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From α-arylation of olefins to acylation with aldehydes: a journey in regiocontrol of the Heck reaction.
Acc Chem Res 2011; 44(8):614-26AC

Abstract

The Pd-catalyzed Mizoroki-Heck reaction of olefins with aryl halides, more often simply called the Heck reaction, was recently recognized with the 2010 Nobel Prize in chemistry. Although highly selective with electron-deficient olefins, which generally yield the linear β-arylated product exclusively, the Heck reaction is less satisfactory with electron-rich olefins. This substrate typically generates a mixture of both α- and β-arylated regioisomeric products, hampering wider application of the reaction in chemical synthesis. Pioneering studies by a number of researchers revealed that high α-regioselectivity could be obtained under Pd-diphosphine catalysis either through (i) the substitution of aryl triflates for halides or (ii) the addition of stoichiometric silver or thallium salts when aryl halides are used. Under these conditions, the arylation is believed to proceed via an ionic pathway. However, silver introduces added cost, thallium salts are toxic, and triflates are generally commercially unavailable, base sensitive, and thermally labile. Believing that the ionic pathway would be promoted in an ionic medium, in the early 2000s, we attempted the Pd-catalyzed arylation of the benchmark electron-rich olefin butyl vinyl ether with aryl bromides in an imidazolium ionic liquid. We were delighted to observe that highly regioselective α-arylation could readily be accomplished, with no need for silver additives, thallium additives, or aryl triflates. A range of other electron-rich olefins has since been shown to be viable as well. The high α-selectivity probably results from the high ionic strength of the medium, which facilitates the dissociation of halide anions from the [L(2)Pd(Ar)X] intermediate, channeling the arylation into the ionic pathway. Hydrogen bonding interactions may also play a role, however. We subsequently discovered that the α-arylation can indeed be significantly accelerated by a hydrogen bond donor salt, in both ionic liquids and common solvents. Evidence shows that the concentration of the cationic Pd(II)-olefin species along the ionic pathway is increased as a result of hydrogen bonding between the hydrogen bond donor and the halide anion. More recently, we reported that cheaper and greener alcohols allow the Heck arylation of electron-rich olefins to proceed in a much faster, productive, and totally α-regioselective manner, circumventing the need for an ionic medium or hydrogen bond donor salt. In particular, aryl chlorides with diverse properties have been demonstrated to be viable substrates for the first time. Significantly, it appears that ethylene glycol facilitates both the oxidative addition of ArCl to Pd(0) and the subsequent dissociation of chloride from Pd(II). A closely related reaction, acylation of aryl halides with aldehydes, was also developed. Proceeding via the intermediacy of an electron-rich enamine, this Pd-pyrrolidine cooperative catalysis affords alkyl aryl ketones in a straightforward manner, extending the Heck reaction from olefins to aldehydes.

Authors+Show Affiliations

Department of Chemistry, University of Liverpool, Liverpool L69 7ZD, United Kingdom.No affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't
Review

Language

eng

PubMed ID

21612205

Citation

Ruan, Jiwu, and Jianliang Xiao. "From Α-arylation of Olefins to Acylation With Aldehydes: a Journey in Regiocontrol of the Heck Reaction." Accounts of Chemical Research, vol. 44, no. 8, 2011, pp. 614-26.
Ruan J, Xiao J. From α-arylation of olefins to acylation with aldehydes: a journey in regiocontrol of the Heck reaction. Acc Chem Res. 2011;44(8):614-26.
Ruan, J., & Xiao, J. (2011). From α-arylation of olefins to acylation with aldehydes: a journey in regiocontrol of the Heck reaction. Accounts of Chemical Research, 44(8), pp. 614-26. doi:10.1021/ar200053d.
Ruan J, Xiao J. From Α-arylation of Olefins to Acylation With Aldehydes: a Journey in Regiocontrol of the Heck Reaction. Acc Chem Res. 2011 Aug 16;44(8):614-26. PubMed PMID: 21612205.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - From α-arylation of olefins to acylation with aldehydes: a journey in regiocontrol of the Heck reaction. AU - Ruan,Jiwu, AU - Xiao,Jianliang, Y1 - 2011/05/25/ PY - 2011/5/27/entrez PY - 2011/5/27/pubmed PY - 2011/12/13/medline SP - 614 EP - 26 JF - Accounts of chemical research JO - Acc. Chem. Res. VL - 44 IS - 8 N2 - The Pd-catalyzed Mizoroki-Heck reaction of olefins with aryl halides, more often simply called the Heck reaction, was recently recognized with the 2010 Nobel Prize in chemistry. Although highly selective with electron-deficient olefins, which generally yield the linear β-arylated product exclusively, the Heck reaction is less satisfactory with electron-rich olefins. This substrate typically generates a mixture of both α- and β-arylated regioisomeric products, hampering wider application of the reaction in chemical synthesis. Pioneering studies by a number of researchers revealed that high α-regioselectivity could be obtained under Pd-diphosphine catalysis either through (i) the substitution of aryl triflates for halides or (ii) the addition of stoichiometric silver or thallium salts when aryl halides are used. Under these conditions, the arylation is believed to proceed via an ionic pathway. However, silver introduces added cost, thallium salts are toxic, and triflates are generally commercially unavailable, base sensitive, and thermally labile. Believing that the ionic pathway would be promoted in an ionic medium, in the early 2000s, we attempted the Pd-catalyzed arylation of the benchmark electron-rich olefin butyl vinyl ether with aryl bromides in an imidazolium ionic liquid. We were delighted to observe that highly regioselective α-arylation could readily be accomplished, with no need for silver additives, thallium additives, or aryl triflates. A range of other electron-rich olefins has since been shown to be viable as well. The high α-selectivity probably results from the high ionic strength of the medium, which facilitates the dissociation of halide anions from the [L(2)Pd(Ar)X] intermediate, channeling the arylation into the ionic pathway. Hydrogen bonding interactions may also play a role, however. We subsequently discovered that the α-arylation can indeed be significantly accelerated by a hydrogen bond donor salt, in both ionic liquids and common solvents. Evidence shows that the concentration of the cationic Pd(II)-olefin species along the ionic pathway is increased as a result of hydrogen bonding between the hydrogen bond donor and the halide anion. More recently, we reported that cheaper and greener alcohols allow the Heck arylation of electron-rich olefins to proceed in a much faster, productive, and totally α-regioselective manner, circumventing the need for an ionic medium or hydrogen bond donor salt. In particular, aryl chlorides with diverse properties have been demonstrated to be viable substrates for the first time. Significantly, it appears that ethylene glycol facilitates both the oxidative addition of ArCl to Pd(0) and the subsequent dissociation of chloride from Pd(II). A closely related reaction, acylation of aryl halides with aldehydes, was also developed. Proceeding via the intermediacy of an electron-rich enamine, this Pd-pyrrolidine cooperative catalysis affords alkyl aryl ketones in a straightforward manner, extending the Heck reaction from olefins to aldehydes. SN - 1520-4898 UR - https://www.unboundmedicine.com/medline/citation/21612205/From_α_arylation_of_olefins_to_acylation_with_aldehydes:_a_journey_in_regiocontrol_of_the_Heck_reaction_ L2 - https://dx.doi.org/10.1021/ar200053d DB - PRIME DP - Unbound Medicine ER -