In Situ Generation and Trapping of Aryllithium and Arylpotassium Species by Halogen, Sulfur, and Carbon Electrophiles

Popov, Ilya; Do, Hien‐Quang; Daugulis, Olafs

doi:10.1021/jo9015369

Cited by 64 publications

(29 citation statements)

References 32 publications

(21 reference statements)

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“…13 Consequently, deprotonative halogenation pathway should be employed. 12 As reported earlier, dioxane solvent in combination with an alkoxide base and iodine proved to be efficient for regioselective iodination of the most acidic arene C-H bond (Scheme 4). 14 The reaction conditions are applicable to the iodination of electron-poor arenes that contain several electron-withdrawing groups as well as the most acidic heterocycles such as oxazoles and thiazoles.…”

Section: Resultsmentioning

confidence: 67%

“…11,12 Both electron-rich and electron-poor arenes can be iodinated under electrophilic or deprotonative reaction conditions, respectively. 11,12 Aryl iodides can be employed as substrates in highly regioselective copper-catalyzed arylation of C-H bonds that is successful for arylation of a variety of heterocycles and electron-deficient arenes. 7b–i The combination of copper-catalyzed direct arylation reaction with an in situ iodination should allow to create a general method for oxidative cross-coupling of two arenes.…”

Section: Methods Development Considerationsmentioning

confidence: 99%

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A General Method for Copper-Catalyzed Arene Cross-Dimerization

Daugulis

2011

J. Am. Chem. Soc.

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149

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A general method for a highly regioselective, copper-catalyzed cross-coupling of two aromatic compounds by using iodine oxidant has been developed. The reactions involve an initial iodination of one arene followed by arylation of the most acidic C-H bond of the other coupling component. Cross-coupling of electron-rich arenes, electron-poor arenes, five- and six-membered heterocycles is possible in many combinations. Typically, 1/1.5 to 1/3 ratio of coupling components is used in contrast to existing methodology that often employs a large excess of one of the arenes. Common functionalities such as ester, ketone, aldehyde, ether, nitrile, nitro, and amine are well-tolerated.

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Section: Resultsmentioning

confidence: 67%

Section: Methods Development Considerationsmentioning

confidence: 99%

A General Method for Copper-Catalyzed Arene Cross-Dimerization

Daugulis

2011

J. Am. Chem. Soc.

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149

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“…Second, choice of base is important. As described earlier,7,8 t BuOLi allows for functionalization of a wide range of substrates possessing DMSO pKa’s below 35-37. Third, the oxidant has to be compatible with all other reagents.…”

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confidence: 98%

Copper-Catalyzed Cyanation of Heterocycle Carbon−Hydrogen Bonds

Daugulis

2010

Org. Lett.

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140

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A method for regioselective cyanation of heterocycles has been developed. A number of aromatic heterocycles as well as azulene can be cyanated in reasonable to good yields by using a copper cyanide catalyst and an iodine oxidant.The nitrile functional group is found in many pharmaceuticals and agrochemicals. 1,2 Sandmeyer and Rosenmund-von Braun reactions are classic methods for the synthesis of aromatic nitriles (scheme 1A). 3 However, both procedures employ a stoichiometric copper(I) cyanide reagent and prefunctionalized starting materials. Cyanation of aryl halides by employing catalytic copper or palladium is also well-known. 4 In contrast, direct cyanation through C-H bond functionalization is more attractive due to use of readily available reactants. 5 Direct cyanation can be achieved by employing an appropriate oxidant in combination with a cyanide source (scheme 1B). 6 Methods for direct cyanation of pyridines, 6b thiophenes,6c,e substituted indoles,6c,e,h pyrroles,6c,e and 2-phenylpyridines6d,f,g have been reported in the literature. However, direct transitionmetal catalyzed cyanation of acidic heterocycles such as azoles, imidazoles, and triazoles has not been described yet.6j,k We report here a method for regioselective, direct cyanation of aromatic heterocycles as well as azulene by employing copper catalysis and an iodine oxidant.Several key issues need to be addressed for achieving a general cyanation procedure. First, high regioselectivity is required for the procedure to be synthetically relevant. High regioselectivity observed in direct arylation 7 and halogenation reactions 8 (scheme 2A) is imparted by the initial deprotonation step. This protocol rules out the use of positive cyanide sources due to their incompatibility with strong bases. Consequently, simple cyanide salts such as NaCN or KCN must be employed. Second, choice of base is important. As described earlier, 7,8 tBuOLi allows for functionalization of a wide range of substrates possessing DMSO pKa's below 35-37. Third, the oxidant has to be compatible with all other reagents. It should not react with the organolithium intermediate producing byproducts that can not be converted to the * olafs@uh.edu.

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“…• reaction of α-isocyanocarboxylates with bromine, followed by DBU-mediated cyclization; [57] • treatment of 5-phenyloxazole with tBuOLi and 1,2-dibromo-1,1,2,2-tetrafluoroethane (DBFTE); [58,59] • modified Sandmayer reaction of for the corresponding aminooxazoles. [32,40] None of these methods was used for the preparation of 5alkyl-2-bromooxazoles, which remained unknown in the literature so far.…”

Section: Introductionmentioning

confidence: 99%

Widely Exploited, Yet Unreported: Regiocontrolled Synthesis and the Suzuki–Miyaura Reactions of Bromooxazole Building Blocks

et al. 2019

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An approach to synthesis of 2‐, 4‐, and 5‐bromooxazoles is described. The method was optimized, and its scope was extended to all three isomeric parents, as well as various alkyl‐ and aryl‐substituted bromooxazoles. It was found that direct regiocontrolled lithiation followed by reaction with electrophilic bromine source was common for all substrates and led exclusively to the target substituted 2‐, 4‐ and 5‐bromooxazoles on multigram scale. The utility of the multipurpose building blocks obtained in this work was demonstrated in the Suzuki–Miyaura cross‐coupling reaction under parallel synthesis conditions.

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In Situ Generation and Trapping of Aryllithium and Arylpotassium Species by Halogen, Sulfur, and Carbon Electrophiles

Cited by 64 publications

References 32 publications

A General Method for Copper-Catalyzed Arene Cross-Dimerization

A General Method for Copper-Catalyzed Arene Cross-Dimerization

Copper-Catalyzed Cyanation of Heterocycle Carbon−Hydrogen Bonds

Widely Exploited, Yet Unreported: Regiocontrolled Synthesis and the Suzuki–Miyaura Reactions of Bromooxazole Building Blocks

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