Diastereoselectivity with organolithium reagents

The equatorial selectivity observed with organolithium reagents is enhanced in diethyl ether as the reaction solvent by the addition of lithium perchlorate (Table l)12. I3C-NMR studies47 indicate that the formation of a complex between lithium perchlorate and the carbonyl group, which also leads to a dramatic enhancement of the rate of the addition reaction, accounts for the increased diastereoselectivity. 

The chiral Fischer-type chromium carbene complex of furan 28, shown in Scheme 14, participated in nucleophilic 1,4-addition with organolithium reagents followed hy alkylation in a regioselective and diastereoselective manner, creating a quaternary C-3 stereocenter in the 2,3-trisubstituted 2,3-dihydrofuran products after oxidative decom-plexation and reductive cleavage of the chiral auxiliary <2003CEJ5725>. 

One of the most successful classes of chiral auxiliaries for asymmetric synthesis is that of Enders proline-based hydrazines, namely (S)-l-amino-2-methoxymethylpyrrolidine (SAMP, 74) and its (R)-enantiomer RAMP (Scheme 11.11) [68]. Enders has reported that chiral hydrazones such as 75 undergo diastereoselective additions with organolithium reagents. The facile removal of the auxiliary by reductive cleavage of the N-N bond enables it as a versatile tool for the synthesis of a wide range of chiral secondary amines [69, 70]. As shown in Scheme 11.11, the secondary amine 77 was thus prepared in 73 % overall yield and 93 % ee [69]. 

Carbamate substituents have also been found to permit the direct removal of allylic, propargylic and allenic protons by organolithium reagents [32, 33]. In the latter case, the resulting lithioallenes can be converted to the allenyltitanium reagents with ClTi(OiPr)3 (Eq. 9.28) [8]. As illustrated, subsequent addition to acetaldehyde proceeds with only modest diastereoselectivity. 

These reagents add to the chiral ketones 3 with high 1,5-asymmetric induction. Grignard and organolithium reagents show slight diastereoselectivity.3 Example ... 

Solvent and temperature effects on the diastereoselective addition of n-BuLi to 2-phenylpropanal have been reassessed95 and the stereochemistry of addition of organolithium reagents to carbohydrate enones has been studied.96 No compelling evidence has been found to support the suggestion that addition of n-BuLi to benzoic acid might compete with formation of the lithium salt and thereby provide an alternative to the sequential route to PhCOBu".97... 

Diastereoselective 1,2- and 1,4-Additions of Chiral Aminals. The organolithium reagent derived from a chiral bromoaminal and BuLi adds to pentanal to afford an optically active lactol. Subsequent oxidation affords the optically active lactone with 88% ee (eq 3). ... 

Organolithium reagents (primary, secondary, tertiary, aryl and vinyl) also add in excellent yield to a-alkoxyaldehyde dimethylhydrazones (146) equation 19) with high threo diastereoselectivity (Table 9). Hydrogenolytic cleavage of the resultant hydrazines provide an attractive route to rAreo-2-amino alcohols. 

The imine 19 derived from a phenylethylamine has been reported to react with various nucleophiles, such as organolithium reagents and cuprates, to generate the diastereoenriched amine following hydrogenolysis (H2/Pd) of the chiral auxiliary. However, the diastereoselectivities of these reactions are typically modest [36 38]. The seminal works of Takahashi [39] and later Pridgen [40] demonstrated that higher... 

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