Sequential Silylcarbocyclization/Silicon- Based Cross-Coupling - PowerPoint PPT Presentation

Sequential Silylcarbocyclization/Silicon- Based Cross-Coupling Reactions Scott E. Denmark and Jack Hung-Chang Liu J. Am. Chem. Soc. 2007 , 129, 3737 O SiR 3 Aryl-I Aryl HSiR 3 X X X X Pd cat., Rh cat. Me Me Me Activator Adam Hoye Current Literature April 7, 2007 Wipf Group Adam Hoye @ Wipf Group 1 4/14/2007

Silylcarbocyclizations Tamao and Ito ( J. Am. Chem. Soc. 1989 , 111 , 6478 ): H H Substrate Elaborations (others) Ni cat. SiX 3 H-SiX 3 H 52 - 70% R N R SiMePh 2 N Ni(0) SiEt 3 MeO 2 C MeO 2 C MeO 2 C MeO 2 C H Me H Ni SiX 3 SiX 3 Me Me Ni H H R Ts N TsN SiMe 2 Ph R • H SiMe 3 SiX 3 H · O Ni H O O OH R H Adam Hoye @ Wipf Group 2 4/14/2007

Ojima Rh-catalyzed Enyne Cyclization HSiMe 2 Ph (1.5 equiv.), R' EtO 2 C Rh 4 (CO) 12 (0.5 mol%) EtO 2 C EtO 2 C SiMe 2 Ph SiMe 2 Ph excess CO, time CHO EtO 2 C CO (1 atm.), hexane, rt EtO 2 C EtO 2 C Me 95% R' [Rh] SiMe 2 Ph R' X X R 3 Si-H* O H R R (H*)[Rh]-SiR 3 R 3 Si-H* R 3 Si [Rh](H*) (H*)[Rh] SiR 3 X X R' SiMe 2 Ph R' X R' Me SiR 3 SiMe 2 Ph X X [Rh](H*) O (*H)[Rh] R 3 Si-H* R' time SiMe 2 Ph X [Rh](H*) CO Ojima, I.; Vu, A. T.; Lee, S.-Y.; McCullagh, J. V.; Maralee, A. C.; Fujiwara, M.; Hoang, T. H. J. Am. Chem. Soc. 2002 , 124 , 9164 Adam Hoye @ Wipf Group 3 4/14/2007

Silicon-Based Cross-Coupling Reactions M X Pd cat. M = SnR 3 (Stille) ZnR (Negishi) B(OR) 2 (Suzuki) MgX (Kumada) SiR (3-n) F n (Hiyama) Proposed Mechanism: X R F - R Pd Ar FR 3 Si Pd(Ar) R Si R Si X Pd Ar X - R 3 SiF R R F R = OH/F/Me Pd(0) Ar Me TBAF HO Si Si C 5 H 11 Me C 5 H 11 Me TBAF, CH 2 Cl 2 Me Si Me Me Me Me Me X = OH/F R Si X Ph Si O H R N( n -Bu) 4 0 °C, 10 min R F Trost, B.M.; Machacek, M. R.; Ball, Z. T. Org. Lett. 2003 , 5 , 1895 Denmark, S. E.; Sweis, R. F. Acc. Chem. Res. 2002 , 35 , 835 Denmark, S. E.; Ober, M. H. Adrichimica Acta , 2003 , 36 , 75 Hatanaka, Y.; Hiyama, T. Synlett , 1991 , 845 Adam Hoye @ Wipf Group 4 4/14/2007

Previous Work in the Denmark Group Hydrosilylation/ Si-Based Cross-Coupling Me H H R'-I, TBAF Me Me H H Si Si Me 2 Me 2 R' H O Me R Pd(dba) 2 Si Si R R O R 82-94% H t Bu 3 P, Pt cat. Denmark, S. E.; Wang, Z. Org. Lett. 2001 , 3 , 1073 Intramolecular Hydrosilylation/ Si-Based Cross-Coupling OH H 3 C X O H 2 PtCl 6 ·9H 2 O 1. TBAF H 3 C SiH H 3 C R Si O CH 2 Cl 2 2. Pd(0) 83% 70-88% X = I,Br R Denmark, S. E.; Pan, W. Org. Lett. 2001 , 3 , 61 Metathesis/ Si-Based Cross-Coupling Me Me R Ph R' 1. TBAF (2 eq) Mo Complex Me Me Si 2. Ar-I Si R (5.0-8.0 mol%) R O O HO (CH 2 ) n 3. Pd(dba) 2 benzene, rt Ph (CH 2 ) n Ph (CH 2 ) n R' 81-95% 81-93% R 3 R' Denmark, S. E.; Yang, S.-M. Org. Lett. 2001 , 3 , 1749 Adam Hoye @ Wipf Group 5 4/14/2007

Denmark Enyne Cyclization Scope Rh 4 (CO) 12 Acid Sensitive (HCl in CDCl 3 ) N-Boc led to decomposition Adam Hoye @ Wipf Group 6 4/14/2007

Optimization of Silylcarbocyclization Adam Hoye @ Wipf Group 7 4/14/2007

Proposed Mechanism Adam Hoye @ Wipf Group 8 4/14/2007

Cross-Coupling Catalyst Screening Adam Hoye @ Wipf Group 9 4/14/2007

Cross-Coupling Reactions (Coupling Partners) -Silanol byproducts (can be difficult to remove) Adam Hoye @ Wipf Group 10 4/14/2007

Cross-Coupling Reactions (Substrate Scope) Adam Hoye @ Wipf Group 11 4/14/2007

Summary/ Future Work R' R' SiR 3 Aryl-I Aryl HSiR 3 R' X X X Pd cat., Rh cat. R'' R'' Activator - Sequential silylcarbocyclization and silicon-based cross-coupling has been developed -Exclusive ( Z )-olefin selectivity -Substitution (X) well tolerated -R’ tolerated (slower coupling) -Ar-I with different electronic properties/substitution patterns tolerated BnO OBn Me Me BnO OBn I O Si O t -BuLi O R O O t- Bu t- Bu OPiv O Si Si O t- Bu Me 2 SiHCl O Pd 2 (dba) 3 ·CHCl 3 Si t- Bu t- Bu O OPiv 89% OTES OTES t- Bu 82% OTES R = H [RuCl 2 ( p -cymene)] 2 H 2 O R = OH, 84% Me OH HO MeMe O HO OH O OH O OH O Papulacandin D Denmark, S. E.; Regens, C. S.; Kobayashi, T. J. Am. Chem. Soc. 2007 , 129 , 2774 Adam Hoye @ Wipf Group 12 4/14/2007