Manuel Alcarazo

Steering the Surprisingly Modular π-Acceptor Properties of N-Heterocyclic Carbenes: Implications for Gold Catalysis

Whereas the excellent s-donor qualities of N-heterocyclic carbenes (NHCs) are undisputed and extensively used as an enabling feature for homogeneous catalysis, the p-acceptor properties of such ligands are usually considered weak or even negligible. Only in the last decade has experimental and in silico 4] evidence been acquired that suggests that the p acidity of NHCs deserves more serious consideration, even though this issue is still a matter of debate. 5] The case study outlined herein may help to clarify this aspect. Rather than relying on the interpretation of spectroscopic and structural fingerprints, we present reactivity data which demonstrate that the course of three mechanistically distinct gold-catalyzed processes can be determined solely by changing the pacceptor properties of the ancillary NHC ligand. We previously introduced the cyclophanic NHCs 2–4 as novel analogues of the known imidazopyridine-2-ylidene derivatives 1 (Table 1). These chiral compounds exhibit interesting spectroscopic characteristics and are studied in some detail by our research group. As part of these investigations, the energies of the orbital occupied by the carbene lone pair of electrons (Es) [9] and of the lowest unoccupied orbital with a nonzero coefficient at the carbene center (Ep) [9] were determined by density functional theory (DFT) calculations at the BP86(RI)/TZVP level. The computed data revealed various salient features (Table 1): whereas the Es values of the parent NHC 1a (R = Me) and its cyclophanic counterpart 2 are almost identical, the Ep value drops significantly from 0.63 eV in 1a to 1.14 eV in 2 ; moreover, the energy of the p-type acceptor orbital is highly responsive to the type of substituents present on the top layer; thus, the Ep values of the tetrafluoroand tetramethoxy-substituted carbenes 3 and 4 are almost 0.5 eV apart. These findings are readily explained by the representation of the p acceptor orbital in Figure 1,

Synthesis, Structure, and Reactivity of a Dihydrido Borenium Cation†

According to the Nçth terminology, borenium cations are singly charged B-derived cationic species possessing a trigonal environment around boron. As expected on the basis of these structural features, borenium cations are very potent electrophiles. This reactivity has recently found application in the borylation of aromatic and heteroaromatic rings, which has sparked great attention owing to its synthetic potential to directly provide aryl boronate esters and other Suzuki–Miyaura coupling partners. Despite this fact, there are only few persistent compounds containing borenium cations that have been isolated. Their preparation relies on two main approaches (Scheme 1): the

Exploring the Reactivity of Carbon(0)/Borane-Based Frustrated Lewis Pairs

DOI 10.1002/anie.201002119 In a series of papers predating the current frustrated Lewis pair (FLP) terminology, the hydrosilation of carbonyl[1] and imine[2] functions as well as the silation of alcohols[3] has been achieved. Strong kinetic arguments point towards a Si H bond activation via a FLP-type mechanism in these processes. The authors would like to thank Prof. W. E. Piers for bringing this precedent to their attention.

Catalysis-Based and Protecting-Group-Free Total Syntheses of the Marine Oxylipins Hybridalactone and the Ecklonialactones A, B, and C

Concise and protecting-group-free total syntheses of the marine oxylipins hybridalactone (1) and three members of the ecklonialactone family (2-4) were developed. They deliver these targets in optically pure form in 14 or 13 steps, respectively, in the longest linear sequence; five of these steps are metal-catalyzed and four others are metal-mediated. The route to either 1 or 2-4 diverges from the common building block 22, which is accessible in 7 steps from 2[5H]furanone by recourse to a rhodium-catalyzed asymmetric 1,4-addition reaction controlled by the carvone-derived diene ligand 35 and a ring-closing alkene metathesis (RCM) catalyzed by the ruthenium indenylidene complex 17 as the key operations. Alternatively, 22 can be made in 10 steps from furfural via a diastereoselective three-component coupling process. The further elaboration of 22 into hybridalactone as the structurally most complex target with seven contiguous chiral centers was based upon a sequence of cyclopropanation followed by a vanadium-catalyzed epoxidation, both of which were directed by the same free hydroxy group at C15. The macrocyclic scaffold was annulated to the headgroup by means of a ring-closing alkyne metathesis reaction (RCAM). In response to the unusually high propensity of the oxirane of the targeted oxylipins for ring opening, this transformation had to be performed with complexes of the type [(Ar(3)SiO)(4)Mo≡CPh][K·OEt(2)] (43), which represent a new generation of exceedingly tolerant yet remarkably efficient catalysts. Their ancillary triarylsilanolate ligands temper the Lewis acidity of the molybdenum center but are not sufficiently nucleophilic to engage in the opening of the fragile epoxide ring. A final semireduction of the cycloalkyne formed in the RCAM step to the required (Z)-alkene completed the total synthesis of (-)-1. The fact that the route from the common fragment 22 to the ecklonialactones could follow a similar logic showcased the flexibility inherent to the chosen approach.

Protecting-Group-Free and Catalysis-Based Total Synthesis of the Ecklonialactones

A concise and protecting-group-free total synthesis of optically pure ecklonialactones A (1) and B (2) is described. The successful route to these oxylipins isolated from various brown algae involves five transition-metal-catalyzed transformations in the longest linear sequence of 13 steps. The first chiral center was set by a rhodium-catalyzed 1,4-addition of an alkenyl boronate to the commercial butenolide 11, which was controlled by Carreiras carvone-derived diene ligand 21. Other key steps involve a ring-closing olefin metathesis effected by the ruthenium indenylidene complex 22 for the formation of the five-membered carbocycle, a vanadium-catalyzed, hydroxy-directed epoxidation, and a ring-closing alkyne metathesis (RCAM) to forge the macrocyclic ring. Because of the unusually high propensity of the oxirane of the ecklonialactones for ring-opening, this transformation was best achieved with [(Ph(3)SiO)(3)Mo[triple bond]CPh].OEt(2) (34) as the catalyst, which is a representative of a new generation of highly tolerant yet remarkably efficient molybdenum alkylidyne complexes. The ancillary triphenylsilanolate ligands in 34 temper the Lewis acidity of the molybdenum center and are not able to nucleophilically open the fragile epoxide ring. The final reduction of the cycloalkyne formed in the RCAM step to the required (Z)-alkene was accomplished either by Lindlar reduction or with the aid of nickel boride.

Polycationic Ligands in Gold Catalysis: Synthesis and Applications of Extremely π-Acidic Catalysts

Very often ligands are anionic or neutral species. Cationic ones are rare, and, when used, the positively charged groups are normally appended to the periphery of the ligand. Here, we describe a dicationic phosphine with no spacer between the phosphorus atom and the two positively charged groups. This structural feature makes its donor ability poorer than that of phosphites and only comparable to extremely toxic or pyrophoric compounds such as PF3 or P(CF3)3. By exploiting these properties, a new Au catalyst has been developed displaying a dramatically enhanced capacity to activate π-systems. This has been used to synthesize very sterically hindered and naturally occurring 4,5-disubstituted phenanthrenes. The present approach is expected to be applicable to the development and improvement of many other transition metal catalyzed transformations that benefit from extremely strong π-acceptor ligands. The mechanism of selected catalytic transformations has been explored by density functional calculations.

Exploiting the π-acceptor properties of carbene-stabilized phosphorus centered trications [L3P]3+: applications in Pt(II) catalysis.

Reaction of tris(dimethylaminocyclopropenium) substituted phosphine 1 with K(2)PtCl(4) afforded the bench stable complex 3 which upon treatment with Ag[CB(11)H(6)Cl(6)] turned out to be an excellent catalyst for the transformation of a variety of ortho-biaryl substituted alkynes into polycyclic homo- and heteroarenes of different size, shape, and curvature through a 6-endo-dig cyclization. This constitutes the first example ever reported of using a P(1)-centered trication as ligand in catalysis. The strong π-acceptor character of 1 that derives from its three positive charges substantially increases the intrinsic π-acidity of Pt in complex 1·PtCl(2) and dramatically enhances its ability to activate π-systems toward nucleophilic attack. As a consequence, a remarkable acceleration of the model transformation is observed when compared with other classical π-acceptor ligands such as P(OPh)(3) or P(C(6)F(5))(3). Moreover, the employment of 1 as ligand also expands the scope of this reaction to previously inaccessible substitution patterns. Kinetic studies and deuterium labeling experiments as well as density functional theory (DFT) calculations were performed in order to explain these findings.

Cyclopropenylylidene-Stabilized Diaryl and Dialkyl Phosphenium Cations: Applications in Homogeneous Gold Catalysis

Phosphenium cations of the general formula [R2PD] + are isolobal with singlet carbenes and can likewise be stabilized by donation of electron density into their empty orbital. This goal is often reached either by embedding the phosphorous atom into a heterocyclic scaffold 3] as in A or by reaction with bases of a different nature to form the corresponding Lewis adducts B (Scheme 1). In both cases, the presence of

Chiral heterobimetallic complexes of carbodiphosphoranes and phosphinidene–carbene adducts

Heterobimetallic complexes derived from carbodiphosphoranes or phosphinidene-carbene adducts are reported, in which the central atom accepts two lone-pairs from two different donor ligands and - at the same time - donates two lone-pairs to two different metal centers. Therefore these complexes are carbogenic yet captodative chiral entities.

Synthesis, Structure, and Reactivity of Carbene-Stabilized Phosphorus(III)-Centered Trications [L3P]3+

Carbene-stabilized [L(3)P](+3) cations have been synthesized for the first time by a reaction between 1-chloro-2,3-bis(dialkylamino)cyclopropenium salts and P(SiMe(3))(3). In addition, the first structural characterization of such an entity is reported. Consistent with the X-ray data, density functional calculations indicate that these P-centered cations, despite their high positive charge, still feature a nonbonding electron pair on the P-atom (HOMO) and a very low-lying LUMO depicting them as poor σ-donors and excellent π-acceptors.