Synlett 2017; 28(18): 2415-2420
DOI: 10.1055/s-0036-1588471
cluster
© Georg Thieme Verlag Stuttgart · New York

Understanding Site Selectivity in the Palladium-Catalyzed Cross-Coupling of Allenylsilanolates

Scott E. Denmark*, Andrea Ambrosi
  • University of Illinois at Urbana-Champaign, Department of Chemistry, 600 S Mathews Ave., Urbana, IL 61801, USA   Email: sdenmark@illinois.edu
We are grateful to the National Science Foundation (NSF CHE-1151566) for generous financial support. A.A. thanks the University of Illinois and Eli Lilly and Co. for graduate fellowships
Further Information

Publication History

Received: 18 April 2017

Accepted after revision: 22 May 2017

Publication Date:
12 July 2017 (eFirst)

Published as part of the Cluster Silicon in Synthesis and Catalysis

Abstract

Allenylsilanolates can undergo cross-coupling at the α- or γ-terminus, and site selectivity appears to be determined by the intrinsic transmetalation mechanism. Fine-tuning of concentration, nucleophilicity, and steric bulk of the silanolate moiety allows for the selective formation of one isomer over the other. Whereas the α-isomer can be obtained in synthetically useful yield, the γ-isomer is favored only when employing reaction conditions that are inevitably associated with diminished reactivity.

Supporting Information

 
  • References and Notes

  • 1 Current address: Gilead Sciences, Inc., Foster City, CA 94404, USA.
    • 3a Denmark SE. Regens CS. Acc. Chem. Res. 2008; 41: 1486
    • 3b Denmark SE. Liu JH.-C. Angew. Chem. Int. Ed. 2010; 49: 2978
    • 3c Chang W.-TT. Smith RC. Regens CS. Bailey AD. Werner NS. Denmark SE. Org. React. 2011; 75: 213
    • 3d Denmark SE. Ambrosi A. Org. Process Res. Dev. 2015; 19: 982
  • 4 Denmark SE. Werner NS. J. Am. Chem. Soc. 2008; 130: 16382
  • 5 Denmark SE. Werner NS. Org. Lett. 2011; 13: 4596
    • 6a Locos OB. Dahms K. Senge MO. Tetrahedron Lett. 2009; 50: 2566
    • 6b Radkowski K. Seidel G. Fürstner A. Chem. Lett. 2011; 40: 950
    • 6c Plunkett S. Dahms K. Senge MO. Eur. J. Org. Chem. 2013; 1566
    • 6d Yang Y. Szabó KJ. J. Org. Chem. 2016; 81: 250
    • 7a Jeffery-Luong T. Linstrumelle G. Synthesis 1982; 738
    • 7b Hornillos V. Giannerini M. Vila C. Fananas-Mastral M. Feringa BL. Chem. Sci. 2015; 6: 1394
    • 8a Kleijn RH. Meijer J. Oostveen EA. Vermeer P. J. Organomet. Chem. 1982; 224: 399
    • 8b de Graaf W. Boersma J. van Koten G. Elsevier CJ. J. Organomet. Chem. 1989; 378: 115
    • 9a Ruitenberg K. Kleijn H. Elsevier CJ. Meijer J. Vermeer P. Tetrahedron Lett. 1981; 22: 1451
    • 9b Wang KK. Wang Z. Tetrahedron Lett. 1994; 35: 1829
    • 10a Badone D. Cardamone R. Guzzi U. Tetrahedron Lett. 1994; 35: 5477
    • 10b Singh Aidhen I. Braslau R. Synth. Commun. 1994; 24: 789
    • 10c Kinderman SS. Hiemstra H. In 3-Trimethylsilyl-1-propyne, Encyclopedia of Reagents for Organic Synthesis . John Wiley and Sons; New York; 2001
    • 10d Huang C.-W. Shanmugasundaram M. Chang H.-M. Cheng C.-H. Tetrahedron 2003; 59: 3635
    • 10e Kjellgren J. Sundén H. Szabó KJ. J. Am. Chem. Soc. 2005; 127: 1787
    • 10f Mukai C. Takahashi Y. Org. Lett. 2005; 7: 5793
    • 10g Williams DR. Shah AA. Chem. Commun. 2010; 46: 4297
    • 10h Mohamed YA. M. Inagaki F. Takahashi R. Mukai C. Tetrahedron 2011; 67: 5133
  • 11 Marshall JA. Gung BW. Grachan ML. Synthesis and Reactions of Allenylmetal Compounds, In Modern Allene Chemistry . Wiley-VCH; Weinheim; 2008: 493
    • 12a Tymonko SA. Smith RC. Ambrosi A. Denmark SE. J. Am. Chem. Soc. 2015; 137: 6192
    • 12b Tymonko SA. Smith RC. Ambrosi A. Ober MH. Wang H. Denmark SE. J. Am. Chem. Soc. 2015; 137: 6200
  • 13 Okada T. Oda N. Suzuki H. Sakaguchi K. Ohfune Y. Tetrahedron Lett. 2010; 51: 3765
  • 14 Analytical Data for Compound 5 1H NMR (500 MHz, C6D6): δ = 7.19–7.16 (m, 4 H), 7.09–7.04 (m, 1 H), 4.93 (h, J = 3.6 Hz, 1 H), 3.19 (dd, J = 14.6, 3.3 Hz, 1 H), 3.14 (dd, J = 14.6, 3.2 Hz, 1 H), 1.59 (d, J = 3.7 Hz, 3 H), 1.13 (s, 1 H), 1.01 (t, J = 7.9 Hz, 3 H), 1.00 (t, J = 7.9 Hz, 3 H), 0.67–0.59 (m, 4 H). 13C NMR (126 MHz, C6D6): δ = 210.9, 140.1, 129.3, 128.6, 126.6, 92.4, 80.0, 40.6, 17.7, 7.3, 7.2, 6.9, 6.9. HRMS (EI+): m/z calcd for C15H22OSi: 246.1440; found: 246.1436.
  • 15 General Procedure for Cross-Coupling Experiments In a glove box, the Pd source and the ligand were added to an oven-dried 4 mL reaction vial containing a stir bar. A stock solution of 6 (0.05 mmol) and biphenyl in toluene (0.17 M) was added and the mixture stirred to homogenize. The vial was sealed with a septum screw cap, transferred outside the glove box and warmed to the indicated temperature. A solution of the silanolate in toluene (0.3–0.4 M) was then added via syringe. 50 μL aliquots were taken at the indicated time points, diluted with EtOAc (1 mL), quenched with acetate buffer (pH = 5), filtered through a silica plug, and analyzed by GC.
    • 16a This mechanistic hypothesis does not exclude the possibility of equilibration of v and vii. Under this circumstance, the α-product would be preferred. The presence of two substituents at the γ-terminus would decrease the rate of reductive elimination from v, and facilitate reductive elimination from vii. Moreover, it is known that reductive elimination to an sp2 carbon is more facile than to an sp3 carbon, see ref. 16b. However, in the presence of a weakly coordinating ligand (such as triphenylarsine), reductive elimination is expected to be faster than the isomerization between the short-lived intermediates v and vii, such that the transmetalation step is selectivity determining.
    • 16b Low JJ. Goddard WA. J. Am. Chem. Soc. 1986; 108: 6115
    • 17a Kurts AL. Macias A. Beletskaya I. Reutov OA. Tetrahedron 1971; 27: 4759
    • 17b Jones P. Harrison R. Wynne-Jones L. J. Chem. Soc., Perkin Trans. 2 1979; 1679
  • 18 Denmark SE. Neuville L. Christy ME. L. Tymonko SA. J. Org. Chem. 2006; 71: 8500