Diastereoselectivity addition reactions

An analogous solvent effect was observed upon treatment of the chiral a-alkoxy aldehyde 11 with 2-lithio-4-methylfuran in the presence of zinc bromide. This highly diastereoselective addition reaction was the key step in a synthesis of the enantiomcrically pure C-10-C-20 fragment of the immunosuppressant KK 506139. 

Another chiral auxiliary used in diastereoselective addition reactions is the 1,3-oxazine derivative 4a which shows a close structural resemblance to the 1,3-oxathiane 16 (vide supra). However, in contrast to the oxathiane, 4a cannot be readily acylatcd in the 2-position. Therefore, the benzoyl derivative 4b was prepared by condensing amino alcohol 3 with phenylglyoxal. 

Besides simple alkyl-substituted sulfoxides, (a-chloroalkyl)sulfoxides have been used as reagents for diastereoselective addition reactions. Thus, a synthesis of enantiomerically pure 2-hydroxy carboxylates is based on the addition of (-)-l-[(l-chlorobutyl)sulfinyl]-4-methyl-benzene (10) to aldehydes433. The sulfoxide, optically pure with respect to the sulfoxide chirality but a mixture of diastereomers with respect to the a-sulfinyl carbon, can be readily deprotonated at — 55 °C. Subsequent addition to aldehydes afforded a mixture of the diastereomers 11A and 11B. Although the diastereoselectivity of the addition reaction is very low, the diastereomers are easily separated by flash chromatography. Thermal elimination of the sulfinyl group in refluxing xylene cleanly afforded the vinyl chlorides 12 A/12B in high chemical yield as a mixture of E- and Z-isomers. After ozonolysis in ethanol, followed by reductive workup, enantiomerically pure ethyl a-hydroxycarboxylates were obtained. 

Piperidine and benzylamine have been utilized in diastereoselective addition reactions to other a,/ -unsaturated vinyl sulfoxides bearing the R absolute configuration92,93 at sulfur. A conjugate addition of piperidine to (f )-l-methyl-4-[(Z)-l-propenylsulfinyl]benzene (20) in a polar solvent such as methanol gives an 83 17 (21A/21B) diastereomeric mixture of adducts94,95. 

For diastereoselective addition reactions of trialkoxysilylalkynes to N tert butanesulfinyl imines, see Lettan, R.B. 

Reaction with a-ketoesters. In a regio- and diastereoselective addition reaction, chelation control provides optically active a-hydroxy esters. 

D.ii. Diastereoselective Addition Reactions. Acyl addition of organolithium reagents to ketones and aldehydes usually follows Cram s rule (sec. 4.8.B), as seen in Table 8.14.251 Since lithium does not coordinate as readily as magnesium in reactions with carbonyls, chelation effects are somewhat diminished relative... 

Diastereoselective Addition Reactions to Iminium Ions Derived from Chiral Amines and Clyoxylic Acid... 

Glyoxylic acid-derived iminolactone 30 has also been used in a diastereoselective addition reaction to form 31 (Equation 3) [47]. Fukuyama attributed the selectivity of this reaction to attack of the nucleophile from the less hindered face of the iminium ion derived from 30. 

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