Chiral Zirconium Catalysts for Enantioselective Synthesis

Asymmetric catalysis is a vital and rapidly growing branch of modern organic chemistry. Within this context, Ti- and Zr-based chiral catalysts have played a pivotal role in the emergence of a myriad of efficient and enantioselective protocols for asymmetric synthesis. In this chapter, a critical overview of enantioselective reactions promoted by chiral Zr-based catalysts is provided. Since an account of this type is most valuable when it provides a context for advances made in a particular area of research, when appropriate, a brief discussion of related catalytic asymmetric reactions promoted by non-Zr-based catalysts is presented as well. 

Zr-Catalyzed Enantioselective Alkylation of Alkenes with Crignard Reagents 

Chiral C2-symmetric ansa-metallocenes, also referred to as bridged metallocenes, find extensive use as catalysts that effect asymmetric C—C bond-forming transformations [4]. In general, bridged ethylene(bis(tetrahydroindenyl))zirconocene dichloride ((ebthi)ZrCl2) 1 or its derived binaphtholate ((ebthi)Zrbinol) 2 [5] and related derivatives thereof have been extensively utilized in the development of a variety of catalytic asymmetric alkene alkylations. 

The aforementioned observations have significant mechanistic implications. As illustrated in Eqs. 6.2—6.4, in the chemistry of zirconocene—alkene complexes derived from longer chain alkylmagnesium halides, several additional selectivity issues present themselves. (1) The derived transition metal—alkene complex can exist in two diastereomeric forms, exemplified in Eqs. 6.2 and 6.3 by (R)-8 anti and syn reaction through these stereoisomeric complexes can lead to the formation of different product diastereomers (compare Eqs. 6.2 and 6.3, or Eqs. 6.3 and 6.4). The data in Table 6.2 indicate that the mode of addition shown in Eq. 6.2 is preferred. (2) As illustrated in Eqs. 6.3 and 6.4, the carbomagnesation process can afford either the n-alkyl or the branched product. Alkene substrate insertion from the more substituted front of the zirconocene—alkene system affords the branched isomer (Eq. 6.3), whereas reaction from the less substituted end of the (ebthi)Zr—alkene system leads to the formation of the straight-chain product (Eq. 6.4). The results shown in Table 6.2 indicate that, depending on the reaction conditions, products derived from the two isomeric metallacydopentane formations can be formed competitively. 

Detailed studies in these laboratories have shed light on the mechanistic intricacies of asymmetric catalytic carbomagnesations, allowing for an understanding of the above trends in regio- and stereoselectivity [9]. Importantly, these mechanistic studies have indicated that there is no preference for the formation of either the anti or the syn (ebthi)Zr—alkene isomers (e. g. 8 anti vs. 8 syn) it is only that one metallocene—alkene 

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A. H. Hoveyda, Chiral Zirconium Catalysts for Enantioselective Synthesis, in Titanium and Zirconium in Organic Synthesis (Ed. I. Marek, Wiley-VCH, Weinheim, 2002, pp. 180-229). 

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