Anilines and ethyl vinyl ether can be combined in a safe continuous-flow process to achieve efficient and mono-selective formal α-arylation of acetaldehyde. The mild non-basic reaction conditions of this method allow for high functional group tolerance. This process also provides means for a safe and scalable generation of aryldiazonium salts and enables preparation of an array of synthetically valuable monoarylated acetaldehydes.
N. Chernyak, S. L. Buchwald, J. Am. Chem. Soc., 2012, 134, 12466-12469.
The use of appropriately designed P,N-ligands proved to be the key to controlling the reactivity and selectivity in Pd-catalyzed mono-α-arylation of acetone with aryl chlorides, bromides, iodides, and tosylates. The reaction affords good yields with substrates containing a range of functional groups at modest Pd loadings using Cs2CO3 as the base and employing acetone as both a reagent and the solvent.
K. D. Hesp, R. J. Lundgren, M. Stradiotto, J. Am. Chem. Soc., 2011, 133, 5194-5197.
A palladium-catalyzed coupling of aryl halides and ester enolates produced α-aryl esters in high yields at room temperature. The reaction was highly tolerant of functionalities and substitution patterns on the aryl halide. Improved protocols for the selective monoarylation of tert-butyl acetate and the efficient arylation of α,α-disubstituted esters were developed with LiNCy2 as base and P(t-Bu)3 as ligand.
M. Jørgensen, S. Lee, X. Liu, J. P. Wolkowski, J. F. Hartwig, J. Am. Chem. Soc., 2002, 124, 12557-12565.
Palladium-catalyzed α-arylations of chloroarenes with the sodium enolates of tert-butyl propionate and methyl isobutyrate occur in high yields using P(t-Bu)3 as ligand. The reactions of chloroarenes with the Reformatsky reagent of tert-butyl acetate were most challenging but occurred in high yields for chlorobenzene and electron-poor chloroarenes.
T. Hama, J. F. Hartwig, Org. Lett., 2008, 10, 1549-1552.
An easily available NHC-Pd(II)-Im complex is an efficient catalyst for the α-arylation reaction between ketones and aryl chlorides. Under the optimal conditions, all reactions proceeded smoothly to give the desired products in very good yields within hours.
Z.-K. Xiao, L.-X. Shao, Synthesis, 2012, 711-716.
An efficient monoarylation of acetate esters and aryl methyl ketones with aryl chlorides is easily accomplished under mild conditions, that tolerate a wide array of heterocyclic substrates, using recently reported palladium precatalysts.
M. R. Biscoe, S. L. Buchwald, Org. Lett., 2009, 11, 1773-1775.
The complex (IPr)Pd(acac)Cl has proven to be a highly active PdII precatalyst in Buchwald-Hartwig reactions and α-ketone arylations of a wide range of substrates including unactivated, sterically hindered, and heterocyclic aryl chlorides.
N. Marion, E. C. Ecarnot, O. Navarro, D. Amoroso, A. Bell, S. P. Nolan, J. Org. Chem., 2006, 71, 3816-3821.
β-Diketones can undergo a reaction with aryl halides in the presence of Cu(I) or Cu(II) salts in DMSO using K3PO4 • 3 H2O without ligands to form various α-aryl ketones. H2O assists the C-C activation. This simple, practical method complements classic methods for the rapid construction of C-C bonds to a carbonyl moiety.
C. He, S. Guo, L. Huang, A. Lei, J. Am. Chem. Soc., 2010, 132, 8273-8275.
An improved protocol for the Pd-catalyzed α-arylation of aldehydes with aryl halides allows the coupling of an array of substrates including challenging electron-rich aryl bromides and less reactive aryl chlorides. The utility of this method has been demonstrated in a total synthesis of (±)-sporochnol.
R. Martín, S. L. Buchwald, Org. Lett., 2008, 10, 4561-4564.
An enantioselective α-arylation of aldehydes has been accomplished using diaryliodonium salts and a combination of copper and organic catalysts. These mild catalytic conditions allow the enantioselective construction and retention of enolizable α-formyl benzylic stereocenters, a valuable synthon for the production of medicinal agents.
A. E. Allen, D. W. C. MacMillan, J. Am. Chem. Soc., 2011, 133, 4260-4263.
A catalytic asymmetric cross-coupling of α-halo carbonyl compounds with aryl metal reagents generates synthetically useful α-aryl carboxylic acid derivatives in good enantiomeric excess. The method can also be applied to enantioselective alkenylation reactions.
X. Dai, N. A. Strotman, G. C. Fu, J. Am. Chem. Soc., 2008, 130, 3302-3303.
2-aryl-1,3-dicarbonyl compounds are produced in good yields by a CuI/L-proline-catalyzed arylation of activated methylene compounds with aryl iodides and aryl bromides in DMSO at 40-50°C in the presence of Cs2CO3.
X. Xie, G. Cai, D. Ma, Org. Lett., 2005, 7, 4693-4695.
An efficient cross-coupling reaction of aryl halides and nitromethane gives arylnitromethane products, that are precursors for numerous useful synthetic products. An efficient method for their direct conversion to the corresponding oximes and aldehydes in a one-pot operation has been discovered. The process exploits inexpensive nitromethane as a carbonyl equivalent, providing a mild and convenient formylation method.
R. R. Walvoord, S. Berritt, M. C. Kozlowski, Org. Lett., 2012, 14, 4086-4089.
The use of tBuXPhos as ligand enabled palladium-catalyzed cross-coupling of aryl bromides with very acidic nitroacetates to afford 2-aryl-2-nitroacetates.
A. E. Metz, S. Berritt, S. D. Dreher, M. C. Kozlowski, Org. Lett., 2012, 14, 760-763.
A general method for the Suzuki-Miyaura and carbonyl enolate coupling of unactivated arenesulfonates was developed utilizing Pd(OAc)2 and XPhos as ligand. The catalyst system effects the coupling of various aryl, heteroaryl, and extremely hindered arylboronic acids and carbonyl enolates with different aryl tosylates, under mild conditions.
H. N. Nguyen, X. Huang, S. L. Buchwald, J. Am. Chem. Soc., 2003, 125, 11818-11819.
The reaction between aryl- or vinylboroxines with α-diazocarbonyl compounds offers an alternative approach for α-arylation and α-vinylation of carbonyl compounds. α-Arylated or α-vinylated carbonyl compounds are formed under mild conditions.
C. Peng, W. Zhang, G. Yan, J. Wang, Org. Lett., 2009, 11, 1667-1670.
Reaction of β-bromo alcohols with 0.6 equiv of Et2Zn forms a zinc complex in CH2Cl2 at room temperature, followed by 1,2-migration to give the corresponding carbonyl compounds. This mild and clean rearrangement is general for acyclic and cyclic bromohydrins, and a variety of ring-expansive and -contractive carbonyl compounds were obtained in very good yields.
L. Li, P. Cai, Q. Guo, S. Xue, J. Org. Chem., 2008, 73, 3452-3459.
The use of zinc enolates (isolated Reformatsky reagents or generated in situ from α-bromo amides or lithium enolates) instead of alkali metal enolates, greatly expands the scope of the palladium-catalyzed α-arylation of aryl bromides and vinyl bromides.
T. Hama, D. A. Culkin, J. F. Hartwig, J. Am. Chem. Soc., 2006, 128, 4976-4985.
The coupling of aryl iodides and diethyl malonate in the presence of Cs2CO3 and catalytic amounts of CuI and 2-phenylphenol gave α-aryl malonates in good to excellent yields. This mild method tolerates various functional groups.
E. J. Hennessy, S. L. Buchwald, Org. Lett., 2002, 4, 269-272.
β-Ketoesters can directly be transformed to the corresponding α-hydroxymalonic esters, tartronic esters, with molecular oxygen catalyzed by calcium iodide under visible light irradiation from a fluorescent lamp. This convenient tandem oxidation/rearrangement reduces consumption of energy, time, and solvents.
N. Kanai, H. Nakayama, N. Tada, A. Itoh, Org. Lett., 2010, 12, 1948-1951.
A one-pot procedure for the synthesis of 2-alkyl-2-arylcyanoacetates based on a Pd(OAc)2/dppf-catalyzed enolate arylation followed by in situ alkylation tolerates a diverse range of aryl and heteroaryl bromides, and provides a rapid entry to a wide range of products in very good to yield.
X. Wang, A. Guram, E. Bunel, G.-Q. Cao, J. R. Allen, M. M. Faul, J. Org. Chem., 2008, 73, 1643-1645.
A one-pot protocol for the cyanomethylation of aryl halides through a palladium-catalyzed reaction with isoxazole-4-boronic acid pinacol ester proceeds through Suzuki coupling, base-induced fragmentation, and deformylation. Under optimized conditions (PdCl2dppf, KF, DMSO/H2O, 130 °C) a broad spectrum of aryl bromides could be converted into arylacetonitriles in good yields.
J. Velcicky, A. Soicke, R. Steiner, H.-G. Schmalz, J. Am. Chem. Soc., 2011, 133, 6948-6951.
A general method for the direct α-arylation of nitriles with aryl chlorides was developed. With a catalytic system generated from palladium and a commercially available ligand, it is now possible to effect direct α-arylation using a wide variety of starting materials.
J. You, J. G. Verkade, Angew. Chem., 2003, 115, 5205-5207.
TMPZnCl·LiCl as a kinetically highly active base enables a Pd-catalyzed α-arylation of nitriles and esters under mild conditions. Remarkably, even a regioselective γ-arylation or a γ-alkenylation of α,β- or β,γ-unsaturated nitriles can be observed.
S. Duez, S. Bernhardt, J. Heppekausen, F. F. Fleming, P. Knochel, Org. Lett., 2011, 13, 1690-1693.
A palladium-catalyzed α-arylation of nitriles was developed by exploring the structure and reactivity of arylpalladium cyanoalkyl complexes. The high yields and short reaction times observed for BINAP-ligated complexes suggested that BINAP-ligated palladium catalysts might be appropriate for the arylation of nitriles. Initial results on a palladium-catalyzed process for the direct coupling of aryl bromides and primary, benzylic, and secondary nitrile anions to form α-aryl nitriles in good yields are reported.
D. A. Culkin, J. F. Hartwig, J. Am. Chem. Soc., 2002, 124, 9330-9331.
α-Cyanohydrin triflates undergo Pd-catalyzed cross-coupling with aryl and vinyl boronic acids under mild conditions. Coupling proceeds with complete inversion of configuration at the stereogenic carbon. The resultant nitrile can be easily converted into a variety of alternative functional groups of value in organic synthesis and thus a high level of molecular diversity can be achieved.
A. He, J. R. Falck, J. Am. Chem. Soc., 2010, 132, 2524-2525.
Palladium-N-heterocyclic carbene (NHC) complexes were found to be active catalysts for the arylation of various ketones with aryl chlorides, bromides, and triflates in short reaction times.
M. S. Viciu, R. F. Germaneau, S. P. Nolan., Org. Lett., 2002, 4, 4053-4056.
A convenient method has been developed for the palladium-catalyzed arylation of malononitrile in high yields with aryl bromides and chlorides, respectively. The influence of several reaction parameters such as base, ligand, solvent or temperature were investigated.
A. Schnyder, A. F. Indolese, T. Maetzke, J. Wenger, H.-U. Blaser, Synlett, 2006, 3167-3168.
An efficient, mild, and general method for the C-arylation of β-enamino esters and ketones with arynes provides a facile and direct access to various substituted aromatic β-enamino compounds in good yield.
Y. K. Ramtohul, A. Chartrand, Org. Lett., 2007, 9, 1029-1032.
An efficient α-arylation of imino amides with arylboronic acids provides an alternative approach for the synthesis of α-functionalized glycine derivatives. Different substrates were examined for this arylation reaction.
L. Zhao, X. Liao, C.-J. Li, Synlett, 2009, 2953-2956.
Cu-catalyzed asymmetric conjugate reduction of β-substituted ketones leads to enantiomerically enriched diphenylsilyl enol ethers, which are utilized in a diastereoselective Pd-catalyzed α-arylation of various aryl bromides to yield disubstituted cycloalkanones with excellent levels of enantiomeric and diastereomeric purity. The procedure can be carried out in one-pot.
J. Chae, J. Yun, S. L. Buchwald, Org. Lett., 2004, 6, 4809-4812.
A very simple method for the α-arylation of N-protected 2-piperidinones in high yield is described. Key factors are the use of ZnCl2 and Pd(dba)2 and the nature of the base.
A. de Filippis, D. G. Pardo, J. Cossy, Tetrahedron, 2004, 60, 9757-9767.
Chiral N-heterocyclic carbene (NHC) ligands having a 2,2′-bisquinoline-based C2 symmetric skeleton exhibited good enantioselectivity in palladium-catalyzed intramolecular α-arylation of amides to give 3,3-disubsituted oxindoles.
L. Liu, N. Ishida, S. Ashida, M. Murakami, Org. Lett., 2011, 13, 1666-1669.
A small library of α,β-unsaturated oxindoles was prepared by an efficient microwave-assisted one-pot sequence comprising an aromatic substitution followed by an ionic Horner-Wadsworth-Emmons olefination.
A. Teichert, K. Jantos, K. Harms, A. Studer, Org. Lett., 2004, 6, 3477-3480.
Functionalized α-tertiary and -quaternary 2-arylcycloalkanones are rapidly accessed by scandium(III) triflate-catalyzed diazoalkane-carbonyl homologations. Pairing readily available bis- and tris(oxazoline) based ligands with scandium triflate allows access to arylated medium ring carbocycles with high enantioselectivities and excellent yield.
V. L. Rendina, H. Z. Kaplan, J. S. Kingsbury, Synthesis, 2012, 686-693.