Communication Cite This: J. Am. Chem. Soc. 2018, 140, 5023−5027
pubs.acs.org/JACS
Exploiting Ancillary Ligation To Enable Nickel-Catalyzed C−O CrossCouplings of Aryl Electrophiles with Aliphatic Alcohols Preston M. MacQueen,‡ Joseph P. Tassone,‡ Carlos Diaz, and Mark Stradiotto* Department of Chemistry, Dalhousie University, 6274 Coburg Road, P.O. 15000, Halifax, Nova Scotia B3H 4R2, Canada S Supporting Information *
Scheme 1. Catalyst Design To Promote the Cross-Coupling of Aliphatic Alcohols and (Hetero)aryl Halides (ArX)
ABSTRACT: The use of (L)Ni(o-tolyl)Cl precatalysts (L = PAd-DalPhos or CyPAd-DalPhos) enables the C(sp2)− O cross-coupling of primary, secondary, or tertiary aliphatic alcohols with (hetero)aryl electrophiles, including unprecedented examples of such nickel-catalyzed transformations employing (hetero)aryl chlorides, sulfonates, and pivalates. In addition to offering a competitive alternative to palladium catalysis, this work establishes the feasibility of utilizing ancillary ligation as a complementary means of promoting challenging nickel-catalyzed C(sp2)−O cross-couplings, without recourse to preciousmetal photoredox catalytic methods.
I
nterest in the synthesis of aromatic ethers of primary and secondary aliphatic alcohols arises from the ubiquity of C(sp2)−O−C(sp3) linkages in a range of compounds of interest, including natural products and active pharmaceutical ingredients.1 Whereas some ethers of this type can be prepared from phenols and alkyl electrophiles by way of SN2 chemistry (Williamson ether synthesis2), complementary methods employing (hetero)aryl electrophiles are sought-after, in that they enable alternative disconnection strategies in which readily accessed aliphatic alcohols can be employed. Only limited success has been achieved in the preparation of alkyl (hetero)aryl ethers by use of SNAr chemistry or copper catalysis (Ullmann ether synthesis3);4 such protocols typically suffer from the requirement of activated (hetero)aryl bromides or iodides and forcing reaction conditions. Conversely, some particularly useful palladium catalysts for the cross-coupling of (hetero)aryl electrophiles with primary or secondary aliphatic alcohols have emerged,1a,5 which enable transformations of comparatively inexpensive and abundant (hetero)aryl chlorides.6 The successful development of such challenging palladium catalysis can be attributed to the judicious selection of ancillary ligand to promote product-forming C(sp2)−O bond reductive elimination over unwanted β-hydrogen elimination in catalytic intermediates of the type LnPd(aryl)(alkoxide) (Scheme 1A), with the electron-rich and sterically demanding phosphines RockPhos,7 Ad-BippyPhos,8 and JosiPhos CyPFtBu9 proving particularly effective (Scheme 1B).10 Notwithstanding such progress, the high cost and scarcity of palladium provides motivation for the development of related methodologies employing more Earth-abundant metals.11 The application of nickel12 catalysis in the cross-coupling of aliphatic alcohols with (hetero)aryl chlorides is attractive, given the more facile C(sp2)−Cl bond oxidative addition and less © 2018 American Chemical Society
favorable β-hydrogen elimination for nickel versus palladium,13 and in light of the utility of nickel in C(sp2)−N14 crosscouplings.15 Nonetheless, no examples of such nickel-catalyzed transformations employing (hetero)aryl chlorides have been reported. In an effort to address difficult C(sp2)−O bond reductive elimination within a presumptive Ni(0/II) cycle (Scheme 1A), MacMillan and co-workers 16 employed (dtbbpy)NiCl2 (5 mol %), in combination with an iridium photocatalyst17 (1 mol %) and quinuclidine (10 mol %), whereby oxidation of putative (dtbbpy)Ni2+(aryl)(alkoxide) intermediates to Ni(III) facilitates C(sp2)−O bond formation (Scheme 1C). Though useful in the cross-coupling of primary or secondary aliphatic alcohols, the electrophile scope is limited to (hetero)aryl bromides.16 The breakthroughs that have been achieved in palladium cross-coupling catalysis via rational ancillary ligand design18 suggest that a similar approach holds promise in nickel chemistry. Nonetheless, reports documenting the design of ancillary ligands for use in enabling nickel-catalyzed crosscouplings are rare.19 Our group recently developed the PAdDalPhos ancillary ligand class (Scheme 1D), which has proven to be useful in otherwise challenging nickel-catalyzed C(sp2)−N Received: February 13, 2018 Published: March 30, 2018 5023
DOI: 10.1021/jacs.8b01800 J. Am. Chem. Soc. 2018, 140, 5023−5027
Communication
Journal of the American Chemical Society cross-coupling applications.20 Unlike the bulky, electron-rich ancillary ligands that have proven optimal for use with palladium, the relatively electron-poor phosphaadamantane cage in PAd-DalPhos was strategically incorporated so as to facilitate product-forming, C(sp2)−N bond reductive elimination. In expanding on this work, we sought to evaluate the viability of utilizing PAd-DalPhos ligation as an alternative to iridium/nickel photoredox catalysis in enabling nickel-catalyzed C(sp2)−O cross-couplings (Scheme 1A). Herein we report on the successful application of PAdDalPhos and CyPAd-DalPhos (Scheme 1D) in the nickelcatalyzed C(sp2)−O cross-coupling of primary, secondary, or tertiary aliphatic alcohols with (hetero)aryl (pseudo)halides, in the absence of photochemical activation. The use of these ancillary ligands allows for a diverse electrophile scope to be accommodated, including (hetero)aryl chlorides, under conditions that are competitive with the best palladium catalysts known for such transformations. We initially examined the cross-coupling of 1-chloronaphthalene (1a) with 4-methylpentan-1-ol (2a) or 2-propanol (2b), employing nickel precatalysts that had proven useful in alternative cross-coupling applications, including: (L)Ni(otolyl)Cl21 (L = CyPAd-DalPhos,20e C1; L = PAd-DalPhos,20a C2; L = dppf,22 C3); (IPr)Ni(styrene)2,23C4; and (PAdDalPhos)NiCl,20d C5 (Table 1). In focusing on reactions of 2a, we were pleased to observe that the use of C1 (5 mol %) in combination with NaOtBu enabled high conversion (80%) to the target alkyl aryl ether 3a after 18 h at 110 °C (entry 1). Inferior selectivity for 3a versus reduction to naphthalene was observed with C2 (entry 2), and naphthalene formation was predominant with C3 or C4 under these conditions (entries 3 and 4). Whereas the use of bases other than NaOtBu with C1 proved less effective (entries 5 and 6), in reactions employing C2 the use of K2CO3 or Cs2CO3 (entries 7 and 8) afforded yields of 3a similar to that achieved using NaOtBu, with the benefit of reduced naphthalene formation. Comparison of the Ni(II) and Ni(I) PAd-DalPhos precatalysts C2 and C5 revealed only minimal variation in performance (entry 7 versus entry 10). Given the efficacy of C1, we sought to evaluate the performance of CyPAd-DalPhos relative to ancillary ligands that had proven useful in related palladium catalysis (Scheme 1B). Using the conditions in entry 1, with the exception of employing Ni(COD)2 (10 mol %) and either CyPAd-DalPhos, RockPhos, Ad-BippyPhos, or CyPF-tBu (10 mol % each), full conversion of 1a was observed in all cases. However, only CyPAd-DalPhos afforded product formation (45% 3a), with reactions employing the other ligands producing naphthalene (>70%) and other unidentified byproducts. These observations highlight the emerging trend that “repurposing” ligands from palladium chemistry is not a broadly effective strategy in nickel catalyst development.20a Furthermore, the superior performance of C1 relative to Ni(COD)2/CyPAd-DalPhos underscores the benefits of precatalyst usage,21 and the possible inhibitory effect of COD on the transformations reported herein. Cross-couplings employing 2b were more challenging than those involving 2a, with C1 proving superior to C2−C4 (entries 11−14), and where NaOtBu out-performed each of LiOtBu, KOtBu, K 3 PO 4 , or Cs 2 CO 3 . The use of 1bromonaphthalene afforded similar results (entry 11 versus entry 15). Improved selectivity for 4a was achieved by using a larger excess of 2b (entry 11 versus entry 16).
Table 1. Catalyst Screening and Reaction Optimizationa
Entry
Precat.
ROH
Base
3a/4ab
1ab
C10H8b
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16
C1 C2 C3 C4 C1 C1 C2 C2 C2 C5 C1 C2 C3 C4 C1g C1
2a 2a 2a 2a 2a 2a 2a 2a 2a 2a 2b 2b 2b 2b 2b 2bh
NaOtBu NaOtBu NaOtBu NaOtBu LiOtBu Cs2CO3c Cs2CO3 K2CO3 K3PO4 Cs2CO3 NaOtBue NaOtBu NaOtBu NaOtBu NaOtBu NaOtBu
80 50
