Chiral molybdenum

AROM)-RCM- and -CM sequences initiated by chiral molybdenum-based catalysts [194] or, more recently, also by ruthenium-based [195] catalysts. 

For a chiral molybdenum-based catalyst available in situ from commercial components, see (a) Aeilts SL, Cefalo DR, Bonitatebus PJ, Houser JH, Hoveyda AH, Schrock RR (2001) Angew Chem Int Ed 40 1452 (b) For the first enantiomerically pure solid-sup-ported Mo catalyst, see Hultzsch KC, Jernelius JA, Hoveyda AH, Schrock RR (2002) Angew Chem Int Ed 41 589 (c) For a chiral Mo catalyst, allowing RCM to small- and medium-ring cyclic amines, see Dolman SJ, Sattely ES, Hoveyda AH, Schrock RR (2002) J Am Chem Soc 124 6991 (d) For a novel adamantyl imido-molybdenum complex with advanced selectivity profiles, see Tsang WCP, Jernelius JA, Cortez GA, Weatherhead GS, Schrock RR, Hoveyda AH (2003) J Am Chem Soc 125 2591... 

As well as organic chiral auxiliaries, organometallic fragments have found some application as chiral auxiliaries in conjugate addition reactions. Particularly noteworthy are chiral molybdenum allyl complexes [69], chiral iron complexes [70], and planar chiral arene chromium species [71]. 

When the chiral molybdenum Ti-allyl-substituted enone 147 was treated with lithium dimethylcuprate, formation of adduct 148 with fair selectivity was observed (Scheme 6.29) [69]. Interestingly, higher selectivities were obtained in the presence of boron trifluoride etherate. It is assumed that Lewis acid coordination induces the s-trans reactive conformation 149 [64]. Consequently, nucleophile attack anti to the molybdenum fragment should afford the major diastereomer 148. 

Scheme 6.29. Diastereoselective cuprate addition to chiral molybdenum Ti-allyl enone complex 147.

Asymmetric Synthesis Using a Chiral Molybdenum Catalyst In olefin metathesis, a double bond is cleaved and a double bond is formed. Thus, a chiral carbon center is not constructed in the reaction. To realize the asymmetric induction by ring-closing metathesis, there are two procedures a kinetic resolution and desym-metrization of symmetric prochiral triene. Various molybdenum complexes are synthesized in order to explore the viabihty of these approaches (Figure 6.2). 

Enantioselective cyclic ether is synthesized by molybdenum-catalyzed olefin metathesis. Cyclopentene derivative 85a is reacted with 5 mol% of chiral molybdenum catalyst 76 to give pyran derivative 86a in high yield and high ee... 

An area, in which catalytic olefin metathesis could have a significant impact on future natural product directed work, would be the desymmetrization of achiral molecules through asymmetric RCM (ARCM) with chiral molybde-num-(for a chiral molybdenum-based catalyst available in situ from commercial components, see Refs 156 and 156a-156c) or ruthenium-based catalysts. 

Chiral molybdenum complexes of llil-pyran.1 Enantiomerically pure Mo-com-plexes, (S)- and (R)-l, of 2//-pyran have been prepared by known methods (13, 194-195) from d- and L-arabinose, respectively. They react with a wide range of nucleophiles at an allylic position with 96% ee. The resulting complex can react with a second nucleophile at the other allylic position to form c/y-disubstituted complexes, also with high enantioselectivity. The sequence can be used to obtain chiral cis-2,6-disubstituted tetrahydropyrans such as 2, a component of the scent gland of the civer cat. 

Recently, chiral molybdenum catalysts such as 11 have been synthesized, giving access to asymmetric ring-closing metathesis [7]. Water-soluble variations of catalyst 10, like catalyst 12, perform metathesis in water or methanol [8], extending the scope of the reaction to substrates which are poorly soluble in organic solvents. 

Hoveyda and co-workers have developed chiral catalysts for asymmetric alkene metathesis. They have demonstrated that with their chiral molybdenum catalyst asymmetric syntheses of dihydrofurans through catalytic kinetic resolution by RCM and enantioselective desymmetrization by RCM are feasible processes (Scheme 40) <1998JA9720>. The use of Schrock s molybdenum catalysts for asymmetric alkene metathesis has been reviewed <2001CEJ945>. 

Figure 3 Chiral molybdenum alkylidene complexes used in asymmetric ring closing metathesis polymerization...

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... 

Scheme 14 Chiral molybdenum-based catalysts for asymmetric olefin metathesis...

Scheme 15 Chiral molybdenum olefin metathesis catalysts with benzhydryl and mesityl substituted bitet ligands...

Figure 1 Adamantylimido substituted chiral molybdenum olefin...

Hoveyda and Schrock attached (97a) to polymer via attached styrene groups yielding the first reported supported chiral molybdenum olefin metathesis catalyst, (290) (Scheme 27). Supported complex (290) is less active than (97a), but it gives similar ranges of ees for enantioselective transformations like desymmetrization. The catalyst is recyclable and, even though the conversions have eroded, the enantioselectivity is still relatively high. Table 14. 

Efficient chiral molybdenum catalysts (Structure 21) which are, at the same time, easy to handle were generated in. situ and used without further purification in asymmetric olefin metathesis. For example, the RCM following eq. (17) yields > 80% of the desired product at >88% stereoselectivity [118]. 

Such a chiral ligand also allowed resolution of chiral molybdenum and tungsten complexes (37) (eq. [18]). 

Asymmetric RCM of substituted 1,6- and 1,7-dienes, taken to partial conversion using a chiral molybdenum carbene complex as catalyst, results in residual reactant having 19-84% excess of one enantiomer (Fujimura 1996a,b). 

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