Gold metal-catalyzed reactions of isocyanides with primary amines and oxygen: analogies with reactions of isocyanides in transition metal complexes

Despite its generally poor catalytic properties, bulk gold metal is observed to catalyze reactions of isocyanides (CN-R) with primary amines (H2N-R') and O2 to give carbodiimides (R-N=C=N-R') at room temperature and above. Detailed infrared reflection absorption spectroscopic (IRRAS) and kinetic studies show that the reaction occurs by initial eta1-adsorption of the isocyanide on the Au surface, which activates the isocyanide to attack by the amine. This attack is the rate-determining step in the catalytic cycle and has characteristics very similar to those of amine reactions with coordinated isocyanides in transition metal complexes. However, the metallic Au surface provides a pathway involving O2 to give the carbodiimide product whereas homogeneous metal ion catalysts give formamidines [HC(=NR)(NHR')].     

Base Metal Catalyzed Isocyanide Insertions

Isocyanides are diverse C₁ building blocks considering their potential to react with nucleophiles, electrophiles, and radicals. Therefore, perhaps not surprisingly, isocyanides are highly valuable as inputs for multicomponent reactions (MCRs) and other one‐pot cascade processes. In the field of organometallic chemistry, isocyanides typically serve as ligands for transition metals. The coordination of isocyanides to metal centers alters the electronic distribution of the isocyano moiety, and reaction pathways can therefore be accessed that are not possible in the absence of the metal. The tunable reactivity of the isocyanide functional group by transition metals has evolved into numerous useful applications. Especially palladium‐catalyzed isocyanide insertion processes have emerged as powerful reactions in the past decade. However, reports on the use of earth‐abundant and cheap base metals in these types of transformations are scarce and have received far less attention. In this Minireview, we focus on these emerging base metal catalyzed reactions and highlight their potential in synthetic organic chemistry. Although mechanistic studies are still scarce, we discuss distinct proposed catalytic cycles and categorize the literature according to 1) the (hetero)atom bound to and 2) the type of bonding with the transition metal in which the (formal) insertion occurs.     

Fluorinated Isocyanides—More than Ligands with Unusual Properties

The substitution of hydrogen by fluorine in organic compounds usually results in drastic changes in their properties. For isocyanides, for which fluorinated examples have only recently become available in preparative quantities, this substitution leads to a significantly increased reactivity and a tendency to polymerize, which, on one hand, makes their handling more difficult. On the other hand, this high reactivity makes the fluorinated isocyanides useful building blocks for the synthesis of compounds like N-trimethylformamide. Energetically favorable π^* orbitals bestow excellent π-acceptor properties towards low-valent transition metal complexes, especially on the ligand trifluoromethyl isocyanide. The pronounced tendency of this ligand to bridge two metal atoms enables the formation of structural types that are not accessible with other π-acceptor ligands. Thus it was possible to prepare [(Os₃(CO)₁₁(μ₂-CNCF₃)₂] (a) derivative of the hypothetical [Os(CO)₁₃]) which may be considered as a model for an associative mechanism of ligand substitution at carbonyl clusters. In contrast to the well-studied chemistry of trifluoromethyl isocyanide, that of the few other known fluorinated isocyanides is only now receiving attention. In particular the only recently synthesized trifluorovinyl isocyanide promises a rich chemistry as a result of its difunctionality.     

Phosphoramidate-mediated conversion of carbonyl ligands into isocyanide ligands: a new approach to chiral isocyanide ligands

Metal isocyanides have been used and studied by organometallic chemists for many years and, as a result, they have a rich and interesting chemistry. The nature of metal-free isocyanides and the methods of making isocyanide complexes, however, has resulted in the vast majority of studies to date being performed with structurally simple isocyanides. We report here a new approach to the synthesis of isocyanide ligands that involves the reaction of a metal carbonyl ligand with the anion of a phosphoramidate. As phosphoramidates can be synthesised in one step from amines, our method means that the structural diversity of readily available amines, particularly chiral amines, can now be incorporated into isocyanide ligands.     

Multicomponent synthesis of 2-imidazolines

[reaction: see text] A multicomponent reaction (MCR) between amines, aldehydes, and isocyanides bearing an acidic alpha-proton gives easy access to a diverse range of highly substituted 2-imidazolines. The limitations of the methodology seem to be determined by the reactivity of the isocyanide and by the steric bulk on the in situ generated imine rather than by the presence of additional functional groups on the imine. Less reactive isocyanides, for example p-nitrobenzyl isocyanide 25a, react successfully with amines and aldehydes, using a catalytic amount of silver(I) acetate. Some of the resulting p-nitrophenyl-substituted 2-imidazolines undergo air oxidation to the corresponding imidazoles. Differences in reactivity of the employed isocyanides are explained with use of DFT calculations. Difficult reactions with ketones instead of aldehydes as the oxo-compound in this MCR are promoted by silver(I) acetate as well.     

Alkenyl Isocyanide Conjugate Additions: A Rapid Route to γ‐Carbolines

Isocyanides are exceptional building blocks, the wide deployment of which in multicomponent and metal‐insertion reactions belies their limited availability. The first conjugate addition/alkylation to alkenyl isocyanides is described, which addresses this deficiency. An array of organolithiums, magnesiates, enolates, and metalated nitriles add conjugately to β‐ and β,β‐disubstituted arylsulfonyl alkenyl isocyanides to rapidly assemble diverse isocyanide scaffolds. The intermediate metalated isocyanides are efficiently trapped with electrophiles to generate substituted isocyanides incorporating contiguous tri‐ and tetra‐substituted centers. The substituted isocyanides are ideally functionalized for elaboration into synthetic targets as illustrated by the three‐step synthesis of γ‐carboline N ‐methyl ingenine B.     

The synthesis and molecular structure of a seven-coordinate rhenium isocyanide complex

Oxidative additions of Br₂ to Re(CO)L₄Br (L = CNMe, p-CNC₆H₄Me) produce the rhenium(III) isocyanide complexes ReL₄Br₃. The structure of the p-tolyl isocyanide complex was determined using single crystal X-ray diffraction techniques. In this complex rhenium is seven coordinate; there is a capped octahedral geometry about the metal with three isocyanide and three bromide ligands in fac-octahedral arrangement and the fourth isocyanide ligand situated on the face bounded by the three isocyanides. The presence of the unique isocyanide causes the three isocyanides to move part distorting the octahedral arrangement so that the average CReC angle is 115°, and the average CReBr angle is 158° instead of 180°.     

Studies on vinyl isocyanides

The vinyl Isocyanides 2,4,6-(CH₃)₃C₆H₂CHCHNC and (CH₃)₃CCHCHNC and the new 1,3-dienyl isocyanide CH₃CHCH(CH₃)-CHCHNC have been prepared from the corresponding aldehydes and methyl isocyanide using a method first developed by Schöllkopf, Stafforst, and Jentsch. ⁵ The new vinyl isocyanides (CH₃)₂CCHNC and CH₃CHC(CH₃)NC have been prepared by the Cu₂O-catalyzed isomerization of the corresponding allyl isocyanides The liquid vinyl isocyanides may be characterized by the formation of solid cis-(RNC)₂Mo(CO)₄ derivatives through reaction with norbornadienetetracarbonylmolybdenum in hexane solution at ambient temperature. Examination of these molybdenum carbonyl complexes by proton and carbon-13 NMR spectroscopy Indicates that the isocyanide carbon atom but not the carbon-carbon double bond of the vinyl 1socyanide ligands is bonded to the molybdenum atom. The proton-decoupled carbon-13 NMR spectra of the vinyl isocyanides, but not their molybdenum carbonyl complexes, indicate coupling of the isocyanide nitrogen to both the isocyanide carbon (¹J(C-N)6 Hz. ) and the vinyl carbon bearing the isocyanide group (¹J(C-N)11-13 Hz. ) leading to 1:1:1 triplets for these resonances. These vinyl carbonyl resonances are used to estimate the cis-trans isomer ratios in vinyl isocyanides of the type RCHCHNC. Such studies suggest that the formation of vinyl isocyanides by the copper(I) catalyzed isomerization of the corresponding allylic isocyanides is more nearly stereospecific than the formation of vinyl isocyanides by the elimination reaction of the Schollkopf/Stafforst/Jentsch synthetic method.     

Catalytic, enantioselective alpha-additions of isocyanides: Lewis base catalyzed Passerini-type reactions

[reaction: see text] The generality of catalytic, enantioselective alpha-additions of isocyanides to aldehydes has been demonstrated (Passerini-type reactions). The catalytic system of silicon tetrachloride and a chiral bisphosphoramide (R,R)-1b provided high yields and good to excellent enantioselectivities for the addition of tert-butyl isocyanide to a wide range of aldehydes (aromatic, heteroaromatic, olefinic, acetylenic, aliphatic). Aqueous workup afforded the alpha-hydroxy tert-butyl amides whereas a low-temperature methanol quench followed by basic workup afforded the alpha-hydroxy methyl esters. The reaction is also successful for other isocyanides, albeit with reduced enantioselectivity. Reaction conditions, particularly the rate of addition of the isocyanide was found to be crucial for good yields and high selectivities.     

Screw-sense-selective polymerization of aryl isocyanides initiated by a Pd-Pt mu-ethynediyl dinuclear complex: a novel method for the synthesis of single-handed helical poly(isocyanide)s with the block copolymerization technique

Living polymerization of chiral aryl isocyanides, such as m- and p-menthoxycarbonylphenyl isocyanides 2 and 5, initiated by the Pd-Pt mu-ethynediyl dinuclear complex 1, proceeds with a high screw-sense selectivity to give the poly(isocyanide)s 3 and 6, which exhibit a large specific rotation and an intense CD band at lambda = 364 nm as a consequence of a helical chirality. The molar optical rotation and molar circular dichroism of the resulting polymers 3 and 6 reach a constant value at a degree of polymerization (Pn) of more than 30. Screw-sense-selective polymerization of achiral aryl isocyanides that bear very bulky substituents, such as 3,5-di(propoxycarbonyl)phenyl isocyanide (11), 3,5-di(butoxycarbonyl)phenyl isocyanide (13), and 3,5-di(cyclohexyloxycarbonyl)phenyl isocyanide (15), is achieved by the use of chiral oligomer complexes 3(30) and 6(30), prepared from the reaction of 1 with 30 equivalents of 2 or 5, as an initiator to give predominantly single-handed helical polymers. In contrast, smaller aryl isocyanides are also polymerized by 3(30) and 6(30) with screw-sense selectivity in the initial stage of the reaction, but the single-handed helix is not preserved up to high molecular weight. Kinetic studies of the polymerization of (L)- and (D)-2, or (L)- and (D)-5 with chiral oligomer complexes (L)-3(50) or (L)-6(100) suggests that the screw sense of the polymer backbone is not controlled kinetically, but rather that the thermodynamically stable screw sense is produced.     

Cyanides and Isocyanides of Zinc,Cadmium and Mercury: Matrix Infrared Spectra and Electronic Structure Calculations for the Linear MNC,NCMCN, CNMNC,NCMMCN, and CNMMNC Molecules

Cadmium atoms from laser ablation react with cyanogen, NC=CN, in excess argon during co-deposition at 4 K, and even more on UV irradiation of the cold samples. Final annealing to 35 K increases bands at 2187.3 and 2089.2 cm⁻¹ at the expense of weaker bands at 2194.6 and 2092.2 cm⁻¹ through addition of another cadmium atom. Reaction products were identified by comparison with B3LYP and CCSD(T) computed frequencies and energies, through frequency differences between Zn and Cd products, and by cyanogen isotopic substitution. The CN radical, ZnNC, and CdNC were observed on sample deposition. Hg arc ultraviolet (UV) irradiation activates the insertion of Cd and Zn to form the NCCdCN, CNCdNC, NCZnCN and CNZnNC molecules. Next annealing increased the dimetal products NCCdCdCN, CNCdCdNC, NCZnZnCN, and CNZnZnNC at the expense of their single metal analogs. Laser ablated mercury amalgam also produced NCHgCN, NCHg−HgCN, CNHgNC and CNHg−HgNC. The Group12 metals form both cyanide and isocyanide products, and the argon matrix also traps the higher energy but much more intensely absorbing isocyanides. In the isocyanide case bond polarity results in very intense infrared absorptions. Group 12 metals produce shorter M−M bonds in the dimetal cyanides NCM−MCN and isocyanides CNM−MNC than in the M−M itself, and their computed M−M bond lengths compare favorably with those measured for dimetal complexes stabilized by large ring containing molecular ligands.     

Palladium‐Catalyzed Migratory Insertion of Isocyanides: An Emerging Platform in Cross‐Coupling Chemistry

Isocyanides have been important building blocks in organic synthesis since the discovery of the Ugi reaction and related isocyanide‐based multicomponent reactions. In the past decade isocyanides have found a new application as versatile C₁ building blocks in palladium catalysis. Palladium‐catalyzed reactions involving isocyanide insertion offer a vast potential for the synthesis of nitrogen‐containing fine chemicals. This Minireview discusses all the achievements in this emerging field.     

Carbon–Nitrogen Bond Cleavage by a Thorium‐NHC‐bpy Complex

Actinide complexes demonstrate unparalleled reactivity towards small molecules. However, utilizing these powerful transformations in a predictable and deliberate manner remains challenging. Therefore, developing actinide systems that not only perform noteworthy chemistry but also demonstrate controllable reactivity is a key goal. We describe a bis(NHC)borate thorium‐bpy complex ( 1 ) that is capable of reductively cleaving the R?NC bond in a series of organic isocyanides. In contrast to most actinide‐mediated bond activations, the dealkylation event mediated by 1 is remarkably general and yields very well‐defined products that assist in mechanistic elucidation. Synthesis of the rearranged but‐3‐enyl product from the reaction of 1 and cyclopropylmethyl isocyanide supports the notion of a radical‐based mechanism.     

Cyanides and isocyanides of first-row transition metals: molecular structure, bonding, and isomerization barriers

Cyanides and isocyanides of first-row transition metal M(CN) (M=Sc-Zn) are investigated with quantum chemistry techniques, providing predictions for their molecular properties. A careful analysis of the competition between cyanide and isocyanide isomers along the transition series has been carried out. In agreement with the experimental observations, late transition metals (Co-Zn) clearly prefer a cyanide arrangement. On the other hand, early transition metals (Sc-Fe), with the only exception of the Cr(CN) system, favor the isocyanide isomer. The theoretical calculations predict the following unknown isocyanides, ScNC(3Delta), TiNC(4Phi), VNC(5Delta), and MnNC(7Sigma+), and agree with the experimental observation of FeNC(6Delta) and the CrCN(6Sigma+) cyanide. First-row transition metal cyanides and isocyanides are predicted to have relatively large dissociation energies with values within the range 80-101 kcal mol(-1), except Zn(CN), which has a dissociation energy around 50-55 kcal mol(-1), and low isomerization barriers. A detailed analysis of the bonding has been carried out employing the topological analysis of the charge density and an energy decomposition analysis. The role of the covalent and electrostatic contributions to the metal-ligand bonding, as well as the importance of pi bonding, are discussed.     

Design of olfactory detection reactions based on isocyanide formation

Information is provided on the design of olfactory detection reactions based on isocyanide formation. Potential detection, warning or identification schemes can be designed by scanning a listing of reagents or classes of compounds to be detected and then tabulating the reagent combinations which will produce isocyanides.     

Determining the adsorptive and catalytic properties of strained metal surfaces using adsorption-induced stress

We demonstrate a model for determining the adsorptive and catalytic properties of strained metal surfaces based on linear elastic theory, using first-principles calculations of CO adsorption on Au and K surfaces and CO dissociation on Ru surface. The model involves a single calculation of the adsorption-induced surface stress on the unstrained metal surface, which determines quantitatively how adsorption energy changes with external strain. The model is generally applicable to both transition- and non-transition-metal surfaces, as well as to different adsorption sites on the same surface. Extending the model to both the reactant and transition state of surface reactions should allow determination of the effect of strain on surface reactivity.     

Fascinating transformations of donor-acceptor complexes of group 13 metal (Al,Ga, In) derivatives with nitriles and isonitriles: from monomeric cyanides to rings and cages

Formation of the donor-acceptor complexes of group 13 metal derivatives with nitriles and isonitriles X(3)M-D (M = Al,Ga,In; X = H,Cl,CH(3); D = RCN, RNC; R = H,CH(3)) and their subsequent reactions have been theoretically studied at the B3LYP/pVDZ level of theory. Although complexation with MX(3) stabilizes the isocyanide due to the stronger M-C donor-acceptor bond, this stabilization (20 kJ mol(-1) at most) is not sufficient to make the isocyanide form more favorable. Relationships between the dissociation enthalpy DeltaH degrees (298)(diss), charge-transfer q(CT), donor-acceptor bond energy E(DA), and the shift of the vibrational stretching mode of the CN group upon coordination Deltaomega(CN) have been examined. For a given metal center, there is a good correlation between the energy of the donor-acceptor bond and the degree of a charge transfer. Prediction of the DeltaH degrees (298)(diss) on the basis of the shift of CN stretching mode is possible within limited series of cyanide complexes (for the fixed M,R); in contrast, complexes of the isocyanides exhibit very poor Deltaomega(CN) - DeltaH degrees (298)(diss) correlation. Subsequent X ligand transfer and RX elimination reactions yielding monomeric (including donor-acceptor stabilized) and variety of oligomeric cage and ring compounds with [MN]n, [MC]n, [MNC]n cores have been considered and corresponding to thermodynamic characteristics have been obtained for the first time. Monomeric aluminum isocyanides X(2)AlNC are more stable compared to Al-C bonded isomers; for gallium and indium situation is reversed, in qualitative agreement with Pearson's HSAB concept. Substitution of X by CN in MX(3) increases the dissociation enthalpy of the MX(2)CN-NH(3) complex compared to that for MX(3)-NH(3), irrespective of the substituent X. Mechanisms of the initial reaction of the X transfer have been studied for the case X = R = H. The process of hydrogen transfer from the metal to the carbon atom in H(3)M-CNH is thermodynamically favorable and is likely to be intramolecular. By contrast, intramolecular hydrogen transfer in H(3)M-NCH has been definitely ruled out. Head-to-tail dimeric species [H(3)M-(NC)H](2) are formed exothermically and exhibit low H.H distances, which can assist in hydrogen transfer, and are likely to be the starting point for H(2) elimination. Elimination of H(2), CH(4), and C(2)H(6) from X(3)M-(NC)R adducts is very favorable thermodynamically; by contrast, elimination of HCl and CH(3)Cl is highly unfavorable even if formation of oligomer species takes place. Thus, high-temperature generation of gas-phase rings and clusters has been predicted viable in the cases X = H,CH(3) and their presence in the reactor media should not be neglected. Moderate stability of [HMCH(2)NH](4) clusters (especially in the cases M = Ga, In) makes these species viable intermediates of gas-phase reactions. Their formation may be responsible for the carbon contamination in the course of metal organic chemical vapor deposition processes of group 13 binary nitrides.     

Structural and rotational isomerism in diaminocarbene complexes of iron

Primary amines react with a variety of cationic and neutral iron isocyanide complexes to yield structural and rotational diaminocarbene isomers characterized by variable temperature ¹H and ¹³C NMR spectra. Structural isomers result from the conversion of amines to isocyanide ligands via the base-catalyzed nucleophilic attack of initially formed diaminocarbenes on $\text{cis}$ isocyanides substituents, the effect on isomer populations is often marked. Factors influencing structural and rotational isomeric preferences are discussed.     

The first catalytic,asymmetric alpha-additions of isocyanides. Lewis-base-catalyzed,enantioselective Passerini-type reactions

The first, catalytic, enantioselective alpha-additions of isocyanides to aldehydes have been demonstrated (Passerini-type reactions). The catalytic system of silicon tetrachloride and a chiral bisphosphoramide 5a provided high yields and good to excellent enantioselectivities for the addition of tert-butyl isocyanide to a wide range of aldehydes (aromatic, olefinic, acetylenic, aliphatic). Aqueous workup afforded the alpha-hydroxy tert-butyl amides, whereas methanolic quench followed by basic workup afforded the alpha-hydroxy methyl esters.     

Tandem oxidative isocyanide-based cycloaddition reactions in the presence of MIL-101(Cr) as a reusable solid catalyst

The tandem oxidative three-component synthesis of two types of the heterocycles such as furans and imidazopyridines, via isocyanides [1+4] cycloaddition reactions in the presence of MIL-101(Cr) under aerobic conditions are reported. When the 4-toluenesulfonylmethyl isocyanide was used, an unexpected [3+2] cycloaddition reaction of isocyanides with aldehydes accomplished and dihydrophenyloxazoles and phenyloxazoles produced. These syntheses were successfully carried out using a wide scope of the substrates.