Stereochemistry asymmetric allylation, enantioselective

The catalytic enantioselective desymmetrization of meso compounds is a powerful tool for the construction of enantiomerically enriched functionalized products." Meso cyclic allylic diol derivatives are challenging substrates for the asymmetric allylic substitution reaction owing to the potential competition of several reaction pathways. In particular, S 2 and 5n2 substitutions can occur, and both with either retention or inversion of the stereochemistry. In the... 

In 2001, Takahashi and his co-workers developed the first asymmetric ruthenium-catalyzed allylic alkylation of allylic carbonates with sodium malonates which gave the corresponding alkylated compounds with an excellent enantioselectivity (Equation (Sy)). Use of planar-chiral cyclopentadienylruthenium complexes 143 with an anchor phosphine moiety is essential to promote this asymmetric allylic alkylation efficiently. The substituents at the 4-position of the cyclopentadienyl ring play a crucial role in controlling the stereochemistry. A kinetic resolution of racemic allylic carbonates has been achieved in the same reaction system (up to 99% ee). ... 

The observed activation of allyltrihalosilanes with fluoride ion and DMF and the proposition that these agents are bound to the silicon in the stereochemistry-determining transition structures clearly suggested the use of chiral Lewis bases for asymmetric catalysis. The use of chiral Lewis bases as promoters for the asymmetric allylation and 2-butenylation of aldehydes was first demonstrated by Denmark in 1994 (Scheme 10-31) [55]. In these reactions, the use of a chiral phos-phoramide promoter 74 provides the homoallylic alcohols in high yield, albeit modest enantioselectivity. For example, the ( )-71 and benzaldehyde affords the anti homoallylic alcohol 75 (98/2 antUsyn) in 66% ee. The sense of relative stereoinduction clearly supports the intermediacy of a hexacoordinate silicon species. The stereochemical outcome at the hydroxy center is also consistent with a cyclic transition structure. 

Allylic alcohols represent a small fraction of the total population of alkenes found in organic molecules. Asymmetric epoxidation of allylic alcohols therefore taps only a small portion of the synthetic potential inherent in a completely general asymmetric epoxidation of isolated (nonfunctionalized) alkenes. A partial solution to this problem now exists. The recent development of a catalytic asymmetric process for the dihydroxylation of aUcenes provides an indirect route to epoxides or epoxide-like functionalization of alkenes. The stereochemistry of the process, the scope of enantioselectivity and chemical yield and a summary of key chemical transformations are presented in this section. Since this roach to alkene functionalization is at an early stage of development, the results sununarized here are certain to benefit from extensions and improvements as research in this area progresses. 

Enantioselective metal-catalysed allylic substitution reactions have attracted considerable attention, especially over recent years. The metal that has been most widely investigated for allylic substitution reactions is palladium. The mechanism of palladium-catalysed allylic substitution typically involves a double inversion, resulting in overall retention of relative stereochemistry. So, if the stereochemistry of the product is simply based on the stereochemistry of the starting material, how can an asymmetric synthesis be possible The answer lies in the choice of substrate for the enantioselective version of the palladium-catalysed allylic substitution reaction. For example, the substrate (10.40) proceeds via a meso intermediate complex (10.41). Which end of the allyl group the nucleophile adds to dictates which enantiomer of product will be formed, (10.42) or e r-(10.42). 

In 2004, Trauner and co-workers published a follow-up communication on their asymmetric catalytic system. Under optimized conditions, they were able to achieve good to excellent levels of enantioselectivity for a variety of substrates using complex 78 with lower catalyst loadings (10 mol %). It is important to note however, that the specific use of an alkoxy dienone substrate lacking a i-substituent on one of the alkenes (such as 76) was required for high yields and good enantioselectivities. Since the stereocenter formed during electrocyclization is subsequent destroyed on deprotonation of the allylic cation (see Section 3.4.3), the control of absolute stereochemistry in this case is solely due to facially selective reprotonation of the enolate. 

Asymmetric Pd-catalyzed allylic alkylations and other allylic transformations can be now performed efficiently with very high enantioselectivity. There are several steps in the catalytic cycle where enantioselection can take place and this is nicely analyzed in a recent review. One of these steps is the nucleophilic attack on a Pd 77 -allyl complex bearing a chiral auxiliary ligand. Considering an equally substituted rf-zWyX and bearing in mind that the stereochemistry of the attack is trans- (exo-), the regiochemistry (Cl or C3) of the attack controls the configuration of the final product (Scheme 67). 

For asymmetric synthesis, we had to prepare the enantiomerically pure allene 55 with the proper relative stereochemistry. The allene moiety could be synthesized from epoxy propargyhc derivative 56 through SN2 -type reaction with a Grignard reagent. The epoxy propargylic substrate would be synthesized from allylic alcohol 57 via Sharpless epoxidation for introducing the appropriate stereochemistry of the protected allenyl alcohol. For the stereoselective synthesis of 56, the allylic alcohol 57 would be prepared enantioselectively (Scheme 16). 

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