Diastereoselectivity external

In the enantioselective synthesis, the asymmetry (i.e., the stereoselectivity) is induced by the external chiral catalyst, while the diastereoselective synthesis does not require a chiral catalyst. The stereogenic center already present in the molecule is able to induce stereoselectivity, assuming that the synthesis starts with a single enantiomer. For instance, imagine that an a,/ -substituted product is formed, and that the reactant already contains a stereogenic carbon at a. If the reaction of (aS) leads, e.g., largely to (aS, / R) and hardly to the (aS, /IS) diastereomer (i.e., stereoisomers that are not mirror-images of each other), the reaction is diastereoselective (Scheme 14.2). 

The bis(oxazoline) S, 5)-(115) has been used as an external chiral ligand to induce asymmetric diastereoselective lithiation by r-BuLi during [2,3]-Wittig rearrangement of achiral substrates, (fj-crotyl propargylic ethers.It is believed that the enantios-electivity is determined predominantly at the lithiation step. 

Repeated deprotonation of 278 removed due to a high H/D kinetic isotope effect the 1-proton, forming the dideuterio compound 279 with low diastereoselectivity . It is quite likely that a dynamic thermodynamic resolution is the origin. Intermediate 277 is configurationally labile, enabling an equilibration of the diastereomeric ion pairs 277 and epi-211. Similar studies were undertaken with 1-phenyl-l-pyrid-2-ylethane (280) and l-(4-chlorophenyl)-l-(pyrid-2-yl)-3-(dimethylamino)propane (281) (50% eef. An improvement of the achieved enantiomeric excesses resulted when external chiral proton sources, such as 282 or 283, were applied (84% ee for 280 with 283 and 75% ee for 281). 

Seebach and Naef1961 generated chiral enolates with asymmetric induction from a-heterosubstituted carboxylic acids. Reactions of these enolates with alkyl halides were found to be highly diastereoselective. Thus, the overall enantioselective a-alkyla-tion of chiral, non-racemic a-heterosubstituted carboxylic acids was realized. No external chiral auxiliary was necessary in order to produce the a-alkylated target molecules. Thus, (S)-proline was refluxed in a pentane solution of pivalaldehyde in the presence of an acid catalyst, with azeotropic removal of water. (197) was isolated as a single diastereomer by distillation. The enolate generated from (197) was allylated and produced (198) with ad.s. value >98 %. The substitution (197) ->(198) probably takes place with retention of configuration 196>. 

If two different external electrophiles are to be added to the dimetallic species, diastere-oselectivity can only be achieved if the two carbon-metal bonds are properly discriminated against the reaction with a first electrophile. Moreover, the resulting monometallic species has to exhibit significant configurational stability. Coordination by a heteroatom, which turned out to be essential for achieving substrate-induced diastereoselection, also nicely served these purposes. 

Amino acid-based dithiazines 281 were lithiated and allowed to react with benzaldehyde, giving products 282 in good yields but with low diastereoselectivity (Scheme 72)451. These adducts underwent externally sensitizer photofragmentation with quantum efficiency comparable to the parent dithiane and trithiane adducts. 

Significant progress has been made towards the understanding of proton delivery 152,165 Diastereomeric silyl ethenyl ethers 145 and 148 decompose on addition of TBAF and AcOH into the corresponding enols 146 and 149, which yield with AcOH two complementary bicyclic ketones (147 and 150, respectively), in different degrees of diastereomeric purity (equations 40 and 41). Two different proton transfer processes take place Bicyclic ketone 147 is formed by external delivery of a proton to 146 on its less hindered face (equation 40) the complementary ketone 150 is formed by protonation of 149 on its more hindered face (equation 41), invoking internal proton dehvery from the intermediate pyridinium acetate 151. For a more sterically demanding and weaker acid, such as phenol, the diastereoselectivity increased for 147 but reversed for 150. ... 

Under neutral conditions Ru(II) complexes catalyze the nucleophilic addition of water to nitriles to yield amides [155], The reaction proceeds via external nucleophilic attack of water to the transition metal-activated nitrile. Under similar conditions <5-ketonitriles are converted into ene-lactams, a reaction that has found elegant application in a short diastereoselective synthesis of (-)-pumiliotoxin C (Sch. 37) [156]. 

The 1,3-diol unit is an important constituent of many highly oxygenated natural products. Consequently, highly diastereoselective methods for reducing -hydroxy ketones to either of the possible dia-stereoisomers have been developed. The syn isomer was produced by attack of an external hydride... 

---