NHC Catalysts

The unique power of Hoveyda s recyclable ruthenium catalyst D in RCM with electron-deficient and sterically demanding substrates is illustrated in Honda s total synthesis of the simple marine lactone (-)-malyngolide (54), which contains a chiral quaternary carbon center (Scheme 10) [35]. Attempted RCM of diene 52 with 5 mol% of NHC catalyst C for 15 h produced the desired... 

Also the novel antifungal antibiotic (-)-PF1163B (211), isolated from Strep-tomyces sp., which features a 13-membered macrocycle incorporating both a lactone and a lactam unit, was synthesized by an RCM route (Scheme 42) [101]. While only poor results were obtained by treatment of diene 210 (containing 8% of an unidentified epimer) with catalyst A, the use of NHC catalyst C led, under the conditions outlined in the scheme, to the corresponding cyclization product in 60% yield along with 10% of a diastereomer resulting from epimer-ization in a previous step. 

The CM reaction between 2-methyl-2-butene (a gera-disubstituted olefin that served in this case also as solvent) and the allylated compound 300, possessing the bicyclo[3.3.1]nonane core of the potential Alzheimer therapeutic garsubellin A (302) [137], underlines the increased activity of the second-generation ruthenium catalysts (Scheme 58). In the presence of 10 mol% of NHC catalyst C, the prenylated compound 301 was formed after only 2 h in 88% yield. 

Various aryl-alkyl ketones and dialkyl ketones could be reduced using the Rh(III) - NHC catalyst 55 in high yields (82-96%) and with good to excellent enantioselectivities (67-98% ee) (Scheme 34). 

The hydrosilylation of alkynes has also been studied using as catalysts Pt, Rh, Ir and Ni complexes. The improvement of the regioselectivity of the catalyst and the understanding of stereoelectronic factors that control it have been major incentives for the ongoing research. From numerous studies involving non-NHC catalysts, it has been established that there is a complex dependence of the product ratio on the type of metal, the aUcyne, the metal coordination sphere, the charge (cationic versus neutral) of the catalytic complex and the reaction conditions. In the Speier s and Karstedt s systems, mixtures of the thermodynamically more stable a- and -E-isomers are observed. Bulky phosphine ligands have been used on many occasions in order to obtain selectively P-f -isomers. 

Allylic substitutions catalysed by palladium NHC complexes have been studied and the activity and selectivity of the catalysts compared to analogous Pd phosphine complexes. A simple catalytic system involves the generation of a Pd(NHC) catalyst in situ in THF, from Pdj(dba)j, imidazolium salt and Cs COj. This system showed very good activities for the substitution of the allylic acetates by the soft nucleophilic sodium dimethyl malonate (2.5 mol% Pdj(dba)3, 5 mol% IPr HCl, 0.1 equiv. C (CO ), THF, 50°C) (Scheme 2.22). Generation of the malonate nncleophile can also be carried out in situ from the dimethyhnalonate pro-nucleo-phile, in which case excess (2.1 equivalents) of Cs COj was used. The nature of the catalytic species, especially the number of IPr ligands on the metal is not clear. 

Fig. 2.20 Chiral Pd-NHC catalysts and ligands used for the asymmetric allyhc alkylation...

For a thorough review of Ru-NHC-catalysts for metathesis, see Samojlowicz C, Bieniek M, Grela K (2009) Chem Rev 109 3708-3742 for ruthenium indenylidene-complexes in cross metathesis, see Boeda F, Bantreil X, Clavier H, Nolan SP (2008) Adv Synth Catal 350 2959-2966 For Hll-types systems, see Schrodi Y, Pederson RL (2007) Aldrichimica Acta 40 45-52... 

Abstract Over the past decade significant advances have been made in the fields of polymerisation, oligomerisation and telomerisation with metal-NHC catalysts. Complexes from across the transition series, as well as lanthanide examples, have been employed as catalysts for these reactions. Recent developments in the use of metal-NHC complexes in a-olefin polymerisation and oligomerisation, CO/olefm copolymerisation, atom-transfer radical polymerisation (ATRP) and diene telomerisation are discnssed in subsequent sections. 

Scheme 5.5 1,3-Dipolar Huisgen oycloaddition catalysed by copper-NHC catalyst Table 5.2 Preparation of 1,2,3-triazoles as described in Scheme 5.5...

M-NHC catalysts in this area. Metal catalysed carbonylation also provides an alternative synthetic ronte to the prodnction of materials that traditionally reqnire highly toxic precnrsors, like phosgene. This section discnsses carbonylation of aryl hahdes, oxidative carbonylation of phenolic and amino componnds, carbonylation of aryl diazoninm ions, alcohol carbonylation, carbonylative amidation, and copolymerisation of ethylene and CO. 

Following this pnblication, the anthors tested a series of Pd-NHC complexes (33-36) for the oxidative carbonylation of amino compounds (Scheme 9.8) [44,45]. These complexes catalysed the oxidative carbonylation of amino compounds selectively to the nreas with good conversion and very high TOFs. Unlike the Cu-NHC catalyst 38-X, the palladium complexes catalysed the oxidative carbonylation of a variety of aromatic amines. For example, 35 converted d-Me-C H -NH, d-Cl-C H -NH, 2,4-Me3-C H3-NH3, 2,6-Me3-C H3-NH3, and 4-Ac-C H3-NH3 to the corresponding nreas with very high TOFs (>6000) in 1 h at 150°C, in 99%, 87%, 85%, 72%, and 60% isolated yields, respectively (Pco,o2 = 3.2/0.8 MPa). 

The ability of enzymes to achieve the selective esterification of one enantiomer of an alcohol over the other has been exploited by coupling this process with the in situ metal-catalysed racemisation of the unreactive enantiomer. Marr and co-workers have used the rhodium and iridium NHC complexes 44 and 45 to racemise the unreacted enantiomer of substrate 7 [17]. In combination with a lipase enzyme (Novozyme 435), excellent enantioselectivities were obtained in the acetylation of alcohol 7 to give the ester product 43 (Scheme 11.11). A related dynamic kinetic resolution has been reported by Corberdn and Peris [18]. hi their chemistry, the aldehyde 46 is readily racemised and the iridium NHC catalyst 35 catalyses the reversible reduction of aldehyde 46 to give an alcohol which is acylated by an enzyme to give the ester 47 in reasonable enantiomeric excess. 

Homoenolate Reactivity The ability to generate homoenolates from enals and its application to the preparation of y-butyrolactones 30, through reaction with an aldehyde or aryl trifluoromethyl ketone, was reported independently by Glorius [8], and Bode and Burstein [9] (Scheme 12.4). A sterically demanding NHC catalyst is required to promote reactivity at the d terminus and to prevent competitive benzoin dimerisation. Nair and co-workers have reported a similar spiro-y-lactone formation reaction using cyclic 1,2-diones, including cyclohexane-1,2-dione and substituted isatin derivatives [10]. 

Based on these findings, another starting point for modifications besides modifying the labile coligand is the NHC ligand itself, especially since there are many more carbenes known and accessible. One of the many possible modifications turned out to be very successful and can—based on its catalytic activity and catalyst lifetime—be considered as the third generation of NHC catalysts in olefin metathesis. The recipe for success is to use NHCs with saturated backbones, i.e., imidazolidin-2-ylidenes. ... 

The Hedrick and Waymouth groups have also studied methods for generating NHC catalysts in situ for ROP without an external base [147-150], Thermal generation occurs readily with chloroform adduct 295 and pentafluorophenyl adduct 296 [147, 149]. Both compounds perform well as polymerization catalysts although 296 is stable at room temperature unlike 295. (lmidazol-2-ylidene)... 

In 2001, Grubbs and co-workers reported the first intermolecular CM reactions for the preparation of unsaturated phosphonates. " Using the highly active NHC catalyst 5, the CM reactions of both allyl and vinyl phosphonates were... 

The remarkable chemoselectivity of ruthenium NHC catalysts to bind olefins in the presence of heteroatomic moieties makes them ideally suited for use in one-pot sequential reactions, as they are stable toward a variety of reaction conditions and reagents and, often, their presence does not impede subsequent transformations. The... 

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