Communication pubs.acs.org/JACS
Cite This: J. Am. Chem. Soc. 2018, 140, 17428−17432
Cationic Alkynyl Heck Reaction toward Substituted Allenes Using BobCat: A New Hybrid Pd(0)-Catalyst Incorporating a Water-Soluble dba Ligand Robynne K. Neff and Doug E. Frantz* Department of Chemistry, The University of Texas at San Antonio, San Antonio, Texas 78249, United States
Downloaded via UNIV OF SOUTH DAKOTA on December 19, 2018 at 08:43:42 (UTC). See https://pubs.acs.org/sharingguidelines for options on how to legitimately share published articles.
S Supporting Information *
ABSTRACT: The cationic alkynyl Heck reaction between aryl triflates and alkynes to give substituted allenes is described. Key to the success of this method was the discovery and development of a new hybrid Pd(0)catalyst, BobCat, that incorporates a water-soluble dbaligand and biaryl phosphine ligand to provide substituted allenes in good yields under mild reaction conditions.
T
he Heck (or Mizoroki−Heck) reaction is arguably the most synthetically versatile method of all Pd(0)-catalyzed cross-coupling reactions in the organic chemist’s toolbox.1 Since the seminal independent reports from both Mizoroki2 and Heck,3 this transformation has been exploited by academic laboratories in countless elegant synthetic strategies toward complex natural products and biologically active small molecules.4 The Heck reaction has also been employed in numerous industrial applications including Merck’s commercial production of its LTD4 receptor antagonist Singulair,5 Albemarle’s large-scale production of naproxen,6 Dow’s production of 2- and 4-vinyltoluenes comonomers for polystyrene7 and in the manufacturing of the herbicide Prosulfuron on ton scale.8 But what makes the Heck reaction ultimately so useful is its ability to inspire creative bond connections that go beyond traditional cross-couplings with olefins. For example, innovative variations including the heteroatomic-Heck,9 oxidative/ dehydrogenative-Heck,10 reductive-Heck11 and decarboxylative-Heck reactions12 have all pioneered new avenues of olefin functionalization. In addition, significant effort has been invested in the discovery and development of new Pd-catalysts that impart improved reactivity and/or selectivity that has evolved the substrate scope of the Heck reaction dramatically over the years.13 Yet despite the numerous diverse applications of olefins in the Heck reaction, it is somewhat surprising that it has rarely been applied to alkynes where the direct products would be substituted allenes. The first example was originally reported by Heck himself over 25 years ago and then rediscovered almost 10 years later by Miura (Figure 1).14,15 In spite of these early reports, we are only aware of two subsequent examples including an intramolecular reaction between aryl chlorides and alkynes to yield a mixture of exocyclic allenes and dienes16 and an intermolecular reaction between aryl bromides and alkynes to access allenes that proceeds via a base-assisted © 2018 American Chemical Society
Figure 1. (a) Original report by Heck for the isolation of an allene from the cross-coupling between an aryl iodide and 3-hexyne. (b) Report from Miura on the Pd-catalyzed cross-coupling between aryl bromides and alkynes toward allenes. (c) Intramolecular Heck reaction between aryl chlorides and alkynes reported by Hamblett. (d) Substituted allenes from aryl bromides and alkynes through a non-Heck base-assisted deprotonation mechanism.
deprotonation rather than a Heck-like Pd-mediated β-hydride elimination.17 Since 2013, our group has become captivated with exploiting β-hydride eliminations from catalytically generated vinyl metal complexes as a practical approach to substituted allenes.18,19 In particular, our focus has centered on accessing cationic vinyl Pd(II) complexes where β-hydride eliminations are facile due to enhanced agostic interactions with the electrophilic metal center. From this perspective, we envisioned that the extension of the Heck reaction between alkynes and aryl triflates (the “cationic alkynyl Heck reaction”) would not only provide a convenient route to substituted allenes but may also provide opportunity for new catalyst discovery. We report here our Received: October 31, 2018 Published: December 6, 2018 17428
DOI: 10.1021/jacs.8b11759 J. Am. Chem. Soc. 2018, 140, 17428−17432
Communication
Journal of the American Chemical Society preliminary results on the cationic alkynyl Heck reaction and the design of a new Pd(0)-catalyst crucial for success of this catalytic method. Our screening efforts began using an aryl triflate (1) and 4octyne (2) using commercial sources of Pd(0) and various phosphine-based ligands (Table 1). On the basis of our Table 1. Preliminary Optimization Data for the Alkyyl Heck Reaction Between Aryl Triflate (1) and 4-Octyne (2)
entry c
1 2c 3f 4 5 6 7 8 9
Pd(0)-catalyst
liganda
Pd[P(o-tol)3]2d Pd[P(t-Bu)3)2d Pd2dba3g Pd2dba3g Pd2dba3g Pd2dba3g Pd2dba3g Pd2dba3g Pd2dba3g
− − PPh3 PCy3 PPhCy2 L1 L2 L3 L4
inherent with this Pd(0)-source (eq 2). Furthermore, relatively long reaction times (18 h) were needed for complete consumption of aryl triflate 1 implicating the inhibitory role that dba continued to play with this Pd(0)-source. Discouraged but not deterred by this result, we embarked on systematically designing several new Pd(0)-catalysts to either further reduce or completely remove dba altogether.22 A brief summary of our efforts is delineated in Table 2. The hybrid
yield (%)b
base e
Hünig’s Hünig’se Na3PO4h Na3PO4h Na3PO4h Na3PO4h Na3PO4h Na3PO4h Na3PO4h
21
