Pd–NHC Catalyzed Conjugate Addition versus the Mizoroki–Heck Reaction

Abstract

[a] chem_201003643_sm_miscellaneous_information.pdf S1General Information: Glassware and Handling:All experiments were carried out in flame dried or oven dried (150 o C) glassware, in an atmosphere of nitrogen, unless specified otherwise, by standard Schlenk techniques. Schlenk reaction tubes with screwcaps, and equipped with a Teflon-coated magnetic stirbar were flame dried under vacuum and allowed to return to room temperature prior to being charged with reactants. A manifold permitting switching between nitrogen atmosphere and vacuum was used to control the atmosphere in the reaction vessel. Once charged with all the reactants, the reaction vessel was cycled through at least 3 cycles of nitrogen-vacuumnitrogen to ensure the atmosphere was inert.Reaction temperature refers to the temperature of the oil bath. Solvents and ReagentsAll solvents used for extraction, filtration and chromatography were of commercial grade, and used without further purification, except for pentane, which was distilled prior to use. Peptide Synthesis grade DMF used for reaction was purchased from BIOSOLVE BV (The Netherlands) and degassed by a freeze-pump-thaw procedure (repeated cycles of freezing under vacuum with liquid nitrogen and thawing to room temperature) prior to use. The degassing was performed regularly in small batches, and once degassed, the DMF was used within a few days.Reagents were purchased from Sigma-Aldrich, Strem or Acros and used without further purification. Analytical grade tri-n-butylamine was purchased from Sigma-Aldrich and stored in an atmosphere of nitrogen. Palladium complex Pd II -NHC was synthesized as described in literature [1] and stored under ambient conditions. Palladium complex Pd 0 -NHC was purchased from Sigma-Aldrich and stored in a nitrogen-filled glovebox, from which the requisite amounts were weighed out. S2Analysis TLC was performed on Merck silica gel 60, 0.25 mm plates and visualization was done by UV and staining with Seebach's reagent (a mixture of phosphomolybdic acid (25 g), cerium (IV) sulfate (7.5 g), H 2 O (500 mL) and H 2 SO 4 (25 mL)). GC-MS measurements were made using a HP 6890 Series Gas Chromatograph system equipped with a HP 5973 Mass Sensitive Detector. GC measurements were made using a Shimadzu GC 2014 gas chromatograph system bearing a AT5 column (Grace Alltech) and FID detection. Whenever GC yield is reported, the quantification was done using cyclo-octane as internal standard.High Resolution Mass measurements were performed using a ThermoScientific LTQ Oribitrap XL spectrometer.

BINAP versus BINAP(O) in Asymmetric Intermolecular Mizoroki–Heck Reactions: Substantial Effects on Selectivities

“…An alternative explanation is provided by Gottumukkala et al (albeit in a different context). [26] The authors Table 1. Enantioselective arylation of 2,3-dihydrofuran (1) employing either (R)-BINAP or (R)-BINAP(O).…”

Heterocyclic Carbene–Metal-catalyzed Csp2–Csp2 and Csp–Csp2 Couplings Using Nonmetallic Substrates

“…Thus, the MizorokiHeck reaction employing bromo-and chloroarenes has been satisfactorily catalyzed by the monoNHC Pd(II) complex 1, 8 bis(NHC) Pd(II) complexes 222, 7,911 the tetraNHC Pd(II) complex 23, 12 and Pd(0) complexes 24 and 25 (Chart 1). 7,13 Complexes 26 adopted a pseudo-square-planar geometry where the NHC ligands were in a cis-configuration.…”

“…Interestingly, the palladium(0) complex 25, which has been prepared by Beller's research group and employed in the MatsudaHeck reaction (vide infra), 15 catalyzed also the reaction between aryl iodides and enones yielding the MizorokiHeck product or the conjugate addition depending on the base employed. 13 The synthesis of complex 26, which bears NHC ligands in "normal" and "abnormal" binding motifs, has been described by direct metalation of the corresponding imidazolium salt with palladium(II) acetate. 16 Interestingly, this atypical bis(NHC) complex was shown to be a more suitable precursor for the MizorokiHeck reaction than the complex 27, and the in situ generated catalyst.…”

“…Thus, the MizorokiHeck reaction employing bromo-and chloroarenes has been satisfactorily catalyzed by the monoNHC Pd(II) complex 1, 8 bis(NHC) Pd(II) complexes 222, 7,911 the tetraNHC Pd(II) complex 23, 12 and Pd(0) complexes 24 and 25 (Chart 1). 7,13 Complexes 26 adopted a pseudo-square-planar geometry where the NHC ligands were in a cis-configuration.14 The comparison of the catalytic activity between 26 complexes did not allow to conclude any universal trend, but complex 4 exhibited higher activity than complex 5 what may be attributed to ·-and ³-contributions of the substituents in the corresponding NHCligand. Interestingly, the palladium(0) complex 25, which has been prepared by Beller's research group and employed in the MatsudaHeck reaction (vide infra), 15 catalyzed also the reaction between aryl iodides and enones yielding the MizorokiHeck…”

Nucleophilic Aromatic Substitution

“…There have been reviews of couplings catalysed by palladium 70 and by palladium in combination with copper. 74 Using palladium catalysis, arenes substituted with a 2-pyridylsulfinyl group have been shown to react with alkenes at the ortho positions which may lead to disubstituted products such as (26). 73 It has been shown that using a palladium-N-heterocyclic carbene catalyst, the reaction of aryl halides with Michael acceptors may result either in conjugate addition or Heck substitution, depending on the base used.…”