Enantioselective olefin metathesis

We will focus on the development of ruthenium-based metathesis precatalysts with enhanced activity and applications to the metathesis of alkenes with nonstandard electronic properties. In the class of molybdenum complexes [7a,g,h] recent research was mainly directed to the development of homochi-ral precatalysts for enantioselective olefin metathesis. This aspect has recently been covered by Schrock and Hoveyda in a short review and will not be discussed here [8h]. In addition, several important special topics have recently been addressed by excellent reviews, e.g., the synthesis of medium-sized rings by RCM [8a], applications of olefin metathesis to carbohydrate chemistry [8b], cross metathesis [8c,d],enyne metathesis [8e,f], ring-rearrangement metathesis [8g], enantioselective metathesis [8h], and applications of metathesis in polymer chemistry (ADMET,ROMP) [8i,j]. Application of olefin metathesis to the total synthesis of complex natural products is covered in the contribution by Mulzer et al. in this volume. 

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. 

Hoveyda synthesized recyclable ruthenium catalyst 104b for enantioselective olefin metathesis. This catalyst is very effective for AROM-CM and can be recovered after chromatography [Eqs. (6.74)-(6.76)]. The recovered catalyst can be reused without significant loss of enantioselectivity and with similar reactivity ... 

A collaborative effort between Schrock and Hoveyda has been extremely fruitful as evidenced by the advent of the hrst efficient enantioselective olefin metathesis... 

Schrock and Hoveyda have reported the synthesis and activity of a number of chiral molybdenum-based catalysts for enantioselective olefin metathesis (for example, 97a, b) (Scheme 14) to date, the majority of successful... 

Molybdenum-catalyzed enantioselective olefin metathesis reactions of P-stereogenic phosphinates (597) which led to formation of five-, six-, and seven-membered P-heterocycles (698) in up to 98% ee has been reported by Hoveyda and co-workers (Scheme 148). ° ... 

The molybdenum complex of 1,1 -biphenyl-2,2 -diol-based ligand (BIPHEN) possessing an axial element of chirality proved to be an efficient catalyst in various modes of enantioselective olefin metathesis (71). (The catalytic precursor is known as the Schrock-Hoveyda catalyst.)... 

The molybdenum(VI) complex with BIPHEN (Schrock-Hoveyda catalyst) has been widely used as an enantioselective olefin metathesis catalyst for a variety of substrates (145). Recently, the synthesis of a tetrahydrocannabiol derivative in molybdenum-catalyzed asymmetric allylic alkylation by using Trost-ligands is carried out. Enhanced regio-, enantio-, and diastereoselectivities relative to the palladium ones have been observed (146). 

The effects of perfluorinated solvents have also found use in enantioselective olefin metathesis (see Grubbs, Handbook of Metathesis, 2nd Edition, Volume 2, Chapter 7) [19]. The asymmetric synthesis of [7]helicene via the kinetic resolution of dienes was achieved using perfluorinated aromatic solvents [20]. Ru-based catalyst 27, bearing a C -symmetric NHC ligand, was added to the diene 28 in the presence of vinyl cyclohexane as an additive in a variety of different solvents (Scheme 12.10). When conventional solvents, such as CH2CI2 and PhH, were... 

Planar, chiral motifs have also been prepared by enantioselective olefin metathesis employing Mo-based catalysts, see Ogasawara, M., Watanabe, S., Fan, L., Nakajima, K., and Takahashi, T. (2006) Organometallics, 25, 5201-5203. 

In the past few years the groups of Schrock at MIT and Hoveyda at Boston College introduced a new type of Mo-alkylidene MonoAryloxide Pyrrolide (MAP) complexes as highly reactive and enantioselective olefin metathesis catalysts [56,57]. These stereogenic-at-metal complexes supported by non-chelating ligands turned out to be fascinating catalysts forZ-selective olefin metathesis reactions with the level of Z-selectivities that was completely out of reach before. 

Ru-catalyzed AROM/CM sequences served as a key step in the total synthesis of baconipyrone C (163, Scheme 24.42), a marine polyketide isolated from Siphonaria baconi The employed Ru carbene [Ru]-VI is generated in situ by treatment of the achiral Ru-PCya complex with Ag-based V-heterocyclic carbene (NHC) and Nal. And then, the [Ru]-VI-catalyzed AROM/RCM of oxabicycle 161 with styrene (8 equiv) afforded the fully substituted pyran 162 in 62% yield and in 88% ee. The additional transformations led to 163 in good overall yield. Although this application of AROM/CM process to 161 was the first and rare example of Ru-catalyzed enantioselective olefin metathesis process, very recently, an application of enantioselective RCM reaction catalyzed by [Ru]-VII to the synthesis of (—)-5-e/>/-citreoviral has been reported by Funk. ... 

Catalytic Enantioselective Olefin Metathesis and Natural Product Synthesis... 

In this chapter, a brief account of various applications of catalytic enantioselective olefin metathesis [1] to the synthesis of biologically active molecules is presented. The availability of chiral catalysts for olefin metathesis offers schemes for enantioselective synthesis of natural products that are more concise than those entailing the use of achiral Ru- or Mo-based complexes and enantiomerically pure substrates [2]. Enantioselective olefin metathesis plays a critical role in the development of more effective catalysts. A less appreciated role of investigations directed toward chiral catalyst development is that such efforts can lead to the identification of better catalysts. In designing a chiral catalyst, the structure - the steric and electronic characteristics - of the promoter molecule might be altered to the extent that a fundamentally new type of catalyst, one that hkely has different reactivity and/or selectivity profiles, emerges. 

In 2005, the first examples of enantioselective olefin metathesis involving substrates that bear Lewis basic amines were reported [3]. Catalytic activity of number of chiral Mo-based diolates (such as 2, Scheme 12.1) were probed enantioselective ring-closing metathesis (RCM) reactions deliver various azacycUc structures in up to 99/1 enantiomeric ratio (er). It should be noted that Ru-based catalysts can be largely inhibited in the presence of the same class of amine substrates... 

Total synthesis of baconipyrone C, summarized in Scheme 12.5 [10], is the first and only application of Ru-catalyzed enantioselective olefin metathesis to natural product synthesis. Treatment of oxabicycle 11 with styrene and 2mol% chiral Ru complex [Ru]-XV [11] leads to the formation of pyran 12 in 62% yield and with an enantiomeric ratio of 94 6. Ru-carbene [Ru]-XV is generated in situ by subjecting the corresponding Ag-based N-heterocyclic carbene (NHC) to an achiral Ru-PCys complex and Nal. It is also worthy of note that the diketone fragment of baconipyrone C was synthesized through a tandem double-allylic alkylation process promoted by a chiral NHC-Cu complex that is structurally related to carbene [Ru]-XV. 

So far, enantioselective olefin metathesis has the largest impact on organic synthesis in the desymmetrization of achiral polyenes [81] an illustrative example refers to the total synthesis of endo-brevicomin [82]. The catalytic asymmetric cycli-zation of achiral trienes and meso-tetraenes via ARCM proceeds in excellent enan-tioselection (e.e. > 99 %) as demonstrated for dihydrofuran 163 (Scheme 11.40). 

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