Metathesis polymer-bound catalysts

Highly Efficient and Recyclable Polymer-Bound Catalyst for Olefin Metathesis Reactions, S. Randl, N. Buschmann, S.J. Connon, et at, Synlett 2001, 1547-1550. 

Metathesis reactions utilizing 70 [58] The substrate was dissolved in CH2CI2 and 5 mol% of polymer-bound catalyst 70 was added. The suspension was heated at 45 °C for 12-18 h. The product was obtained as a colorless oil or solid after filtration and concentration. 

Metathesis reactions have been known for many years and can be carried out using both homogeneous and heterogeneous341 catalysts. Although other catalysts have been used, 42 ruthenium complexes s j ve been the most common. With the development of the Grubbs catalyst (428) the reaction has taken on increa-ed synthetic utility. The Grubbs catalyst is also stable to Lewis acidic conditions.Catalysts have been developed that allow the reaction to take place in aqueous and alcohol solution and polymer-bound catalysts have been used.346... 

Chemistry on solid support has gained tremendous importance during the last few years, mainly driven by the needs of the pharmaceutical sciences. Due to the robust and tolerable nature of the available catalysts, metathesis was soon recognized as a useful technique in this context. Three conceptually different, RCM-based strategies are outlined in Fig. 11. In the approach delineated in Fig. 1 la, a polymer-bound diene 353 is subjected to RCM. The desired product 354 is formed with concomitant traceless release from the resin. This strategy is very favorable, since only compounds with the correct functionality will be liberated, while unwanted by-products remain attached to the polymer. However, as the catalyst is captured in this process by the matrix (355), a higher catalyst loading will be required, or ancillary alkenes have to be added to liberate the catalyst. 

The first published report on the use of this catalyst for the cross-metathesis of functionalised acyclic alkenes was by Blechert and co-workers towards the end of 1996 [37]. This report was also noteworthy for its use of polymer-bound alkenes in the cross-metathesis reaction. Tritylpolystyrene-bound AT-Boc N-al-lylglycinol 18 was successfully cross-metathesised with both unfunctionalised alkenes and unsaturated esters (Eq. 17) (Table 1). 

Only recently a selective crossed metathesis between terminal alkenes and terminal alkynes has been described using the same catalyst.6 Allyltrimethylsilane proved to be a suitable alkene component for this reaction. Therefore, the concept of immobilizing terminal olefins onto polymer-supported allylsilane was extended to the binding of terminal alkynes. A series of structurally diverse terminal alkynes was reacted with 1 in the presence of catalytic amounts of Ru.7 The resulting polymer-bound dienes 3 are subject to protodesilylation (1.5% TFA) via a conjugate mechanism resulting in the formation of products of type 6 (Table 13.3). Mixtures of E- and Z-isomers (E/Z = 8 1 -1 1) are formed. The identity of the dominating E-isomer was established by NOE analysis. 

A Soluble Polymer-Bound Ruthenium Carbene Complex A Robust and Reusable Catalyst for Ring-Qosing Olefin Metathesis, Q. Yao, Angew. Chem. 2000,... 

A chiral polymer-bound metathesis catalyst has been developed. The supported chiral complex 75d shows appreciable levels of reactivity and excellent enantios-electivity. " This complex 75d can be recycled and easily removed from unpurified mixtures. In the first and second cycles of the recycle experiment, almost the same reactivity has been shown. In the third cycle, high enantioselection and conversion are still obtained, but catalyst activity is notably diminished ... 

The alternative strategy for heterogenization has been pursued by Blechert and co-workers, for a polymer-supported olefin metathesis catalyst. A polymer-anchored carbene precursor was prepared by coupling an alkoxide to a cross-linked polystyrene Merrifield-type resin. Subsequently, the desired polymer-bound carbene complex was formed by thermolytically induced elimination of ferf-butanol while heating the precursor resin in the presence of the desired transition metal fragment (Scheme 8.30). 

Cleavage of polymer-bound allyl esters with palladium catalysts provides general access to 7i-allyl complexes, which can react with a variety of nucleophiles. This has been used in the development of re-allyl-based linkers. Ene-yne cross metathesis and subsequent cleavage in the presence of different nucleophiles yields the corresponding functionalized dienes 93 [93] (Scheme 6.1.19). 

Ahmed and coworkers have developed analogues of 2 and 4 immobilised on PS via the alkylidene moiety. Catalysts 77 [ 124] and 78 [ 125] promoted efficient RCM they could also be recovered (by simple filtration) and recycled several times. Jafarpour and coworkers [ 126] later prepared less-polymer-swelling-dependent analogues 79-81 bound to macroporous PS. We have developed the permanently immobilised catalyst 82, which was the first polymer-supported catalyst reported to be active across a range of metathesis reactions such as RCM, enyne CM and RRM [ 127]. Catalysts which incorporate readily modified... 

Ligand 29 (Table 15.1, entry 9) was also nsed in intramolecular Mizoroki-Heck reactions [72]. In combination with Pd(OAc)2, it catalysed a cascade ring-closing metathesis (RCM)/Mizoroki-Heck reaction. The RCM step was conducted at room temperature on (bromo or iodo) iV-alkenyl-A-allyl-2-halo-benzenesnlfonamides and the Mizoroki-Heck reaction was run at 110°C for 16 h in a perflnorons solvent system. The overall yield with fluorous conditions (0-67%) was significantly lower than a reference system with polymer-bound palladinm catalyst (58-80%). 

C.iii.b. Functionalization During Cleavage. The cleavage of polymer-bound allyl esters with palladiiim catalysts provides a general access to rr-allyl complexes, which in turn may react with various nucleophiles. Schiirer and Blechert used an ene-yne ctoss metathesis and a subsequent cleavage in the presence of various nucleophiles to yield corresponding functionalized dienes (Scheme 43). ... 

Recently, olefin metathesis has attracted much attention as a versatile carbon-carbon bond-forming reaction. In addition to methods using polymer-bound substrates, which are covered in this section, there are numerous examples of metathesis where the catalyst is immobilized on a solid support with a recent review published on this subject [37]. 

This chapter is divided into six subsections which cover the most prominent applications of the metathesis reaction in solid-phase organic chemistry RCM for cleavages from the resin synthesis of small rings to macrocycles on the resin via RCM the use of the metathesis reaction for dimerization of polymer-bound small molecules RCM to constrict peptide conformations (while this is formally an RCM, it is treated separately because of the unique considerations of peptide chemistry) CM between a polymer-bound alkene and an alkene in solution and ene-yne metathesis. As the field evolved relatively rapidly with major advances in the catalysts, each subsection is organized in chronological order for the sake of clarity. 

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