Asymmetric induction with Grignard reactions

Metals other than palladium and molybdenum can be used for allylic substitution reactions. For example, nickel in the presence of the oxazolinylferrocenylphosphine 9 provides good asymmetric induction for the reaction of a Grignard reagent with allylic electrophilic systems such as acetates.151... 

The carbonyl carbon of an unsymmetrical ketone is a prochiral center reaction with a Grignard reagent 2 (R 7 R, R") can take place on either face of the carbonyl group with equal chance. The products 8a and 8b are consequently formed in equal amounts as racemic mixture, as long as no asymmetric induction becomes effective ... 

Sodium cuprate yielded less reduction product and less thiophilic addition product than lithium cuprate at both —50 and 0 °C. In the case of silyl thiones chiral at silicon, the reactions with organolithium derivatives and Grignard reagents produce a-silylsulfides with medium to good levels of asymmetric induction and, interestingly, the asymmetry induced at the a-carbon is retained in the subsequent desilylation431 (equation 118), the process being stereoselective. 

Asymmetric reactions of a chiral glyoxylate ester. Grignard reagents add to the glyoxylate ester (2) of ( — )-l with unusually high asymmetric induction. The chirality... 

Appreciable diastereoselectivity (50%) was found in the cycloaddition with buta-1,3-diene at -78 °C and the protiodesilylation of the diastereomeric mixture of the adducts with TBAF gave dihydrothiopyran with 51% ee (Scheme 28). Similar diastereoselectivity was observed in the reaction with organo-lithium and Grignard reagents which gave a-silyl sulfides in moderate yields with medium to good levels of asymmetric induction (de = 40-76%).45 As an example, the derivative with E = D gave with protiodesilylation a-deuterio benzyl methyl sulfide with 45% ee. These results lead to the conclusion that in both cases protiodesilylation occurs stereospecifically without loss of the induced chirality (Scheme 28). 

Iron catalysts are very effective for the substitution of acyl chlorides [Eq. (198) 439.440] and thiol esters [Eq. (199) 376] with Grignard reagents to yield ketones. 1.4-Addition of Grignard reagents to an alkylidenemalonate derivative, as shown in Eq. (158) [182,183] was also promoted with an iron catalyst, but the degree of the asymmetric induction was inferior to that of the reaction catalyzed by nickel. 

Zirconocene dichloride was used as a catalyst for allylic displacement of allyl ethers with Grignard reagents [449]. An asymmetric version of this reaction by the use of a catalytic amount of a chiral zirconocene dichloride was independently reported, and it achieved a nearly complete chirality induction [Eq. (205) 450]. 

Imines derived from benzylamine and a,3-unsaturated ketones which represent 1-azadiene systems can be isomerized to the corresponding 2-azadienes with potassium t-butoxide. Addition of r-butyl-lithium occurs smoothly to afford simple imine anions that undergo alkylation in the usual fashion. 3S The two examples provided in Scheme 17 illustrate the power of this method to provide either a,a- or a,a -substitution. On the other hand, reaction of similar 1-azadiene systems with Grignard reagents results in addition to form the imine anion directly (equation 44). This example represents one of the early contributions to asymmetric induction in this area and will be elaborated in Section 4.1.3.5. 

Cross-aldol reactions involving the optically active keto-esters menthyl pyruvate and phenylglyoxylate and either silyl enol ethers or keten silyl acetals have been shown to result in appreciable asymmetric induction, considerably larger than that observed in the reactions of the same chiral a-keto-esters with Grignard... 

The asymmetric alkylation additions of the prochiral aldehydes and ketones with organometallic reagents have been studied extensively during the last several decades. Alkyltitanium complexes can be obtained from metal carbanions via titanation. Introduction of chirality at the titanium center or on the ligand (or a combination of both) enables the possibility of asymmetric induction in the carbonyl addition reaction. Since the alkyllithiums and Grignard reagents are... 

---