1 / 18

Binder, J. T.; Cordier, C. J.; Fu, G. C. J. Am. Chem . Soc. 2012 , ASAP

Catalytic Enantioselective Cross-Couplings of Secondary Alkyl Electrophiles with Secondary Alkylmetal Nucleophiles. Binder, J. T.; Cordier, C. J.; Fu, G. C. J. Am. Chem . Soc. 2012 , ASAP. « CRAZY » COUPLINgS !!. Lea Constantineau November 21, 2012.

roden
Télécharger la présentation

Binder, J. T.; Cordier, C. J.; Fu, G. C. J. Am. Chem . Soc. 2012 , ASAP

An Image/Link below is provided (as is) to download presentation Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author. Content is provided to you AS IS for your information and personal use only. Download presentation by click this link. While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server. During download, if you can't get a presentation, the file might be deleted by the publisher.

E N D

Presentation Transcript

  1. Catalytic Enantioselective Cross-Couplings of Secondary Alkyl Electrophiles with Secondary Alkylmetal Nucleophiles Binder, J. T.; Cordier, C. J.; Fu, G. C. J. Am. Chem. Soc. 2012, ASAP « CRAZY » COUPLINgS!! Lea Constantineau November 21, 2012

  2. The Challenges of C(sp3)-C(sp3) Cross-Coupling • Slow oxidative addition: Homocoupling or β-elimination of the electrophile • Spontaneous decomposition of alkyl organometallics via β-elimination or proto-demetalation • Slow transmetalation: needs of additives 1) Jana,R.; Pathak, T. P.; Sigman, M. S. Chem. Rev.2011, 111, 1417.

  3. C(sp3)-C(sp3) Cross-Couplings in Total Synthesis 1) Raghavan, S.; Babu, V. S. Chem. Eur. J.2011, 17, 8487. 2) Fuwa, H.; Kainuma, N.; Tachibana, K.; Sasaki, M. J. Am. Chem. Soc.2002, 124, 14983. 3) Son, S.; Fu, G. C. J. Am. Chem. Soc. 2008, 130, 2756.

  4. Examples of asymmetric Cross-Coupling with Alkylzinc Reagents First AsymmetricNegishi Cross-Coupling 1) Fisher, C; Fu, G. C. J. Am. Chem. Soc. 2005, 127, 4594. 2) Son, S.; Fu, G. C. J. Am. Chem. Soc. 2008, 130, 2756.

  5. Only one Example of a Secondary-Secondary Cross-Coupling Zultanski, S. L.; Fu, G.C. J. Am. Chem. Soc.2011, 133, 15362.

  6. Cross-Couplings of Secondary Alkyl Electrophiles with Primary Alkylzinc Nucleophiles Alkylzinc reagents synthesis by Knochel’s method 1) Arp, F.O.; Fu, G.C. J. Am. Chem. Soc.2005, 127, 10482. 2) Krasovskiy, A.; Knochel, P. Synthesis2006, 890.

  7. Optimization of the Reaction 1) Binder, J. T.; Cordier, C. J.; Fu, G. C. J. Am. Chem. Soc. 2012, ASAP. 2) Choi, J.; Fu, G. C. J. Am. Chem. Soc. 2012, 134, 9102. 3) Son, S.; Fu, G. C. J. Am. Chem. Soc. 2008, 130, 2756.

  8. Cross-Couplings of Secondary Alkyl Electrophiles with Secondary Alkylzinc Nucleophiles Binder, J. T.; Cordier, C. J.; Fu, G. C. J. Am. Chem. Soc. 2012, ASAP

  9. Scope of the Reaction 1) Binder, J. T.; Cordier, C. J.; Fu, G. C. J. Am. Chem. Soc. 2012, ASAP.

  10. Cross-Couplings of Secondary Alkyl Electrophiles with Acyclic Secondary Alkylzinc Nucleophiles First time that a branchedproductisformedfrom a linearalkylmetal compound.2 1) Binder, J. T.; Cordier, C. J.; Fu, G. C. J. Am. Chem. Soc. 2012, ASAP. 2) Han, C.; Buchwald, S. L. J. Am. Chem. Soc. 2009, 131, 7532.

  11. Possible Mechanism for Nickel-catalyzed Secondary-Secondary Cross-Couplings • Isomerisation: β-hydride elimination and β-migratory insertion • Use of a bidentate, rather than tridentate, ligand • Transmetalation occuring before oxidative addition (NiI catalyzed) Binder, J. T.; Cordier, C. J.; Fu, G. C. J. Am. Chem. Soc. 2012, ASAP 2) Han, C.; Buchwald, S. L. J. Am. Chem. Soc. 2009, 131, 7532.

  12. Syn Selective mechanism • The β-hydride elimination and β-migratory insertion are Syn specific • D always trans from the Nickel • Reaction with 0.5 equiv of cyclopentene did not give incorporation of unlabeled cyclopentane 1) Binder, J. T.; Cordier, C. J.; Fu, G. C. J. Am. Chem. Soc. 2012, ASAP.

  13. Conclusion • New enantioselective cross-coupling of secondaryelectrophileswithsecondaryalkylzincreagents. • New class of ligand wasused (UsuallyNegishireactions are donewithPybox ligand). • Discovery of a unusualisomerization: formation of a branchedproductfrom a linearalkylzincreagents.

  14. First Asymmetric Suzuki-Miyaura Cross-Coupling of an Unactived Secondary Alkyl Halide Saito, B. Fu, G. C. J. Am. Chem. Soc.2008, 130, 6694.

  15. β-hydride elimination and β-migratory insertion • Use of a bidentate, rather than tridentate, ligand • Transmetalationoccuring before oxidative addition 1) Binder, J. T.; Cordier, C. J.; Fu, G. C. J. Am. Chem. Soc. 2012, ASAP. 2)

  16. C(sp3)-C(sp3) Cross-Couplings in Total Synthesis 1) Raghavan, S.; Babu, V. S. Chem. Eur. J.2011, 17, 8487. 2) Fuwa, H.; Kainuma, N.; Tachibana, K.; Sasaki, M. J. Am. Chem. Soc.2002, 124, 14983

More Related