Imidazolidine catalysts

Seven-membered lactones can also be prepared in good yields by ruthenium-catalysed cyclocarbonylation of alkenyl alcohols (e.g. 119 from 118) [01TL5459] or by ring closing metathesis using Grubbs imidazolidine catalyst (e.g. 121 from 120, n=2) [02H85]. 

Inspired by the proline-catalyzed Robinson annulation pioneered by Wiechert, Hajos, Parrish and coworkers [39], they were able to construct cyclohexanones of type 2-107 with up to four stereogenic centers with excellent enantio- and di-astereoselectivity from unsaturated ketones 2-104 and acyclic ( i-ketoesters 2-105 in the presence of 10 mol% phenylalanine-derived imidazolidine catalyst 2-106. The final products can easily be converted into useful cyclohexanediols, as well as y- and E-lactones. 

After the preliminary studies on the reaction, a wide variety of efficient chiral organocatalysts has been developed by dilferent groups for the Michael addition of nitroalkanes to enones. For instance, Jprgensen s group has reported that imidazolidine catalyst 106 (Scheme 2.54), easily prepared from phenylalanine, promotes the conjugate addition of acyclic- and cyclic nitroalkanes with a wide variety of acyclic... 

A highly enantioselective organocatalytic Michael addition of 4-hydroxycouma-rines and related compounds to a,p-unsaturated ketones has been also achieved using imidazolidine catalyst 137 [213]. The reaction, which gives high yields and enantioselectivities for a wide range of cyclic 1,3-dicarbonyl compounds and enones, has been successfully employed for the asymmetric synthesis of the anticoagulant warfarin (Scheme 2.78) and derivatives [213], With respect to the reaction mechanism, very recent studies have demonstrated that the truly active catalyst in the process was the chiral diamine 138, which is formed in catalytic amounts under the reaction conditions by reaction with the hydroxycoumarine (Schane 2.79)... 

Finally, an enamine-catalyzed asymmetric a-chlorination of ketones was reported by J0rgensen (Scheme 13.23) [51]. Using a Ca-symmetric imidazolidine catalyst, both cyclic and acyclic symmetric ketones were amenable to this transformation. 

J0rgensen and co-workers [67] have also reported the a-bromination of three cyclic ketone substrates (Scheme 13.33). This reaction employed the same C2-symmetric imidazolidine catalyst developed by J0rgensen for the a-chlorination of ketones (Scheme 13.23), and the same bromine source used in the a-bromination of aldehydes (Scheme 13.31). 

Halland N, Hazell RG, Jorgensen KA (2002) Oiganocatalytic asymmetric conjugate addition of nitroalkanes to alpha, beta-imsaturated enones using novel imidazolidine catalysts. J Oig Chem 67 8331 8338. doi 10.1021/jo0261449... 

BOTH (Enantioselective Organocatalytic Transfer Hydrogenation) The group led by MacMillan showed that the combination of an imidazolidine catalyst 3 and a Hantzsch ester 4a is a powerful and versatile reducing agent (Scheme 32.2). They were able to selectively reduce 1,4-unsaturated enals and enones with yields up to 95% and ees up to 97%. 

The synthesis of these complexes can easily be accomplished by substitution of one or both PCy3 groups of 3 by NHC ligands. The X-ray structure of 6 shows significantly different bond lengths the Schrock double bond to the CHPh group is 1.821(3) A, while the NHC bond to the l,3-diisopropylimidazolin-2-ylidene is 2.107(3) A. Complexes with imidazolidin-2-ylidenes were also synthesized and screened in an extensive study by Fiirstner [153], who found that the performance of those catalysts depends strongly on the application and that... 

These results suggest that imidazolidin- and imidazol-based skeletons transfer similar amounts of electron density to the metal. The conclusion that changes in the bridge of the NHC skeleton have such a small effect on the electronic properties of the NHC is quite surprising, considering that SIMes- and IMes-based catalysts often show remarkably different catalytic behaviour. It is still unclear if these small changes in the electronic properties of the NHC ligand confer such different catalytic behaviours, or other effects (steric, flexibility, etc.) should be invoked. 

Fig. 2.22 Combination of chiral imidazolidin-2-ylidenes and biphenyl linkers in the chiral catalysts or catalyst precursors for the asymmetric allylic alkylations...

In the course of studying a large nnmber of examples where the side chains of the imidazol- and imidazolidin-2-ylidene were altered, several research groups found that NHCs bearing exclnsively alkyl side chains did not provide catalysts with better characteristics when compared to SIMes- and DVIes-derived systems 14 and 15. While Herrmann and co-workers showed that an unsaturated NHC bearing cyclohexyl wing tips conld be incorporated into a second-generation catalyst that was active in metathesis [20-23], more recent studies showed that similar complexes were either very difficult to prepare or were unstable and showed dramatically decreased catalytic properties [24-26] (complexes 17-19, Fig. 3.4). 

In 2001, Furstner reported the preparation and characterisation of the NHC-Ru complex 22 containing iV,iV -bis[2,6-(diisopropyl)phenyl]imidazolidin-2-ylidene (SIPr) [29] (Fig. 3.6), which is the congener of complex 20. Subsequently, Mol and co-workers revealed that complex 22 was a highly active metathesis initiator [30]. More recent comparative studies showed that catalyst 22 could catalyse the RCM of 1 faster than any other NHC-Ru catalyst, while it was not stable enough to obtain complete conversion in the RCM of 3 and was inefficient for the construction of the tetrasubstituted double bond of cyclic olefin 6 [31]. 

Carbene ligands can replace phosphines dne to similar electronic properties. The development of NHC design concepts featnring different substituents and backbones eventually culminated in the most prominent derivative, the SIMes (SDVtes = A, A -bis[2,4,6-(trimethyl)phenyl]imidazolidin-2-ylidene) ligand that is nsed in the second and later also third generation catalysts (complexes 72, 73, 74b and 74c in Fig. 3.28) [105, 109, 114,116],... 

The BS2 catalyst was more selective toward the formation of the dialkylated product than the Pd catalysts tested. The activity of BS2 for DAE-MIBK reaction was slower than that with acetone due to steric effects posed by the larger ketone. Here again, the imine tends to rapidly cychze to form imidazolidines or pyrimidines. Figure 17.2 shows the stepwise formation of various side products observed during the reductive alkylation of DAE with acetone. 

The current work indicates that sulfided platinum catalysts are, in general, more active and selective than Pt, Pd, or sulfided Pd catalysts for reductive alkylation of primary amines with ketones. The choice of the catalyst preparation parameters, especially the support, plays a major role in determining the performance of the catalyst. Diamines, especially of lower molecular weight, tend to react with ketones even at room temperature to form heterocycles such as imidazolidine, diazepanes, and pyrimidines. Hence, a continuous reactor configuration that minimizes the contact between the amine and the ketone, along with a highly active catalyst is desired to obtain the dialkylated product. In general, sulfided Pt appears to be more suited for the reductive alkylation of ethylenediamine while unsulfided Pd or Pt may also be used if 1,3-diaminopropane is the amine. 

Imino derivatives 61 were obtained directly from 3-formylchromone [36] 59 and creatinine [37] 60, with DM SO as solvent and boric acid as catalyst, and with micro-wave irradiation and classical heating (Tab. 8.4). The authors have also investigated the preparation of the 2-thioxo-5-imidazolidin-4-ones 63 from thiohydantoin 62 in... 

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. ... 

Ruthenium(n) systems containing imidazol-2-ylidene or imidazolidin-2-ylidene have been used to catalyze the synthesis of 2,3-dimethylfuran starting at (Z)-3-methylpent-2-en-4-yn-l-ol [Eq. (54)]. The activity of the catalyst strongly depends on the nature of the NHC ligand. Benzimidazolin-2-ylidenes give the best results for this transformation. Similar systems have also been used for olefin metathesis reactions. ... 

Acyclic ureas have been obtained in moderate yield (up to 66%, after 20 h) by the thermal decomposition of carbamate salts (RNH3)02CNHR at high temperature (453 K), without the use of a catalyst [127a, b]. At high temperatures and pressures, diamines can also react with C02, in the absence of a catalyst, to afford cyclic ureas (imidazolidin-2-ones, tetrahydro-pyrimidin-2-ones) in moderate to good yield and selectivity [69c, 127c]. 

Literature reports on iron-catalyzed alkene diamination are scarce. Li et al. described the synthesis of imidazolidine derivatives with an FeCl3-PPh3 complex. As substrates, a, 3-unsaturated ketones and a,P-unsaturated esters were used. The products were obtained in good to high yields and with excellent stereoselectivity (Scheme 3.18). Interestingly, the iron catalyst system worked much better than a previously described rhodium catalyst. Furthermore, the iron catalyst is inexpensive and easier to handle because it is less hygroscopic [104],... 

There have been investigations of the reaction of cyclic thioureas with unsaturated carbonyls. For example, interactions involving imidazolidine-2-thione 64 (n = 1) or tetrahydropyrimidine-2-thione 64 (n = 2) with ketones 65 (k = 1-3) in the presence of the catalyst boron trifluoroetherate yielded only one stereoisomer 66 according to Perjesi et al. [70] (Scheme 3.20). 

The Michael addition of nitroalkanes to a,f -unsaturated enones, catalysed by the novel chiral imidazolidine-2-yltetrazole (151), has been investigated. The new, more soluble organocatalyst decreases reaction times and improves enantioselectivities com- pared with other catalysts. The Michael addition adducts were obtained with up to 92% ee.179... 

Park, J., Sreekanth, P., and Kim, B. (2004) Recycling chiral imidazolidin-4-one catalyst for asymmetric Diels-Alder reactions ... 

Imidazoline-2-thiones and imidazolidine-2-thiones react with 1,2-dibromoethane in the presence of aqueous sodium hydroxide and a charge transfer catalyst (CTC), or with a-cyanobenzyl benzenesulfonate, to give the corresponding imidazo[3,l-f>]thiazoles (equation 10) (80JHC393, 61JOC2715). In an analogous reaction, the condensation of 5,5-diphenyl-2-thiohydantoin with ethylene dibromide yielded two isomeric products, (99 major) and (100 minor) (8lJCS(P2)789). 

Benaglia M, Celentano G, Cinquini M, Cozzi F, Puglisi A (2002) Poly(ethylene glycol)-supported chiral imidazolidin-4-one an efficient organic catalyst for the enantioselective diels-alder cycloaddition. Adv Synth Catal 344 149-152... 

The unsaturated sultones 82 were also formed from 81 (prepared in turn by esterification of the alcohol 80 with the sulfonyl chloride 79) using Grubbs imidazolidine — based ruthenium catalyst <03SL667>. 

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