The copper complex Tp (CF3)2,Br Cu(NCMe) (1, Tp (CF3)2,Br = hydrotris((3,5-bis(trifluoromethyl)-4-bromo)-pyrazol-1-yl)borate) catalyzes the insertion of the CHCO 2 Et group (from ethyl diazoacetate N 2 CHCO 2 Et, EDA) into the C-H bonds of methane, in a homogeneous process that uses supercritical carbon dioxide (scCO 2 ) as the reaction medium.Other light alkanes such as ethane, propane and butane have been also functionalized with this copper-based catalyst, in the first example of the derivatization of the series of C 1 -C 4 alkanes with this metal with a soluble catalyst.

We report quantitative measurements of the relative reactivities of a series of C-H bonds of gaseous or liquid C H alkanes (n=1-8, 29 different C-H bonds) towards in situ generated electrophiles (copper, silver, and rhodium carbenes), with methane as the reference. This strategy surpasses the drawback of previous model reactions of alkanes with strong electrophiles suffering from C-C cleavage processes, which precluded direct comparison of the relative reactivities of alkane C-H bonds.

The functionalization of the primary sites of alkanesi so ne of the more challenginga reas in catalysis. In this context, an ovel effect has been discovered that is responsible for an enhancement in the reactivity of the primary CÀHb onds of alkanes in ac atalytic system. The copperc omplex Tp (CF 3 ) 2 ,Br Cu(NCMe) (Tp (CF 3 ) 2 ,Br = hydrotris{[3,5-bis(trifluoromethyl)-4-bromo]-pyrazol-1-yl}borate) catalyzes the functionalization of C n H 2n + 2 with ethyl diazoacetate upon inserting the CHCO 2 Et unit into CÀH bonds. In addition, the selectivity of the reactiont oward the primarys ites significantly increased relative to that obtained in neat alkane upon using supercritical carbon dioxide as ther eaction medium. This was attributed to the effect of the carbon dioxide molecules that withdraw electron density from the fluorine atoms of the ligand, which enhances the electrophilic nature of the metal center. DFT studies validated this proposal.The catalytic selective functionalizationofnonactivated alkanes C n H 2n + 2 remains one of the challenges in currentc hemistry. [1, 2] In spite of decades of effort towardt hat end, very few examples (e.g.,e lectrophilic activation, [3] dehydrogenation, [4] silylation, [5] and borylation [6] )o fm etal-catalyzed transformationso f these compounds into value-added products have been described (Scheme 1). This lack of successc an be explained not only in terms of their inertness (mainly because of their poor s nucleophilicity,t heir high bond dissociation energies, [7] and their low polarity) but also in terms of the unavailability of further subsequentt ransformationst hat provide neat functionalization. Moreover,f unctionalization of the primary sites in ap referential manner is even more difficult to achieve. In fact, only the alkane borylation catalytic systemd eveloped by Hartwig and co-workers [6] could be considered as selective toward the terminal CÀHb onds of alkanes.There is af actor that is common to the examples shown in Scheme 1: the interaction of the reactingC ÀHb ond with the metal center. Actually,t his is the origin of the small number of catalytic systems for alkanef unctionalization:i nm any cases, the formation of very stable metal-carbon and/orm etal-hydride bond(s) precludest he intermediate from going further into the functionalization step. An alternative approach consists of the design of catalytic systemsi nw hich the CÀHb ond interacts with an Xl igand,v ery often as parto fa ni nsitu generated unsaturated M=Xb ond, and not with the metal center.[8] This is the basis of as eries of catalytic systems in which C n H 2n + 2 molecules have been functionalized by the neat, formal insertion of carbene, nitrene, or oxo units into their CÀHb onds (Scheme 2). Group 11 metal based catalysts have been found as efficient catalysts for those transformations, [9] particularly if they contain pyrazolylborate ligands. In an example of the potentialo ft his strategy,w ef irst described silver-based catalysts containing highly fluorinated trisindazolylborate l...

The cross‐coupling reaction of chloro‐ and bromomethyl oxime ethers with a wide range of aryl‐, heteroaryl‐ and vinylboronic acids in the presence of catalytic palladium complexes with different phosphines has been carried out with good yields (60–98%, 40 examples). Regioselective cross‐coupling reactions differentiating between an alkyl or aryl position are achieved from dihalo oxime ethers containing Csp2‐ and Csp3‐halogen bonds using mono‐ or dicoordinated palladium catalysts such as Pd(dba)2/P(o‐tolyl)3 or Pd(PPh3)4. The selective orthogonal functionalization of dihalo oxime ethers is also described. Site‐selective transformations allow the introduction of the biaryl motif into dihalo oxime ethers preserving the highly activated alkyl halide moiety vicinal to the oxime group for further transformations. In this context, Z‐ and E‐oxime ethers could be considered as synthetic equivalents of ketones in palladium‐catalyzed Suzuki reactions.magnified image

A first quantitative model for calculating the nucleophilicity of alkanes is described. A statistical treatment was applied to the analysis of the reactivity of 29 different alkane C−H bonds towards in situ generated metal carbene electrophiles. The correlation of the recently reported experimental reactivity with two different sets of descriptors comprising a total of 86 parameters was studied, resulting in the quantitative descriptor‐based alkane nucleophilicity (QDEAN) model. This model consists of an equation with only six structural/topological descriptors, and reproduces the relative reactivity of the alkane C−H bonds. This reactivity can be calculated from parameters emerging from the schematic drawing of the alkane and a simple set of sums.

The C‐C ring closure of α‐chloromethyl alkyl or aryl N‐aryl imines catalyzed with 1 to 10 % Pd(OAc)2/P(p‐tolyl)3 afford efficiently 2‐aryl‐ and 2‐alkyl‐1H‐indoles. The heterocyclization reaction involves the initial formation of [2‐(arylimino)ethyl]palladium(II) chloride complexes with subsequent C‐H activation of the aromatic amine ring. Readily or commercially available α‐chloromethyl‐aryl or ‐alkyl ketones are used as the precursors. Functionalized indoles at the benzene ring are obtained when the imines are derived from substituted anilines.

We report quantitative measurements of the relative reactivities of a series of C−H bonds of gaseous or liquid CnH2n+2 alkanes (n=1–8, 29 different C−H bonds) towards in situ generated electrophiles (copper, silver, and rhodium carbenes), with methane as the reference. This strategy surpasses the drawback of previous model reactions of alkanes with strong electrophiles suffering from C−C cleavage processes, which precluded direct comparison of the relative reactivities of alkane C−H bonds.

The three‐component reaction of α‐halomethyl oxime ethers, boronic acids and carbon monoxide at atmospheric pressure catalyzed by tetrakis(triphenylphosphine)palladium(0) gives efficiently unsymmetrical β‐alkoxyimino carbonyl compounds with total control of the regioselectivity, in high yield and atomic economy. Simple commercially available starting materials are used in this synthetic procedure. The three components assembly takes place preferentially versus the competing direct coupling or other possible side reactions. The mechanism of the transformation was investigated by NMR and intermediate palladium(II) complexes were detected.magnified image