- Combined Photoredox/Enzymatic C?H Benzylic Hydroxylations
-
Chemical transformations that install heteroatoms into C?H bonds are of significant interest because they streamline the construction of value-added small molecules. Direct C?H oxyfunctionalization, or the one step conversion of a C?H bond to a C?O bond, could be a highly enabling transformation due to the prevalence of the resulting enantioenriched alcohols in pharmaceuticals and natural products,. Here we report a single-flask photoredox/enzymatic process for direct C?H hydroxylation that proceeds with broad reactivity, chemoselectivity and enantioselectivity. This unified strategy advances general photoredox and enzymatic catalysis synergy and enables chemoenzymatic processes for powerful and selective oxidative transformations.
- Betori, Rick C.,May, Catherine M.,Scheidt, Karl A.
-
supporting information
p. 16490 - 16494
(2019/11/03)
-
- Construction of Di(hetero)arylmethanes Through Pd-Catalyzed Direct Dehydroxylative Cross-Coupling of Benzylic Alcohols and Aryl Boronic Acids Mediated by Sulfuryl Fluoride (SO2F2)
-
A practical Pd-catalyzed direct dehydroxylative coupling of (hetero)benzylic alcohols with (hetero)arylboronic acids for the constructions of di(hetero)arylmethane derivatives under SO2F2 was described. This new method provided a strategically distinct approach to di(hetero)arylmethane derivatives from readily available and abundant benzylic alcohols under mild condition.
- Zhao, Chuang,Zha, Gao-Feng,Fang, Wan-Yin,Rakesh,Qin, Hua-Li
-
p. 1801 - 1807
(2019/02/07)
-
- Nickel-catalyzed cross-coupling of aldehydes with aryl halides: Via hydrazone intermediates
-
Traditional cross-couplings require stoichiometric organometallic reagents. A novel nickel-catalyzed cross-coupling reaction between aldehydes and aryl halides via hydrazone intermediates has been developed, merging the Wolff-Kishner reduction and the classical cross-coupling reactions. Aromatic aldehydes, aryl iodides and aryl bromides are especially effective in this new cross-coupling chemistry.
- Tang, Jianting,Lv, Leiyang,Dai, Xi-Jie,Li, Chen-Chen,Li, Lu,Li, Chao-Jun
-
p. 1750 - 1753
(2018/02/21)
-
- Cross-Coupling of Phenol Derivatives with Umpolung Aldehydes Catalyzed by Nickel
-
A nickel-catalyzed cross-coupling to construct the C(sp2)-C(sp3) bond was developed from two sustainable biomass-based feedstocks: phenol derivatives with umpolung aldehydes. This strategy features the in situ generation of moisture/air-stable hydrazones from naturally abundant aldehydes, which act as alkyl nucleophiles under catalysis to couple with readily available phenol derivatives. The avoidance of using both halides as the electrophiles and organometallic or organoboron reagents (also derived from halides) as the nucleophiles makes this method more sustainable. Water tolerance, great functional group (ketone, ester, free amine, amide, etc.) compatibility, and late-stage elaboration of complex biological molecules exemplified its practicability and unique chemoselectivity over organometallic reagents.
- Lv, Leiyang,Zhu, Dianhu,Tang, Jianting,Qiu, Zihang,Li, Chen-Chen,Gao, Jian,Li, Chao-Jun
-
p. 4622 - 4627
(2018/05/22)
-
- Bisulfate Salt-Catalyzed Friedel-Crafts Benzylation of Arenes with Benzylic Alcohols
-
We report here a method of direct Friedel-Crafts benzylation of arenes with benzylic alcohols using cheap and readily available bisulfate salt as the catalyst in hexafluoroisopropanol. The catalytic system is powerful with a quite diverse group of functionalized arenes and benzylic alcohols. These mild conditions provide a straightforward synthesis of a variety of unsymmetrical diarylmethanes in high yield with good to high regioselectivity. An SN1 mechanism involving activation of the hydroxy group through a hydrogen bond is proposed.
- Tang, Ren-Jin,Milcent, Thierry,Crousse, Benoit
-
p. 14001 - 14009
(2018/11/23)
-
- Synthesis of zwitterionic palladium complexes and their application as catalysts in cross-coupling reactions of aryl, heteroaryl and benzyl bromides with organoboron reagents in neat water
-
N-(3-Chloro-2-quinoxalinyl)-N′-arylimidazolium salts (aryl = 2,6-diisopropylphenyl [HL1Cl]Cl, aryl = mesityl [HL2Cl]Cl) have been synthesized by treating 2,3-dichloroquinoxaline with the corresponding N′-arylimidazole in neat water. Facile reactions of these imidazolium salts with Pd(PPh3)4 and Pd2(dba)3/PPh3 (dba = dibenzyledene acetone) at 50 °C have afforded zwitterionic palladium(ii) complexes [Pd(HL1)(PPh3)Cl2] (I) and [Pd(HL2)(PPh3)Cl2] (II) in excellent yields. I and II have been tested for their ability to catalyze Suzuki-Miyaura cross coupling (SMC) reactions in neat water/K2CO3 and are found to be highly active for carrying out these reactions between aryl bromides and organoboron reagents. Furthermore, the scope of the catalyst I was also examined by employing (hetero)aryl bromides, hydrophilic aryl bromides, benzyl bromides and various organoboron reagents. More than 80 aryl/benzyl bromide-arylboronic acid combinations were screened in neat water/K2CO3 and it was found that I was a versatile catalyst, which produced biaryls/diarylmethanes in excellent yields. A TON of 82 000 was achieved by using I. Studies on the mechanism have also been carried out to investigate the involvement of carbene complexes in the catalytic path. Poison tests and a two-phase test were also conducted and the results are reported.
- Ramakrishna,Dastagiri Reddy
-
p. 8598 - 8610
(2017/07/12)
-
- Cobalt-Catalyzed Reductive Cross-Coupling Between Benzyl Chlorides and Aryl Halides
-
A new protocol for the direct reductive cobalt-catalyzed arylation of benzyl chlorides has been developed in order to form functionalized diarylmethanes. A variety of reactive groups either on the aryl or the benzyl halide was employed. This represents the first cobalt-catalyzed reductive cross-coupling which does not require any ligand and pyridine. A reaction pathway is proposed involving a radical benzyl species. (Figure presented.).
- Pal, Suman,Chowdhury, Sushobhan,Rozwadowski, Elodie,Auffrant, Audrey,Gosmini, Corinne
-
supporting information
p. 2431 - 2435
(2016/08/16)
-
- N-Heterocyclic carbene-palladium(II)-1-methylimidazole complex-catalyzed Suzuki-Miyaura coupling of benzyl carbamates with arylboronic acids
-
The Suzuki-Miyaura coupling of benzyl carbamates with arylboronic acids was achieved in an environmentally benign medium. Using water as the sole solvent, such transformation took place very well to give the desired diarylmethane derivatives in good to almost quantitative yields in the presence of a well-defined NHC-Pd(ii)-Im complex under mild conditions. It is worth noting here that this is the first example of benzyl carbamates used in coupling reaction, thus affording a new method for the formation of diarylmethanes by palladium-catalyzed C-O bond activation.
- Wang, Xiao-Xia,Luo, Mao-Jun,Lu, Jian-Mei
-
p. 11438 - 11444
(2015/12/04)
-
- Ethers as hydrogen sources in BF3·OEt2 promoted reduction of diphenylmethyl alcohols, ethers and esters to hydrocarbons
-
A novel ether/BF3 reductive system has been described, in which diphenylmethanols and their ether and ester derivatives are used as starting materials. Reductions are performed in ether under reflux and an argon atmosphere, and the addition of extra water is beneficial to this reduction. A series of alkanes are able to be prepared with good to excellent yields. A deuterated experiment exhibits that the reductive hydrogen is generated from ether. The mechanism is discussed in detail to explain the observed reactivity.
- Li, Jiaqiang,Liu, Qing,Shen, Hang,Huang, Ruofeng,Zhang, Xiaohui,Xiong, Yan,Chen, Changguo
-
p. 85291 - 85295
(2015/11/02)
-
- Synthesis of structurally diverse diarylketones through the diarylmethyl sp3 C-H oxidation
-
Under open-flask conditions, an efficient method to assemble a series of diversely functionalized diarylketones in the presence of commercially available NBS has been developed. Yields of up to 99% have been achieved employing diarylmethanes as starting material. Based on 18O-labeled experiment, the addition of stoichiometric water eventually leads to excellent yields in all carbonylation cases.
- He, Chao,Zhang, Xiaohui,Huang, Ruofeng,Pan, Jing,Li, Jiaqiang,Ling, Xuege,Xiong, Yan,Zhu, Xiangming
-
p. 4458 - 4462
(2014/08/05)
-
- Direct electrosynthesis of ketones from benzylic methylenes by electrooxidative C-H activation
-
Electrify your chemistry! Direct electrosynthesis of ketones from benzylic methylenes in an undivided cell was realized in moderate to good yields (see scheme). In this electrosynthesis, electrons instead of conventional oxidants and catalysts are employed to make the reaction environmentally benign. Moreover, the reaction intermediate radical was detected by ESR spectroscopy and the reaction mechanism was clarified.
- Meng, Li,Su, Jihu,Zha, Zhenggen,Zhang, Li,Zhang, Zhenlei,Wang, Zhiyong
-
p. 5542 - 5545
(2013/05/23)
-
- Nickel-catalyzed cross couplings of benzylic ammonium salts and boronic acids: Stereospecific formation of diarylethanes via C-N bond activation
-
We have developed a nickel-catalyzed cross coupling of benzylic ammonium triflates with aryl boronic acids to afford diarylmethanes and diarylethanes. This reaction proceeds under mild reaction conditions and with exceptional functional group tolerance. Further, it transforms branched benzylic ammonium salts to diarylethanes with excellent chirality transfer, offering a new strategy for the synthesis of highly enantioenriched diarylethanes from readily available chiral benzylic amines.
- Maity, Prantik,Shacklady-Mcatee, Danielle M.,Yap, Glenn P. A.,Sirianni, Eric R.,Watson, Mary P.
-
supporting information
p. 280 - 285
(2013/02/25)
-
- Benzothiazolin-2-ylidene and azole mixed-ligand complexes of palladium
-
A series of mixed-ligand, mononuclear complexes trans[PdX 2(NSHC)(azole)] [NSHC = N,S-heterocyclic carbene; azole = imidazole, l-(2,4,6-trimethylphenyl)-1H-imidazole, benzimidazole, benzothiazole and benzoxazole] have been prepared and characterised by X-ray single-crystal diffrac-tion. These complexes catalyse the sp2-sp3 cross-coupling of fluoroaryl halides with arylboronic acid to give diarylmethanes with good yields and high turnovers, Wiley-VCH Verlag GmbH & Co. KGaA.
- Yen, Swee Kuan,Koh, Lip Lin,Huynh, Han Vinh,Hor, T. S. Andy
-
experimental part
p. 4288 - 4297
(2010/01/31)
-
- Fluorination of fluorene, dibenzofuran and their open analogues with caesium fluoroxysulfate and related fluorinating reagents
-
Fluorination of fluorene (1) with caesium fluoroxysulfate (CFS), 2,6-dichloro-l-fluoropyridinium tetrafluoroborate (FP-B800) and 1-fluoro-4-hydroxy-1,4-diazoniabicyclo[2.2.2]-octane bis(tetrafluoroborate) (Accufluor NFTh) occurred only on the aromatic ring in the position ortho and para to the biphenyl central bond with the ratio 2-fluoro- (2a) vs 4-fluorofluorene (2b) 1.7-2.4:1. Regioselectivity of fluorination of both open-chain analogues - diphenylmethane (3a) and biphenyl (3b) was different and more ortho-fluorinated product was formed. Furthermore, the reaction of diphenylmethane (3a) with CFS occurred also on central carbon forming benzophenone (6) and fluorodiphenylmethane (7), while fluorination with FP-B800 and Accufluor NFTh occurred only at the aromatic ring. Similar effect of the structure of fluorinating reagent on the regioselectivity was also observed with dibenzofuran (8) and its open-chain analogues diphenyl ether (10) and biphenyl (3b), where the regioselectivity of fluorination with CFS (1- (9a):2- (9b):3- (9c) = 27:46:27) was similar to fluorination with Selectfluor. Product distribution of fluorination of fluorene (1) and dibenzofuran (8) with CFS is similar to nitration and is in accordance with the calculated HOMO electron density, which indicates the presence of the electron transfer pathway.
- Iskra, Jernej,Stavber, Stojan,Zupan, Marko
-
experimental part
p. 1671 - 1680
(2009/05/27)
-
- Rare earth(III) perfluorooctanesulfonates catalyzed Friedel-Crafts alkylation in fluorous biphase system
-
The catalyst of rare earth(III) perfluorooctanesulfonates (RE(OSO 2C8F17)3, RE = Sc, Y, La-Lu) were prepared from either rare earth chlorides(III) or oxides and perfluorooctanesulfonic acid. The perflates thus obtained act as novel catalysts for Friedel-Crafts alkylation in fluorous biphasic system. Perfluorohexane (C6F14), perfluoromethylcyclohexane (C7F 14), perfluorotoluene (C7F8), perfluorooctane (C8F18), perfluorooctyl bromide (C8F 17Br) and perfluorodecalin (C10F18, cis- and trans-mixture) can be used as fluorous solvents for this reaction. By simple separation of the fluorous phase containing only catalyst, alkylation can be repeated many times.
- Yi, Wen-Bin,Cai, Chun
-
p. 831 - 833
(2007/10/03)
-
- Suzuki cross-coupling reaction of benzylic halides with arylboronic acids in the presence of a tetraphosphine/palladium catalyst
-
The cis,cis,cis-1,2,3,4-tetrakis(diphenylphosphinomethyl) cyclopentane-[PdCl(C3H5)]2 system catalyses efficiently the Suzuki cross-coupling reaction of benzylic halides with arylboronic acids. A wide variety of benzylic bromides or chlorides and functionalised arylboronic acids lead selectively to the corresponding diarylmethane adducts in good yields. Furthermore, this catalyst can be used at low loading in many cases.
- Chahen, Ludovic,Doucet, Henri,Santelli, Maurice
-
p. 1668 - 1672
(2007/10/03)
-
- The role of geometry on regioselectivity and rate of fluorination of fluorene and diphenylmethane with selectfluor F-TEDA-BF4
-
Diphenylmethane and fluorene were used as target molecules in an investigation of the effect of the geometry of aromatic molecules on the regioselectivity and rate of fluorination with 1-chloromethyl-4-fluoro-1,4-diazonia-bicyclo[2.2.2]octane bis(tetrafluoroborate) (Selectfluor F-TEDA-BF4). In acetonitrile at 80°C ring fluorination of diphenylmethane was accompanied by oxidation of the saturated carbon atom, while in trifluoroacetic acid only ring fluorination with an ortho-para regioselectivity of 1.8:1 was observed. Fluorene was converted in acetonitrile as well as in trifluoroacetic acid into 2- and 4-fluoro substituted products in the relative ratio of 2:1 and 1.2:1, respectively. The reactions in acetonitrile obey a simple rate equation: v = d[F-TEDA]/dt=k2 × [F-TEDA] × [Substrate] and the second order rate constants for the reactions in acetonitrile at 65°C were determined; values of 0.6 × 10-4 M-1 s-1 for diphenylmethane and 35.5 × 10-4 M-1 s-1 for fluorene were obtained. The reaction rates for the various functionalisations of fluorene relative to those for diphenylmethane were found to be considerably influenced by the type of functionalisation. Relative rate factors (krel=k2(fluorene)/k2(diphenylmethane)) with values between 59 for fluorination and 712 for chlorination were determined, while the corresponding data for the biphenyl/diphenylmethane pair were only slightly dependent on the type of functionalisation. A reaction pathway involving electron transfer, thus forming cation radical intermediates, was proposed as the main process in the case of fluorination of fluorene with F-TEDA-BF4.
- Iskra, Jernej,Zupan, Marko,Stavber, Stojan
-
p. 1528 - 1531
(2007/10/03)
-
- Synthesis and comparison of N-fluorobis[(perfluoroalkyl)sulfonyl]imides with different perfluoroalkyl groups
-
N-fluorobis[(perfluoroalkyl)sulfonyl]imides, CF3SO2N(F)SO2Rf (Rf′=C4F9, C6F13, C8F17) and (C4F9SO2)2NF, were prepared by direct fluorination of corresponding N-H compounds using elemental fluorine without a solvent in good to excellent yields. All of these N-F compounds are electrophilic fluorination agents and can easily deliver F+ to certain molecules. Their reactions with aromatic rings, beta-diketones, and alkenes were investigated to compare their fluorination power.
- Zhang, Jie,Desmarteau, Darryl D.
-
p. 253 - 257
(2007/10/03)
-
- Ring-substituted histaprodifen analogues as partial agonists for histamine H1 receptors: Synthesis and structure-activity relationships
-
Thirteen racemic benzene ring-substituted analogues of histaprodifen (8a; 2-[2-(3,3-diphenylpropyl)-1H-imidazol-4-yl]ethanamine), a novel lead for potent and selective histamine H1-receptor agonists, have been prepared from substituted 4,4-diphenylbutyronitriles 5 via cyclization of the corresponding methyl butyrimidates 6 with 2-oxo-4-phthalimido-1-butyl acetate in liquid ammonia, followed by deprotection. Nitriles 5 were accessible by alkylation of either substituted diphenylmethanes with 3-bromopropionitrile or diethyl malonate with substituted 1-chloro-diphenylmethanes and subsequent standard reactions. The title compounds 8 displayed partial agonism on conctractile H1 receptors of the guinea-pig ileum (E(max) = 2-98% relative to histamine) and, compared with the endogenous agonist, were endowed with agonist potencies of 4-92%. The meta fluorinated (8c) and meta chlorinated (8f) analogues showed the highest relative potency in this series (95% confidence limits 85-99% and 78-102%), but did not exceed the value of the lead 8a (99- 124%). Compound 8c (2-[2-[3-(3-fluorophenyl)-3-phenylpropyl]-1H-imidazol-4- yl]ethanamine) was a partial agonist at contractile H1 receptors of the guinea-pig aorta (relative potency 154% vs. 100% for histamine) and at relaxation-mediating endothelial H1 receptors of the rat aorta (relative potency 556% vs. 100% for histamine) and matched with the functional behaviour of 8a. Agonism observed for each compound was sensitive to blockade by the selective H1-receptor antagonist mepyramine (pA2 ? 9 (guinea-pig) and pA2 ? 8 (rat aorta)). All histaprodifen analogues 8 stimulated neither histaminergic H2/H3 nor cholinergic M3 receptors. They displayed only low to moderate affinity for these sites (H2: pD'2 3/M3: pA2 1-receptor agonist, viz. 2- phenylhistamine. (C) 2000 Editions scientifiques et medicales Elsevier SAS.
- Elz, Sigurd,Kramer, Kai,Leschke, Christian,Schunack, Walter
-
-
- Direct Formation of (Haloaryl)copper Nucleophiles from Haloiodobenzenes and Active Copper
-
(o-Halophenyl)-, (m-halophenyl)-, and (p-halophenyl)copper reagents have been formed in moderate to high yields at room temperature from active copper and the corresponding haloiodobenzenes.These reagents have been cross-coupled with a variety of alkyl and acyl halides to produce the respective haloarenes and haloaryl ketones.Remarkably, (o-fluorophenyl)- and (o-chlorophenyl)copper are produced in good yields by this procedure without undergoing elimination to form benzyne making this approach a convenient method for generating o-halophenyl nucleophiles.
- Ebert, Greg W.,Pfennig, Deborah R.,Suchan, Scott D.,Donovan, Thomas A.,Aouad, Emmanuel,et al.
-
p. 2361 - 2364
(2007/10/02)
-
- Activation of Clayzic and its Effect on the Relative Rates of Benzylation of Aromatic Substrates
-
The effects of the activation of K10 montmorillonite supported zinc chloride ('Clayzic') by different methods on the reactivity of the catalyst in the Friedel-Crafts benzylation of benzene and halobenzenes have been investigated.There is an optimum temperature for thermal activation in air at which point a rate enhancement, compared to unactivated Clayzic, in the benzylation of benzene of greater than 30 has been achieved.The rate limiting factor for these reactions is believed to be the ability of the aromatic substrate to enter the polar mesopores containing the active zinc ions in Clayzic, causing unexpected and activation-dependent rate trends to be observed.Activation of Clayzic is believed to reduce the polar nature of the pores, so aiding partitioning of the substrate into the catalyst.
- Barlow, Simon J.,Bastock, Tony W.,Clark, James H.,Cullen, Stephen R.
-
p. 411 - 414
(2007/10/02)
-
- Remarkably stable ortho-halophenylcopper reagents
-
We wish to report the generation of remarkably stable o-halophenlycopper reagents at room temperature by the direct oxidative addition of activated copper to o-flouro-and o-choloriodobenzene. The reagents will undergo substitution reactions with suitable organic halides at 25°C.
- Ebert, Greg W.,Pfennig, Deborah R.,Suchan, Scott D.,Donovan Jr., Thomas A.
-
p. 2279 - 2282
(2007/10/02)
-
- Synthetic Methods and Reactions; 126. Trifluoromethanesulfonic Acid/Triethylsilane: A New Ionic Hydrogenation Reagent for the Reduction of Diaryl and Alkyl Aryl Ketones to Hydrocarbons
-
Benzophenones (except for 4,4'-dialkoxy- and sterically hindered derivatives), certain acetophenones, and 1-indanone can be reduced to the corresponding hydrocarbons in good yields by reaction with trifluoromethanesulfonic acid and triethylsilane.
- Olah, George A.,Arvanaghi, Massoud,Ohannesian, Lena
-
p. 770 - 772
(2007/10/02)
-