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The oxime-substituted NCN-pincer molecules HON{double bond, long}CH-1-C6H3(CH2NMe2)2-3,5 (2a) and HON{double bond, long}CH-4-C6H2(CH2NMe2)2-2,6-Br-1 (2b) were accessible by treatment of the benzaldehydes H(O)C-4-C6H3(CH2NMe2)2-3,5 (1a) and H(O)C-4-C6H2(CH2NMe2)2-2,6-Br-1 (1b) with an excess of hydroxylamine. In the solid state both compounds are forming polymers with intermolecular O-H?N connectivities between the Me2NCH2 substituents and the oxime entity of further molecules of 2a and 2b, respectively. Characteristic for 2a and 2b is a helically arrangement involving a crystallographic 21 screw axis of the HON{double bond, long}CH-1-C6H3(CH2NMe2)2-3,5 and HON{double bond, long}CH-4-C6H2(CH2NMe2)2-2,6-Br-1 building blocks. The reaction of 2b with equimolar amounts of [Pd2(dba)3 · CHCl3] (3) (dba = dibenzylidene acetone) or [Pt(tol)2(SEt2)]2 (4) (tol = 4-tolyl) gave by an oxidative addition of the C-Br unit to M coordination polymers with a [(HON{double bond, long}CH-4-C6H2(CH2NMe2)2-2,6)MBr] repeating unit (5: M = Pd, 6: M = Pt). Complexes 5 and 6 are in the solid state linear hydrogen-bridged polymers with O-H?Br contacts between the oxime entities and the metal-bonded bromide.

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Reference:
Chapter 1 An introduction to palladium catalysis,
Palladium/carbon catalyst regeneration and mechanical application method

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An efficient method for the enantioselective synthesis of beta-tertiary beta-amino alcohol derivatives through Pd-catalyzed decarboxylative cycloaddition of vinylethylene carbonates with imines was developed. By using a palladium complex generated in situ from [Pd2(dba)3]·CHCl3 and phosphoramidite L2 as a catalyst under mild reaction conditions, the process provided 4-substituted-4-vinyloxazolidines in good to high yields with high levels of enantio- and diastereoselectivities.

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Reference:
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Optically pure hinckdentine A was synthesized on a 300 mg scale via an asymmetric catalysis-based strategy. The key steps to the first asymmetric synthesis involved (i) enantioselective dearomative cyclization of an achiral N-acyl indole that allowed for the efficient construction of the key polycyclic indoline intermediate with a crucial tetrasubstituted stereogenic carbon center, (ii) Beckmann fragmentation-mediated ring expansion, (iii) rearrangement-based introduction of an anilinic nitrogen atom, (iv) regioselective tribromination, and (v) final closure of the cyclic amidine moiety.

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Reference:
Chapter 1 An introduction to palladium catalysis,
Palladium/carbon catalyst regeneration and mechanical application method

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We report a palladium-catalyzed method to synthesize acid chlorides by the chlorocarbonylation of aryl bromides. Mechanistic studies suggest the combination of sterically encumbered PtBu3 and CO coordination to palladium can rapidly equilibrate the oxidative addition/reductive elimination of carbon-halogen bonds. This provides a useful method to assemble highly reactive acid chlorides from stable and available reagents, and can be coupled with subsequent nucleophilic reactions to generate new classes of carbonylated products. The Good, the Bad and the Bulky! By employing a sterically encumbered phosphine ligand, tri-tert-butyl phosphine, under palladium catalysis inert aryl bromides are chlorocarbonylated to create reactive acid chlorides by reversible carbon-halogen bond reductive elimination. This general platform allows for an expanded scope of the Heck carbonylation reaction to include previously incompatible nucleophiles.

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Chapter 1 An introduction to palladium catalysis,
Palladium/carbon catalyst regeneration and mechanical application method

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A stereogenic center, placed at an exocyclic location next to a chiral carbon in a ring to which it is attached, is a ubiquitous structural motif seen in many bioactive natural products, including di- and triterpenes and steroids. Installation of these centers has been a long-standing problem in organic chemistry. Few classes of compounds illustrate this problem better than serrulatanes and amphilectanes, which carry multiple methyl-bearing exocyclic chiral centers. Nickel-catalyzed asymmetric hydrovinylation (AHV) of vinylarenes and 1,3-dienes such as 1-vinylcycloalkenes provides an exceptionally facile way of introducing these chiral centers. This Article documents our efforts to demonstrate the generality of AHV to access not only the natural products but also their various diastereoisomeric derivatives. Key to success here is the availability of highly tunable phosphoramidite Ni(II) complexes useful for overcoming the inherent selectivity of the chiral intermediates. The yields for hydrovinylation (HV) reactions are excellent, and selectivities are in the range of 92-99% for the desired isomers. Discovery of novel, configurationally fluxional, yet sterically less demanding 2,2?-biphenol-derived phosphoramidite Ni complexes (fully characterized by X-ray) turned out to be critical for success in several HV reactions. We also report a less spectacular yet equally important role of solvents in a metal-ammonia reduction for the installation of a key benzylic chiral center. Starting with simple oxygenated styrene derivatives, we iteratively install the various exocyclic chiral centers present in typical serrulatane [e.g., a (+)-p-benzoquinone natural product, elisabethadione, nor-elisabethadione, helioporin D, a known advanced intermediate for the synthesis of colombiasin and elisapterosin] and amphilectane [e.g., A-F, G-J, and K,L pseudopterosins] derivatives. A concise table showing various synthetic approaches to these molecules is included in the Supporting Information. Our attempts to synthesize a hitherto elusive target, elisabethin A, led to a stereoselective, biomimetic route to pseudopterosin A-F aglycones.

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Reference:
Chapter 1 An introduction to palladium catalysis,
Palladium/carbon catalyst regeneration and mechanical application method

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The reactions of 3-iodotropolone with styrenes (styrene, p-methoxystyrene, and 2-vinylpyridine), methyl acrylate, and allylic compounds (methyl 3-butenoate, 3-butenenitrile, 1-allyl-3,4-dimethoxybenzene, and 1-allyl-3,4-methylenedioxybenzene) were carried out, according to the modified Heck’s procedure, to give 3-styryl-, 3-(2-carboxyvinyl)-, and 3-(3-substituted 1-propenyl)tropolones, respectively.Similarly, 4-bromo- or 5-bromotropolone was made to react with these olefins to yield 4-styryltropolone or the corresponding 5-(2-substituted vinyl)- and 5-(3-substituted1-propenyl)tropolones.Substitution of 2-chlorotropone by styrenes produced 2-styryltropones.Extension of the vinylation to 2-amino-6-bromoazulenes, ethyl 3-bromo-1-azulenecarboxylate, and diethyl 2-chloro-1,3-azulenedicarboxylate resulted in a similar substitution.

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Reference:
Chapter 1 An introduction to palladium catalysis,
Palladium/carbon catalyst regeneration and mechanical application method

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New chiral NCN-pincer palladium complexes containing bulky diphenylhydroxymethyl pyrrolidinyl moieties as chiral auxiliaries have been synthesized. Oxidative palladium addition to ligand 2 (2 = 2,6-bis{[(S)-2- (diphenylhydroxymethyl)-1-pyrrolidinyl]memyl}-1-bromobenzene) initially yielded neutral arylpalladium bromide complex 3 in a moderate yield as a consequence of the bulky pyrrolidinyl functional groups. Performing the palladation reaction under microwave irradiation for only 5 min gave 3 in 79% yield. Abstraction of the bromide ion from 3 subsequently yielded the cationic complexes [4]PF 6 and [4]BF4. Palladium complexes 3, [4]PF6, and [4]BF4 are all formed as single diastereoisomers with an R NRNSCSC configuration. X-ray crystal structure determinations of [4]PF6 and [4]BF4 revealed an unusual kappa5-N,C,N,O,O coordination around palladium, in which the normal meridional kappa3-coordination mode of the pincer framework is complemented by two rather long Pd-O interactions (2.622(2)-2.649(2) A). Theoretical calculations (Mulliken population analysis and “atoms in molecules” analysis) confirmed that there is a coordinative interaction between the palladium and the oxygen atoms of both hydroxyl groups despite the long Pd-O distance. Complexes [4]PF6 and [4]BF4 catalyze the aldol condensation between alpha-methyl isocyanoacetate and various aromatic aldehydes with enhanced regio- (up to 70%) and stereoselectivity (up to 42% ee) for the cis-oxazolines. These observations are in contrast to prior literature results on other pincer systems, where the trans-oxazolines were the main product, and point to a deeper chiral cavity pointing away from palladium toward the coordinated isocyanoacetate substrate.

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Bis(thieno[3,2-b]thiophene)-fused 1,2-dithiin reacts with a stoichiometric amount of Ni(cod)2/2PPh3 to produce a dimeric Ni(II) complex via the oxidative addition of the disulfide bond in the 1,2-dithiin skeleton to the Ni(0) center. An X-ray crystal structure analysis revealed that this complex has a dimeric structure in which one sulfur atom derived from the disulfide bond bridges two metal centers. The resultant Ni complex undergoes desulfurization at elevated temperature to produce a fully fused thiophene-based heteroacene.

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Chapter 1 An introduction to palladium catalysis,
Palladium/carbon catalyst regeneration and mechanical application method

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The synthesis and catalytic properties of ditopic mono-pincer-mono- porphyrin complexes were investigated. The statistical Adler condensation reaction of 3,5-bis(methoxymethyl)-4-bromo-benzaldehyde, p-tolylaldehyde, and pyrrole, furnished an AB3-type tetraphenylporphyrin, containing three meso-p-tolyl groups and one meso-3,5-bis(methoxymethyl)-4-bromophenyl group. This material was converted into the ditopic ligand [2H(Br)], which comprises one porphyrin site and an NCN-pincer type ligand moiety. In order to metalate this compound in a stepwise, site-selective manner, two distinct synthetic routes were followed. Route A relies on the introduction of a metal in the porphyrin cavity followed by pincer metalation and a reversal of this order is employed for route B. For the hetero-bimetallic pincer-porphyrin target compounds, route A invariably proved to be the highest yielding alternative, giving pincer-porphyrin hybrids of general formula [M1(M 2X)] (M1 = 2H, Mg, Co, Ni, Zn; M2 = Pd, Br; X = Cl, Br). 195Pt NMR spectroscopy revealed that the porphyrin metal has a modest influence on the electron density on the NCN-pincer Pt site. When the analogous cationic Pd complexes were used as Lewis acid catalysts for the double Michael addition between methyl vinyl ketone and ethyl alpha-cyanoacetate, it was noted that the catalytic activity did not depend on the central metal for M1 = 2H, Ni, and Zn. However, when Mg occupied the porphyrin cavity, the rate of the reaction increased by a factor of six. Although a rate enhancement was observed when catalysis was conducted with a mixture of the two constituents of [Mg(PdOH2)]BF4 (i.e. MgTTP and [PdOH2(NCN)]BF4) this could not fully account for the rate enhancement. We believe that the rationale for this behaviour is dual, consisting of “cooperative dual catalysis” and supramolecular aggregation of two or more catalyst-substrate complexes.

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The first palladium-catalysed coupling of the carbonates of (E)-configured conjugated enynols with terminal alkynes is described. This method allows the synthesis of vinyl-allenynes with good yields. It has been determined that the method is not suitable for the (Z)-configured substrates.

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Reference:
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Palladium/carbon catalyst regeneration and mechanical application method