Enantioselective carbomagnesation

Zirconium-Catalyzed Enantioselective Carbomagnesation-Elimination Tandem Reaction of Allylic Derivatives... 

Because of the availability of the chiral catalyst 31, it was obvious to investigate the enantioselective carbomagnesation of prochiral substrates. Hoveyda and co-workers demonstrated that asymmetric carbomagnesations of cyclic allylic... 

In more recent work, Hoveyda et al. go a step further and utilize the enantioselective carbomagnesation (catalyzed by 31) for the kinetic resolution of racemic dihydropyrans of type rac-42, rac-43, or rac-44. 

The zirconium-catalyzed carbometalation reaction has been developed from the initial observation by Dzhemilev in 1983 that Cp2ZrCl2 (1) catalyzes the addition of ethyl-magnesium halide to unactivated alkenes [104-106]. A plausible mechanism for this carbometalation involves zirconocene and zirconacyclopentane species (Scheme 6.5) [107-109]. Diastereo- and enantioselective carbomagnesation is accomplished by use of chiral fl .sa-zirconocene derivative [110]. 

Table 2. (EBTHI)Zr-catalyzed enantioselective carbomagnesation of unsaturated heterocycles with longer chain alkylmagnesium chlorides ... 

Table 4.7. (EBTHl) Zr-Catalyzcd Enantioselective Carbomagnesation of Unsaturalcd Hctcrocyclc.s with Longer Chain Alkylmagnesium Chlorides."... 

A2. Ziiconiom-Calalyzed Enantioselective Carbomagnesation-Eliniination llindeni Reaction vi Allylic Derivatives... 

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

The chemistry described in this review article demonstrates the impressive positive influence that catalytic RCM has had on our research in connection to the development of other catalytic and enantioselective C-C bond forming reactions. There is no doubt that in the absence of pioneering work by Schrock and Grubbs, the Zr-catalyzed alkylation and kinetic resolution would be of less utility in synthesis. The number of unsaturated heterocyclic and carbocyclic substrates available for Zr-catalyzed asymmetric carbomagnesation would be far more limited without catalytic RCM. 

In 1997, Whitby reported that treatment of 2,5-dihydrofuran with Et3Al in the presence of 5 mol% 31 leads to the enantioselective formation of 39 (Scheme 6.13), rather than the product obtained from catalytic carbomagnesations (40) [34]. This outcome can be rationalized on the basis of Dzhemilev s pioneering report that with Et3Al, in contrast to the mechanism that ensues with EtMgCl (see Scheme 6.2), the intermediate alumina-cyclopentane (i) is converted to the corresponding aluminaoxacyclopentane ii. To ensure the predominant formation of 39, catalytic alkylations must be carried out in absence of solvent. 

In view of the Zr-catalyzed enantioslective carbomagnesation-elimination tandem reaction of allylic derivatives discussed earlier, a similar process with EtjAl might be expected and has indeed been developed recently [29]. As a representative example, the reaction of 2,5-dihydro-furan with 3 equiv. of Et3Al in the presence of (i )-(EBTHI)Zr[B[NOL-(5)] (8) and (NMTHI)ZrCpCl2 (9) produced, after hydrolysis, (S)-2-ethyl-3-buten-1 -ol in 90 and 67% yields, respectively. The enantioselectivity observed with 8 was >99% ee, whereas that observed with 9 was 85-90% ee. Upon deuterolysis of the organoaluminum products, a mixture of monodeuterated and nondeuterated products was obtained and the extent of D incorporation increased to 94% with neat Et3Al without any solvent. The results indicate that the reaction must produce two organoaluminum products, 10 and 11 (Scheme 4.18). On oxidation with 02 only... 

Zirconium-Catalyzed Enantioselective Cyclic Carbomagnesation of Diallylamines... 

As depicted in Eqs (3)-(5), kinetic resolution of a variety of cyclic allylic ethers is effected by asymmetric Zr-catalyzed carbomagnesation. Importantly, in addition to six-membered ethers, seven- and eight-membered ring systems can be readily resolved by the Zr-catalyzed protocol. It is worthy of note that the powerful Ti-catalyzed asymmetric epoxidation procedure of Sharpless [15] is often used in the preparation of optically pure acyclic allylic alcohols through the catalytic kinetic resolution of easily accessible racemic mixtures [16]. When the catalytic epoxidation is applied to cyclic allylic substrates, reaction rates are retarded and lower levels of enantioselectivity are observed. Ru-catalyzed asymmetric hydrogenation has been employed by Noyori to effect resolution of five-... 

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