A Rational Approach towards the Nucleophilic Substitutions of Alcohols “on Water”

Cozzi, Pier Giorgio; Zoli, Luca

doi:10.1002/ange.200800622

Cited by 61 publications

(20 citation statements)

References 54 publications

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“…These results suggested that C3-palladated indole could not react with benzyl alcohol 2a after C-H activation of indole 1 occurred in CD 3 OD, and organic solvents could not activate the benzyl alcohol 2a (Figure 3, intermediate 24). Therefore, we have demonstrated an important role of water for water-promoted sp 3 C-O bond activation of benzyl alcohols 2 in our catalytic system (Figure 3, intermediate 9) [15][16][17].…”

mentioning

confidence: 51%

“…Recently, direct application of benzyl alcohols as electrophiles in various reactions was achieved via Brønsted/Lewis acid [10][11][12], transition metal [13,14] or water-promoted [15][16][17] We have developed a unique strategy for benzylation and C-H activation [18][19][20][21][22][23][24] by the (η 3 -benzyl)palladium system from a palladium catalyst and benzyl alcohol in water [25][26][27][28]. Water activates the benzyl alcohol via hydration of the hydroxyl group for generation of the (η 3 -benzyl)palladium species, which can then undergo innovative direct transformation reactions.…”

Section: Open Accessmentioning

confidence: 99%

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Mechanistic Studies for Synthesis of Bis(indolyl)methanes: Pd-Catalyzed C–H Activation of Indole–Carboxylic Acids with Benzyl Alcohols in Water

et al. 2013

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mentioning

confidence: 51%

Section: Open Accessmentioning

confidence: 99%

Mechanistic Studies for Synthesis of Bis(indolyl)methanes: Pd-Catalyzed C–H Activation of Indole–Carboxylic Acids with Benzyl Alcohols in Water

et al. 2013

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“…In order to achieve regioselectivity on indole derivates and related heterocycles alkylation, methods have been widely investigated [12][13][14][15][16][17]. The nucleophilic nature of the carbon atom in the 3-position [18] makes the indole susceptible towards direct alkylation reactions.…”

Section: Resultsmentioning

confidence: 99%

Regioselective Catalytic Alkylation of N-Heterocycles in Continuous Flow

Sipőcz¹,

Lengyel²,

Sipos³

et al. 2016

J Flow Chem

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A novel method for C-H functionalization of heteroaromatic rings by using continuous-flow reactors is reported. Direct alkylation reactions were investigated under heterogeneous catalytic conditions using simple transition metal catalysts at elevated temperature and pressure. As a model reaction, the alkylation of indole was attempted using cheap Raney W Nickel catalyst. Alcohols served both as alkylating agent and as reaction media. The targeted 3-alkyl-indoles were obtained in moderate to good yield with reasonable selectivity. Transient protection on the N-atom increased the selectivity up to 80%. The scope and limitations were also investigated. In summary, direct alkylation with alcohols represents a rapid (residence time of <1 min) and traceless process with high atom economy (88-92%, in those cases where transient protection was not applied).

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“…[6] Notably,w ater activates the sp 3 C À Ob ond by hydrogen bonds between water and the hydroxy group of the alcohols.T heoreticalc alculationsb yS hinokubo and Oshima have elucidated the importance of hydration of the hydroxy group for the smooth generation of the p-allylpalladium species. [8] Furthermore,t he hydrophobic effect would also accelerate the benzylationi no ur catalytic system. [8] Furthermore,t he hydrophobic effect would also accelerate the benzylationi no ur catalytic system.…”

Section: Introductionmentioning

confidence: 99%

Direct Use of Benzylic Alcohols for Gold(III)‐Catalyzed S‐Benzylation of Mercaptobenzoic Acids in Water

et al. 2016

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We demonstrate the gold(III)-catalyzed direct substitution of benzylic alcohols in water. These atom economic and environmentally benign protocols afford S-benzylated productsi nm oderate to excellent yields.I nc ontrast, common Lewis or Brønsted acids as catalyst, ando rganic solventss uch as dichloromethane or toluene were ineffectivef or the S-benzylation of mercaptobenzoic acids.W ater can be an attractive toolf or newt ransitionm etalcatalyzed reactions.AHammetts tudy for the rate constants with various substituted alcohols shows ag ood correlation (R 2 = 0.97) between the log(k X / k H )a nd the s + + value of the respective substituents. From the slope negative 1 valueso f2 .35 are ob-tained,s uggesting that there is ab uild-up of positive charge in the transitions tate.O ur catalytic system can be performed with the use of only 2mol% of gold(III) catalyst without any other additives in water, and scaled up to 10 mmol scale (85% isolated yield). Notably,t he present method can accomplish the S-benzylation of unprotected mercaptobenzoic acids,w hich is chemoselective andl eaves the carboxyl group intact. Furthermore,t he direct substitution of allylica nd propargylic alcohols also proceeded smoothlyi ngoody ields.

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A Rational Approach towards the Nucleophilic Substitutions of Alcohols “on Water”

Cited by 61 publications

References 54 publications

Mechanistic Studies for Synthesis of Bis(indolyl)methanes: Pd-Catalyzed C–H Activation of Indole–Carboxylic Acids with Benzyl Alcohols in Water

Mechanistic Studies for Synthesis of Bis(indolyl)methanes: Pd-Catalyzed C–H Activation of Indole–Carboxylic Acids with Benzyl Alcohols in Water

Regioselective Catalytic Alkylation of N-Heterocycles in Continuous Flow

Direct Use of Benzylic Alcohols for Gold(III)‐Catalyzed S‐Benzylation of Mercaptobenzoic Acids in Water

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