Hydrogen diastereoselectivity

R)-Amino ketone A in Scheme 1.44 is hydrogenated diastereoselectively with a neutral (5)-(R)-BPPFOH- RhCl(cod)]2 in ethyl acetate to give the R,R amino alcohol B [229]. The... 

The menthyl group has often been employed as an easily available chiral auxiliary. 8-Phenylmenthyl 2-amino-3,3-difluorocyclopentenecarboxylate 222 prepared from 219 via 221 was hydrogenated diastereoselectively to form ds-2-aminocarboxylate 223 (see Scheme 9.49) [77]. The higher diastereoselectivity induced by the 8-phenylmenthyl group was also observed in Znl2-catalyzed NaBH4 reduction of open-chain 3-amino-a, 3-unsaturated esters 224. In contrast, the unsubstituted menthyl ester was reduced with no practical diastereoselectivity (see table in Scheme 9.49). 

In the presence of 2, aryl ketones in which the a-carbon carries a heteioatom substituent undergo hydrogenation diastereoselectively and enantioselectively. ... 

Asymmetric induction is used in the stereoselective synthesis of silanes via the hvdrosilyla-tion of a,/l-unsaturated esters30. The addition of the tris(trimethylsilyl)silyl radical to the double bond is highly regioselective. yielding an ester-substituted radical that abstracts hydrogen diastereoselectively. 

Why is this hydrogenation diastereoselective Is it subject to equilibration or isomerization ... 

Amino ketone A in Scheme 1.44 is hydrogenated diastereoselectively with a neutral... 

Diastereoselective Hydrogenation since -OH directs the H2, there is a possibility for control of stereochemistry - sensitive to H2 pressure catalyst cone, substrate cone, solvent. 

Conducting the hydrogenation at high H2 pressures supresses olefin isomerization and often gives higher diastereoselectivity. 

Asymmetric synthesis is a method for direct synthesis of optically active amino acids and finding efficient catalysts is a great target for researchers. Many exceUent reviews have been pubHshed (72). Asymmetric syntheses are classified as either enantioselective or diastereoselective reactions. Asymmetric hydrogenation has been appHed for practical manufacturing of l-DOPA and t-phenylalanine, but conventional methods have not been exceeded because of the short life of catalysts. An example of an enantio selective reaction, asymmetric hydrogenation of a-acetamidoacryHc acid derivatives, eg, Z-2-acetamidocinnamic acid [55065-02-6] (6), is shown below and in Table 4 (73). 

Lewis acids, results in the formation of isopulegol (43) with greater than 98% diastereoselectivity isopulegol (43), wherein all of the ring substituents are equatorially oriented, arises naturally from a chairlike transition state structure in which the C-3 methyl group, the coordinated C-l aldehyde carbonyl, and the A6,7 double bond are all equatorial (see 48). A low-temperature crystallization raises the chemical and enantiomeric purity of isopulegol (43) close to 100%. Finally, hydrogenation of the double bond in 43 completes the synthesis of (-)-menthol (1). 

When a solution of 25 in a 1 1 mixture of methanol and methylene chloride is exposed to periodic acid, the dithiane group is cleaved oxidatively to give, after treatment of the crude product with camphorsulfonic acid (CSA) in methanol, bisacetal 12 as a 2 1 mixture of C-12 anomers in a yield of 80% (Scheme 3). Although the conversion of 12 into 10 could be carried out on the mixture of anomers, it was found to be more convenient to carry each isomer forward separately. When 12 is treated with lithium diethylamide, the methine hydrogen adjacent to the lactone carbonyl is removed as a proton to give an enolate which is then oxidized in a completely diastereoselective fashion with Davis s oxaziridine18 to afford 11. 

It is important to emphasize that the hydroxy dithioketal cyclization can be conducted under mild reaction conditions and can be successfully applied to a variety of substrates.15 However, the utility of this method for the synthesis of didehydrooxocane-contain-ing natural products requires the diastereoselective, reductive removal of the ethylthio group. Gratifyingly, treatment of 13 with triphenyltin hydride and a catalytic amount of the radical initiator, azobisisobutyronitrile (AIBN), accomplishes a homolytic cleavage of the C-S bond and furnishes didehydrooxocane 14 in diastereo-merically pure form (95 % yield), after hydrogen atom transfer. 

In an effort to make productive use of the undesired C-13 epimer, 100-/ , a process was developed to convert it into the desired isomer 100. To this end, reaction of the lactone enolate derived from 100-) with phenylselenenyl bromide produces an a-selenated lactone which can subsequently be converted to a,) -unsaturated lactone 148 through oxidative syn elimination (91 % overall yield). Interestingly, when 148 is treated sequentially with lithium bis(trimethylsilyl)amide and methanol, the double bond of the unsaturated lactone is shifted, the lactone ring is cleaved, and ) ,y-unsaturated methyl ester alcohol 149 is formed in 94% yield. In light of the constitution of compound 149, we were hopeful that a hydroxyl-directed hydrogenation52 of the trisubstituted double bond might proceed diastereoselectively in the desired direction In the event, however, hydrogenation of 149 in the presence of [Ir(COD)(py)P(Cy)3](PF6)53 produces an equimolar mixture of C-13 epimers in 80 % yield. Sequential methyl ester saponification and lactonization reactions then furnish a separable 1 1 mixture of lactones 100 and 100-) (72% overall yield from 149). 

This thoroughly revised and updated new edition is a must for every synthetic organic chemist. New material has been added on homogene- ous diastereoselective hydrogenations, enantioselective oxidations, and novel chiral auxiliaries. 

Simple diastereoselection has also been reported for Strecker syntheses using pentanedial or butanedial with primary amines or hydrogen cyanide which affords 2,5-dicyanopiperidine or 2,5-dicyanopyrrolidine derivatives, respectively35. In both cases, the achiral svn-diastereomers are slightly preferred. At 70 °C, the pure rA-compounds can be partially transformed to the /rfflM-isomcrs. 

An efficient stereoselective Strecker synthesis of phenylglycine has been achieved using the tert-butyl ester tm-leucine as the chiral auxiliary. Its benzaldimine reacts with hydrogen cyanide in hexane at — 23 °C to furnish the ( )-diastereomer with the excellent diastereoselectivity of >98 254. 

The diastereoselectivity and the stereochemical outcome of the addition of 2,3,4,6-tetrahydro-3, 4-dimethyl-2-phenyl-1,4-oxazepine-5,7-dione, derived from ephedrine and methyl hydrogen malonate, to 1 -nitrocyclohexene was found to be dependent on the nature of the base and the solvent. The highest diastereoselectivity was obtained when potassium /tr/-butoxide in the presence of dicyclohcxyl-18-crown-6 was employed. In the absence of crown ether the diastereoselection was poor and the sense of the stereochemical outcome was reversed26. 

Diastereoselective addition has been carried out with achiral reagents and chiral substrates, similar to the reduction shown on page. 1201, but because the attacking atom in this case is carbon, not hydrogen, it is also possible to get diastereoselective addition with an achiral substrate and an optically active reagent. Use of suitable reactants creates, in the most general case, two new chiral centers, so the product can exist as two pairs of enantiomers ... 

With most of these reagents the alcohol is not isolated (only the alkene) if the alcohol has a hydrogen in the proper position. However, in some cases the alcohol is the major product. With suitable reactants, the Knoevenagel reaction, like the aldol (16-2), has been carried out diastereoselectively and enantioselectively. ... 

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