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

Adam Hoye

Current Literature April 7, 2007 Wipf Group

X HSiR3 Rh cat. X SiR3 Me Aryl-I Pd cat., Activator X Aryl Me X O Me

Sequential Silylcarbocyclization/Silicon- Based Cross-Coupling Reactions

Scott E. Denmark and Jack Hung-Chang Liu

• J. Am. Chem. Soc. 2007, 129, 3737

Adam Hoye @ Wipf Group 1 4/14/2007

Silylcarbocyclizations

Tamao and Ito (J. Am. Chem. Soc. 1989, 111, 6478):

N N SiMePh2 MeO2C MeO2C MeO2C MeO2C Me SiEt3 N Ts

• TsN

Me SiMe2Ph Me O · O O SiMe3 OH H H

Substrate Elaborations (others)

R H H-SiX3 Ni cat. H SiX3 H R Ni SiX3 H R H Ni H SiX3 H R Ni SiX3 H R H Ni(0) 52 - 70%

Adam Hoye @ Wipf Group 2 4/14/2007

Ojima Rh-catalyzed Enyne Cyclization

R' X X [Rh](H*) SiR3 R' X SiMe2Ph [Rh](H*) R' R3Si-H* Me X SiMe2Ph R' CO time X SiMe2Ph O R' (*H)[Rh] X SiMe2Ph O R' H R3Si-H* (H*)[Rh]-SiR3 R3Si-H*

[Rh]

X R R3Si [Rh](H*) X R (H*)[Rh] SiR3

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 R' EtO2C EtO2C HSiMe2Ph (1.5 equiv.), Rh4(CO)12 (0.5 mol%) CO (1 atm.), hexane, rt 95% Me EtO2C EtO2C SiMe2Ph excess CO, time EtO2C EtO2C SiMe2Ph CHO

Adam Hoye @ Wipf Group 3 4/14/2007

Silicon-Based Cross-Coupling Reactions

M X Pd cat. M = SnR3 (Stille) ZnR (Negishi) B(OR)2 (Suzuki) MgX (Kumada) SiR(3-n)Fn (Hiyama) Si R R R R = OH/F/Me Pd X Ar R3SiF X- Si R F R R X FR3Si Pd(Ar) Pd Ar Ar Pd(0) F-

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 Trost, B.M.; Machacek, M. R.; Ball, Z. T. Org. Lett. 2003, 5, 1895

Si C5H11 Me TBAF Si C5H11 HO Me Me Si Me O H R F N(n-Bu)4 Me

Si Me Me R Ph R Si X Me Me X = OH/F TBAF, CH2Cl2 0 °C, 10 min

Proposed Mechanism:

Adam Hoye @ Wipf Group 4 4/14/2007

Previous Work in the Denmark Group

Metathesis/ Si-Based Cross-Coupling

Si R O Me Me Ph (CH2)n R' Mo Complex (5.0-8.0 mol%) benzene, rt 81-95% O (CH2)n Si Ph R R'

• 1. TBAF (2 eq)
• 2. Ar-I
• 3. Pd(dba)2

81-93% HO (CH2)n Ph R' R R3 Me Me

Denmark, S. E.; Yang, S.-M. Org. Lett. 2001, 3, 1749

Hydrosilylation/ Si-Based Cross-Coupling

R O Si Si H Me Me H Me Me tBu3P, Pt cat. Me2 Si R H O Me2 Si R H R'-I, TBAF Pd(dba)2 R H H R' 82-94%

Denmark, S. E.; Wang, Z. Org. Lett. 2001, 3, 1073

Intramolecular Hydrosilylation/ Si-Based Cross-Coupling

Si O H3C X R

• 1. TBAF

X = I,Br

• 2. Pd(0)

H3C O SiH H2PtCl6·9H2O CH2Cl2 83% H3C OH R 70-88%

Denmark, S. E.; Pan, W. Org. Lett. 2001, 3, 61

Adam Hoye @ Wipf Group 5 4/14/2007

Denmark Enyne Cyclization Scope

Acid Sensitive (HCl in CDCl3) N-Boc led to decomposition

Rh4(CO)12

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

X HSiR3 Rh cat. X SiR3 R'' Aryl-I Pd cat., Activator X Aryl R'' R' R' R'

• 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

Denmark, S. E.; Regens, C. S.; Kobayashi, T. J. Am. Chem. Soc. 2007, 129, 2774

O O OTES O Si t-Bu t-Bu t-BuLi Me2SiHCl O O OTES O Si t-Bu t-Bu Si Me Me R R = H R = OH, 84% [RuCl2(p-cymene)]2 H2O I BnO OBn OPiv Pd2(dba)3·CHCl3 O O OTES O Si t-Bu t-Bu BnO OBn OPiv O Me MeMe OH O O OH HO OH O HO OH Papulacandin D 89% 82%

Adam Hoye @ Wipf Group 12 4/14/2007