Asymmetric ring opening cross metathesis

The significant potential of the ruthenium complex 65 was further underlined in the catalytic asymmetric ring-opening/cross metathesis of the cyclic alkene 70 (Scheme 44). This transformation is catalyzed by 5% mol of 65 at room temperature, in air, and with undistilled and nondegassed THF to deliver the corresponding diene 71 in 96% ee and 66% isolated yield. In standard conditions (distilled and degassed THF), the alkene 70 reacts in 75 min to give the diene in 95% ee and 76% yield, with only 0.5 mol % of catalyst. 

Asymmetric ring-opening cross-metathesis (AROCM), 26 922... 

For a review of asymmetric Mo-catalyzed metathesis, see Catalytic Asymmetric Olefin Metathesis, A. H. Hoveyda, R. R. ScHROCK, Chem. Eur. J. 2001, 7, 945-950 for reports on chiral Ru-based complexes, see (b) Enantioselective Ruthenium-Catalyzed Ring-Qosing Metathesis, T.J. Sei-DERS, D.W. Ward, R.H. Grubbs, Org. Lett. 2001, 3, 3225-3228 (c) A Recyclable Chiral Ru Catalyst for Enantioselective Olefin Metathesis. Efficient Catalytic Asymmetric Ring-Opening/Cross Metathesis In Air, J. J. Van Veldhuizen, S. B. 

J. M. Berlin, S. D. Goldberg, and R. H. Grubbs, Highly Active Chiral Ruthenium Catalysts for Asymmetric Cross- and Ring-Opening Cross-Metathesis, Angew. Chem. Int. Ed. 45, 7591-7595 (2006). 

Gillingham DG, Hoveyda AH (2007) Chiral N-Heterocyclic Carbenes in Natural Product Synthesis Application of Ru-Catalyzed Asymmetric Ring-Opening/Cross-Metathesis and Cu-Catalyzed Allylic Alkylation to Total Synthesis of Baconipyrone C. Angew Chem Int Ed 46 3860... 

Scheme 7.19 E- and Z-selective asymmetric ring-opening cross-metathesis of oxabicyclic alkenes with enol ethers and aryl olefins. From Ref [81].

Blechert et al. successfully introduced a desymmetrization approach. An asymmetric ring-opening cross metathesis of norbornenedicarboxylic anhydride was rendered possible by a Hoveyda- Blechert type ruthenium- carbene complex with a chiral N-heterocyclic carbene (NHC) ligand (Scheme 5.6). The chiral iirforma-tion of the NHC backbone was translated into ruthenium s active coordination sphere by the steric repulsion of an isopropyl group with a skewed ort/ro-biphenyl substituent [17]. 

Gillingham DG, Hoveyda AH. Chiral N-heterocyclic car-benes in natural product synthesis application of Ru-catalyzed asymmetric ring-opening/cross-metathesis and Cu-catalyzed allylic alkylation to total synthesis of baconipyrone C. Angew. Chem. Int. Ed. 2007 46(21) 3860-3864. 

A structural variant of these carbene complexes was showcased in a double asymmetric allylation reaction to give 108 (98% ee, Scheme 14.18) [100]. This synthesis also featured an enantioselective ring-opening/cross-metathesis [98, 101] (110- 111) en route to the siphonariid metabolite baconipyrone C (112) [100]. 

Takao K, Yasui H, Yamamoto S, Sasaki D, Kawasaki S, Watanabe G, Tadano K. Asymmetric total syntheses of (-l-)-mycoepoxydiene and related natural product (—)-1893A application of one-pot ring-opening/cross/ring-closing metathesis to construct their 9-oxahicyclo[4.2.1]nona-2,4-diene skeleton. J. Org. Chem. 2004 69 8789-8795. 

Alkyne cross metathesis Acyclic diene metathesis Asymmetric ring-closing metathesis Asymmetric ring-opening metathesis Cross metathesis... 

The appreciable levels of asymmetric induction observed in the catalytic ARCM reactions mentioned above suggest a high degree of enantiodifferentiation in the association of olefinic substrates and chiral complexes. This stereochemical induction may also be exploited in asymmetric ring-opening metathesis (AROM). Catalytic ROM transformations [20] offer unique and powerful methods for the preparation of complex molecules [2d, 2g]. The chiral Mo-alkyli-denes that are products of AROM reactions can be trapped either intramolecu-larly (RCM) or intermolecularly (cross metathesis, CM) to afford a range of optically enriched adducts. 

Asymmetric ring opening metathesis reactions can also be performed.67-66 In these cases, it is common for the reaction to be coupled with a cross metathesis or other reaction to avoid polymerization of the product.51 The catalysts are constantly being improved to provide higher selectivities and faster reactions. The catalyst 35 is recyclable and air-stable (Scheme 28.24).60-71... 

The molybdenum complex Mo(NAr)(CHCMe2Ph)[(3)-Me2SiBiphen] 43 was used for catalytic asymmetric olefin metathesis reactions such as desymmetrization of trienes, kinetic resolution of allylic ethers, tandem catalytic asymmetric ring-opening metathesis/cross-metathesis. Interestingly, tandem catalytic asymmetric ring-opening... 

A later report describes AROM/CM of norbomyl alkenes and styrene coupling partners to create asymmetrically functionalized cyclopentanes with alkenyl groups that can be further elaborated. High yields (>98%) of trans (>98) cross metathesis products (predominantly the desired ring-opened, A-B metathesis product) can be achieved using (97a) (equation 22). 

Hoveyda, Schrock, and coworkers [19] reported using chiral cross-linking compounds immobilized on heterogeneous polystyrene resins. The chiral moiety was then used as a ligand in asymmetric catalyses. In one application, they used the material to prepare a recyclable chiral molybdenum olefin metathesis catalyst that was used in enantioselective ring opening and ringclosing metathesis reactions. The material can be illustrated as follows ... 

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