Palladacycles phenols

Rawal s group developed an intramolecular aryl Heck cyclization method to synthesize benzofurans, indoles, and benzopyrans [83], The rate of cyclization was significantly accelerated in the presence of bases, presumably because the phenolate anion formed under the reaction conditions was much more reactive as a soft nucleophile than phenol. In the presence of a catalytic amount of Herrmann s dimeric palladacyclic catalyst (101) [84], and 3 equivalents of CS2CO3 in DMA, vinyl iodide 100 was transformed into ortho and para benzofuran 102 and 103. In the mechanism proposed by Rawal, oxidative addition of phenolate 104 to Pd(0) is followed by nucleophilic attack of the ambident phenolate anion on o-palladium intermediate 105 to afford aryl-vinyl palladium species 106 after rearomatization of the presumed cyclohexadienone intermediate. Reductive elimination of palladium followed by isomerization of the exocyclic double bond furnishes 102. 

Oxidative phenolic coupling. Biosynthesis of the alkaloid narwedine (3) is known to involve oxidative phenolic coupling of norbelladine derivatives (1), but the usual oxidants for such coupling in vitro convert 1(R = H) into the oxomaritidine skeleton (4) rather than 3. A new biomimetic synthesis of 3 involves the palladacycle 2, formed by reaction of 1(R = CH3) with Li2PdCl4, which is known to form complexes with allylic amines or sulfides (8,176-177). Oxidation of 2 with thallium(III) trifluoroacetate effects the desired coupling to give 3. 

The general procedure for the coupling of styrenes with bromo- and chloroarcnes [16] is exemplified by this preparation (Scheme 3-56). In a 100-mL three-necked flask equipped with a reflux condenser, stirrer, and internal thermometer were placed, under a stream of nitrogen, 4-bromoacetophenone (23a-Br) (5.0 g, 25 mmol) [or 4-chloroacetophenone (23a-Cl) (3.3 mL, 3.9 g, 25 mmol) plus TBABr (1.64 g. 5 mmol)], styrene (4.3 mL, 3.9 g, 37 mol), 2,6-di(tert-butyl)phenol (20 mg, as a radical scavenger), NaOAc (2.5 g, 30 mmol), and A(A-dimethylacetamide (50 mL). To the well-stirred suspension was added 12 mg (0.1 mol%) of the palladacycle la, and the mixture was heated at 130 "C for 24 h (54 h with 4-chloroacetophenone). After the reaction mixture had cooled to rt, it was poured into ice-water (200 mL). The precipitate was collected on a filter, carefully washed with water and recrystallized from acetone/water to yield 4.9 g (89%) of 258a (3.8 g, 69% from 4-chloroacetophenone). 

Acceleration of the intramolecular coupling of phenol and aryl halide moieties that is effected with a fJC-palladacycle by a base is realized. o-AminophenyIdiphenylphosphine is a ligand that forms effective Pd complexes for the Heck reaction. ... 

Rawal has developed a new route to indoles and benzofurans via the anion-accelerated palladium-mediated intramolecular cyclizations of phenols containing various vinyl halide side chains <97TL6379>. For example, heating a mixture of the symmetrical phenol 70 and cesium carbonate in dimethylacetamide (DMA) in the presence of a catalytic amount of Hermann s palladacyclic catalyst (HC) promoted the cyclization to the indole 71. 

Formation of 2(biphenyl-2-yl)phenol (51) from 50 is explained by electrophilic attack of 57 to form 59 and its reductive elimination. As another explanation, oxidative addition of aromatic ortho C—H bond to 57 generates the palladacycle 58 and its reductive elimination affords 59. Domino arylations by a similar sequence of the reactions via 60 finally give rise to the pentaphenylated product 49 in 58 % yield. Certainly the reaction occurs by strong participation of OH group. It is surprising that efficient polyarylation of phenol with bromobenzene proceeds smoothly in the presence of CS2CO3 which is sparingly soluble in xylene and since it is difficult to abstract protons from phenol. 

Cobalt Oxazoline Palladacycles (COPs) are organocobalt-palladium complexes which catalyse the asymmetric rearrangements of non-chiral allylic trichloroacetamidates with very high enantiomeric selectivity (>90%) to provide chiral allylic amines [it is an aza-Claisen rearrangement, The Overman Rearrangement Overman Carpenter Org React 66 2005, Kirsch, Overman and Watson J Org Chem 69 8101 2004] and in the presence of phenols stereospecific cross-couphng also occurs to provide chiral phenoxyallyl ethers with veiy high (>90%) enantiomeric selectivity [Kirsch, Overman and White Org Lett 9 911 2007, Overman Carpenter Org React 66 2005]. 

Encountering these disadvantages, a significant improvement was achieved with palladacycle 174 assembled from a readily available phosphite which was in turn derived from a commercially available sterically hindered phenol [230], A direct comparison of 174 with the prototype palladacycle 52 is not viable, as the reactions with phosphite palladacycle 174 were generally conducted under more stringent conditions (temperatures of 160-180 °C). Yet, formidable TONs up to 1000000 in the reactions of -butyl acrylate with activated substrates such as 4-bromoacetophenone (0.0001 mol% 174, NaOAc, DMA, 180 °C) were accessible. Moreover, with a TON of 9800 for 4-bromoanisole (0.01 mol% 174, K2CO3, DMA, 160 °C), 174 was quite reactive for type 2 reactions [230]. 

Ramesh et al. synthesized a cyclometallated dimeric palladium) ) catalyst with covalently bonded based on the concept that release slowly the highly active species from structurally more stable catalyst precursors [110]. By utilizing this dimeric oxime-type palladacycle as the catalyst, various aryl iodides were reacted with aliphatic alcohols and phenols in a highly selective manner and gave the corresponding esters in excellent yields. Based on these excellent yields, apparently no by-products were formed. Remarkably, the complex was stable even at high temperatures (120 °C) and under 10 bar of carbon monoxide. 

Intramolecular Pd-catalyzed aryl-aryl coupling reactions under dehydrohalogenation are assumed to proceed via palladacycles as illustrated by the example in Scheme 47.[33]-P7] Several mechanistic pathways may explain the cyclopalladation step including the C,H-activation however, a reaction of an electrophilic arylpalladium bromide with the electron-rich phenolate in the sense of an electrophilic aromatic substitution is certainly a plausible explanation. C—C bond formation finally takes place by reductive elimination. 

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