, D. F.; Stiriba, S.-E. Chem. Eur. J. 1998, 4, 990 and references therein. David Wipf Group 5 Current Literature 24 th July /29/04

6 Reactions Based on Transition Metal-Mediated sp 3 C- Bond Activation: the Shilov Reaction R + Pt (II) xidant R-Y Y =, Cl,.. R- + (II) Pt (II) Pt R + R Y xidant Reduced xidant Y (IV) Pt R Shilov, A. E.; Shul`pin, G. B. Chem. Rev. 1997, 97, Stahl, S. S. and coworkers Angew. Chem., Int. Ed. 1998, 37, Sen, A. and coworkers J. Am. Chem. Soc. 2001, 123, David Wipf Group 6 Current Literature 24 th July /29/04

7 Unactivated sp 3 C- Bond xidative Functionalization by Group 10 Metals PRBLEMS: a) arsh reaction conditions: no applications to complex organic molecules b) Low T c) Low functional group tolerance d) Low level of regioselectivity TE KEY: The use of substrates containing coordinating functional groups that can bind the metal catalyst and direct the oxidation process to a specific sp 3 C- bond within the molecule. David Wipf Group 7 Current Literature 24 th July /29/04

8 Unactivated sp 3 C- Bond xidative Functionalization by Group 10 Metals: Stoichiometric Version 2 DMF 100 o C Br 2 Br Ag 2 C 3 Toluene 2 1. CCl 3 CCl 2. ame, 3. 2, Pd/C 2 90% 70% 88% cex 1. Ph Ts, Toluene 2. [Me 2 Pt(µ-SMe 2 )] 2 30% Me Pt Me Ph cex Tf DCM Pt Me cex Tf CF 3 C 2 70 o C - C 4 Pt cex Tf KC 2 1. Pd/C, C, C 42% 3 steps quantitative dr 4.4 / 1 (PLC separation) cex Sames, D. and coworkers J. Am. Chem. Soc. 2002, 124, a, then Cl 45 % (-)-Rhazinilam For other Stoichiometric Examples see: Sames, D. and coworkers J. Am. Chem. Soc. 2002, 124, Gribble, G. W. and coworkers J. rg. Chem. 2000, 65, David Wipf Group 8 Current Literature 24 th July /29/04

9 Unactivated sp 3 C- Bond xidative Functionalization by Group 10 Metals: Catalytic Version K 2 PtCl 4 5 mol% α-aminoacid CuCl 2 7 eq o C 10h oxidized α aminoacid 1. Boc 2 2. Ac product Entry Substrate Products Distribution γ / δ Yield (%) 1 L-Valine C Boc Boc L-orvaline 2 C 2 Boc Boc C 2 BoC L-Leucine 2 C 2 Boc C 2 BoC C 2 BoC L-Proline C 2 REACTI Sames, D. and coworkers J. Am. Chem. Soc. 2001, 123, For an another Catalytic example see: Sames, D. and coworkers J. Am. Chem. Soc. 2002, 124, David Wipf Group 9 Current Literature 24 th July /29/04

10 Authors Precedent Paper: A ighly Selective Catalytic Method for the xidative Functionalization of C- Bonds Substrate Pd(Ac) mol% PhI(Ac) eq. Ac or C 3 C 100 o C h Product Entry Product Yield (%) Entry Product Yield (%) Ac 1 Ac Ac Ac 3 Ac Ac 4 Ac Ph Ac 62 8 Ph 47 Sanford, M. S. and coworkers J. Am. Chem. Soc. 2004, 126, David Wipf Group 10 Current Literature 24 th July /29/04

11 (I) Palladium-Catalyzed xygenation of Unactivated sp 3 C- Bonds Pd(Ac) 2 5 mol% PhI(Ac)2 1.1 eq. Ac R R` Ac -Ac o C h R R` Entry Substrate Product Yield (%) 1 Ac 74 Ac Ac 39 4 REACTI 5 REACTI Sanford, M. S. and coworkers J. Am. Chem. Soc. 2004, 126,ASAP. David Wipf Group 11 Current Literature 24 th July /29/04

12 (II) Palladium-Catalyzed xygenation of Unactivated sp 3 C- Bonds Substrate Pd(Ac) 2 5 mol% PhI(Ac) eq. Ac -Ac o C 5 min- 12h Product Entry Substrate Product Yield (%) Entry Substrate Product Yield (%) 1 Ac Ac Ac 2 Me Me Ac 3 Me Me Ac Ac Me Me Ac Ac Sanford, M. S. and coworkers J. Am. Chem. Soc. 2004, 126,ASAP. David Wipf Group 12 Current Literature 24 th July /29/04

13 (III) Palladium-Catalyzed xygenation of Unactivated sp 3 C- Bonds ypothesized Mechanism (II) Pd L C L C Pd (II) - L C Y xidant Reduced xidant Y L Pd (IV) C Y Y David Wipf Group 13 Current Literature 24 th July /29/04

14 Summary - An efficient and highly β selective sp 3 C- bond oxidative functionalization for -methyl oximes and pyridines have been described. - The level of regioselectivity displayed by the described methodology is unprecedented. - The mild reaction conditions used along with the selectivity displayed, make the methodology a significant potential synthetic tool. - Future work aimed to elucidate the scope and the mechanism of the transformation described would be of particular interest for the synthetic community. David Wipf Group 14 Current Literature 24 th July /29/04