Enantioselective metathesis

Keywords Catalytic metathesis, Enantioselective synthesis, Catalytic kinetic resolution, Catalytic carbomagnesation, Catalytic rearrangement, 2-Substituted chromenes, Catalytic m aero cyclization... 

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. 

In Ghosh s enantioselective total synthesis of the cytotoxic marine macrolide (+)-amphidinolide T1 (318) [143], the C1-C10 fragment 317 was constructed by CM of subunits 315 and 316 (Scheme 62). The reaction mediated by catalyst C (5 mol%) afforded in the first cycle an inconsequential 1 1 mixture of (E/Z)-isomeric CM products 317 in 60% yield, along with the homodimers of 315 and 316. The self-coupling products were separated by chromatography and exposed to a second metathesis reaction to provide olefins 317 in additional 36% yield [144]. 

Initial studies indicated that this ruthenium complex is an effective chiral catalyst for enantioselective metathesis. For example, desymmetrization of the anhydride 68 (Scheme 43) in the presence of 10 mol % of 65 and 10... 

Negishi E, Tan Z (2005) Diastereoselective, Enantioselective, and Regioselective Carbo-alumination Reactions Catalyzed by Zirconocene Derivatives. 8 139-176 Netherton M, Fu GC (2005)Pa]ladium-catalyzed Cross-Coupling Reactions of Unactivated Alkyl Electrophiles with Organometallic Compounds. 14 85-108 Nicolaou KC, King NP, He Y (1998) Ring-Closing Metathesis in the Synthesis of EpothUones and Polyether Natmal Products. 1 73-104 Nishiyama H (2004) Cyclopropanation with Ruthenium Catalysts. 11 81-92 Noels A, Demonceau A, Delaude L (2004) Ruthenium Promoted Catalysed Radical Processes toward Fine Chemistry. 11 155-171... 

The pioneering work on enantioselective ruthenium olefin metathesis was carried out by Grubbs and co-workers in 2001 [69] (Fig. 3.23). Catalysts 55a-b and 56a-b were designed and prepared from C -symmetric NHC hgands with a combination of chiral backbone and mono-ortfto-substituted aryl side chains, a motif that was expected to form a chiral environment around the metal centre. 

The synthesis in Scheme 13.49 features use of an enantioselective allylic boronate reagent derived from diisopropyl tartrate to establish the C(4) and C(5) stereochemistry. The ring is closed by an olefin metathesis reaction. The C(2) methyl group was introduced by alkylation of the lactone enolate. The alkylation is not stereoselective, but base-catalyzed epimerization favors the desired stereoisomer by 4 1. 

Scheme 6/4.29. Enantioselective domino ring-opening/ring-closing metathesis with a Mo-catalyst.

Catalytic Ring-Closing Metathesis and the Development of Enantioselective Processes... 

Catalytic ring-closing metathesis makes available a wide range of cyclic alkenes, thus rendering a number of stereoselective olefin functionalizations practical. The availability of effective metathesis catalysts has also spawned the development of a variety of methods that prepare specially-outfitted diene substrates that can undergo catalytic ring closure. The new metathesis catalysts have already played a pivotal role in a number of enantioselective total syntheses. 

Perhaps the most compelling research objective in this area will involve the development of a chiral metathesis catalyst that effects C-C bond formation efficiently and with excellent levels of enantioselectivity [41 ]. In such a case, all the reactions discussed herein, in addition to those expertly developed in other laboratories [40], will become subject to asymmetric catalysis. Such a development should prove to have an enormous impact on the field of inorganic, organome-tallic and synthetic organic chemistry. 

Scheme 6.3. Zr-catalyzed enantioselective ethylmagnesation and metal-catalyzed alkene metathesis make effective partners. In the two cases shown here, the alkene substrate is synthesized and enantioselectively alkylated in the same vessel.

Catalytic olefin metathesis, in only a few years, has risen to be one of the most important and reliable processes in organic synthesis. Recently, several reports by Schrock and Hoveydallsbbond forming transformations efficiently and enan-tioselectively. A recent concise and enantioselective synthesis of exo-brevicomin by Burke utilizes chiral catalyst 91 (Scheme 13) to effect the desymmetriza-tion of 90 through a ring-closing metathesis.11531... 

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